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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright C 2009 Mosby, An Imprint of Elsevier

Ferri's CLINICAL ADVISOR 2009 Instant Diagnosis and Treatment FRED F. FERRI, M.D., F.A.C.P. Clinical Professor, Alpert Medical School, Brown University, Providence, Rhode Island Dedication To our families. Their constant support and encouragement made this book a reality. MOSBY ELSEVIER 1600 John F. Kennedy Blvd., Suite 1800, Philadelphia, PA 19103-2899 FERRI'S CLINICAL ADVISOR 2009: INSTANT DIAGNOSIS AND TREATMENT ISBN-13: 978-0-323-04134-8 Copyright C 2009, 2008, 2007, 2006, 2005, 2004, 2003, 2002, 2001, 2000, 1999 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier's Health Sciences Rights Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: [email protected] . You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/permissions .

Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book. The Publisher.

International Standard Serial Number (ISSN) 1541-4515

ISBN-13: 978-0-323-04134-8 Acquisitions Editor: Druanne Martin Developmental Editor: Mary Beth Murphy Editorial Assistant: John Ingram Design Direction: Teresa McBryan Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Section Editors RUBEN ALVERO, M.D. Associate Professor, Obstetrics and Gynecology, University of Colorado Health Sciences Center, Aurora, Colorado SECTION I MICHAEL G. BENATAR, M.B.CH.B., D.PHIL. Assistant Professor of Neurology, Department of Neurology, Emory University, Atlanta, Georgia SECTION I JEFFREY M. BORKAN, M.D., PH.D. Professor and Chair, Department of Family Medicine Physician-in-Chief, Alpert Medical School, Brown University, Memorial Hospital of Rhode Island, Pawtucket and Providence, Rhode Island SECTION I MITCHELL D. FELDMAN, M.D., M.PHIL. Professor of Medicine, Director of Faculty Mentoring, University of California, San Francisco, Division of General Internal Medicine, San Francisco, California SECTION I FRED F. FERRI, M.D., F.A.C.P. Clinical Professor, Alpert Medical School, Brown University, Providence, Rhode Island SECTIONS I-V GLENN G. FORT, M.D., M.P.H. Clinical Associate Professor of Medicine, Alpert Medical School, Brown University Chief, Infectious Diseases, Our Lady of Fatima Hospital, North Providence, Rhode Island SECTION I LONNIE R. MERCIER, M.D. Clinical Instructor, Department of Orthopedic Surgery, Creighton University School of Medicine, Omaha, Nebraska SECTION I DENNIS J. MIKOLICH, M.D., F.A.C.P., F.C.C.P. Chief, Division of Infectious Diseases, VA Medical Center Clinical Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island SECTION I IRIS TONG, M.D. Clinical Assistant Professor, Alpert Medical School, Brown University, Division of Ambulatory General Internal Medicine, Rhode Island Hospital, Providence, Rhode Island SECTION I WEN-CHIH WU, M.D. Assistant Professor of Medicine, Alpert Medical School, Brown University Cardiologist, Providence VA Medical Center, Providence, Rhode Island SECTION I

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Contributors SONYA S. ABDEL-RAZEQ, M.D. Clinical Assistant Instructor, Department of Obstetrics and Gynecology/Resident Education, State University of New York at Buffalo Women's and Children's Hospital, Buffalo, New York ABDULBAKI ABDULRAHMAN, M.D. Department of Internal Medicine, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, Rhode Island PURVA AGARWAL, M.D. Department of Internal Medicine, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, Rhode Island TANYA ALI, M.D. Clinical Assistant Professor of Medicine, Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island PHILIP J. ALIOTTA, M.D., M.S.H.A., F.A.C.S. Clinical Instructor, Department of Urology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York Medical Director, Center for Urologic Research of Western New York, Williamsville, New York GEORGE O. ALONSO, M.D. Director, Department of Infection Control, Elmhurst Hospital Center, Elmhurst, New York Instructor in Medicine, Mount Sinai School of Medicine, New York, New York RUBEN ALVERO, M.D. Associate Professor, Obstetrics and Gynecology, University of Colorado Health Sciences Center, Aurora, Colorado SRIVIDYA ANANDAN, M.D. Attending Physician, Internal Medicine, Harvard Vanguard Medical Associates, Quincy, Massachusetts GOWRI ANANDARAJAH, M.D. Clinical Associate Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MEL L. ANDERSON, M.D., F.A.C.P Assistant Professor of Medicine, University of Colorado School of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado MICHELLE STOZEK ANVAR, M.D. Clinical Instructor, Division of General Internal Medicine, Rhode Island Hospital Clinical Instructor, Alpert Medical School, Brown University, Providence, Rhode Island ETSUKO AOKI, M.D., PH.D Fellow, Leukemia Department, University of Texas, M.D. Anderson Cancer Center, Houston, Texas

PATRICIA AREAN, PH.D. Associate Professor, Department of Psychiatry, University of California, San Francisco, San Francisco, California VASANTHI ARUMUGAM, M.D. Assistant Professor, Department of Medicine, Mount Sinai School of Medicine, New York, New York Attending Physician, Division of Infectious Diseases/Department of Medicine, Elmhurst Hospital Center, Elmhurst, New York AMAAR ASHRAF, M.D. Assistant Professor, Department of Medicine, Mount Sinai School of Medicine, New York, New York Attending Physician, Division of Infectious Diseases, Elmhurst Hospital Center, Elmhurst, New York SUDEEP KAUR AULAKH, M.D., C.M., F.R.C.P.C. Associate Professor of Medicine, Albany Medical College, Albany, New York MICHAEL G. BENATAR, M.B.CH.B., D.PHIL. Assistant Professor of Neurology, Department of Neurology, Emory University, Atlanta, Georgia AGNIESZKA K. BIALIKIEWICZ, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island NIRALI BORA, M.D. Family Medicine Resident, Department of Family Medicine, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Pawtucket, Rhode Island JEFFREY M. BORKAN, M.D., PH.D. Professor and Chair, Department of Family Medicine Physician-in-Chief, Alpert Medical School, Brown University, Memorial Hospital of Rhode Island, Pawtucket and Providence, Rhode Island KELLY BOSSENBROK, M.D. Assistant Clinical Instructor, Alpert Medical School, Brown University, Providence, Rhode Island LYNN BOWLBY, M.D. Attending Physician, Division of General Internal Medicine, Rhode Island Hospital Clinical Instructor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MANDEEP K. BRAR, M.D. Clinical Assistant Professor, Department of Obstetrics and Gynecology, State University of New York at Buffalo, Buffalo, New York JOANNA BROWN, M.D. Fellow, Adolescent/Young Adult Program, Children's Hospital, Boston, Massachusetts JONATHAN BURNS, M.A., M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island

STEVEN BUSSELEN, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Pawtucket, Rhode Island BRIAN CASSERLY, M.D. Reading Internal Medicine, Reading, Massachusetts GAURAV CHAUDHARY, M.D. Assistant Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island KARA CHEW, M.D. Department of Medicine, University of California, San Francisco, San Francisco, California MARIA A. CORIGLIANO, M.D., F.A.C.O.G. Clinical Assistant Professor, Department of Obstetrics and Gynecology, State University of New York at Buffalo, Buffalo, New York BRIAN J. COWLES, PHARM.D. Clinical Assistant Professor, Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island JOHN E. CROOM, M.D., PH.D. Co-Director, Comprehensive Epilepsy Center, Saint Luke's Mid America Brain and Stroke Institute, Neurological Consultants of Kansas City, Inc., Kansas City, Missouri ALICIA J. CURTIN, PH.D., G.N.P. Assistant Professor, Division of Geriatrics, Alpert Medical School, Brown University, Providence, Rhode Island CLAUDIA L. DADE, M.D. Attending Physician, Division of Infectious Diseases, Elmhurst Hospital Center, Elmhurst, New York Instructor in Medicine, Mount Sinai School of Medicine, New York, New York GEORGE T. DANAKAS, M.D., F.A.C.O.G. Clinical Assistant Professor, Department of Obstetrics and Gynecology, State University of New York at Buffalo, Buffalo, New York ALEXANDRA DEGENHARDT, M.D. Director, Multiple Sclerosis Center, New York Methodist Hospital, Brooklyn, New York JOSEPH DIAZ, M.D. Assistant Professor of Medicine, Division of General Internal Medicine, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, Rhode Island CHRISTINE M. DUFFY, M.D., M.P.H. Fellow, Center for Gerontology and Health Care Research, Alpert Medical School, Brown University, Providence, Rhode Island

JEFFREY S. DURMER, M.D., PH.D., D.ABSM. Chief Medical Officer, Fusion Sleep Center, Johns Creek, Georgia JANE V. EASON, M.D. Attending Physician, Division of Infectious Diseases, Elmhurst Hospital Center, Elmhurst, New York Instructor in Medicine, Mount Sinai School of Medicine, New York, New York STUART EISENDRATH, M.D. Professor of Clinical Psychiatry, University of California, San Francisco, San Francisco, California PAMELA ELLSWORTH, M.D. Associate Professor of Urology, Alpert Medical School, Brown University, Providence, Rhode Island RAMI ELTIBI, M.D. Department of Internal Medicine, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, Rhode Island GREGORY J. ESPER, M.D. Director, General Neurology, Emory University, Atlanta, Georgia MARILYN FABBRI, M.D. Instructor, Department of Medicine, Mount Sinai School of Medicine, New York, New York Attending Physician, Division of Infectious Diseases/Department of Medicine, Elmhurst Hospital Center, Elmhurst, New York MARK J. FAGAN, M.D. Director, Medical Primary Care Unit, Rhode Island Hospital Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island GIL M. FARKASH, M.D. Assistant Clinical Professor, State University of New York at Buffalo, School of Medicine, Buffalo, New York TIMOTHY W. FARRELL, M.D. Clinical Assistant Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MITCHELL D. FELDMAN, M.D., M.PHIL. Professor of Medicine, Director of Faculty Mentoring, University of California, San Francisco, Division of General Internal Medicine, San Francisco, California FRED F. FERRI, M.D., F.A.C.P. Clinical Professor, Alpert Medical School, Brown University, Providence, Rhode Island STACI A. FISCHER, M.D., F.A.C.P. Assistant Professor of Medicine, Division of Infectious Diseases, Alpert Medical School, Brown University, Rhode Island Hospital, Providence, Rhode Island TAMARA G. FONG, M.D., PH.D.

Instructor in Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts GLENN G. FORT, M.D., M.P.H. Clinical Associate Professor of Medicine, Alpert Medical School, Brown University Chief, Infectious Diseases, Our Lady of Fatima Hospital, North Providence, Rhode Island GENNA GEKHT, M.D. Chief Resident in Neurology, Department of Neurology, Emory University, Atlanta, Georgia PAUL F. GEORGE, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Pawtucket, Rhode Island DAVID R. GIFFORD, M.D., M.P.H. Assistant Physician, Division of Geriatrics, Rhode Island Hospital Assistant Professor of Community Health and Medicine, Alpert Medical School, Brown University, Providence, Rhode Island ANNGENE A. GIUSTOZZI, M.D., M.P.H. Assistant Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island CINDY GLEIT, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island GEETHA GOPALAKRISHNAN, M.D. Assistant Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island NANCY R. GRAFF, M.D. Associate Clinical Professor, Department of Pediatrics, University of California, San Diego, San Diego, California REBECCA A. GRIFFITH, M.D. Attending Physician, Department of Medicine, Morristown Memorial Hospital, Morristown, New Jersey JOSEPH GRILLO, M.D. Fellow, Department of Infectious Diseases, Roger Williams Medical Center, Providence, Rhode Island LAWRENCE HABER, M.D. Department of Medicine, University of California, San Francisco, San Francisco. California MOHAMMED HAJJIRI, M.D. Internal Medicine Resident, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, Rhode Island MICHELE HALPERN, M.D. Attending Physician, Division of Infectious Diseases, Sound Shore Medical Center of Westchester, New Rochelle, New York

Clinical Assistant Professor of Medicine, New York Medical College, Valhalla, New York MUSTAFA A. HAMMAD, M.D. Clinical Neurophysiology Fellow, Department of Neurology, Emory University, Atlanta, Georgia SAJEEV HANDA, M.D. Director, Division of Hospitalist Medicine, Rhode Island Hospital Clinical Instructor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MIKE HARPER, M.D. Associate Professor of Medicine, Division of Geriatrics, Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California, San Diego, San Diego, California TAYLOR HARRISON, M.D. Assistant Professor of Neurology, Department of Neurology, Emory University, Atlanta, Georgia CHRISTINE HARTLEY, M.D. Assistant Clinical Instructor, Department of Family Medicine, Memorial Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, Rhode Island ANNE L. HUME, PHARM.D. Professor of Pharmacy, Department of Pharmacy Practice, University of Rhode Island, Kingston, Rhode Island Adjunct Professor of Family Medicine, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island JENNIFER ROH HUR, M.D. Assistant Professor of Clinical Medicine, Indiana University School of Medicine, Indianapolis, Indiana RICHARD S. ISAACSON, M.D. Resident in Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts JENNIFER JEREMIAH, M.D. Clinical Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MICHAEL P. JOHNSON, M.D. Staff Physician, Division of General Internal Medicine, Rhode Island Hospital Assistant Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island KOHAR JONES, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island LUCY KALANITHI, M.D. Internal Medicine/Primary, University of California, San Francisco, San Francisco, California BHARAT K. KANTHARIA, M.D. Division of Cardiology, Albert Einstein Medical Center, Philadelphia, Pennsylvania DANIEL KAPLON, M.D.

Associate Professor of Surgery (Urology), Division of Urology, Alpert Medical School, Brown University, Providence, Rhode Island WAN J. KIM, M.D. Clinical Instructor, Department of Obstetrics and Gynecology, State University of New York at Buffalo, Buffalo, New York MELVYN KOBY, M.D. Associate Clinical Professor of Medicine, Department of Ophthalmology, University of Louisville School of Medicine, Louisville, Kentucky DAVID KURSS, M.D., F.A.C.O.G. Clinical Assistant Professor, Department of Obstetrics and Gynecology, State University of New York at Buffalo, Buffalo, New York CINDY LAI, M.D. Department of Medicine, University of California, San Francisco, San Francisco, California SUZETTE M. LAROCHE, M.D. Assistant Professor of Neurology, Emory University, Atlanta, Georgia JOSEPH J. LIEBER, M.D. Associate Director of Medicine, Chief, Medical Consultation Service, Elmhurst Hospital Center Clinical Associate Professor of Medicine, Mount Sinai School of Medicine, New York, New York CHUN LIM, M.D., PH.D. Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts MARA LINSCOTT, M.D. Department of Medicine, Women and Infants Hospital of Rhode Island, Providence, Rhode Island ZEENA LOBO, M.D. Attending Physician, Division of Infectious Diseases, Elmhurst Medical Center, Elmhurst, New York RICHARD LONG, M.D. Clinical Associate Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MICHAEL MAHER, M.D. Assistant Professor of Internal Medicine, Alpert Medical School, Brown University, Rhode Island Hospital, Providence, Rhode Island ACHRAF A. MAKKI, M.D., M.SC. Resident, Department of Neurology, Emory University, Atlanta, Georgia JOSEPH R. MASCI, M.D. Director of Medicine, Elmhurst Hospital Center Professor of Medicine, Mount Sinai School of Medicine, Elmhurst, New York

DANIEL T. MATTSON, M.D., M.S.C. (MED.) St. Louis Neurological Institute, St. Louis, Missouri JEFFREY MAZER, M.D. Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MAITREYI MAZUMDAR, M.D., M.P.H., M.SC. Instructor in Neurology, Harvard Medical School, Children's Hospital Boston, Department of Neurology, Boston, Massachusetts KELLY A. MCGARRY, M.D. Associate Program Director, General Internal Medicine Residency Program, Rhode Island Hospital Assistant Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island CRAIG J. MCMACKIN, M.D. Fellow, Cardiovascular Diseases, Alpert Medical School, Brown University, Rhode Island Hospital, Providence, Rhode Island LYNN MCNICOLL, M.D. Assistant Professor of Medicine, Alpert Medical School, Brown University Geriatrician, Division of Geriatrics, Rhode Island Hospital, Providence, Rhode Island LONNIE R. MERCIER, M.D. Clinical Instructor, Department of Orthopedic Surgery, Creighton University School of Medicine, Omaha, Nebraska DENNIS J. MIKOLICH, M.D., F.A.C.P., F.C.C.P. Chief, Division of Infectious Diseases, VA Medical Center Clinical Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MICHELE MONTANDON, M.D. University of California, San Francisco, San Francisco, California TAKUMA NEMOTO, M.D. Research Associate Professor of Surgery, State University of New York at Buffalo, Buffalo, New York JAMES J. NG, M.D. Staff Physician, The Vancouver Clinic, Vancouver, Washington MELISSA NOTHNAGLE, M.D. Assistant Professor of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island ELIZABETH NOWAK, D.O. Clinical Instructor of Family Medicine, Department of Family Medicine, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island JUDITH NUDELMAN, M.D. Clinical Assistant Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence,

Rhode Island GAIL M. O'BRIEN, M.D. Medical Director, Adult Ambulatory Services, Rhode Island Hospital Clinical Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island CAROLYN J. O'CONNOR, M.D. Assistant Clinical Professor, Yale University School of Medicine, Department of Medicine, St. Mary's Hospital, Waterbury, Connecticut ALEXANDER B. OLAWAIYE, M.D. Fellow, Division of Gynecologic Oncology, Vincent Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts MICHAEL K. ONG, M.D., PH.D. Assistant Professor, UCLA Division of General Internal Medicine/Health Services Research, UCLA School of Medicine, Los Angeles, California STEVEN M. OPAL, M.D. Professor of Medicine, Infectious Disease Division, Alpert Medical School, Brown University, Providence, Rhode Island CRISTINA A. PACHECO, M.D. Clinical Assistant Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MINA B. PANTCHEVA, M.D. Internal Medicine, Roger Williams Medical Center, Providence, Rhode Island JANICE PATACSIL-TRULL, M.D. Clinical Instructor of Family Medicine, Department of Family Medicine, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island PRANAV M. PATEL, M.D. Assistant Professor of Medicine, Division of Cardiology, University of California, Irvine Medical Center, Orange, California SHALINI PATEL, M.D. Associate Physician, Department of Medicine, University of California, San Francisco, San Francisco, California ELENI PATROZOU, M.D. Division of Infectious Diseases, Alpert Medical School, Brown University, Rhode Island Hospital, Providence, Rhode Island STEVEN PELIGIAN, D.O. Medical Director, CODAC Behavioral Healthcare, Providence, Rhode Island PETER PETROPOULOS, M.D., F.A.C.C.

Clinical Assistant Professor, Alpert Medical School, Brown University, Department of Veterans Affairs, Providence, Rhode Island PAUL A. PIRRAGLIA, M.D., M.P.H. Assistant Professor of Medicine, Alpert Medical School, Brown University, Rhode Island Hospital, Providence, Rhode Island SHARON S. HARTMAN POLENSEK, M.D., PH.D. Clinical Associate, Department of Neurology, Emory University, Atlanta, Georgia MAURICE POLICAR, M.D. Chief of Infectious Diseases, Elmhurst Hospital Center, Elmhurst, New York Assistant Professor of Medicine, Mount Sinai School of Medicine, New York, New York ARUNDATHI G. PRASAD, M.D. Clinical Instructor, Department of Obstetrics and Gynecology/Resident Education, State University of New York at Buffalo, Women's and Children's Hospital, Buffalo, New York KITTICHAI PROMRAT, M.D. Assistant Professor, Division of Gastroenterology, Department of Medicine, Alpert Medical School, Brown University Chief, Gastroenterology Section, Providence Veterans Affairs Medical Center, Providence, Rhode Island JOHN RAGSDALE, M.D. Clinical Assistant Professor of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island CHAITANYA V. REDDY, D.O. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island VICTOR I. REUS, M.D. Professor of Psychiatry, Department of Psychiatry, Langley Porter Psychiatric Institute, University of California, San Francisco, San Francisco, California HARLAN G. RICH, M.D. Director of Endoscopy, Rhode Island Hospital Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island LUTHER K. ROBINSON, M.D. Associate Professor of Pediatrics Director, Dysmorphology and Clinical Genetics, State University of New York at Buffalo, Buffalo, New York HEMANT K. SATPATHY, M.D. Assistant Professor, Department of Family Medicine Chief Resident, Department of OBGYN, Creighton University Medical Center, Omaha, Nebraska RUBY SATPATHY, M.D. Fellow, Cardiology, Department of Internal Medicine, Creighton University, Omaha, Nebraska

JASON M. SATTERFIELD, PH.D. Director, Behavioral Medicine Associate Professor of Clinical Medicine, University of California, San Francisco, San Francisco, California SEAN I. SAVITZ, M.D. Assistant Professor of Neurology, University of Texas, Houston, Texas JACK L. SCHWARTZWALD, M.D. Clinical Assistant Professor of Medicine, Rhode Island Hospital, Providence, Rhode Island CATHERINE SHAFTS, D.O. Assistant Clinical Instructor, Alpert Medical School, Brown University, Providence, Rhode Island MADHAVI SHAH, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island HARVEY M. SHANIES, M.D., PH.D. Director of Critical Care Medicine, Vassar Brothers Medical Center, Poughkeepsie, New York DEBORAH L. SHAPIRO, M.D. Chief, Division of Rheumatology, Elmhurst Hospital Center, Elmhurst, New York Clinical Assistant Professor of Medicine, Mount Sinai School of Medicine, New York, New York GRACE SHIH, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island MARK SIGMAN, M.D. Associate Professor of Surgery (Urology), Division of Urology, Alpert Medical School, Brown University, Providence, Rhode Island JOANNE M. SILVIA, M.D. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island CLIFFORD MILO SINGER, M.D. Associate Professor of Psychiatry Director, Insomnia and Chronobiology Clinic, Vermont Regional Sleep Center, University of Vermont College of Medicine, Burlington, Vermont NICOLE SIROTIN, M.D. Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California U. SHIVRAJ SOHUR, M.D., PH.D. Assistant Professor of Neurology, Harvard Medical School, Boston, Massachusetts

JENNIFER SOUTHER, M.D. Attending Physician, Department of Family Practice, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island JULIE ANNE SZUMIGALA, M.D. Clinical Instructor, Department of Obstetrics and Gynecology, State University of New York at Buffalo, Buffalo, New York DOMINICK TAMMARO, M.D. Associate Director, Categorical Internal Medicine Residency Co-Director, Medicine-Pediatrics Residency, Division of General Internal Medicine, Rhode Island Hospital Associate Professor of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island IRIS TONG, M.D. Clinical Assistant Professor, Alpert Medical School, Brown University, Division of Ambulatory General Internal Medicine, Rhode Island Hospital, Providence, Rhode Island MARGARET TRYFOROS, M.D. Clinical Assistant Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island EROBOGHENE E. UBOGU, M.B.B.S. (HONS.) Assistant Professor of Neurology, Case Western Reserve University School of Medicine Staff Neurologist, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio SEAN H. UITERWYK, M.D. Clinical Assistant Professor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island NICOLE J. ULLRICH, M.D., PH.D. Clinical Fellow in Neurology/Neurooncology, Children's Hospital Boston, Boston, Massachusetts JORGE A. VILLAFUERTE, M.D. Attending Orthopedic Surgeon, VA Medical Center, West Roxbury, Massachusetts HANNAH VU, D.O. Assistant Clinical Instructor, Department of Family Medicine, Alpert Medical School, Brown University, Providence, Rhode Island TOM J. WACHTEL, M.D. Physician-in-Charge, Division of Geriatrics, Rhode Island Hospital Professor of Community Health and Medicine, Alpert Medical School, Brown University, Providence, Rhode Island DENNIS M. WEPPNER, M.D., F.A.C.O.G. Associate Professor of Clinical Gynecology/Obstetrics, State University of New York at Buffalo Clinical Chief, Department of Gynecology/Obstetrics, Millard Fillmore Hospital, Buffalo, New York LAUREL M. WHITE, M.D. Clinical Assistant Professor, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, State University of New York at Buffalo, Buffalo, New York

DAVID P. WILLIAMS, M.D. Neurologist, Peachtree Neurological Clinics, PC, Atlanta, Georgia MARIE ELIZABETH WONG, M.D. Physician, Family Medicine, Baystate Brightwood Health Center, Springfield, Massachusetts WEN-CHIH WU, M.D. Assistant Professor of Medicine, Alpert Medical School, Brown University Cardiologist, Providence VA Medical Center, Providence, Rhode Island WEN Y. HELENA WU-CHEN, M.D. Department of Neurology, Temple University Hospital, Philadelphia, Pennsylvania AMANDA WULFSTAT, M.D. Department of Medicine, University of California, San Francisco, San Francisco, California BETH J. WUTZ, M.D. Clinical Assistant Professor of Medicine, Division of Internal Medicine/Pediatrics, Kajeida Health–Buffalo General Hospital, State University of New York at Buffalo, Buffalo, New York JOHN Q. YOUNG, M.D., M.P.P. Assistant Director, Adult Psychiatry Clinic Associate Director, Residency Training Program, Langley Porter Psychiatric Hospitals and Clinics, Department of Psychiatry, University of California, San Francisco, San Francisco, California CINDY ZADIKOFF, M.D., F.R.C.P.C. Assistant Professor of Neurology, Parkinson's Disease and Movement Disorders Center, Davee Department of Neurology and Clinical Neurological Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois SCOTT J. ZUCCALA, D.O., F.A.C.O.G. Staff Physician, Mercy Hospital of Buffalo, Buffalo, New York

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Preface This book is intended to be a clear and concise reference for physicians and allied health professionals. Its user-friendly format was designed to provide a fast and efficient way to identify important clinical information and to offer practical guidance in patient management. The book is divided into five sections and an appendix, each with emphasis on clinical information. The tremendous success of the previous editions and the enthusiastic comments from numerous colleagues have brought about several positive changes. Each section has also been significantly expanded from prior editions, bringing the total number of medical topics covered in this book to more than 1000. Illustrations have been added to several topics to enhance recollection of clinically important facts. The use of ICD-9CM codes in all the topics will expedite claims submission and reimbursement. Section I describes in detail over 700 medical disorders. Several new topics have been added to the 2009 edition. Medical topics in this section are arranged alphabetically, and the material in each topic is presented in outline format for ease of retrieval. Topics with an accompanying algorithm in Section III are identified with an algorithm symbol (ALG). Similarly, if topics also have a Patient Teaching Guide (PTG) available online, this has been noted. Key, quick-access information is consistently highlighted; clinical photographs are used to further illustrate selected medical conditions; and relevant ICD-9CM codes are listed. Most references focus on current peer-reviewed journal articles rather than outdated textbooks and old review articles. Evidence-based medicine data have been added to relevant topics. Topics in this section use the following structured approach: 1.

Basic Information (Definition, Synonyms, ICD-9CM Codes, Epidemiology & Demographics, Physical Findings & Clinical Presentation, Etiology)

2.

Diagnosis (Differential Diagnosis, Workup, Laboratory Tests, Imaging Studies)

3.

Treatment (Nonpharmacologic Therapy, Acute General Rx, Chronic Rx, Disposition, Referral)

4.

Pearls and Considerations (Comments, Suggested Readings)

5.

Evidence-Based Data and References

Section II includes the differential diagnosis, etiology, and classification of signs and symptoms. This section has been significantly expanded for the 2009 edition. It is a practical section that allows the user investigating a physical complaint or abnormal laboratory value to follow a “workup” leading to a diagnosis. The physician can then easily look up the presumptive diagnosis in Section I for the information specific to that illness. Section III includes clinical algorithms to guide and expedite the patient's workup and therapy. For the 2009 edition, several new algorithms have been added and many others have been revised. Many physicians describe this section as particularly valuable in today's managed-care environment. Section IV includes normal laboratory values and interpretation of results of commonly ordered laboratory tests. By providing interpretation of abnormal results, this section facilitates the diagnosis of medical disorders and further adds to the comprehensive, “one-stop” nature of our text. Section V focuses on preventive medicine and offers essential guidelines from the U.S. Preventive Services Task Force. It has been significantly expanded for the 2009 edition. Information in this section includes recommendations for the periodic health examination, screening for major diseases and disorders, patient counseling, and immunization and chemoprophylaxis recommendations.

The Appendix contains extensive information on complementary and alternative medicine (CAM). It has been completely revised in the 2009 edition. With the material in this appendix, we hope to lessen the current lack of exposure of allopathic and osteopathic physicians to the diversity of CAM therapies. Another important addition to the Appendix for the 2009 edition is an extensive section on primary care procedures. As clinicians, we all realize the importance of patient education and the need for clear communication with our patients. Toward that end, practical patient instruction sheets, organized alphabetically and covering the majority of the topics in this book, are available online and can be easily customized and printed from any computer. Most of them have been updated and over 100 new instruction sheets have been added to the 2009 edition. They represent a valuable addition to patient care and are useful for improving physician-patient communication, patient satisfaction, and quality of care. I believe that we have produced a state-of-the-art information system with significant differences from existing texts. It contains five sections and patient education guides that could be sold separately based on their content, yet are available under a single cover, offering the reader a tremendous value. I hope that the Clinical Advisor's user-friendly approach, numerous unique features, and yearly updates will make this book a valuable medical reference, not only to primary care physicians but also to physicians in other specialties, medical students, and allied health professionals. FRED F. FERRI, M.D., F.A.C.P.

EVALUATION OF EVIDENCE Ferri's Clinical Advisor evaluates all evidence based on a rating system published by the American Academy of Family Physicians. In order to indicate the strength of the supporting evidence, each summary statement is accorded one of three levels:

LEVEL A •

Systematic reviews of randomized controlled trials, including meta-analyses

•

Good-quality randomized controlled trials

LEVEL B •

Good-quality nonrandomized clinical trials

•

Systematic reviews not in Level A

•

Lower-quality randomized controlled trials not in Level A

•

Other types of study: case-control studies, clinical cohort studies, cross-sectional studies, retrospective studies, and uncontrolled studies

LEVEL C •

Evidence-based consensus statements and expert guidelines

SOURCES OF EVIDENCE Evidence is summarized principally from three critically evaluated, very highly regarded sources:

•

Cochrane Systematic Reviews are respected throughout the world as one of the most rigorous searches of medical journals for randomized controlled trials. They provide highly structured systematic reviews, with evidence included or excluded on the basis of explicit quality-related criteria, and they often use metaanalyses to increase the power of the findings of numerous studies.

•

Clinical Evidence is produced by the BMJ Publishing Group. It provides synopses of the best currently available evidence on the treatment and prevention of many clinical conditions, based on searches and appraisals of the available literature.

•

The National Guideline Clearinghouse is a comprehensive database of evidence-based clinical practice guidelines and related documents produced by the Agency for Healthcare Research and Quality in partnership with the American Medical Association and the American Association of Health Plans.

In addition, where evidence exists that has not yet been critically reviewed in one of the three sites listed here, the evidence is summarized briefly, categorized, and fully referenced. Guidelines are also sourced from governmental and professional bodies.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

SECTION I – Diseases and Disorders

A Abruptio Placentae

BASIC INFORMATION DEFINITION Abruptio placentae is the separation of placenta from the uterine wall before delivery of the fetus. There are three classes of abruption based on maternal and fetal status, including an assessment of uterine contractions, quantity of bleeding, fetal heart rate monitoring, and abnormal coagulation studies (fibrinogen, PT, PTT). •

Grade I: mild vaginal bleeding, uterine irritability, stable vital signs, reassuring fetal heart rate, normal coagulation profile (fibrinogen 450 mg %)

•

Grade II: moderate vaginal bleeding, hypertonic uterine contractions, orthostatic blood pressure measurements, unfavorable fetal status, fibrinogen 150 mg % to 250 mg %

•

Grade III: severe bleeding (may be concealed), hypertonic uterine contractions, overt signs of hypovolemic shock, fetal death, thrombocytopenia, fibrinogen female PREDOMINANT AGE: All ages PEAK INCIDENCE: Not seasonal; common GENETICS: None known PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Localized perirectal or anal pain—often worsened with movement or straining

•

Perirectal erythema or cellulitis

•

Perirectal mass by inspection or palpation

•

Fever and signs of sepsis with deep abscess

•

Urinary retention

ETIOLOGY

•

Polymicrobial aerobic and anaerobic bacteria involving one of the anatomic spaces (see “Definition”), often associated with localized trauma

•

Microbiology: most bacteria are polymicrobial, mixed enteric and skin flora

•

Predominant anaerobic bacteria:

•

1.

Bacteroides fragilis

2.

Peptostreptococcus spp.

3.

Prevotella spp.

4.

Porphyromonas spp.

5.

Clostridium spp.

6.

Fusobacterium spp.

Predominant aerobic bacteria: 1.

Staphylococcus aureus

2.

Streptococcus spp.

3.

Escherichia coli

4.

Enterococcus spp.

DIAGNOSIS Many patients will have predisposing underlying conditions including: •

Malignancy or leukemia

•

Immune deficiency

•

Diabetes mellitus

•

Recent surgery

•

Steroid therapy

DIFFERENTIAL DIAGNOSIS

•

Neutropenic enterocolitis

•

Crohn's disease (inflammatory bowel disease)

•

Pilonidal disease

•

Hidradenitis suppurativa

•

Tuberculosis or actinomycosis; Chagas' disease

•

Cancerous lesions

•

Chronic anal fistula

•

Rectovaginal fistula

•

Proctitis—often STD-associated, including: syphilis, gonococcal, chlamydia, chancroid, condylomata acuminata

•

AIDS-associated: Kaposi's sarcoma, lymphoma, CMV

WORKUP

•

Examination of rectal, perirectal/perineal areas

•

Rule out necrotic process and crepitance suggesting deep tissue involvement

•

Local aerobic and anaerobic culture

•

Blood cultures if toxic, febrile, or compromised

•

Possible sigmoidoscopy

IMAGING STUDIES

Usually not indicated unless extensive disease abscess

TREATMENT ACUTE GENERAL RX

•

Incision and drainage of abscess

•

Debridement if necrotic tissue

•

Rule out need for fistulectomy

•

Local wound care—packing

•

Sitz baths

Antibiotic treatment: Directed toward coverage for mixed skins and enteric flora Outpatient—oral: Amoxicillin/clavulanic acid 875 to 1000 mg bid Ciprofloxacin 750 mg by mouth every 12 hr plus metronidazole 500 to 750 mg by mouth every 8 hr or Clindamycin 150 to 300 mg by mouth every 8 hr Inpatient—intravenous: Ampicillin/sulbactam (Unasyn) 1.5 to 3 gm IV every 6 hr Cefotetan 1 to 2 gm IV every 8 hr Piperacillin/Tazobactam 3.375 gm IV every 6 to 8 hr Imipenem 500 to 1000 mg IV every 8 hr DISPOSITION

Follow-up with a general surgeon or infectious disease physician is often warranted.

REFERRAL

•

General surgeon or colorectal surgeon for drainage.

•

AIDS specialist may be needed for perirectal complications of HIV infection.

•

Gastroenterologist follow-up may be warranted in Crohn's disease with perirectal fistula and other complications.

PEARLS & CONSIDERATIONS Perirectal abscess may be a presenting manifestation of type 2 diabetes mellitus in older adults. Check the blood sugar in patients to exclude the possibility of unrecognized diabetes mellitus. AUTHORS: GLENN G. FORT, M.D., M.P.H., and DENNIS J. MIKOLICH, M.D. Abuse, Child

BASIC INFORMATION DEFINITION

Definition from the Federal Child Abuse Prevention and Treatment Act (CAPTA): any recent act or failure to act on the part of a parent or caretaker which results in death, serious physical or emotional harm, sexual abuse or exploitation of a child; or an act or failure to act which presents an imminent risk of serious harm to a child.

•

Neglect: failure to provide for the basic needs of a child (e.g., food, shelter, supervision) 1.

Medical neglect: failure to provide basic medical or mental health care

2.

Educational neglect: failure to meet educational needs

3.

Emotional neglect: failure to attend to emotional needs, exposure to domestic violence

•

Physical abuse: injury inflicted by an adult intentionally or in the course of excessive discipline

•

Sexual abuse: sexual act inflicted by parent or caretaker, includes exploitation and pornography

•

Emotional abuse: pattern of behavior of caretaker toward a child that impairs emotional development, such as verbal abuse or cruelty

SYNONYMS

Child maltreatment Physical abuse Sexual abuse Battered child syndrome Shaken baby syndrome Shaken impact syndrome Abusive head trauma

ICD-9CM CODES

995.5

Child maltreatment

995.50 Child abuse, unspecified 995.51 Child abuse, emotional or psychological 995.52 Child neglect 995.53 Child abuse, sexual 995.54 Child abuse, physical 995.55 Shaken infant syndrome 995.59 Multiple forms of child abuse EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Any reports of incidence are underestimates because many cases are never recognized or reported. These are collected based on Child Protective Services (CPS) state aggregates. Roughly 899,000 children were determined to be victims of abuse or neglect.

•

•

Types of abuse by percentage. Note that the following amounts add to greater than 100% because many children are subject to more than one type of victimization: 1.

Neglect 62.8%

2.

Physical abuse 16.6%

3.

Sexual abuse 9.3%

4.

Emotional abuse 7.1%

5.

Medical neglect 2%

6.

Other 14.3% (e.g., abandonment, threats of harm, congenital drug addiction)

For 2005, an estimated 1460 child deaths were caused by abuse or neglect. Overall annual death rate resulting from abuse or neglect is estimated to be 2 deaths/100,000 children. More than 40% of these deaths are due to neglect. 77% of these children are 1 yr) have the highest death rate: 17 per 100,000 boys of the same age vs. 14 per 100,000 infant girls of the same age.

PREDOMINANT AGE: Youngest children (0 to 3 years old) have the highest rates of victimization (16.5

victims/1000 children of the same age). GENETICS: No known genetic factors. ETIOLOGY

Multiple factors contribute to the incidence. No factor or combination of factors can definitively predict which children will be victimized. Factors contributing to risk of abuse or neglect include the following: •

•

•

•

Parent 1.

Substance abuse

2.

Mental illness

3.

Intellectual impairment

4.

Parental history of being abused as a child

5.

Domestic violence

Child 1.

Low birth weight or prematurity

2.

Chronic physical disability

Family 1.

Social isolation

2.

Poor parent-child bonding

3.

Stress: unemployment, chronic illness, eviction, arrest, poverty

Community/society 1.

Limited transportation

2.

Limited day care

3.

Unsafe neighborhoods

4.

Poverty

DIAGNOSIS Careful history and physical exam are the most important aspects of the evaluation. Careful documentation of any statements regarding origin of injuries or history of abuse are crucial. Chart and photographic documentation of injuries is also essential. The following are keys to the final diagnosis:

•

Patterned bruising (e.g., loop-shaped, square, oval) is indicative of being struck with an object.

•

Injury observed is incompatible with the history provided.

•

History of injury provided is incompatible with the developmental capabilities of the child.

•

There is delay in seeking care for a significant injury (e.g., callus formation on a fracture, eschar formation on a burn).

•

Bruising is rare in healthy precruising infants and warrants further investigation.

•

There are multiple significant injuries of different ages.

•

Infant with clinically significant head trauma attributed to a trivial cause (e.g., a short fall). Often associated with retinal hemorrhages and skeletal fractures is indicative of shaken baby syndrome or abusive head trauma.

•

Certain fractures in infants without a history of significant trauma (e.g., MVA) are characteristic of abuse: metaphyseal, rib, sternum, scapula, vertebral body.

•

Inflicted contact burns are indicated by an impression of the burning object: lighter, iron, cigarette.

•

Inflicted immersion burns are indicated by “stocking” burns of the feet or “glove” burns of the hands. Stocking burns are often associated with buttocks/perineal burns from immersion of a minor in a flexed position.

•

Most sexual abuse victims will have a normal or nonspecific genital examination. A normal genital examination does not mean the child was not abused. History is the most important part of the diagnosis. Examination by an experienced health care provider is essential for child and adolescent victims of sexual abuse.

•

The identification of a sexually transmitted disease in a prepubertal child who is beyond the neonatal period is suggestive of sexual abuse. Reporting and further careful investigation are warranted. Consult current CDC guidelines for further guidance.

DIFFERENTIAL DIAGNOSIS

In all categories, accidental injury is the most common entity to be distinguished from abuse. Accidental injuries are most common over bony prominences: forehead, elbows, knees, shins; soft, fleshy areas are more common for inflicted injury: buttocks, thighs, upper arms.

Bruising •

Bleeding disorder (ITP, hemophilia, leukemia, hemorrhagic disease of the newborn, von Willebrand's disease)

•

Connective tissue disorder (Ehlers-Danlos syndrome, vasculitis)

•

Pigments (Mongolian spots)

•

Dermatitis (phytophotodermatitis, nickel allergy)

•

Folk treatment (coining, cupping)

Burns •

Chemical burn

•

Impetigo

•

Folk treatment (moxibustion)

•

Dermatitis (phytophotodermatitis)

Intracranial hemorrhage

•

Bleeding disorder

•

Perinatal trauma (should resolve by 4 wk)

•

AVM rupture

•

Glutaric aciduria

Fractures •

Osteogenesis imperfecta

•

Ricketts

•

Congenital syphilis

•

Very low birth weight (osteopenia of prematurity)

Sexual abuse •

Normal variants

•

Lichen sclerosis et atrophicus

•

Congenital abnormalities

•

Urethral prolapse

•

Hemangioma

•

Nonsexually acquired infection (group A Streptococcus, Shigella)

WORKUP

History and physical

•

Careful history from all caretakers and child.

•

Scene investigation may be necessary.

•

Complete physical examination.

•

Sexual abuse: forensic interview and magnified examinations by trained professionals is the standard for evaluation and evidence collection.

Laboratory tests for physical abuse

•

Tests performed may vary depending on the severity of abuse and clinical presentation of the child.

•

CBC with differential and platelets.

•

PT, aPTT.

•

Consider closure time (PFA-100), VWB panel.

•

SGPT, amylase, UA.

Laboratory tests for sexual abuse

•

If within 72 hr of acute sexual assault/abuse, swabs are obtained for sperm, acid phosphatase, P30, MHS5 antigen, blood group typing, DNA testing. Also collect samples of foreign hair, blood, saliva, or other tissue if present.

•

Per current CDC recommendations, adolescent victims of acute assault should have appropriate specimens collected from sites of penetration for Neisseria gonorrhea and Chlamydia. Nucleic acid amplification tests (NAATs) may be used and are preferred. In females, wet mount for bacterial vaginosis and trichomonas should also be done. Serum should be obtained for HIV, hepatitis B, and syphilis testing acutely. If negative, HIV and syphilis testing should be repeated 6, 12, and 24 wk after the assault.

•

Child victims (i.e., prepubertal) should have specimens collected if considered high risk for a sexually transmitted disease (STD) per current CDC recommendations. Cervical specimens are not collected and vaginal specimens must be collected with care to avoid further traumatizing the child. Gonorrhea and Chlamydia culture are the gold standard for diagnosis and legal purposes. However, some providers analyze specimens via NAAT followed by culture confirmation if any positive results are obtained. Specimens should be collected for Gonorrhea and Chlamydia, wet mount, and blood for serologic testing (HIV, hepatitis B, syphilis) in the following cases: 1.

Presence of vaginal discharge or genital ulcer

2.

Alleged assailant is known to have an STD or be at high risk for an STD

3.

A sibling or adult in the same household has a known STD

4.

High prevalence of STDs in the community

5.

Evidence of ejaculation or penetration is present on the examination

6.

Child or parent requests testing

IMAGING STUDIES

Physical abuse

•

Radiographic skeletal survey for all children 150,000 ARDS cases/yr. Incidence is 1.5 to 8.3 cases/100,000/yr. About 50% of patients who develop ARDS do so within 24 hours of the inciting event. Mortality is 40% to 50%. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

Signs and symptoms 1.

Dyspnea

2.

Chest discomfort

3.

Cough

4.

Anxiety

Physical examination 1.

Tachypnea

2.

Tachycardia

3.

Hypertension

4.

Coarse crepitations of both lungs

5.

Fever may be present if infection is the underlying etiology

ETIOLOGY

•

Sepsis (>40% of cases)

•

Aspiration: near drowning, aspiration of gastric contents (>30% of cases)

•

Trauma (>20% of cases)

•

Multiple transfusions, blood products

•

Drugs (e.g., overdose of morphine, methadone, heroin; reaction to nitrofurantoin)

•

Noxious inhalation (e.g., chlorine gas, high O 2 concentration)

•

Post-resuscitation

•

Cardiopulmonary bypass

•

Pneumonia

•

Burns

•

Pancreatitis

•

A history of chronic alcohol abuse significantly increases the risk of developing ARDS in critically ill patients

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Cardiogenic pulmonary edema

•

Viral pneumonitis

•

Lymphangitic carcinomatosis

WORKUP

The search for an underlying cause should focus on treatable causes (e.g., infections such as sepsis or pneumonia)

•

ABGs

•

Hemodynamic monitoring

•

Bronchoalveolar lavage (selected patients)

LABORATORY TESTS

•

•

•

ABGs: 1.

Initially: varying degrees of hypoxemia, generally resistant to supplemental oxygen

2.

Respiratory alkalosis, decreased Pco2

3.

Widened alveolar-arterial gradient

4.

Hypercapnia as the disease progresses

Bronchoalveolar lavage: 1.

The most prominent finding is an increased number of polymorphonucleocytes.

2.

The presence of eosinophilia has therapeutic implications, because these patients respond to corticosteroids.

Blood and urine cultures

IMAGING STUDIES

Chest x-ray ( Fig. 1-10 ).

FIGURE 1-10 ARDS. AP radiograph in an elderly woman reveals widespread consolidation with air bronchograms. The heart size is normal. There are no pleural effusions. (From McLoud TC: Thoracic radiology: the requisites, St Louis, 1998, Mosby.)

•

The initial chest radiogram might be normal in the initial hours after the precipitating event.

•

Bilateral interstitial infiltrates are usually seen within 24 hr; they often are more prominent in the bases and periphery.

•

“White out” of both lung fields can be seen in advanced stages.

•

CT scan of chest: diffuse consolidation with air bronchograms, bullae, pleural effusions. Pneumomediastinum and pneumathoraces may also be present.

TREATMENT NONPHARMACOLOGIC THERAPY

Hemodynamic monitoring:

•

Hemodynamic monitoring can be used for the initial evaluation of ARDS (in ruling out cardiogenic pulmonary edema) and its subsequent management. Recent studies, however, have shown that clinical management involving the early use of pulmonary artery catheters in patients with ARDS did not significantly affect mortality and morbidity.

•

Although no dynamic profile is diagnostic of ARDS, the presence of pulmonary edema, a high cardiac output and a low pulmonary capillary wedge pressures (PCWP) is characteristic of ARDS.

•

It is important to remember that partially treated intravascular volume overload and flash pulmonary edema can have the hemodynamic features of ARDS; filling pressures can also be elevated by increased intrathoracic pressures or with fluid administration; cardiac function can be depressed by acidosis, hypoxemia, or other factors associated with sepsis.

Ventilatory support: mechanical ventilation is generally necessary to maintain adequate gas exchange (see Section III). A low tidal volume and low plateau pressure ventilator strategy is recommended to avoid ventilatorinduced injury. Assist-control is generally preferred initially with the following ventilator settings: •

Fio2 1.0 (until a lower value can be used to achieve adequate oxygenation). When possible, minimize oxygen toxicity by maintaining Fio2 at 2 wk of mechanical ventilation; discussion regarding tracheostomy should begin with patient (if alert and oriented) and family members/legal guardian, after 5 to 7 days of ventilatory support.

•

Some form of DVT prophylaxis is indicated in all patients with ARDS.

•

Stress ulcer prophylaxis with sucralfate suspension (via NG tube), or IV proton pump inhibitors (PPIs) or IV H2 blockers.

•

The use of surfactant remains controversial. Patients who receive surfactant have a greater improvement in gas exchange in the initial 24-hour period than patients who receive standard therapy alone; however, the use of exogenous surfactant does not improve survival.

DISPOSITION

•

Prognosis for ARDS varies with the underlying cause. Prognosis is worse in patients with chronic liver disease, nonpulmonary organ dysfunction, sepsis, and advanced age.

•

Elevated values of dead space fraction ([Paco2-Peco 2]/Paco2) (normal is 60%)

•

Idiopathic hyperaldosteronism (>30%)

•

Glucocorticoid-suppressible hyperaldosteronism (15 µg).

•

Captopril test: administer 25 to 50 mg of captopril (ACE inhibitor) and measure plasma renin and aldosterone levels 1 to 2 hr later. A plasma aldosterone level >15 ng/dl confirms the diagnosis of primary aldosteronism. This test is more expensive and is best reserved for situations in which the 24-hr urine for aldosterone is ambiguous.

•

24-hr urinary tetrahydroaldosterone (10 ng/dl) can also be used in ambiguous cases.

•

The renin-aldosterone stimulation test (posture test) is helpful in differentiating IHA from aldosteroneproducing adenoma (APA). Patients with APA have a decrease in aldosterone levels at 4 hr, whereas patients with IHA have an increase in their aldosterone levels.

•

As a screening test for primary aldosteronism, an elevated plasma aldosterone-renin ratio (ARR), drawn randomly from patients on hypertensive drugs, is predictive of primary aldosteronism (positive predictive value 100% in a recent study). ARR is calculated by dividing plasma aldosterone (mg/dl) by plasma renin activity (mg/ml/hour). ARR >100 is considered elevated.

•

Bilateral adrenal venous sampling may be done to localize APA when adrenal CT scan is equivocal. In APA, ipsilateral/contralateral aldosterone level is >10:1, and ipsilateral venous aldosterone concentration is very high (>1000 ng/dl).

•

A diagnostic evaluation of hypertensive patients with suspected aldosteronism is described in Section III, Hyperaldosteronism.

LABORATORY TESTS

Routine laboratory tests can be suggestive but are not diagnostic of primary aldosteronism. Common abnormalities are: •

Spontaneous hypokalemia or moderately severe hypokalemia while receiving conventional doses of diuretics

•

Possible alkalosis and hypernatremia

IMAGING STUDIES

•

Adrenal CT scans (with 3-mm cuts) may be used to localize neoplasm.

•

Adrenal scanning with iodocholesterol (NP-59) or 6-beta-iodomethyl-19-norcholesterol after dexamethasone suppression. The uptake of tracer is increased in those with aldosteronoma and absent in those with idiopathic aldosteronism and adrenal carcinoma.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Regular monitoring and control of blood pressure

•

Low-sodium diet, tobacco avoidance, maintenance of ideal body weight, and regular exercise program

ACUTE GENERAL RX

•

Control of blood pressure and hypokalemia with spironolactone, amiloride, or ACE inhibitors

•

Surgery (unilateral adrenalectomy) for APA

CHRONIC RX

Chronic medical therapy with spironolactone, amiloride, or ACE inhibitors to control blood pressure and hypokalemia is necessary in all patients with bilateral idiopathic hyperaldosteronism. DISPOSITION

•

Unilateral adrenalectomy normalizes hypertension and hypokalemia in 70% of patients with APA after 1 yr. After 5 yr, 50% of patients remain normotensive.

•

Experimental animal studies have suggested that long-term exposure to increased aldosterone levels in untreated aldosteronism may result in renal structural damage. However, clinical trials have shown that primary aldosteronism is characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect.

REFERRAL

Surgical referral for unilateral adrenalectomy following confirmation of unilateral APA or carcinoma

PEARLS & CONSIDERATIONS COMMENTS

Frequent monitoring of blood pressure and electrolytes postoperatively is necessary, because normotension after unilateral adrenalectomy may take up to 4 mo.

•

Recent investigations regarding serum aldosterone and the incidence of hypertension in nonhypertensive persons indicate that increased aldosterone levels within the physiologic range predispose to the development of hypertension.

SUGGESTED READINGS Sechi L, et al: Long-term renal outcomes in patients with primary aldosteronism. JAMA 2006; 295:2638. Vasan RS, et al: Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 2004; 351:33.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Allergic Rhinitis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Allergic rhinitis is an IgE-mediated hypersensitivity response to nasally inhaled allergens that causes sneezing, rhinorrhea, nasal pruritus, and congestion. SYNONYMS

Hay fever IgE-mediated rhinitis

ICD-9CM CODES

477.9 Allergic rhinitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Allergic rhinitis affects approximately 10% to 20% of the U.S. population.

•

Mean age of onset is 8 to 12 yr.

•

The prevalence of allergic rhinitis in patients presenting to their primary care provider with nasal symptoms is estimated to be 30% to 60%.

PHYSICAL FINDINGS & CLINICAL presentation

•

Pale or violaceous mucosa of the turbinates caused by venous engorgement (this can distinguish it from erythema present in viral rhinitis)

•

Nasal polyps

•

Lymphoid hyperplasia in the posterior oropharynx with cobblestone appearance

•

Erythema of the throat, conjunctival and scleral injection

•

Clear nasal discharge

•

Clinical presentation: usually consists of sneezing, nasal congestion, cough, postnasal drip, loss of or alteration of smell, and sensation of plugged ears

ETIOLOGY

•

Pollens in the springtime, ragweed in fall, grasses in the summer

•

Dust, mites, animal allergens

•

Smoke or any irritants

•

Perfumes, detergents, soaps

•

Emotion, changes in atmospheric pressure or temperature

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Infections (sinusitis; viral, bacterial, or fungal rhinitis)

•

Rhinitis medicamentosa (cocaine, sympathomimetic nasal drops)

•

Vasomotor rhinitis (e.g., secondary to air pollutants)

•

Septal obstruction (e.g., deviated septum), nasal polyps, nasal neoplasms

•

Systemic diseases (e.g., Wegener's granulomatosis, hypothyroidism [rare])

WORKUP

•

The initial strategy should be to determine whether patients should undergo diagnostic testing or receive empirical treatment.

•

Workup is often unnecessary if the diagnosis is apparent. A detailed medical history is useful in identifying the culprit allergen.

•

Selected patients with allergic rhinitis that is not controlled with standard therapy may benefit from allergy testing to target allergen avoidance measures or guide immunotherapy. Allergy testing can be performed using skin testing or radioallergosorbent (RAST) testing. Immunoglobulin E (IgE) testing using newest generation assays is also an excellent tool for diagnosing the cause of symptoms related to rhinitis. Allergy testing should generally be reserved for ambiguous or complicated cases.

•

Examination of nasal smears for the presence of neutrophils to rule out infectious causes and the presence of eosinophils (suggestive of allergy) may be useful in selected patients.

•

Peripheral blood eosinophil counts are not useful in allergy diagnosis.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Maintain allergen-free environment by covering mattresses and pillows with allergen-proof casings, eliminating carpeting, eliminating animal products, and removing dust-collecting fixtures.

•

Use of air purifiers and dust filters is helpful.

•

Maintain humidity in the environment below 50% to prevent dust mites and mold.

•

Use air conditioners, especially in the bedroom.

•

Remove pets from homes of patients with suspected sensitivity to animal allergens.

ACUTE GENERAL RX

•

Determine if the patient is troubled by swollen turbinates (best treated with decongestants) or blockages secondary to mucus (effectively treated by antihistamines).

•

Most first-generation antihistamines can cause considerable sedation and anticholinergic symptoms. The second-generation antihistamines (loratadine, fexofenadine, cetirizine, desloratadine) are preferred because they do not have any significant anticholinergic or sedative effects.

•

Montelukast (Singulair), a leukotriene receptor antagonist commonly used for asthma, is also effective for allergic rhinitis. Usual adult dose is 10 mg qd.

•

Azelastine (Astelin) is an antihistamine nasal spray effective for seasonal allergic rhinitis.

•

Topical nasal steroids are very effective and are preferred by many as first-line treatment for allergic rhinitis in adults. Patients should be instructed on proper use and informed that improvement might not occur for at least 1 wk after initiation of therapy. Commonly available inhalers are: 1.

Beclomethasone dipropionate (Beconase AQ): one to two sprays in each nostril bid

2.

Fluticasone (Flonase): initially two sprays in each nostril qd or one spray in each nostril bid, decreasing to one spray in each nostril qd based on response

3.

Flunisolide (Nasalide): initially two sprays in each nostril bid

4.

Budesonide (Rhinocort): two sprays in each nostril bid or four sprays in each nostril qam

CHRONIC RX

•

Cromolyn sodium (Nasalcrom): one spray to each nostril three to four times daily can be used for prophylaxis (mast cell stabilizer).

•

Immunotherapy is generally reserved for patients responding poorly to the above treatments.

DISPOSITION

Most patients experience significant relief with avoidance of allergens and proper use of medications. REFERRAL

Allergy testing in patients with severe symptoms that are unresponsive to therapy or when the diagnosis is uncertain

EVIDENCE

A meta-analysis found that intranasal steroids are more effective for the treatment of nasal blockage and discharge, sneezing, postnasal drip, and nasal itch than antihistamines.[[1]]

Evidence-Based Reference 1. Weiner JM, Abramson MJ, Puy RM: Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomized controlled trials. BMJ 1998; 317:1624.

SUGGESTED READINGS Quillen DM, Feller DB: Diagnosing rhinitis: allergic vs. nonallergic. Am Fam Physician 2006; 73:1583.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Alpha-1-Antitrypsin Deficiency JOSEPH A. DIAZ, M.D.

BASIC INFORMATION DEFINITION

Alpha-1-antitrypsin deficiency is a genetic deficiency of the protease inhibitor, alpha-1-antitrypsin, that results in a predisposition to pulmonary emphysema and hepatic cirrhosis. SYNONYMS AAT

ICD-9CM CODES

277.6 Alpha-1-antitrypsin deficiency EPIDEMIOLOGY & DEMOGRAPHICS

•

Accounts for approximately 2% of COPD cases in Americans

•

Inherited as an autosomal codominant disorder

•

Most frequent mutation is in the SERPINA 1 gene (previously known as PI)

•

Most common alleles are: normal “M” allele (95% frequency in the U.S.) deficient variant “Z” allele (1% to 2%) deficient variant “S” allele (2% to 3%)

•

Severe deficiency is most commonly due to homozygotes ZZ

•

Risk of lung disease in heterozygotes (MZ) is uncertain

•

One in 10 individuals of European descent carry one of two mutations that may result in partial alpha-1antitrypsin deficiency

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical findings and clinical presentation are varied and dependent upon phenotype (see “Etiology”)

•

Most often affects the lungs but can also involve liver and skin

•

Classically associated with early-onset, severe, lower-lobe predominant emphysema; bronchiectasis may also be seen

•

Symptoms are similar to “typical” COPD presentation (dyspnea, cough, sputum production)

•

Liver involvement includes neonatal cholestasis, cirrhosis in children and adults, and primary carcinoma of the liver

•

Panniculitis is the major dermatologic manifestation

ETIOLOGY

•

Degree of alpha-1-antitrypsin deficiency is dependent on phenotype.

•

“MM” represents the normal genotype and is associated with alpha-1-antitrypsin levels in the normal range.

•

Mutation most commonly associated with emphysema is Z, with homozygote (ZZ) resulting in approximately 85% deficit in plasma alpha-1-antitrypsin concentrations.

•

Development of emphysema is believed to be a result from an imbalance between the proteolytic enzyme, elastase, produced by neutrophils, and alpha-1-antitrypsin, which normally protects lung elastin by inhibiting elastase.

•

Deficiency of alpha-1-antitrypsin increases risk of early-onset emphysema, but not all alpha-1-antitrypsin deficient individuals will develop lung disease.

•

Smoking increases risk and accelerates onset of COPD.

•

Liver disease is caused by pathologic accumulation of alpha-1-antitrypsin in hepatocytes.

•

Similar to lung disease, skin involvement is thought to be secondary to unopposed proteolysis in skin.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

See “COPD” See “Cirrhosis” WORKUP

•

Suspicion for alpha-1-antitrypsin deficiency usually results from emphysema developing at an early age and with basilar predominance of disease.

•

Suspicion for alpha-1-antitrypsin deficiency resulting in liver disease or skin involvement may arise when other more common etiologies are excluded.

LABORATORY TESTS

•

Serum level of alpha-1-antitrypsin is decreased or not detected in lung disease.

•

Investigate possibility of abnormal alleles with genotyping.

•

Pulmonary function testing is generally consistent with “typical” COPD.

IMAGING STUDIES

•

Chest x-ray examination shows characteristic emphysematous changes at lung bases.

•

High-resolution chest CT usually confirms the lower-lobe predominant emphysema and may also show significant bronchiectasis.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoidance of smoking is paramount

•

Avoidance of other environmental and occupational exposures that may increase risk of COPD

ACUTE GENERAL RX

Acute exacerbations of COPD secondary to alpha-1-antitrypsin deficiency are treated in a similar fashion to “typical” COPD exacerbations. CHRONIC RX

•

The goal of treatment in alpha-1-antitrypsin deficiency is to increase serum alpha-1-antitrypsin levels above a minimum, “protective” threshold.

•

Although there are several therapeutic options under investigation, IV administration of pooled human alpha-1-antitrypsin is currently the only approved method to raise serum alpha-1-antitrypsin levels.

•

Organ transplantation for patients with end-stage lung or liver disease is also an option.

DISPOSITION

•

Prognosis of patients with alpha-1-antitrypsin deficiency will depend on phenotype and level of deficiency.

•

Among patients with severe alpha-1-antitrypsin deficiency, the most common underlying causes of death are emphysema (72%) and cirrhosis (10%).

REFERRAL

•

Pulmonary and hepatology referrals for advanced lung and liver disease, or if replacement therapy is contemplated (e.g., moderate-severe lung disease)

•

Lung and liver transplantation in suitable cases

PEARLS & CONSIDERATIONS

•

The liver damage arising from the mutation is not from a deficiency in alpha-1-antitrypsin but from a pathologic accumulation of alpha-1-antitrypsin in hepatocytes.

•

Consider alpha-1-antitrypsin deficiency in patients presenting with lower-lobe predominant emphysema; in most smokers without alpha-1-antitrypsin deficiency, emphysema predominates in the upper lobes.

•

Alpha-1-antitrypsin deficiency is felt to be under recognized.

EVIDENCE

Observational data demonstrate that in patients with AAT, augmentation therapy with human plasma a1 antitrypsin lowers the decline in FEV1 and improves overall mortality compared to patients who received no such therapy.[[1]]

Evidence-Based Reference 1. Alpha-1 Antitrypsin Deficiency Registry Study Group: Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. Am J Respir Crit Care Med 1998; 158:49.

SUGGESTED READINGS American Thoracic Society/European Respiratory Society Statement: Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2003; 168:818. Hersh CP, et al: Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ herterozygotes: a metaanalysis. Thorax 2004; 59(10):843. Kohnlgin T, Welte T: Alpha-1-antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. Am J Med 2008; 121:3-9. Stoller J, Aboussouan L: Alpha 1-antitrypsin deficiency. Lancet 2005; 365:2225. Stoller JK, et al: Mortality in individuals with severe deficiency of a1-antitrypsin. Chest 2005; 127:1196.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Altitude Sickness JEFFREY MAZER, M.D., GAURAV CHOUDHARY, M.D.

BASIC INFORMATION DEFINITION

Altitude sickness refers to a spectrum of illnesses related to hypoxia occurring in people rapidly ascending to high altitudes. Common acute syndromes occurring at high altitudes include acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE). SYNONYMS

Acute mountain sickness High-altitude pulmonary edema High-altitude cerebral edema

ICD-9CM CODES

289

Mountain sickness, acute

993.2 High altitude, effects EPIDEMIOLOGY & DEMOGRAPHICS

•

More than 30 million people are at risk of developing altitude sickness.

•

AMS is the most common of the altitude diseases. Approximately 40% to 50% of people ascending to 14,000 ft (4200 m) from lowland living develop AMS.

•

HAPE generally arises in people who rapidly ascend to 12,000 to 13,000 ft (3600 to 3900 m), but it has been reported at altitudes as low as 8000 ft.

•

Men are 5 times more likely to develop HAPE than women.

•

AMS and HACE affect men and women equally.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Acute mountain sickness

•

Occurs within hours to a few days after rapid ascent over 8000 ft (2500 m)

•

Headache is the most common symptom

•

Dizziness and lightheadedness

•

Nausea, vomiting, and loss of appetite

•

Fatigue

•

Sleep disturbance resulting from an exaggerated hyperventilatory phase of Cheynes-Stokes respiration in response to hypoxia and alkalosis.

•

AMS can evolve into HAPE and HACE Pulmonary edema ( Fig. 1-11 and Section III, “High-Altitude Pulmonary Edema”)

•

Occurs typically 2 to 4 days after ascent over 8000 ft (2500 m)

•

Dyspnea

•

Dry cough or cough with frothy rust- or pink-tinged sputum

•

Chest tightness

•

Tachycardia, tachypnea, rales, cyanosis High-altitude cerebral edema

•

Usually presents several days after AMS

•

Confusion, irritability, drowsiness, stupor, hallucinations

•

Headache, nausea, vomiting

•

Ataxia, paralysis, and seizures

•

Coma and death may develop within hours of the first symptoms

FIGURE 1-11 Chest radiograph showing high-altitude pulmonary edema. (From Strauss RH [ed]: Sports medicine, ed 2, Philadelphia, 1991, WB Saunders.)

ETIOLOGY

•

As one ascends to altitudes above sea level, the atmospheric pressure decreases. Although the percentage of oxygen in the air remains the same, the partial pressure of oxygen decreases with altitude.

•

Thus, the cause of altitude sickness is primarily hypoxia resulting from low partial pressures of oxygen.

•

The body responds to low oxygen partial pressures through a process of acclimatization (see “Comments”).

DIAGNOSIS The diagnosis of altitude sickness is made by clinical presentation and physical findings described previously.

DIFFERENTIAL DIAGNOSIS

•

Dehydration

•

Carbon monoxide poisoning

•

Hypothermia

•

Infection

•

Substance abuse

•

Congestive heart failure

•

Pulmonary embolism

•

Cerebrovascular accident

WORKUP Typically the diagnosis is self-evident after history and physical examination. Laboratory tests and imaging studies help monitor cardiopulmonary and CNS status in patients admitted to the intensive care unit for pulmonary and/or cerebral edema. In patients with HAPE occurring at lower altitudes (15, low MCV, elevated TIBC, and low serum iron.

•

The reticulocyte hemoglobin content (CHr) may be a good screening test for iron deficiency. It can be measured on an automated hematology analyzer and represents a relatively inexpensive and fast way to detect iron deficiency.

TREATMENT NONPHARMACOLOGIC THERAPY

Patients should be instructed to consume foods containing large amounts of iron, such as liver, red meat, and legumes.

ACUTE GENERAL RX

•

Treatment consists of ferrous sulfate 325 mg PO qd for at least 6 mo. Calcium supplements can decrease iron absorption; therefore, these two medications should be staggered.

•

Parenteral iron therapy is reserved for patients with poor tolerance, noncompliance with oral preparations, or malabsorption.

•

Transfusion of packed RBCs is indicated in patients with severe symptomatic anemia (e.g., angina) or lifethreatening anemia.

CHRONIC RX

Patients should be instructed to continue their iron supplements for at least 6 mo or longer to correct depleted body iron stores. DISPOSITION

Most patients respond rapidly to iron supplementation with improvement in CBC and general well-being. GI side effects from oral iron therapy are common and may require decreased dose to once every other day. REFERRAL

GI referral for evaluation of GI malignancy is recommended in all patients with iron deficiency and suspected GI blood loss.

PEARLS & CONSIDERATIONS COMMENTS

If the diagnosis of iron deficiency anemia is made, it is mandatory to try to locate the suspected site of iron loss.

EVIDENCE

A systematic review found that iron supplementation in pregnancy appears to prevent low hemoglobin at birth or 6 weeks postpartum.[[1]] Another systematic review found inconclusive evidence on the effects of treatment for iron deficiency anemia in pregnancy due to a shortage of good-quality trials.[[2]]

Evidence-Based References 1. Mahomed K: Iron supplementation in pregnancy. Cochrane Database Syst Rev 2000;CD001135, 2. Cuervo LG, Mahomed K: Treatments for iron deficiency anaemia in pregnancy. Cochrane Database Syst Rev 2001;CD003094,

SUGGESTED READINGS

Killip S, et al: Iron deficiency anemia. Am Fam Physician 2007; 75:671. Tefferi A: Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc 2004; 78:1274.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Anemia, Pernicious PETER PETROPOULOS, M.D.

BASIC INFORMATION DEFINITION

Pernicious anemia is an autoimmune disease resulting from antibodies against intrinsic factor and gastric parietal cells. SYNONYMS

Megaloblastic anemia resulting from vitamin B 12 deficiency

ICD-9CM CODES

281.0 Pernicious anemia EPIDEMIOLOGY & DEMOGRAPHICS

•

Increased incidence in females and older adults (diagnosis is unusual before age 35 yr)

•

The overall prevalence of undiagnosed PA over age 60 yr is 1.9%

•

Prevalence is highest in women (2.7%), particularly in black women (4.3%)

•

Increased incidence of autoimmune disease (e.g., type 1 DM, Graves' disease, Addison's disease), Helicobacter pylori infection

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Mucosal pallor, glossitis

•

Peripheral sensory neuropathy with paresthesias initially and absent reflexes in advanced cases

•

Loss of joint position sense, pyramidal or long track signs

•

Possible splenomegaly and mild hepatomegaly

•

Generalized weakness and delirium/dementia

ETIOLOGY

•

Antigastric parietal cell antibodies in >70% of patients, antiintrinsic factor antibodies in >50% of patients

•

Atrophic gastric mucosa

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Nutritional vitamin B12 deficiency

•

Malabsorption

•

Chronic alcoholism (multifactorial)

•

Chronic gastritis related to H. pylori infection

•

Folic acid deficiency

•

Myelodysplasia

WORKUP

•

The clinical presentation of pernicious anemia varies with the stage. Initially, patients may be asymptomatic. In advanced stages, patients may present with impaired memory, depression, gait disturbances, paresthesias, and complaints of generalized weakness.

•

Investigation consists primarily of laboratory evaluation.

•

Endoscopy and biopsy for atrophic gastritis may be performed in selected cases.

•

Diagnosis is crucial because failure to treat may result in irreversible neurologic deficits.

LABORATORY TESTS

•

CBC generally reveals macrocytic anemia and leukopenia with hypersegmented neutrophils.

•

MCV is generally significantly elevated in the advanced stages.

•

Reticulocyte count is low/normal.

•

Falsely low serum cobalamin levels can occur in patients with severe folate deficiency, in patients using high doses of ascorbic acid, and when cobalamin levels are measured following nuclear medicine studies (radioactivity interferes with cobalamin RIA measurement).

•

Falsely high normal levels in patients with cobalamin deficiency can occur in severe liver disease or chronic granulocytic leukemia.

•

The absence of anemia or macrocytosis does not exclude the diagnosis of cobalamin deficiency. Anemia is absent in 20% of patients with cobalamin deficiency, and macrocytosis is absent in >30% of patients at the time of diagnosis. It can be blocked by concurrent iron deficiency or anemia of chronic disease and may be masked by thalassemia trait.

•

Schilling test is abnormal in part I; part II corrects to normal after administration of intrinsic factor.

•

Laboratory tests used for detecting cobalamin deficiency in patients with normal vitamin B12 levels include serum and urinary methylmalonic acid level (elevated), total homocysteine level (elevated), intrinsic factor antibody (positive).

•

An increased concentration of plasma methylmalonic acid (P-MMA) does not predict clinical manifestations of vitamin B12 deficiency and should not be used as the only marker for diagnosis of B12 deficiency.

•

Additional laboratory abnormalities can include elevated LDH, direct hyperbilirubinemia, and decreased haptoglobin.

TREATMENT

NONPHARMACOLOGIC THERAPY

Avoid folic acid supplementation without proper vitamin B12 supplementation. ACUTE GENERAL RX

Traditional therapy of a cobalamin deficiency consists of IM injections of vitamin B12 1000 µg/wk for the initial 4 to 6 wk followed by 1000 µg/mo IM indefinitely. When hematologic parameters have returned to normal range, intranasal cyanocobalamin may be used in place of IM cyanocobalamin. The initial dose of intranasal cyanocobalamin (Nascobal) is one spray (500 µg) in one nostril once per week. Cost generally exceeds $120/mo. Monitor response and increase dose if serum B12 levels decline. Consider return to intramuscular vitamin B 12 supplementation if decline persists. CHRONIC RX

Parenteral vitamin B12 1000 µg/mo or intranasal cyanocobalamin 500 µg/wk (see “Acute General Rx”) for the remainder of life DISPOSITION

Anemia generally resolves with appropriate treatment. Neurologic deficits, if present at diagnosis, may be permanent. REFERRAL

GI referral for endoscopy upon diagnosis of pernicious anemia and surveillance endoscopy every 5 yr to rule out gastric carcinoma

PEARLS & CONSIDERATIONS COMMENTS

•

Patients must understand that therapy is lifelong.

•

Self-injection of vitamin B12 may be taught in selected patients. Cost of monthly injection is 90% since most patients do not reach the hospital in time for surgical repair. Of those patients who reach the hospital, the mortality rate is still 50%, compared with the 1% to 4% mortality rate for elective repair of a nonruptured AAA.

REFERRAL

Vascular surgical referral should be made in asymptomatic patients with AAA 4.0 cm or greater or in rapidly expanding aneurysms of 0.6 to 0.8 cm/yr, especially if symptoms are present.

PEARLS & CONSIDERATIONS Screening by physical exam and ultrasound should be performed for men 60 years or older who are either the siblings or offspring of patients with AAA and for men age 65 to 75 who have ever smoked. COMMENTS

•

Most AAAs are infrarenal.

•

Surgical risk is increased in patients with coexisting coronary artery disease, pulmonary disease, liver cirrhosis, and chronic renal failure. Evaluation for ischemia and aggressive perioperative hemodynamic monitoring help identify high-risk patients and decrease postoperative complications.

•

It is estimated that AAAs 6 wk.

Urticaria is commonly known as “hives” and is: 1.

Pruritic

2.

Palpable and well demarcated

3.

Erythematous

4.

Millimeters to centimeters in size

5.

Multiple in number

6.

Fades within 12 to 24 hr

7.

Reappears at other sites

Angioedema is characterized by the following: 1.

Nonpruritic

2.

Burning

3.

Not well demarcated

4.

Involves eyelids ( Fig. 1-17 ), lips, tongue, and extremities

5.

Can involve the upper airway causing respiratory distress

6.

Can involve the GI tract leading to cyclic abdominal pain

7.

Resolves slowly

FIGURE 1-17 Angioedema of the upper lip, with severe swelling of deeper tissues. (From Goldstein BG, Goldstein AO: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

ETIOLOGY

•

Angioedema, with or without urticaria, is classified as acquired (allergic or idiopathic) or hereditary.

•

Angioedema is primarily due to mast cell activation and degranulation with release of vasoactive mediators (e.g., histamine, serotonin, bradykinins) resulting in postcapillary venule inflammation, vascular leakage, and edema in the deep layers of the dermis and subcutaneous tissue.

•

Pathologically angioedema has both immunological and nonimmunological mediated mechanisms. 1.

Immunoglobulin E (Ig E)-mediated angioedema may result from antigen exposure (e.g., foods [milk, eggs, peanuts, shell fish, tomatoes, chocolate, sulfites] or drugs [penicillin, aspirin, NSAIDs, phenytoin, sulfonamides, rt-PA]).

2.

Complement-mediated angioedema involving immune complex mechanisms can also lead to mast cell activation that manifests as serum sickness.

3.

Hereditary angioedema is an autosomal dominant disease caused by a deficiency of C1 esterase inhibitor (C1-INH). C1-INH is a protease inhibitor that is normally present in high concentrations in the plasma. C1-INH serves many functions, one of which is to inhibit plasma kallikrein, a protease that cleaves kininogen and releases bradykinin. A deficiency in C1-INH results in excess concentration of kininogen and the subsequent release of kinin mediators.

4.

Acquired angioedema is usually associated with other diseases, most commonly B-cell lymphoproliferative disorders, but may also result from the formation of autoantibodies directed against C1 inhibitor protein.

5.

Other causes of angioedema include infection (e.g., herpes simplex, hepatitis B, coxsackie A and B, streptococcus, candida, ascaris, and strongyloides), insect bites and stings, stress, physical factors (e.g., cold, exercise, pressure, and vibration), connective tissue diseases (e.g., SLE, Henoch-Schönlein purpura), and idiopathic causes. ACE inhibitors can increase kinin activity and lead to angioedema.

DIAGNOSIS A detailed history and physical examination usually establishes the diagnosis of angioedema. Extensive lab testing is of limited value. DIFFERENTIAL DIAGNOSIS

•

Cellulitis

•

Arthropod bite

•

Hypothyroidism

•

Contact dermatitis

•

Atopic dermatitis

•

Mastocytosis

•

Granulomatous cheilitis

•

Bullous pemphigoid

•

Urticaria pigmentosa

•

Anaphylaxis

•

Erythema multiforme

•

Epiglottitis

•

Peritonsillar abscess

WORKUP

•

An extensive workup searching for the cause of angioedema is often unrevealing (90%).

•

Workup including diagnostic blood tests and allergy testing is performed based on the history and physical examination.

LABORATORY TESTS

•

CBC, ESR, and urinalysis are sometimes helpful as part of the initial evaluation

•

Stools for ova and parasites

•

Serology testing

•

C4 levels are reduced in acquired and hereditary angioedema (occuring without urticaria). If C4 levels are low, C1-INH levels and activity should be obtained. There are isolated reports of hereditary angioedema with normal C4 levels but reduced C1-INH levels

•

Skin and radioallergosorbent (RAST) testing may be done if food allergies are suspected

•

Skin biopsy is usually done in patients with chronic angioedema refractory to corticosteroid treatment

TREATMENT NONPHARMACOLOGIC THERAPY

•

Eliminate the offending agent

•

Avoid triggering factors (e.g., cold, stress)

•

Cold compresses to affected areas

ACUTE GENERAL RX

•

•

•

•

Acute life-threatening angioedema involving the larynx is treated with: 1.

Epinephrine 0.3 mg in a solution of 1:1000 given SC

2.

Diphenhydramine 25 to 50 mg IV or IM

3.

Cimetidine 300 mg IV or ranitidine 50 mg IV

4.

Methylprednisolone 125 mg IV

Mainstay therapy in angioedema is H1 antihistamines. 1.

Diphenhydramine 25 to 50 mg q6h

2.

Chlorpheniramine 4 mg q6h

3.

Hydroxyzine 10 to 25 mg q6h

4.

Cetirizine 5 to 10 mg qd

5.

Loratadine 10 mg qd

6.

Fexofenadine 60 mg qd

H2 antihistamines can be added to H1 antihistamines. 1.

Ranitidine 150 mg bid

2.

Cimetidine 400 mg bid

3.

Famotidine 20 mg bid

Tricyclic antidepressants 1.

•

Doxepin 25 to 50 mg qd can be tried.

Corticosteroids are rarely required for symptomatic relief of acute angioedema.

CHRONIC RX

•

Chronic angioedema is treated as described under “Acute General Rx.”

•

Corticosteroids are used more often in chronic angioedema.

•

Prednisone 1 mg/kg/day for 5 days and then tapered over a period of weeks.

•

Androgens are used for the treatment of hereditary angioedema, which does not respond to antihistamines or corticosteroids. C1-INH replacement therapy is available in some countries.

DISPOSITION

•

Antihistamines achieve symptomatic relief in more than 80% of patients with angioedema.

•

In chronic angioedema, corticosteroids are given in addition to antihistamines.

•

A small percentage of people will have recurrence of symptoms after steroid treatment.

•

Chronic angioedema can last for months and even years.

Referral

Dermatology consultation is recommended in patients with chronic angioedema, hereditary angioedema, and recurring angioedema.

PEARLS & CONSIDERATIONS

ACE inhibitors can cause angioedema up to many months after initiation. There are multiple case reports and case series of Angiotensin Receptor Blocker (ARB) induced angioedema, although the risk is substantially less than that of ACEIs. COMMENTS

•

Identifying a cause for angioedema in patients is often difficult and met with frustration.

•

Chronic angioedema, unlike acute angioedema, is rarely caused by an allergic reaction.

SUGGESTED READINGS Baxi S, Dinakar C: Urticaria and angioedema. Immunol Allergy Clin North Am 2005; 25(2):353. Bowen T, et al: Canadian 2003 international concensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol 2004; 114(3):629. Frigas E, Park M: Idiopathic recurrent angioedema. Immunol and Allergy Clin North Am 2006; 26(4):739. Kaplan AP: Clinical practice: chronic urticaria and angioedema. N Engl J Med 2002; 346(3):175. Muller B: Urticaria and angioedema: a practical approach. Am Fam Physician 2004; 69(5):1123.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ankle Fracture LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Ankle fractures involve the lateral, medial, or posterior malleolus of the ankle and may occur either alone or in some combination. Associated ligamentous injuries are included.

ICD-9CM CODES

824.8 Ankle fracture (malleolus) (closed) 824.2 Lateral malleolus fracture (fibular) 824.0 Medial malleolus fracture (tibial) PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Deformity usually dependent on extent of displacement

•

Pain, tenderness, and hemorrhage at the site of injury

•

Gentle palpation of ligamentous structures (especially deltoid ligament) to determine the extent of soft tissue injury

•

Evaluation of distal neurovascular status; results recorded

ETIOLOGY

•

The ankle depends on its ligamentous and bony support for stability. The joint, or mortise, is an inverted U with the dome of the talus fitting into the medial and lateral malleoli. The posterior margin of the tibia is often called the third or posterior malleolus.

•

Most common ankle fractures are the result of eversion or lateral rotation forces on the talus (in contrast to common sprains, which are caused usually by inversion).

DIAGNOSIS The diagnosis is usually established on the basis of the nature of the injury, the presence of typical findings of bony tenderness with swelling, and abnormal imaging studies. Differential diagnosis

•

Ankle sprain

•

Avulsion fracture of hindfoot or metatarsal

IMAGING STUDIES

Standard AP and lateral views accompanied by an AP taken 15° internally rotated. The last view is taken to properly visualize the mortise.

TREATMENT All fractures: elevation and ice to control swelling for 48 to 72 hr. ACUTE GENERAL RX

•

Clinical and roentgenographic assessment of the status of the ankle mortise and stability of the injury is mandatory to determine treatment.

•

There is potential for displacement if both sides of the joint are significantly injured (e.g., fracture of the lateral malleolus with deltoid ligament injury).

•

Deviation of the position of the talus in the mortise could lead to traumatic arthritis.

•

If there is no widening of the ankle mortise, many injuries can be safely treated with simple casting without reduction: 1.

2.

3.

Undisplaced or avulsion fractures of either malleolus below the ankle joint line: a.

Stability of the joint is not compromised and a short leg walking cast or ankle support is sufficient.

b.

Weight bearing is allowed as tolerated.

c.

In 4 to 6 wk, protection may be discontinued.

Isolated undisplaced fractures of the medial, lateral, or posterior malleolus: a.

Usually stable and require only the application of a short leg walking cast with the ankle in the neutral position or fracture cast boot.

b.

Immobilization should be continued for 8 wk.

c.

Fracture line of lateral malleolus may persist roentgenographically for several months, but immobilization beyond 8 wk is usually unnecessary.

d.

Undisplaced bimalleolar fractures are treated with a long leg cast flexed 30 degrees at the knee to prevent motion and displacement of the fracture fragments. In 4 wk, a short leg walking cast may be applied for an additional 4 wk.

Isolated fractures of the lateral malleolus that are slightly displaced:

4.

5.

a.

May be treated with casting if no medial injury is present.

b.

A below-knee walking cast is applied with ankle in the neutral position and weight bearing is allowed as tolerated.

c.

Six weeks of immobilization is sufficient.

d.

If medial tenderness is present, suggesting deltoid ligament rupture, a carefully molded cast may suffice if weight bearing is not allowed and the patient is followed closely for signs of instability, especially after swelling recedes. If significant widening of the medial ankle mortise (increase in the “medial clear space”) develops as a result of lateral displacement of the talus, referral for possible reduction is indicated.

e.

If signs of instability are already present at initial examination (widening of the medial clear space with medial tenderness), referral is indicated.

Undisplaced fracture of the distal fibular epiphysis: a.

Often diagnosed clinically.

b.

There is tenderness over the epiphyseal plate.

c.

Roentgenographic findings are often negative.

d.

A short leg walking cast or fracture boot is applied for 4 wk.

e.

Growth disturbance is rare.

Isolated posterior malleolar fractures involving less than 25% of the joint surface on the lateral roentgenogram: Safely treated by applying a short leg walking cast or fracture brace. (Fractures involving >25% of the weight-bearing surface should be referred because of the potential for instability and subsequent traumatic arthritis.)

CHRONIC RX

•

Early motion is encouraged through a home exercise program.

•

Protection from reinjury is appropriate for 4 to 6 wk following cast or brace removal.

•

Temporary increase in lower extremity swelling that frequently occurs after short leg cast removal may benefit from the use of support hose.

DISPOSITION

Significant factors involved in the development of traumatic arthritis: •

Amount of joint trauma at the time of injury

•

Eventual position of the talus in the mortise

Fracture nonunion is uncommon unless displacement is significant. REFERRAL

Orthopedic consultation for: •

Unstable ankle joint

•

Widened ankle mortise

•

Posterior malleolar fracture over 25% of joint with incongruity

•

Marked displacement of fracture fragment

SUGGESTED READINGS

Bachmann LM, et al: Accuracy of Ottawa rules to exclude fractures of the ankle and mid-foot. BMJ 2003; 326:417. Chaudhary SB, et al: Complications of ankle fracture in patients with diabetes. J Am Acad Orthop Surg 2008; 16:159. Egol KA, et al: Predictors of short-term functional outcome following ankle fracture surgery. J Bone Joint Surg 2006; 88A:974. Haraguchi N, et al: Pathoanatomy of posterior malleolar fractures of the ankle. J Bone Joint Surg 2006; 88A:1085. Schnetzler KA, Hoernschemeyer D: The pediatric triplane fracture. J Am Acad Orthop Surg 2007; 15:738. Tejwani NC, et al: Are outcomes of bimalleolar fractures poorer than those of lateral malleolar fractures with medial ligamentous injury?. J Bone Joint Surg Am 2007; 89:1438.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ankle Sprain LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

An ankle sprain is an injury to the ligamentous support of the ankle. Most (85%) involve the lateral ligament complex ( Fig. 1-18 ). The anterior inferior tibiofibular (AITF) ligament, deltoid ligament, and interosseous membrane may also be injured. Damage to the tibiofibular syndesmosis is sometimes called a high sprain because of pain above the ankle.

FIGURE 1-18 The lateral ankle ligaments, anterior and posterior talofibular (ATF, PTF) and calcaneofibular (CF). Also shown are the anterior inferior tibiofibular ligament (AITF) and the beginning of the interosseous membrane (IM). (From Mercier LR [ed]: Practical orthopaedics, ed 4, St Louis, 1995, Mosby.)

ICD-9CM CODES

845.00 Sprain, ankle or foot EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 1 case/10,000 people each day PREDOMINANT SEX: Varies according to age and level of physical activity PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Often a history of a “pop”

•

Variable amounts of tenderness and hemorrhage

•

Possible abnormal anterior drawer test (pulling the plantar flexed foot forward to determine if there is any abnormal increase in forward movement of the talus in the ankle mortise) ( Fig. 1-19 )

•

Inversion sprains: tender laterally; syndesmotic injuries: area of tenderness is more anterior and proximal

•

Evaluation of motor function ( Fig. 1-20 )

FIGURE 1-19 Anterior drawer test of the ankle (tests the integrity of the anterior talofibular ligament). (From Brinker MR, Miller MD: Fundamentals of orthopaedics, Philadelphia, 1999, WB Saunders.)

FIGURE 1-20 Talar tilt test (inversion stress) of the ankle (tests the integrity of the anterior talofibular ligament and the calcaneofibular ligament). (From Brinker MR, Miller MD: Fundamentals of orthopaedics, Philadelphia, 1999, WB Saunders.)

ETIOLOGY

•

Lateral injuries usually result from inversion and plantar flexion injuries.

•

Eversion and rotational forces may injure the deltoid or AITF ligament or the interosseous membrane.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Fracture of the ankle or foot, particularly involving the distal fibular growth plate in the immature patient

•

Avulsion fracture of the fifth metatarsal base

WORKUP

•

History and clinical examination are usually sufficient to establish the diagnosis.

•

Plain radiographs are always needed.

IMAGING STUDIES

Roentgenographic evaluation 1.

Usually normal but always performed

2.

Should include the fifth metatarsal base

3.

All minor avulsion fractures noted

Varying opinions on the usefulness of arthrograms, tenograms, and stress films

TREATMENT ACUTE GENERAL RX

Ankle sprains are often graded I, II, or III, according to severity, with Grade III injury implying complete rupture. The first line of treatment is described by the mnemonic device, RICE: •

Rest

•

Ice

•

Compression

•

Elevation

•

Varying opinions regarding the initial use of NSAIDs

•

In 48 to 72 hr, active range of motion and weight bearing as tolerated

•

In 4 to 5 days, exercise against resistance added

•

Possible cast immobilization for some patients who require early independent walking; short leg orthoses also available for the same purpose

•

Surgery is rarely recommended, even for Grade III sprains; reports of equally satisfactory outcomes with nonsurgical treatment

CHRONIC RX

•

Lateral heel and sole wedge to prevent inversion

•

Protective taping or bracing during vigorous activities ( Fig. 1-21 )

•

Strengthening exercises

FIGURE 1-21 A, The most effective method of supporting most acute ankle sprains is by using an Ace wrap reinforced with 1-in medial and lateral tape strips. The anterior and posterior aspects of the ankle are left free to allow the patient to flex and extend the ankle. The patient is encouraged to bear weight with crutches. B, Diagram of an air splint. Straps are adjusted to heel size, the lower straps are wrapped about the ankle, and the side extensions are centered. The splint is then pressurized and straps adjusted until comfortable support and pressure are attained. C, As the ankle pain subsides, about the third to fifth day, balancing exercises can begin to allow the patient to regain ankle proprioception and avoid recurrent instability problems. (From Jardon OM, Mathews MS: Orthopedics. In Rakel RE [ed]: Textbook of family practice, ed 5, Philadelphia, 1995, WB Saunders.)

DISPOSITION

•

•

Lateral sprains of any severity may cause lingering symptoms for weeks and months. 1.

Some syndesmotic sprains take even longer to heal.

2.

Heterotopic ossification may even develop in the interosseous membrane, but long-term results do not seem to be affected by such ossification.

Continuing lateral symptoms may require surgical reconstruction, although late traumatic arthritis or chronic instability is rare regardless of treatment.

REFERRAL

For orthopedic consultation for cases that fail to respond to conservative treatment

PEARLS & CONSIDERATIONS COMMENTS

If healing seems delayed (more than 6 wk), the following conditions should be considered:

1.

Talar dome fracture

2.

Reflex sympathetic dystrophy

3.

Chronic tendinitis

4.

Peroneal tendon subluxation

5.

Other occult fracture

6.

Peroneal weakness (poor rehabilitation)

7.

A “high” (syndesmotic) sprain

Repeat plain roentgenograms, bone scan, or MRI may be indicated. SUGGESTED READINGS Bachman LM, Kolb E, et al: Accuracy of Ottawa ankle rules to exclude fractures of the ankle and mid-foot: systematic review. BMJ 2003; 326:417. Berkowitz MJ, Kim DH: Process and tubercule fractures of the hindfoot. J Am Acad Orthop Surg 2005; 13:492. Dahners LE, Mullis BH: Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft tissue healing. J Am Acad Orthop Surg 2004; 12:139. Hale SA, et al: The effect of a 4-week comprehensive rehabilitation program on postural control and lower extremity function in individuals with chronic ankle instability. J Orthop Sports Phys Ther 2007; 37:303. Judd DB, Kim DH: Foot fractures misdiagnosed as ankle sprains. Am Fam Physician 2002; 66:785. Le Gall F, et al: Injuries in young elite female soccer players: an 8-season prospective study. Am J Sports Med 2008; 36:276. Mizel MS, Hecht PJ, et al: Evaluation and treatment of chronic ankle pain. J Bone Joint Surg 2004; 86A:622. O'Neill PJ, et al: Excursion and strain of the superficial peroneal nerve during inversion ankle sprain. J Bone Joint Surg 2007; 89A:979. Pedowtiz DI, et al: Prophylactic bracing decreases ankle injuries in collegiate female volleyball players. Am J Sports Med 2008; 36:324. Zalavras C, Thordarson D: Ankle syndesmotic injury. J Am Acad Orthop Surg 2007; 15:330.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ankylosing Spondylitis LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Ankylosing spondylitis is a chronic inflammatory condition involving the sacroiliac joints and axial skeleton characterized by ankylosis and enthesitis (inflammation at tendon insertions). It is one of a group of several overlapping syndromes, including spondylitis associated with Reiter's syndrome, psoriasis, and IBD. Patients are typically seronegative for the rheumatoid factor, and these disorders are now commonly called rheumatoid variants or seronegative spondyloarthropathies. SYNONYMS

Marie-Strümpell disease

ICD-9CM CODES

720.0 Ankylosing spondylitis EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 0.15% of male population (rare in blacks) PREDOMINANT AGE AT ONSET: 15 to 35 yr PREDOMINANT SEX: Male:female ratio of 10:1 PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Morning stiffness

•

Fatigue, weight loss, anorexia, and other systemic complaints in more severe forms

•

Bilateral sacroiliac tenderness (sacroiliitis)

•

Limited lumbar spine motion ( Fig. 1-22 )

•

Loss of chest expansion measured at the nipple line girls

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Acute stage: perianal swelling, pain, and fever

•

Chronic stage: history of rectal drainage or bleeding; previous abscess with drainage

•

Tender external fistulous opening, with 2 to 3 cm of the anal verge, with purulent or serosanguineous drainage on compression; the greater the distance from the anal margin, the greater the probability of a complicated upward extension

•

Goodsall's rule:

•

1.

Location of the internal opening related to the location of the external opening.

2.

With external opening anterior to an imaginary line drawn horizontally across the midpoint of the anus: fistulous tract runs radially into the anal canal.

3.

With opening posterior to the transanal line: tract is usually curvilinear, entering the anal canal in the posterior midline.

4.

Exception to this rule: an external, anterior opening that is >3 cm from the anus. In this case the tract may curve posteriorly and end in the posterior midline.

If perianal abscess recurs, presence of a fistula is suggested

ETIOLOGY

•

Most common: nonspecific cryptoglandular infection (skin or intestinal flora)

•

Fistulas more common when intestinal microorganisms are cultured from the anorectal abscess

•

Tuberculosis

•

Lymphogranuloma venereum

•

Actinomycosis

•

Inflammatory bowel disease (IBD): Crohn's disease, ulcerative colitis

•

Trauma: surgery (episiotomy, prostatectomy), foreign bodies, anal intercourse

•

Malignancy: carcinoma, leukemia, lymphoma

•

Treatment of malignancy: surgery, radiation

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hidradenitis suppurativa

•

Pilonidal sinus

•

Bartholin's gland abscess or sinus

•

Infected perianal sebaceous cysts

WORKUP

•

Digital rectal examination: 1.

Assess sphincter tone and voluntary squeeze pressure

2.

Determine the presence of an extraluminal mass

3.

Identify an indurated track

4.

Palpate an internal opening or pit

•

Gentle probing of external orifice to avoid creating a false tract; 50% do not have clinically detectable opening

•

Anoscopy

•

Proctosigmoidoscopy to exclude inflammatory or neoplastic disease

•

All studies done under adequate anesthesia

LABORATORY TESTS

•

CBC

•

Rectal biopsy if diagnosis of IBD or malignancy suspected; biopsy of external orifice is useless

IMAGING STUDIES

•

Colonoscopy or barium enema if: 1.

Diagnosis of IBD or malignancy is suspected

2.

History of recurrent or multiple fistulas

3.

Patient < 25 yr old

•

Small bowel series: occasionally obtained for reasons similar to above

•

Fistulography: unreliable but may be helpful in complicated fistulas

TREATMENT NONPHARMACOLOGIC THERAPY

Sitz baths ACUTE GENERAL RX

•

Treatment of choice: surgery

•

Broad-spectrum antibiotic given if:

•

1.

Cellulitis present

2.

Patient is immunocompromised

3.

Valvular heart disease present

4.

Prosthetic devices present

Stool softener/laxative

CHRONIC RX

•

Surgery

•

Surgical goals are as follows:

•

1.

Cure the fistula

2.

Prevent recurrence

3.

Preserve sphincter function

4.

Minimize healing time

Methods for the management of anal fistulas: fistulotomy, setons, rectal advancement flaps, colostomy

DISPOSITION

Outpatient surgery REFERRAL

Refer to a surgeon with expertise in this area.

PEARLS & CONSIDERATIONS COMMENTS

•

HIV-positive and diabetic patients with perirectal abscesses/fistulas are true surgical emergencies.

•

Risk of septicemia, Fournier's gangrene, and other septic complications make immediate drainage imperative.

SUGGESTED READINGS Pfenninger JL, Zainea GG: Common anorectal condition. Am Fam Physician 2001; 64:22. Rickard MJ: Anal abscesses and fistulas. ANZ J Surg 2005; 75(1–2):64. Schwartz DA, Herdman CR: The medical treatment of Crohn's perianal fistulas. Aliment Pharmacol Ther 2004; 19(9):953.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Anorexia Nervosa FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Anorexia nervosa is a psychiatric disorder characterized by abnormal eating behavior, severe self-induced weight loss, and a specific psychopathology (see “Workup”).

ICD-9CM CODES

307.1 Anorexia nervosa EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE/PREVALENCE (IN U.S.): •

Anorexia nervosa occurs in 0.2% to 1.3% of the general population, with an annual incidence of 5 to 10 cases/100,000 persons.

•

Participation in activities that promote thinness (athletics, modeling) is associated with a higher incidence of anorexia nervosa.

PREDOMINANT SEX: Female:male ratio is 9:1. Approximately 0.5% to 1% of women between the ages of 15 and 30 yr have anorexia nervosa. PREDOMINANT AGE: Adolescence to young adulthood is the predominant age. Mean age of onset is 17 yr. Approximately 0.5% to 1% of college-aged women have anorexia nervosa. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Primary care physicians must be skilled at recognizing this disorder because patients with mild cases usually present with nonspecific symptoms such as asthenia, cold intolerance, lack of energy, or dizziness. The physical examination may be normal in the early stages or in mild cases. Patients with moderate to severe anorexia have the following physical characteristics:

•

Patient is emaciated and bundled in clothing.

•

Skin is dry and has excessive growth of lanugo. Skin may also be yellow-tinged from carotenodermia.

•

Brittle nails, thinning scalp hair are present.

•

Bradycardia, hypotension, hypothermia, and bradypnea are common.

•

Female fat distribution pattern is no longer evident.

•

Axillary and pubic hair is preserved.

•

Peripheral edema may be present.

ETIOLOGY

•

Etiology is unknown, but probably multifactorial (sociocultural, psychologic, familial, and genetic factors).

•

A history of sexual abuse has been reported in as many as 50% of patients with anorexia nervosa.

•

Psychologic factors: anorexics often have an incompletely developed personal identity. They struggle to maintain a sense of control over their environment, they usually have a low self-esteem, and they lack the sense that they are valued and loved for themselves.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Depression with loss of appetite

•

Schizophrenia

•

Conversion disorder

•

Occult carcinoma, lymphoma

•

Endocrine disorders: Addison's disease, diabetes mellitus, hypothyroidism or hyperthyroidism, panhypopituitarism

•

GI disorders: celiac disease, Crohn's disease, intestinal parasitosis

•

Infectious disorders: AIDS, TB

•

A clinical algorithm for the evaluation of anorexia is described in Section III

WORKUP

•

A diagnosis can be made using the following DSM-IV diagnostic criteria for anorexia nervosa: 1.

Refusal to maintain body weight (BW) at or above a minimally normal weight for age and height (e.g., weight loss leading to maintenance of BW < 85% of that expected or failure to make expected weight gain during a period of growth, leading to BW < 85% of that expected)

2.

Intense fear of gaining weight or becoming fat, even though underweight

3.

Disturbance in the way in which BW or shape is experienced, undue influence of BW or shape on self-evaluation, or denial of the seriousness of the current low BW

4.

In postmenarchal females, amenorrhea, that is, the absence of at least three consecutive menstrual cycles (A woman is considered to have amenorrhea if her periods occur only following hormone, [e.g., estrogen] administration.)

Specify type: Restricting type: During the current episode of anorexia nervosa, the person has not regularly engaged in binge-eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas). Binge-eating/purging type: During the current episode of anorexia nervosa, the person has regularly engaged in binge-eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas). •

The SCOFF questionnaire is a useful screening tool used in England for eating disorders. It consists of the following five questions: 1.

Do you make yourself Sick because you feel full?

2.

Have you lost Control over how much you eat?

3.

Have you lost more than One stone (about 6 kg) recently?

4.

Do you believe yourself to be Fat when others say you are thin?

5.

Does Food dominate your life?

•

A positive response to two or more questions has a reported sensitivity of 100% for anorexia and bulimia, and an overall specificity of 87.5%.

•

In college-aged females a positive response to any of the following screening questions also warrants further evaluation: 1.

How many diets have you been on in the past year?

2.

Do you think you should be dieting?

3.

Are you dissatisfied with your body size?

4.

Does your weight affect the way you think about yourself?

•

Baseline ECG should be performed on all patients with anorexia nervosa. Routine monitoring of patients with prolonged QT interval is necessary; sudden death in these patients is often caused by ventricular arrhythmias related to QT interval prolongation.

•

A DEXA scan to screen for osteopenia should be considered after 6 months of amenorrhea in patients suspected of anorexia nervosa.

LABORATORY TESTS

•

In mild cases, laboratory findings might be completely normal.

•

Endocrine abnormalities: 1.

Decreased FSH, LH, T4, T3, estrogens, urinary 17-OH steroids, estrone, and estradiol

2.

Normal free T 4, TSH

3.

Increased cortisol, GH, rT3, T3RU

4.

Absence of cyclic surge of LH

•

Leukopenia, thrombocytopenia, anemia, reduced ESR, reduced complement levels, and reduced CD4 and CD8 cells may be present.

•

Metabolic alkalosis, hypocalcemia, hypokalemia, hypomagnesemia, hypercholesterolemia, and hypophosphatemia may be present.

•

Increased plasma ß-carotene levels are useful to distinguish these patients from others on starvation diets.

TREATMENT

NONPHARMACOLOGIC THERAPY

•

A multidisciplinary approach with psychologic, medical, and nutritional support is necessary.

•

A goal weight should be set and the patient should be initially monitored at least once a week in the office setting. The target weight is 100% of ideal BW for teenagers and 90% to 100% for older patients.

•

Weight gain should be gradual (1 to 3 lb/wk) to prevent gastric dilation. Begin with 800 to 1200 kcal in frequent small meals (to avoid bloating sensation), then increase calories to 1500 to 3000 depending on height and age.

•

Add, as necessary, vitamin and mineral supplements.

•

In severe cases, total parenteral nutrition must be used (starting at 800 to 1200 kcal/day).

•

Electrolyte levels should be strictly monitored.

•

Mealtime should be a time for social interaction, not confrontation.

•

Postprandially, sedentary activities are recommended. The patient's access to a bathroom should be monitored to prevent purging.

ACUTE GENERAL RX

•

Criteria to decide on the appropriate initial course of treatment for patients with anorexia nervosa are usually based on the presence of complications, percentage of ideal body weight, and severity of body image distortion.

•

Outpatient treatment is adequate for most patients.

•

Indications for hospitalization are described in the “Referral” section.

•

Medically stable patients who are within 85% of ideal body weight can be followed up by the primary care physician at 3- or 4-wk intervals, which can be lengthened as the patient improves.

•

Pharmacologic treatment generally has no role in anorexia nervosa unless major depression or another psychiatric disorder is present. SSRIs can be used to alleviate the depressed mood and moderate obsessive-compulsive behavior in some individuals.

CHRONIC RX

•

Psychotherapy continued for years and focused specifically on self-image, family and peer interactions, and relapse prevention is an integral part of a successful recovery.

•

Family therapy is also recommended, especially in younger patients.

DISPOSITION

•

The long-term prognosis is generally poor and marked by recurrent exacerbations. The percentage of patients with anorexia nervosa who fully recover is modest. Most patients continue to suffer from a distorted body image, disordered eating habits, and psychic difficulties.

•

Most patients with anorexia nervosa will recover menses within 6 months of reaching 90% of their ideal body weight. It is important to note that patients with anorexia nervosa can become pregnant despite amenorrhea.

•

Mortality rates vary from 5% to 20% and are six times that of peers without anorexia. Frequent causes of death are electrolyte abnormalities, starvation, or suicide.

•

Factors that predict improved outcome in patients with eating disorders include early age at diagnosis, brief interval before initiation of treatment, good parent-child relationships, and having other healthy relationships with friends or therapists.

•

A prolonged QT interval is a marker for risk of sudden death.

REFERRAL

Hospitalization should be considered in the following situations: 1.

Severe dehydration or electrolyte imbalance

2.

ECG abnormalities (prolonged QT interval, arrhythmias)

3.

Significant physiologic instability (hypotension, orthostatic changes)

4.

Intractable vomiting, purging, or bingeing

5.

Patient having suicidal thoughts

6.

Weight loss exceeds 30% of ideal BW and is unresponsive to outpatient treatment

7.

Rapidly progressing weight loss (>2 lbs in a week)

8.

Failure to progress in nutritional rehabilitation in outpatient treatment

EVIDENCE

A small randomized clinical trial (RCT) found limited evidence that fluoxetine reduced relapse in women discharged from hospital.[[1]] Another RCT aimed to compare psychotherapy with dietary advice. Cognitive therapy led to significant improvements compared with baseline. There was a 100% withdrawal rate with dietary advice, thus making comparison between the groups impossible.[[2]] Several small RCTs found no overall significant difference between different types of psychotherapy.[[3]]

Evidence-Based References 1. Kaye WH, et al: Double-blind placebo-controlled administration of fluoxetine in restricting- and restricting-purging-type anorexia nervosa. Soc Biol Psych 2001; 49:644. 2. Serfaty MA: Cognitive therapy versus dietary counselling in the outpatient treatment of anorexia nervosa: effects of the treatment phase. Eur Eat Dis Rev 1999; 7:334. 3. Treasure J, Schmidt U: Anorexia nervosa. Clinical Evidence, London: BMJ Publishing Group; 2005:13.

SUGGESTED READINGS American Psychiatric Association: Practice guideline for the treatment of patients with eating disorders. Am J Psychiatry 2000; 157(suppl):4.(revision). Anstine D, Grinenko D: Rapid screening for disordered eating in college-aged females in the primary care setting. J Adolesc Health 2000; 26:338. Mehler PS: Diagnosis and care of patients with anorexia nervosa in primary care setting. Ann Intern Med 2001; 134:1048. Miller KK, et al: Medical findings in outpatients with anorexia nervosa. Arch Intern Med 2005; 165:561. Morgan JF, et al: The SCOFF questionnaire: assessment of a new screening tool for eating disorders. BMJ 1999; 319:1467. Pritts SD, Susman J: Diagnosis of eating disorders in primary care. Am Fam Physician 2003; 67:297. Williams PM, et al: Treating eating disorders in primary care. Am Fam Physician 2008; 77(b):187-195. Yager J, Andersen AE: Anorexia nervosa. N Engl J Med 2005; 353:1481.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Anthrax FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis.

ICD-9CM CODES

022.0 Cutaneous anthrax 022.1 Inhalation anthrax 022.2 Gastrointestinal anthrax 022.3 Sepsis from anthrax EPIDEMIOLOGY & DEMOGRAPHICS

•

Anthrax most commonly occurs in hoofed animals and can only incidentally infect humans who come in contact with infected animals or animal products. Between 20,000 and 100,000 cases of cutaneous anthrax occur worldwide annually. In the U.S. the annual incidence was about 130 cases before 2001.

•

Until the recent bioterrorism attack in 2001, most cases of anthrax occurred in industrial environments (contaminated raw materials used in manufacturing process) or in agriculture.

•

In 2001 there were more than 20 confirmed cases of anthrax resulting from bioterrorism, most of which were associated with handling of contaminated mail. Inhalation anthrax is the most lethal form of anthrax and results from inspiration of 8000-50,000 spores of Bacillus anthracis. Before 2001 there had not been a case of inhalation anthrax in the U.S. for 20 years.

•

Direct person-to-person spread of anthrax is extremely unlikely, if it occurs at all; therefore, there is no need to immunize or treat contacts of persons ill with anthrax, such as household contacts, friends, or coworkers, unless they also were exposed to the same source of infection.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms of disease vary depending on how the disease was contracted, but usually occur within 7 days after exposure. The serious forms of human anthrax are inhalation anthrax, cutaneous anthrax, and intestinal anthrax.

•

Inhalation anthrax begins with a brief prodrome resembling a viral respiratory illness followed by development of hypoxia and dyspnea, with radiographic evidence of mediastinal widening. Host factors, dose of exposure, and chemoprophylaxis may affect the duration of the incubation period. Initial symptoms include mild fever, muscle aches, and malaise and may progress to respiratory failure and shock; meningitis often develops.

•

Cutaneous anthrax is characterized by a skin lesion evolving from a papule, through a vesicular stage, to a depressed black eschar. The incubation period ranges from 1 to 12 days. The lesion is usually painless, but patients also may have fever, malaise, headache, and regional lymph-adenopathy. The eschar dries and falls off in 1 to 2 wk with little scarring.

•

Gastrointestinal anthrax is characterized by severe abdominal pain followed by fever and signs of septicemia. Bloody diarrhea and signs of acute abdomen may occur. This form of anthrax usually follows after eating raw or undercooked contaminated meat and can have an incubation period of 1 to 7 days. Gastric ulcers may occur and may be associated with hematemesis. An oropharyngeal and an abdominal form of the disease have been described. Involvement of the pharynx is usually characterized by lesions at the base of the tongue, dysphagia, fever, and regional lymphadenopathy. Lower bowel inflammation typically causes nausea, loss of appetite, and fever followed by abdominal pain, hematemesis, and bloody diarrhea.

ETIOLOGY

The disease is caused by Bacillus anthracis, a gram-positive, spore-forming bacillus. It is aerobic, nonmotile, nonhemolytic on sheep's blood agar, and grows readily at temperature of 37° C, forming large colonies with irregularly tapered outgrowths (a Medusa's head appearance). In the host it appears as single organisms or chains of two or three bacilli.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Inhalation anthrax must be distinguished from influenza-like illness (ILI) and tularemia. Most cases of ILI are associated with nasal congestion and rhinorrhea, which are unusual in inhalation anthrax. Additional distinguishing factors are the usual absence of abnormal chest x-ray in ILI (see below).

•

Cutaneous anthrax should be distinguished from staphylococcal disease, ecthyma, ecthyma gangrenosum, plague, brown recluse spider bite, and tularemia.

•

The differential diagnosis of gastrointestinal anthrax includes viral gastroenteritis, shigellosis, and yersiniosis.

LABORATORY TESTS

•

Presumptive identification is based on Gram stain of material from skin lesion, CSF, or blood showing encapsulated gram-positive bacilli.

•

Confirmatory tests are performed at specialized labs. Virulent strains grow on nutrient agar in the presence of 5% CO2. Susceptibility to lysis by gamma phage or DFA staining of cell-wall polysaccharide antigen are also useful confirmatory tests.

•

Nasal swab culture to determine inhalation exposure is of limited diagnostic value. A negative result does not exclude the possibility of exposure. It may be used by public health officials to assist in epidemiologic investigations of exposed persons to evaluate the dispersion of spores.

•

Serologic testing by enzyme-linked immunosorbent assay (ELISA) can confirm the diagnosis.

•

A skin test (Anthracin Test) that detects anthrax cell-mediated immunity is also available in specialized labs.

IMAGING STUDIES

Chest x-ray usually reveals mediastinal widening. Additional findings include infiltrates and pleural effusion.

TREATMENT NONPHARMACOLOGIC THERAPY

IV hydration and ventilator support may be necessary in inhalation anthrax ACUTE GENERAL THERAPY

•

Most naturally occurring B. anthracis strains are sensitive to penicillin. The FDA has approved penicillin, doxycycline, and ciprofloxacin for the treatment of inhalational anthrax infection.

•

Table 1-4 describes a treatment protocol for inhalation anthrax.

•

Initial postexposure prophylaxis therapy in adults is with ciprofloxacin, 500 mg PO bid or doxycycline 100 mg bid. The total duration of treatment is 60 days.

TABLE 1-4 -- Inhalation Anthrax Treatment Protocol[a],[b] Category Initial Therapy (Intravenous)[c],[d] Adults

Ciprofloxacin 400 mg every 12 hr [a]

Duration IV treatment initially.[e] Switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin 500 mg PO bid

or Doxycycline 100 mg every 12 hr[f] and One or two additional antimicrobials[d]

or Doxycycline 100 mg PO bid Continue for 60 days (IV and PO combined) [g]

Children

Ciprofloxacin 10-15 mg/kg every 12 hr [h],[i]

IV treatment initially.[e] Switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin 10-15 mg/kg PO every 12 hr [i]

or Doxycycline[j]: >8 yr and >45 kg: 100 mg every 12 hr

or

>8 yr and =45 kg: 2.2 mg/kg every 12 hr

Doxycycline [j]:

=8 yr: 2.2 mg/kg every 12 hr

>8 yr and >45 kg: 100 mg PO bid

and One or two additional antimicrobials[d]

>8 yr and =45 kg: 2.2 mg/kg PO bid =8 yr: 2.2 mg/kg PO bid Continue for 60 days (IV and PO combined) [g]

Pregnant women[k]

MMRW 5:987, 2001.

Same for nonpregnant adults (the high death rate from the infection outweighs the risk posed by the antimicrobial agent)

IV treatment initially. Switch to oral antimicrobial therapy when clinically appropriate.[b] Oral therapy regimens same for nonpregnant adults

Category

Initial Therapy (Intravenous)[c],[d]

Duration

Immunocompromised persons

Same for nonimmunocompromised persons and children

Same for nonimmunocompromised persons and children

MMRW 5:987, 2001. a For gastrointestinal and oropharyngeal anthrax, use regimens recommended for inhalational anthrax. b Ciprofloxacin or doxycycline should be considered an essential part of first-line therapy for inhalational anthrax. c Steroids may be considered as an adjunct therapy for patients with severe edema and for meningitis based on experience with bacterial meningitis of other etiologies. d Other agents with in vitro activity include rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. Because of concerns of constitutive and inducible beta-lactamases in Bacillus anthracis, penicillin and ampicillin should not be used alone. Consultation with an infectious disease specialist is advised. e Initial therapy may be altered based on clinical course of the patient; one or two antimicrobial agents (e.g., ciprofloxacin or doxycycline) may be adequate as the patient improves. f

If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration.

g Because of the potential persistence of spores after an aerosol exposure, antimicrobial therapy should be continued for 60 days. h If intravenous ciprofloxacin is not available, oral ciprofloxacin may be acceptable because it is rapidly and well absorbed from the gastrointestinal tract with no substantial loss by first-pass metabolism. Maximum serum concentrations are attained 1-2 hours after oral dosing but may not be achieved if vomiting or ileus are present. i

In children, ciprofloxacin dosage should not exceed 1 g/day.

j

The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever).

k Although tetracyclines are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse effects on developing teeth and bones are dose related; therefore, doxycycline might be used for a short time (7-14 days) before 6 months of gestation.

DISPOSITION

•

Case fatality estimates for inhalation anthrax are extremely high (>90%).

•

The case fatality rate for cutaneous anthrax is 20% without and 80%])

•

Presence of anti ß2-glycoprotein I antibody

Antiphospholipid Antibody Syndrome

TREATMENT ACUTE GENERAL RX

•

For positive aPL and venous thrombosis: Initial anticoagulation with heparin, then lifelong warfarin treatment, INR 2.0 to 3.0

•

For positive aPL with arterial thrombosis: Cerebral arterial thrombosis: ASA 325 mg daily or warfarin therapy (INR 1.4 to 2.8) Noncerebral arterial thrombosis: Warfarin therapy (INR 2.0 to 3.0)

•

For pregnant women with previously diagnosed APS: Warfarin should be discontinued secondary to its teratogenic effects. ASA, 81 mg, and heparin SQ to PTT of 1.5 to 2 times control value. IVIG and prednisone have also been used with success if aspirin and heparin fail.

•

For pregnant women with (+) aPL antibodies and a history of 3.0) to warfarin therapy (INR females PEAK INCIDENCE: Ages 60 to 80; mean 63 RISK FACTORS: •

Hypertension

•

Atherosclerosis

•

Family history of aortic aneurysms/dissection

•

History of cardiac surgery, intraaortic catheterization

•

Disorders of collagen (Marfan syndrome, Ehlers-Danlos syndrome)

•

Vascular inflammation (giant cell arteritis, Takayasu arteritis, rheumatoid arthritis, syphillitic aortitis)

•

Aortic coarctation, bicuspid aortic valve

•

Turner's syndrome

•

Cocaine abuse

•

Trauma

CLASSIFICATION

Two main classification schemes based on the location of dissection ( Fig. 1-23 ): •

DeBakey: type I ascending and descending aorta, II ascending aorta, III descending aorta

•

Stanford: type A ascending aorta (proximal), type B descending aorta (distal)

FIGURE 1-23 Classification systems for aortic dissection. (From Isselbacher EM, Eagle KA, DeSanctis RW: Disease of the aorta. In Braunwald E [ed]: Heart disease: a textbook of cardiovascular medicine, ed 5, Philadelphia, 1997, WB Saunders.)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Sudden onset of severe sharp, tearing, or ripping chest pain

•

Anterior chest pain (ascending dissection)

•

Back pain, abdominal pain (descending dissection)

•

Syncope, congestive heart failure (CHF), malperfusion may occur

•

Most present with severe hypertension, 25% with hypotension (systolic blood pressure < 100), which can indicate bleeding, cardiac tamponade, or severe aortic regurgitation

•

Pulse and blood pressure differentials (>20 mm Hg between arms) in 9% to 30% of cases, caused by partial compression of subclavian arteries

•

Aortic regurgitation in 18% to 50% of cases of proximal dissection, often with diastolic decrescendo murmur

•

Myocardial ischemia caused by coronary artery occlusion

•

Stroke in 5% to 10% of patients

ETIOLOGY

•

Degeneration or alteration of the intimal and medial layers seems to be the common pathology involved with acquired (e.g., hypertension, vascular inflammation) and genetic (e.g., collagen vascular disease) risk factors for dissection.

•

Aortic dissection reflects systemic illness of vasculature.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Known as the great imitator: PE, ACS, aortic stenosis/insufficiency, nondissecting aneurysm, pericarditis, cholecystitis, peptic ulcer disease, pancreatitis.

•

Acute MI needs to be ruled out.

•

Consider aortic dissection in patients with unexplained stroke, chest pain, syncope, acute onset CHF, abdominal pain, back pain, malperfusion of extremities or internal organs.

LABORATORY TESTS

•

ECG: helpful to rule out MI, although dissection can lead to coronary ischemia

•

Currently no readily available, reliable serum biomarker

•

Smooth muscle myosin heavy chain protein (released from damaged medial smooth muscle), CRP, fibrinogen, D-dimer, and elastin fragments under investigation

IMAGING STUDIES

•

Chest x-ray may show widened mediastinum (62%) and displacement of aortic intimal calcium.

•

Transesophageal echocardiography (TEE) is study of choice in unstable patients, but operator dependent.

•

MRI has the highest sensitivity and specificity but limited availability; not suitable for unstable patients; contraindicated with pacemakers, metal devices.

•

Helical CT is least operator dependent, but involves intravenous contrast.

•

TEE, MRI, helical CT are imaging modalities of choice. Sensitivities (98% to 100%) and specificities (95% to 98%) nearly equal in skilled hands. Test of choice depends on clinical circumstances and availability.

•

With medium or high pretest probability, a second diagnostic test should be done if the first is negative.

•

Transthoracic echocardiography has poor sensitivity

•

Aortography rarely done now.

TREATMENT ACUTE GENERAL RX

•

Admit to ICU for monitoring.

•

Target SBP 100 to 120, heart rate < 60 to reduce aortic wall stress.

•

IV beta-blockers are cornerstones of treatment.

•

Propanolol 1 mg every 3 to 5 min; metoprolol 5 mg IV every 5 min; or labetalol 20 mg IV, then 20 to 80 mg every 10 min, followed by nitroprusside 0.3 to 10 mg/kg/min.

•

Nitroprusside should not be used without beta-blockade because vasodilation can induce reflex sympathetic stimulation and increased aortic sheer stress.

•

IV calcium channel blockers with negative inotropy may be used.

•

Pain control, often with morphine.

•

Multiple medications may be needed.

•

Proximal dissections require emergent surgery to prevent rupture or pericardial effusion.

•

Distal dissections are treated medically unless distal organ involvement or impending rupture occurs.

•

Evolving role for endovascular stent placement as less invasive treatment for high-risk surgical patients.

CHRONIC RX

•

Chronic aortic dissection (>2 wk) managed with aggressive BP control: target < 120/80 in most patients.

•

Target LDL < 70 mg/dl.

•

Statins can directly modulate the biology of the aorta.

•

Serial imaging of the aorta at 1, 3, 6, 9, and 12 months and every 6 to 12 months thereafter, usually with contrast CT.

•

Ongoing research on role of endovascular stents in chronic dissection.

DISPOSITION

•

85% mortality within 2 wk if untreated.

•

Proximal dissection is a surgical emergency. Time is critical; mortality is 1% to 3% per hr.

•

Overall, in-hospital mortality is 30% with proximal dissections and 10% with distal dissections.

REFERRAL

For ICU management and surgery

PEARLS & CONSIDERATIONS

•

Blood pressure control is essential; beta-blocker is first-line medication.

•

Proximal dissection is a surgical emergency.

SUGGESTED READINGS Mukherjee D, Eagle KA: Aortic dissection—an update. Curr Probl Cardiol 2005; 30(6):287. Shiga T, et al: Diagnostic accuracy of TEE, helical CT, and MRI for suspected thoracic aortic dissection. Arch Intern Med 2006; 166:1350. Tsai TT, et al: Acute aortic syndromes. Circulation 2005; 112:3802.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Aortic Regurgitation FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Aortic regurgitation is retrograde blood flow into the left ventricle from the aorta secondary to incompetent aortic valve. SYNONYMS

Aortic insufficiency AI AR

ICD-9CM CODES

424.1 Aortic valve disorders EPIDEMIOLOGY & DEMOGRAPHICS

•

Prevalence ranges from 4.9% to 10% and increases with age.

•

The most common cause of isolated severe aortic regurgitation is aortic root dilation.

•

Infectious endocarditis is the most frequent cause of acute aortic regurgitation.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

The clinical presentation varies depending on whether aortic insufficiency is acute or chronic. Chronic aortic insufficiency is well tolerated (except when secondary to infective endocarditis), and the patients remain asymptomatic for years. Common manifestations after significant deterioration of left ventricular function are dyspnea on exertion, syncope, chest pain, and CHF. Acute aortic insufficiency manifests primarily with hypotension caused by a sudden fall in cardiac output. A rapid rise in left ventricular diastolic pressure results in a further decrease in coronary blood flow. Physical findings in chronic aortic insufficiency include the following:

•

Widened pulse pressure (markedly increased systolic blood pressure, decreased diastolic blood pressure) is present.

•

Bounding pulses, head “bobbing” with each systole (de Musset's sign) are present; “water hammer” or collapsing pulse (Corrigan's pulse) can be palpated at the wrist or on the femoral arteries (“pistol shot” femorals) and is caused by rapid rise and sudden collapse of the arterial pressure during late systole; capillary pulsations (Quincke's pulse) may occur at the base of the nail beds.

•

A to-and-fro “double Duroziez” murmur may be heard over femoral arteries with slight compression.

•

Popliteal systolic pressure is increased over brachial systolic pressure =40 mm Hg (Hill's sign).

•

Cardiac auscultation reveals: 1.

Displacement of cardiac impulse downward and to the patient's left

2.

S3 heard over the apex

3.

Decrescendo, blowing diastolic murmur heard along left sternal border

4.

Low-pitched apical diastolic rumble (Austin-Flint murmur) caused by contrast of the aortic regurgitant jet with the left ventricular wall

5.

Early systolic apical ejection murmur

In patients with acute aortic insufficiency both the wide pulse pressure and the large stroke volume are absent. A short blowing diastolic murmur may be the only finding on physical examination. ETIOLOGY

•

Infective endocarditis

•

Rheumatic fibrosis (most common cause in developing countries)

•

Trauma with valvular rupture

•

Congenital bicuspid aortic valve (most common cause in U.S.)

•

Myxomatous degeneration

•

Annuloaortic ectasia

•

Syphilitic aortitis

•

Rheumatic spondylitis

•

SLE

•

Aortic dissection

•

Fenfluramine, dexfenfluramine, pergolide, cabergoline

•

Takayasu's arteritis, granulomatous arteritis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Patent ductus arteriosus, pulmonary regurgitation, and other valvular abnormalities

•

The differential diagnosis of cardiac murmurs is described in Section II

WORKUP

•

Echocardiogram, chest x-ray, ECG, and cardiac catheterization (selected patients)

•

Medical history and physical examination focused on the following clinical manifestations: 1.

Dyspnea on exertion

2.

Syncope

3.

Chest pain

4.

CHF

IMAGING STUDIES

•

Chest x-ray 1.

Left ventricular hypertrophy (chronic aortic regurgitation)

2.

Aortic dilation

3.

Normal cardiac silhouette with pulmonary edema: possible in patients with acute aortic regurgitation

•

ECG: left ventricular hypertrophy

•

Echocardiography: coarse diastolic fluttering of the anterior mitral leaflet; LVH in patients with chronic aortic regurgitation. Use of Doppler echo can quantify regurgitant orifice (severe if >0.30 cm2) and regurgitant volume (severe if >60 ml per beat).

•

Cardiac catheterization in selected patients to assess degree of left ventricular dysfunction, confirm the presence of a wide pulse pressure, assess surgical risk, and determine if there is coexistent coronary artery disease.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoidance of competitive sports and strenuous activity

•

Salt restriction

ACUTE GENERAL RX

MEDICAL: •

ACE inhibitors, diuretics, and sodium restriction for CHF; nitroprusside in patients with acute aortic regurgitation

•

Long-term vasodilator therapy with ACE inhibitors or nifedipine for reducing or delaying the need for aortic valve replacement in asymptomatic patients with severe aortic regurgitation and normal left ventricular function

•

Bacterial endocarditis prophylaxis for surgical and dental procedures

SURGICAL: Reserved for:

•

Symptomatic patients with chronic aortic regurgitation despite optimal medical therapy

•

Patients with acute aortic regurgitation (i.e., infective endocarditis) producing left ventricular failure

•

Evidence of systolic failure:

•

1.

Echocardiographic fractional shortening < 25%

2.

Echocardiographic and diastolic dimension >55 mm

3.

Angiographic ejection fraction < 50% or end-systolic volume index (ESVI) >60 ml/m2

Evidence of diastolic failure: 1.

Pulmonary pressure >45 mm Hg systolic

2.

Left ventricular end-diastolic pressure (LVEDP) >15 mm Hg at catheterization

3.

Pulmonary hypertension detected on examination

•

In general, the “55 rule” has been used to determine the timing of surgery: surgery should be performed before EF 55 mm

•

The operative mortality rate for aortic regurgitation is 4% when performed alone and 6.8% when performed with CABG

SUGGESTED READINGS Enriquez-Sarano M, Tajik J: Aortic regurgitation. N Engl J Med 2004; 351:1539.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Aortic Stenosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Aortic stenosis is obstruction to systolic left ventricular outflow across the aortic valve. Symptoms appear when the valve orifice decreases to 50 mm Hg and valve area 24 hr, leukocytosis >20,000/mm3, temperature >102° F, palpable abdominal mass, and peritoneal findings.

•

In general, prognosis is excellent. Mortality is 50,000 cells/mm3 with >80% polymorphonuclear cells.

2.

Counts are highly variable, with similar findings in gout, pseudogout, or rheumatoid arthritis.

3.

The differential diagnosis of synovial fluid abnormalities is described in Section II.

•

Blood cultures

•

Culture of possible extraarticular sources of infection

•

Elevated peripheral WBC count and ESR (nonspecific)

IMAGING STUDIES

•

X-ray examination of the affected joint to rule out osteomyelitis

•

CT scan for early diagnosis of infections of the spine, hips, and sternoclavicular and sacroiliac joints

•

Technetium and gallium scintigraphic scans (positive, but do not permit differentiation of infection from inflammation)

•

Indium-labeled WBC scans (less sensitive, but more specific)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Affected joints aspirated daily to remove necrotic material and to follow serial WBC counts and cultures

•

If no resolution with IV antibiotics and closed drainage: open debridement and lavage, particularly in nongonococcal infections

•

Prevention of contractures: 1.

After acute stage of inflammation, range-of-motion exercises of the affected joint

2.

Physical therapy helpful

ACUTE GENERAL RX

•

IV antibiotics immediately after joint aspiration and Gram stain of the synovial fluid

•

For infections caused by gram-positive cocci: penicillinase-resistant penicillin, such as nafcillin (2 g IV q4h), unless there is clinical suspicion of methicillin-resistant Staphylococcus aureus, in which case vancomycin (1 g IV q12h)

•

Infections caused by gram-negative bacilli: treated with a third-generation cephalosporin or an antipseudomonal penicillin plus an aminoglycoside, pending C&S results

•

For suspected gonococcal infection, including young adults when the synovial fluid Gram stain is nondiagnostic: ceftriaxone 1 g IV q24h

CHRONIC RX

See indications for surgical drainage. DISPOSITION

•

With prompt treatment, complete resolution is expected.

•

Delay in treatment may result in permanent destruction of cartilage and loss of function of the affected joint.

REFERRAL

To an orthopedist for open drainage if the infected joint fails to improve on appropriate antibiotics and closed aspiration

PEARLS & CONSIDERATIONS COMMENTS

Any patient with an acute monoarticular arthritis should undergo an urgent joint aspiration to rule out septic arthritis, even if there is a history of gout. SUGGESTED READINGS Berendt T, Byren I: Bone and joint infection. Clin Med 2004; 4(6):510. Garc'a-De La Torre I, et al: Advances in the management of septic arthritis. Rheum Dis Clin North Am 2003; 29(1):61. Weisfelt M, et al: Arthritis in adults with community-acquired bacterial meningitis: a prospective cohort study. BMC Infect Dis 2006; 6:64. Yagupsky P: Differentiation between septic arthritis and transient synovitis of the hip in children. J Bone Joint Surg Am 2005; 87(2):459.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Arthritis, Psoriatic LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Psoriatic arthritis is an inflammatory spondyloarthritis occurring in patients with psoriasis who are usually seronegative for rheumatoid factor. It is often included in a class of disorders called rheumatoid variants or seronegative spondyloarthropathies.

ICD-9CM CODES

696.0 Psoriatic arthritis EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 5% to 10% of patients with psoriasis (psoriasis affects 1% to 1.5% of general population) PREDOMINANT SEX: Males = females PREDOMINANT AGE: 30 to 55 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usually gradual clinical onset

•

Asymmetric involvement of scattered joints

•

Selective involvement of the DIP joints (described in “classic” cases but present in only 5% of patients; Fig. 1-24 )

•

Symmetric arthritis similar to RA in 15% of patients

•

Possible development of predominant sacroiliitis in a small number of cases

•

Advanced form of hand involvement (arthritis mutilans) in some patients

•

Dystrophic changes in the nails (pitting, ridging) in many patients with DIP involvement

•

Fingers often assume a “sausage” appearance (dactylitis)

FIGURE 1-24 The hands of a woman with symmetric polyarthritis. Initially, this was indistinguishable from rheumatoid disease, but note the distal interphalangeal joint involvement, which is uncommon in rheumatoid arthritis, as well as the skin psoriasis. (From Klippel J, Dieppe P, Ferri F [eds]: Primary care rheumatology, London, 1999, Mosby.)

ETIOLOGY

Unknown. Destructive changes probably due to release of cytokines and tumor necrosis factor.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Rheumatoid arthritis

•

Erosive osteoarthritis

•

Gouty arthritis

•

Ankylosing spondylitis

•

The differential diagnosis of spondyloarthropathies is described in Section II

WORKUP

•

Early diagnosis may be difficult to establish because the arthritis may develop before skin lesions appear.

•

Laboratory studies show no specific abnormalities in most cases.

LABORATORY TESTS

•

Slight elevation of ESR

•

Possible mild anemia

•

Possible HLA-B27 antigen (especially in patients with sacroiliitis)

IMAGING STUDIES

•

Peripheral joint findings similar to those in rheumatoid arthritis but erosive changes in the distal phalangeal tufts characteristic of psoriatic arthritis

•

Bony osteolysis; periosteal new bone formation

•

Changes in axial skeleton: sacroiliitis, development of vertebral syndesmophytes (osteophytes) that often bridge adjacent vertebral bodies

•

Paravertebral ossification

•

Spinal changes: do not have same appearance as ankylosing spondylitis; however, spine abnormalities are less common than sacroiliitis

TREATMENT NONPHARMACOLOGIC THERAPY

•

Rest

•

Splinting

•

Joint protection

•

PT

ACUTE GENERAL RX

•

NSAIDs

•

Occasional intraarticular steroid injections

•

DMARDs: rarely are required

DISPOSITION

•

Different from rheumatoid arthritis in both prognosis and response to treatment.

•

Generally, mild joint symptoms in psoriatic arthritis although some patients develop a more severe form which requires intensive treatment.

•

Disease-free intervals lasting for several years in many patients.

REFERRAL

•

Orthopedic surgery consultation for painful joint deformity.

•

Rheumatology for uncontrolled symptoms.

PEARLS & CONSIDERATIONS

•

There is often a strong family history of psoriasis in patients who develop psoriatic arthritis.

•

Enthesitis (inflammation of tendon and fascial attachments) is a common feature of the spondyloarthropathies typically involving the plantar fascia and tendo Achilles.

SUGGESTED READINGS Ali Y, et al: Improved survival in psoriatic arthritis with calendar time. Arthritis Rheum 2007; 56(8):2708. Griffiths CE, Barker JN: Pathogenesis and clinical features of psoriasis. Lancet 2007; 370(9583):263. Heiberg MS, et al: The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Rheum 2008; 59:234. Kataria RK, Brent LH: Spondyloarthiopathies. Am Fam Phys 2004; 69:2853. Liu Y, Cortinovis D, Stone MA: Recent advances in the treatment of the spondyloarthropathies. Curr Opin Rheumatol 2004; 16:357. Scarpa R, et al: Early psoriatic arthritis: the clinical spectrum. J Rheumatol 2007; 57(8):1560. Taylor WJ: Assessment of outcome in psoriatic arthritis. Curr Opin Rheumatol 2004; 16:350.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Asbestosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Asbestosis is a slowly progressive diffuse interstitial fibrosis resulting from dose-related inhalation exposure to fibers of asbestos.

ICD-9CM CODES

501 Asbestosis EPIDEMIOLOGY & DEMOGRAPHICS

•

In U.S.: 5 to 10 new cases/100,000 persons/yr

•

Prolonged interval (20 to 30 yr) between exposures to inhaled fibers and clinical manifestations of disease

•

Most common in workers involved in the primary extraction of asbestos from rock deposits and in those involved in the fabrication and installation of products containing asbestos (e.g., naval shipyards in World War II, installation of floor tiles, ceiling tiles, acoustic ceiling coverings, wall insulation, and pipe coverings in public buildings)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Insidious onset of shortness of breath with exertion is usually the first sign of asbestosis.

•

Dyspnea becomes more severe as the disease advances; with time, progressively less exertion is tolerated.

•

Cough is frequent and usually paroxysmal, dry, and nonproductive.

•

Scant mucoid sputum may accompany the cough in the later stages of the disease.

•

Fine end respiratory crackles (rales, crepitations) are heard more predominantly in the lung bases.

•

Digital clubbing, edema, jugular venous distention are present.

ETIOLOGY

Inhalation of asbestos fibers

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Silicosis

•

Siderosis, other pneumonoconioses

•

Lung cancer

•

Atelectasis

WORKUP

Documentation of exposure history, diagnostic imaging, pulmonary function testing LABORATORY TESTS

•

Generally not helpful

•

Possible mild elevation of ESR, positive ANA and RF (These tests are nonspecific and do not correlate with disease severity or activity.)

•

Pulmonary function testing: decreased vital capacity, decreased total lung capacity, decreased carbon monoxide gas transfer

•

ABGs: hypoxemia, hypercarbia in advanced stages

IMAGING STUDIES

Chest x-ray ( Fig. 1-25 ): •

Small, irregular shadows in lower lung zones

•

Thickened pleural, calcified plaques (present under diaphragms and lateral chest wall)

FIGURE 1-25 Asbestosis. PA radiograph shows coarse linear opacities at both lung bases obscuring the cardiac borders. (From McLoud TC: Thoracic radiology: the requisites, St Louis, 1998, Mosby.)

CT scan of chest confirms the diagnosis. Typical findings on high-resolution CT of the chest include increased interstitial markings found mainly at the bases. As the disease progresses, honeycombing is noted.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Smoking cessation, proper nutrition, exercise program to maximize available lung function

•

Home oxygen therapy prn

•

Removal of patient from further asbestos fiber exposure

GENERAL RX

•

Prompt identification and treatment of respiratory infections

•

Supplemental oxygen on a prn basis

•

Annual influenza vaccination, pneumococcal vaccination

DISPOSITION

•

There is no specific treatment for asbestosis.

•

Death is usually secondary to respiratory failure from cor pulmonale.

•

Patients with asbestosis have increased risk for mesotheliomas, lung cancer, and TB. Recent reports indicate that the risk of asbestos-induced lung cancer may be overestimated.

•

Survival in patients following development of mesothelioma is 4 to 6 yr.

REFERRAL

To pulmonologist initially

PEARLS & CONSIDERATIONS COMMENTS

Patient information on asbestosis can be obtained from the American Lung Association, 1740 Broadway, New York, NY 10019. SUGGESTED READINGS American Thoracic Society: Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Resp Crit Care Med 2004; 170:691. O'Reilly K, et al: Asbestos-related lung disease. Am Fam Physician 2007; 75:683.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ascariasis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., GEORGE O. ALONSO, M.D.

BASIC INFORMATION DEFINITION

Ascariasis is a parasitic infection caused by the nematode Ascaris lumbricoides. The majority of those infected are asymptomatic; however, clinical disease may arise from pulmonary hypersensitivity, intestinal obstruction, and secondary complications. Synonyms

round worms worms

ICD-9CM CODES

127.0 Ascariasis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Unknown

•

Three times the infection rates found in blacks as in whites

PEAK INCIDENCE: Unknown PREVALENCE (IN U.S.): Estimated at 4,000,000, the majority of which live in the rural southeastern part of the country PREDOMINANT SEX: Both sexes probably equally affected, with a possible slight female preponderance PREDOMINANT AGE: Most common in children, with estimated mean age of approximately 5 yr based on surveys in highly endemic areas NEONATAL INFECTION: Probable transmission, though not specifically studied

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Occurs approximately 9 to 12 days after ingestion of eggs (corresponding to the larva migration through the lungs)

•

Nonproductive cough

•

Substernal chest discomfort

•

Fever

•

In patients with large worm burdens, especially children, intestinal obstruction associated with perforation, volvulus, and intussusception

•

Migration of worms into the biliary tree giving clinical appearance of biliary colic and pancreatitis as well as acute appendicitis with movement into that appendage

•

Rarely, infection with A. lumbricoides producing interstitial nephritis and acute renal failure

•

In endemic areas in Asia and Africa, malabsorption of dietary proteins and vitamins as a consequence of chronic worm intestinal carriage

ETIOLOGY

•

Transmission is usually hand to mouth, but eggs may be ingested via transported vegetables grown in contaminated soil.

•

Eggs are hatched in the small intestine, with larvae penetrating intestinal mucosa and migrating via the circulation to the lungs.

•

Larval forms proceed through the alveoli, ascend the bronchial tree, and return to the intestines after swallowing, where they mature into adult worms.

•

Estimated time until the female adult worm begins producing eggs is 2 to 3 mo.

•

Eggs are passed out of the intestines with feces.

•

Within human host, adult worm lifespan is 1 to 2 yr.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Radiologic manifestations and eosinophilia to be distinguished from drug hypersensitivity and Löffler's syndrome

•

The differential diagnosis of intestinal helminths is described in Section II

LABORATORY TESTS

•

Examination of the stool for Ascaris ova

•

Expectoration or fecal passage of adult worm

•

Eosinophilia: most prominent early in the infection and subsides as the adult worm infestation established in the intestines

•

Anti-ascaris IgG4 blood levels by ELISA is a sensitive and specific marker of infection and may be useful in the evaluation of treatment

•

Malondialdehyde levels clearly increase in patients infected with A. lumbricoides

IMAGING STUDIES

•

Chest x-ray examination to reveal bilateral oval or round infiltrates of varying size (Löffler's syndrome); note: infiltrates are transient and eventually resolve.

•

Plain films of the abdomen and contrast studies to reveal worm masses in loops of bowel.

•

Ultrasonography and endoscopic retrograde cholangiopancreatography (ERCP) to identify worms in the pancreaticobiliary tract.

TREATMENT NONPHARMACOLOGIC THERAPY

Aggressive IV hydration, especially in children with fever, severe vomiting, and resultant dehydration ACUTE GENERAL RX

•

Mebendazole (Vermox) 1.

Drug of choice for intestinal infection with A. lumbricoides

2.

100 mg PO tid given for 3 days or 500 mg as a single dose

•

Albendazole, given as a single 400-mg dose PO

•

Both mebendazole and albendazole are contraindicated in pregnancy

•

Pyrantel pamoate (Antiminth)

•

•

1.

Given at a dose of 11 mg/kg PO (maximum dose of 1 g/day)

2.

Considered safe for use in pregnant women

Piperazine citrate 1.

Recommended in cases of intestinal or biliary obstruction

2.

Administered as a syrup, given via nasogastric tube, a 150 mg/kg loading dose, followed by six doses of 65 mg/kg q12h

3.

Considered safe in pregnancy, but cannot be given concurrently with chlorpromazine

Complete obstruction should be managed surgically

DISPOSITION

Overall prognosis is good. Patients should be reevaluated in 2 to 3 months. Reinfection is common. REFERRAL

•

To gastroenterologist in cases of visualized pancreaticobiliary tract or appendiceal obstruction

•

To surgeon in cases of complete obstruction or suspected secondary complication (e.g., perforation or volvulus)

PEARLS & CONSIDERATIONS COMMENTS

•

Hepatic abscess, containing both viable and dead worms, complicating Ascaris-induced biliary duct disease has been documented.

•

Given the known transmission of the parasite, routine hand washing and proper disposal of human waste would significantly decrease the prevalence of this disease.

SUGGESTED READINGS Bradley JE, Jackson JA: Immunity, immunoregulation, and the ecology of trichuriasis and ascariasis. Parasite Immunol 2004; 26(11–12):429. Kilic E, et al: Serum malondialdehyde level in patients infected with. Ascaris lumbricoides, World J Gastroenterol 2003; 9(10):2332. Legesse M, Erko B, Medhin G: Comparative efficacy of albendazole and three brands of mebendazole in the treatment of ascariasis and trichuriasis. East Afr Med J 2004; 81(3):134. Sangkhathat S, et al: Massive gastrointestinal bleeding in infants with ascariasis. J Pediatr Surg 2003; 38(11):1696. Shah OJ, et al: Biliary ascariasis: a review. World J Surg 2006; 30(8):1500.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ascites JOANNE M. SILVIA, M.D., PAUL F. GEORGE, M.D.

BASIC INFORMATION DEFINITION

Ascites is the accumulation of excess fluid in the peritoneal cavity, most commonly caused by liver cirrhosis. SYNONYMS

Fluid in peritoneal cavity, hydroperitoneum, hydroperitonia, hydrops abdominis

ICD-9CM CODES

789.5 Ascites EPIDEMIOLOGY & DEMOGRAPHICS

Ascites is the most common complication of cirrhosis. Ascites occurs in 50% of individuals with cirrhosis within 10 years of diagnosis. Cirrhosis is the cause of 75% of cases of ascites. Other causes include malignancy (10%), cardiac failure (3%), tuberculosis (3%), and pancreatitis (5%). CLINICAL PRESENTATION

•

Important information to elicit within history: Viral hepatitis Alcoholism Increasing abdominal girth Increasing lower extremity edema Intravenous drug use Sexual history (i.e., men who have sex with men) History of transfusions

•

Important physical exam findings:

Bulging flanks Flank dullness to percussion Fluid wave on abdominal exam Lower extremity edema Shifting dullness on abdominal exam Physical signs associated with liver cirrhosis: spider angiomas, jaundice, loss of body hair, Dupuytren's contracture, muscle wasting, bruising, palmar erythema, gynecomastia, testicular atrophy, hemorrhoids, caput medusae ETIOLOGY

Pathophysiology of ascites: increased hepatic resistance to portal flow leads to portal hypertension. The splanchnic vessels respond by increased secretion of nitric oxide causing splanchnic artery vasodilation. Early in the disease increased plasma volume and increased cardiac output compensate for this vasodilation. However, as disease progresses the effective arterial blood volume decreases causing sodium and fluid retention through activation of the renin-angiotensin system. The change in capillary pressure causes increased permeability and retention of fluid in the abdomen.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Chronic parenchymal liver disease, leading to portal hypertension

•

Peritoneal carcinomatosis

•

Congestive heart failure

•

Peritoneal tuberculosis

•

Nephrotic syndrome

•

Pancreatitis

LABORATORY TESTS

•

Initial evaluation should always include: Diagnostic paracentesis. Laboratory tests on this fluid should include a CBC with differential, albumin, total protein, culture and a gram stain. Optional tests on paracentesis fluid include amylase, LDH, acid-fast bacilli and glucose levels AST, ALT, total and direct bilirubin, albumin, alkaline phosphatase, GGTP CBC, coagulation studies Electrolytes, BUN, creatinine

•

A serum to ascites albumin gradient should be calculated in all patients. If the SAAG is greater than 1.1, the cause of ascites can be attributed to portal hypertension. If SAAG is less than 1.1, a nonportal hypertension etiology of ascites must be sought.

IMAGING STUDIES

•

Endoscopy of the upper GI tract to evaluate for esophageal varices if ascites secondary to portal hypertension.

•

Abdominal ultrasound is the most sensitive measure for detecting ascitic fluid; a CT scan is a viable alternative.

•

Liver biopsy in selected patients (i.e., those with portal hypertension of uncertain etiology).

TREATMENT NONPHARMACOLOGIC THERAPY

•

Sodium-restricted diet (maximum 60 to 90 milliequivalents per day).

•

Fluid restriction to 1 liter per day in patients with hyponatremia.

ACUTE GENERAL RX

•

Patients with moderate-volume ascites causing only moderate discomfort may be treated on an outpatient basis with the following diuretic regimen: spironolactone 50 to 200 mg daily or amiloride 5 to 10 mg daily. Add Lasix 20 to 40 mg per day in the first several days of treatment, monitoring renal functions carefully for signs of prerenal azotemia (in patients without edema goal weight loss is 300 to 500 grams/day, in patients with edema 800 to 1000 grams/day).

•

Patients with large-volume ascites causing marked discomfort or decrease in activities of daily living may also be treated as outpatients if there are no complications. There are two options for treatment in these patients: (1) large-volume paracentesis or (2) diuretic therapy until loss of fluid is noted (maximum spironolactone 400 mg daily and Lasix 160 mg daily). No difference in long-term mortality was found; however paracentesis is faster, more effective, and associated with fewer adverse effects.

CHRONIC RX

5% to 10% of patients with large-volume ascites will be refractory to high-dose diuretic treatment. Treatment strategies include repeated large-volume paracentesis with infusion of albumin every 2 to 4 weeks or placement of a transjugular intrahepatic portosystemic shunt (TIPS). DISPOSITION

Monitor closely for worsening liver function, development of SBP. REFERRAL

Referral to gastroenterology for endoscopy in patients with ascites secondary to cirrhosis

PEARLS & CONSIDERATIONS COMMENTS

Prevalence of spontaneous bacterial peritonitis (SBP) in patients with ascites ranges between 10% and 30%. Presence of at least 250 neutrophils per cubic millimeter of ascitic fluid is diagnostic. Gram-negatives such as E. coli are the most common isolates. Third-generation cephalosporins are the treatment of choice. By 1 year, 70% of patients have recurrence of SBP and may be prophylaxed with quinolones. PREVENTION

Prevention of liver cirrhosis through avoidance of long-term use of alcohol, immunization against hepatitis B, and treatment of hepatitis C SUGGESTED READINGS Bickley L: Bates' Guide to Physical Examination and History Taking, Philadelphia: Lippincott, Williams and Wilkins; 1999:374-375.53. Gines P, et al: Management of cirrhosis and ascites. N Engl J Med 2004; 350:1646-1654. Moore , et al: The management of ascites in cirrhosis. Report on the Consensus Conference of the International Ascites Club. Hepatology 2003; 38:258-266.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Aseptic Necrosis FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Aseptic necrosis is cell death in components of bone: hematopoietic fat marrow and mineralized tissue. Osteonecrosis is not a specific disease entity but a final common pathway to several disorders that impair blood supply to the femoral head and other locations. SYNONYMS

Osteonecrosis Avascular necrosis

ICD-9CM CODES

733.40 Aseptic necrosis 733.43 Aseptic necrosis of femoral condyle 733.42 Aseptic necrosis of femoral head 733.41 Aseptic necrosis of humeral head 733.44 Aseptic necrosis of talus EPIDEMIOLOGY & DEMOGRAPHICS

•

15,000 new cases per year in the U.S.

•

Associated conditions:

•

1.

Corticosteroid treatment: 35%

2.

Alcohol abuse: 22%

3.

Idiopathic and other: 43%

Common sites involved 1.

Femoral head

2.

Femoral condyle

3.

Humeral head

4.

Navicular and lunate wrist bones

5.

Talus

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

May be asymptomatic

•

Pain in the involved area exacerbated by movement or weight bearing

•

Decreased range of motion as the disease progresses

•

Functional limitation

ETIOLOGY

Final common pathway of conditions that lead to impairment of the blood supply to the involved bone. Stages: Stage 0 •

Asymptomatic

•

Normal imaging

•

Histologic findings only (i.e., silent osteonecrosis)

Stage 1 •

Asymptomatic or symptomatic

•

Normal x-ray and CT scan

•

Abnormal bone scan or MRI

Stage 2 •

Abnormal x-rays or CT scan including linear sclerosis, focal bead mineralization, cysts; however, the overall architecture of the involved bone is normal

Stage 3 •

Early evidence of mechanical bone failure (subchondral fracture), but the overall shape of the bone is still intact

Stage 4 •

Flattening or collapse of the bone

Stage 5 •

Joint space narrowing

Stage 6 •

Extensive joint destruction

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

None in late stages

•

Early: any condition causing focal musculoskeletal pain including arthritis, bursitis, tendinitis, myopathy, neoplastic bone and joint diseases, traumatic injuries, pathologic fractures

IMAGING STUDIES ( Fig. 1-26 )

1.

X-ray: insensitive early in the course. The earliest changes include diffuse osteopenia, areas of radiolucency with sclerotic border, and linear sclerosis. Later a subchondral lucency (crescent sign) indicates subchondral fracture. More advanced cases reveal flattening, collapsed bone, and abnormal bone contour. In late disease, osteoarthritic changes are seen.

2.

Bone scan: •

Early: “cold” area.

•

Later: increased radionuclide uptake as a result of remodeling.

•

Sensitivity in early disease is only 70% and specificity is poor.

3.

CT scan: may reveal central necrosis and area of collapse before those are visible in x-ray.

4.

MRI: the most sensitive technology to diagnose early aseptic necrosis. The first sign is a margin of low signal. An inner border of high signal associated with a low-signal line is specific of aseptic necrosis (“double line sign”). Sensitivity is 75% to 100%.

FIGURE 1-26 Aseptic necrosis of the hips. A, Aseptic necrosis can occur from a number of causes, including trauma and steroid use. In this patient, an anteroposterior view of the pelvis shows a transplanted kidney (K) in the right iliac fossa. Use of steroids has caused this patient to have bilateral aseptic necrosis. The femoral heads are somewhat flattened, irregular, and increased in density. B, Aseptic necrosis in a different patient is demonstrated on an MRI scan as an area of decreased signal (arrows) in the left femoral head. This is the most sensitive method for detection of early aseptic necrosis. (From Mettler FA [ed]: Primary care radiology, Philadelphia, 2000, WB Saunders).

TREATMENT PREVENTION

•

Management of etiologic conditions

•

Minimize corticosteroid use

NONPHARMACOLOGIC THERAPY

•

Core decompression: effectiveness 35% to 95% in early phases

•

Bone grafting

•

Osteotomies

•

Joint replacement

ACUTE GENERAL RX

•

Decrease weight bearing of affected area.

•

Pulsing electromagnetic fields applied externally (still experimental).

•

Peripheral vasodilators (e.g., dihydrogotamine) (unproven).

PROGNOSIS

•

When diagnosed at an early stage treatment is appropriate in all cases because 85% to 90% can be expected to progress to a more advanced stage.

•

Contralateral joint involvement is common (30% to 70%).

SUGGESTED READINGS Glesby MJ, et al: Osteonecrosis in patients infected with HIV. J Infect Dis 2001; 184:519-523. Mont MA, et al: Atraumatic osteonecrosis of the knee. J Bone Joint Surg 2000; 82A:1279-1290.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Aspergillosis SAJEEV HANDA, M.D.

BASIC INFORMATION DEFINITION

Aspergillosis refers to several forms of a broad range of illnesses caused by infection with Aspergillus species.

ICD-9CM CODES

117.3 Aspergillosis 117.3 Aspergillosis with pneumonia 117.3 Aspergillus infection (flavus, fumigatus, terreus) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE & PREVALENCE:

•

Aspergillus species are ubiquitous in the environment internationally and occur as a mold found in soil.

•

Cause a variety of illness from hypersensitivity pneumonitis to disseminated overwhelming infection in immunosuppressed patients.

•

Frequently cultured from hospital wards from unfiltered outside air circulating through open windows as well as water sources.

•

Reaches the patient by airborne conidia (spores) that are small enough (2.5 to 3 µm) to reach the alveoli on inhalation.

•

Can invade the nose, paranasal sinuses, external ear, or traumatized skin.

RISK FACTORS: •

The clinical syndrome is dependent on the underlying lung architecture, the host's immune response, and the degree of inoculum.

•

Incidence of invasive aspergillosis is increasing with advances in the treatment of life-threatening diseases: aggressive chemotherapy; bone marrow and organ transplantation, although it rarely can occur in normal hosts especially associated with influenza A. Liver and lung transplant recipients are at highest risk for pulmonary disease.

•

Patients with AIDS and a CD4 10 mm Hg)

•

Wheezing: absence of wheezing (silent chest) or decreased wheezing can indicate worsening obstruction

•

Mental status changes: generally secondary to hypoxia and hypercapnia and constitute an indication for urgent intubation

•

Paradoxic abdominal and diaphragmatic movement on inspiration (detected by palpation over the upper part of the abdomen in a semirecumbent position): important sign of impending respiratory crisis, indicates diaphragmatic fatigue

•

The following abnormalities in vital signs are indicative of severe asthma: 1.

Pulsus paradoxus >18 mm Hg

2.

Respiratory rate >30 breaths/min

3.

Tachycardia with heart rate >120 beats/min

ETIOLOGY

•

Intrinsic asthma: occurs in patients who have no history of allergies; may be triggered by upper respiratory infections or psychologic stress.

•

Extrinsic asthma (allergic asthma): brought on by exposure to allergens (e.g., dust mites, cat allergen, industrial chemicals).

•

Exercise-induced asthma: seen most frequently in adolescents; manifests with bronchospasm following initiation of exercise and improves with discontinuation of exercise.

•

Drug-induced asthma: often associated with use of NSAIDs, beta blockers, sulfites, certain foods and beverages.

•

There is a strong association of the ADAM 33 gene with asthma and bronchial hyperresponsiveness.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

CHF

•

COPD

•

Pulmonary embolism (in adult and elderly patients)

•

Foreign body aspiration (most frequent in younger patients)

•

Pneumonia and other upper respiratory infections

•

Rhinitis with postnasal drip

•

TB

•

Hypersensitivity pneumonitis

•

Anxiety disorder

•

Wegener's granulomatosis

•

Diffuse interstitial lung disease

WORKUP

•

For symptomatic adults and children aged >5 years who can perform spirometry, asthma can be diagnosed after a medical history and physical examination documenting an episodic pattern of respiratory symptoms and from spirometry that indicates partially reversible airflow obstruction (>12% increase and 200 ml in forced expiratory volume in 1 second [FEV1] after inhaling a short bronchodilator or receiving a short [2 to 3 week] course of oral corticosteroids). For children aged50%)

•

Nausea and vomiting

•

Focal neurologic deficit (cranial nerve palsy, hemiplegia, ataxia)

•

Change in mental status

•

Papilledema (rare)

ETIOLOGY

•

The specific etiology of astrocytoma is unknown.

•

The only proven risk factor for development of astrocytoma has been significant exposure to ionizing radiation.

•

Other risk factors, such as increased exposure to certain chemicals (petroleum, solvents, lead, pesticides and herbicides) have been proposed, but not proven.

DIAGNOSIS A provisional diagnosis of astrocytoma is made on clinical grounds and radiographic imaging studies. Tissue pathology is needed to establish the diagnosis and to grade the astrocytoma.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis is vast and includes any cause of headache, seizures, change in mental status, and focal neurologic deficits. WORKUP

•

A CT scan or MRI of the head makes the diagnosis of an intracranial brain tumor. However, tissue is needed to establish a diagnosis of astrocytoma.

•

Electroencephalography (EEG) is sometimes useful to localize the lesion in patients who present with seizures.

•

Stereotactic biopsy under CT or MRI guidance has been shown to be a relatively safe and accurate method for diagnosis of LGA.

•

In the presence of mass effect, either clinically or radiologically, craniotomy with open biopsy and tumor debulking is more appropriate than stereotactic biopsy to establish a tissue diagnosis.

•

Lumbar puncture (LP) is useful for detection of microscopic leptomeningeal dissemination in malignant astrocytomas. It should be avoided for most patients who are thought to have spinal tumor because the withdrawal of CSF may decompensate spinal mass effect.

LABORATORY TESTS

Blood tests are not very specific. IMAGING STUDIES

•

MRI is the diagnostic imaging study of choice. MRI and magnetic resonance angiography (MRA) are used to locate the margins of the tumor, distinguish vascular masses from tumors, detect low-grade astrocytomas not seen by CT scan, and provide clear views of the posterior fossa.

•

Low-grade astrocytomas usually show mass effect and blurring of anatomic boundaries due to their infiltrative nature. Cystic change, focal calcification, or extension into contralateral structures may also be seen.

•

High-grade astrocytomas are typically more associated with enhancement after IV contrast administration due to disruption of the blood-brain barrier. Only about 8% to 15% of LGAs enhance.

•

PET scanning and MR spectroscopy are newer imaging modalities that may be indicated in some patients to assess metabolic and vascular features of a tumor.

ACUTE GENERAL RX

•

When there is evidence of increased intracranial pressure, initiation of intravenous mannitol followed by IV dexamethasone is indicated while waiting for surgical intervention.

•

Mechanical ventilation with hyperventilation may be considered if there is depressed consciousness.

•

Surgery remains the initial treatment of almost all astrocytomas, particularly if the tumor is in an anatomically accessible location. Surgery helps in: 1.

Establishing a pathologic diagnosis

2.

Debulking the tumor

3.

Alleviating intracranial pressure

4.

Offering complete excision with hope for a cure

•

Before surgery, dexamethasone 10 mg IV is given followed by 4 to 6 mg IV q6h.

•

Surgical morbidity and mortality is related to tumor location. Patients with deep tumors or tumors in eloquent cortex are at high risk for neurologic deterioration from surgical resection or biopsy.

•

Stereotactic radiosurgery is reserved for nonresectable lesions.

•

Observation is one option that may be justified if risks of surgical or radiation treatment are greater than risks of medical treatment of presenting symptoms.

•

Single or recurrent seizures should be treated with anticonvulsants. Common choices are phenytoin, valproate, carbamazepine, or levetiracetam. The latter has no drug interactions as compared with the older antiepileptic medications.

CHRONIC RX

•

Postoperative radiation therapy is controversial in patients with LGA, but standard in high-grade astrocytoma. Some authorities recommend waiting for symptoms to occur after surgery in patients with LGA before using radiation therapy.

•

A randomized controlled trial has shown no survival benefit in treating LGA with adjuvant chemotherapy.

•

Chemotherapeutic drugs have been used with some effect in patients with high-grade astrocytoma. The addition of adjuvant chemotherapy in these patients has been shown to increase the proportion of longterm survivors from less than 5% to approximately 15% to 20%.

•

Current options for adjuvant chemo-therapy include single agent carmustine or temozolomide, the PCV regimen (procarbazine/lomustine/vincristine), or placement of Gliadel wafers into the resection cavity at the time of surgery.

•

High-dose chemotherapy followed by autologous bone marrow transplantation is a consideration.

DISPOSITION

•

Approximately 10% to 35% of astrocytomas (usually grade I pilocytic astrocytomas) are amenable to complete surgical excision and cure. WHO grade I astrocytomas do not usually progress to higher-grade tumors.

•

In LGAs, the tumor is more infiltrative and therefore not amenable to complete excision. Nevertheless, most studies recommend surgery to remove as much of the tumor burden as possible.

•

The prognosis of patients with LGA is highly variable. A median of 7 yr survival is cited.

•

Most LGAs typically progress to higher-grade tumors, and progression occurs more rapidly in older patients.

•

Young age at diagnosis is by far the most important prognostic factor correlating with long survival. Other factors associated with a more favorable prognosis include good clinical condition at the time of diagnosis, seizure as a presenting symptom, and small preoperative tumor volume.

•

Patient presentation with focal neurologic deficit or changes in personality/mental status is indicative of worse prognosis. Large preoperative tumor volume and high mitotic activity index are associated with a poorer prognosis.

•

Malignant astrocytomas, grades III and IV, usually require surgery for debulking. It is not known from prospective studies if surgery improves survival; however, retrospective studies suggest a survival benefit in the surgically treated group.

•

Median survival for patients with high-grade astrocytomas is 2 yr for anaplastic type and 1 yr for GBM. Median survival of patients with GBM treated with supportive care is approximately 14 wk. This increases to 20 wk with surgical resection alone, 36 wk with surgery plus XRT, and 40 to 50 wk with the addition of adjuvant chemotherapy.

REFERRAL

A team of specialty consultations is indicated in patients diagnosed with astrocytoma. A neurosurgeon, radiation oncologist, and neurooncologist are all needed to assist in establishing the diagnosis and to provide immediate and follow-up treatment.

PEARLS & CONSIDERATIONS

•

Astrocytomas should be resected if possible.

•

Approximately two thirds of LGAs will progress to higher-grade lesions, but it is not possible to predict which tumors will progress.

•

Other treatment modalities include stereotactic radiosurgery using a gamma knife, and interstitial brachytherapy.

COMMENTS

Controversy exists as to proper management of LGA. It has not been proven that earlier treatment of LGA produces an increase in patient survival as measured from the time of diagnosis. SUGGESTED READINGS Claus EB, Black PM: Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973-2001. Cancer 2006; 106:1358. Grossman SA, Batara JF: Current management of glioblastoma multiforme. Semin Oncol 2004; 31(5):635. Reardon DA, et al: Recent advances in the treatment of malignant astrocytoma. J Clin Oncol 2006; 24:8. See SJ, Gilbert MR: Anaplastic astrocytoma: diagnosis, prognosis, and management. Semin

Oncol 2004; 31(5):618. Siker ML, et al: Should concomitant and adjuvant treatment with temozolomide be used as standard therapy in patients with anaplastic glioma?. Crit Rev Oncol Hematol 2006; 60:2.

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Ataxia Telangiectasia NICOLE J. ULLRICH, M.D., PH.D.

BASIC INFORMATION DEFINITION

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder of childhood that results from defective DNA damage repair. A-T is a multisystemic disease characterized by progressive cerebellar ataxia, choreoathetosis, telangiectasias of the skin and conjunctiva (see Fig. 1-29 ), frequent infections, increased sensitivity to ionizing radiation, and predisposition to malignancies, particularly leukemia and lymphoma.

FIGURE 1-29 Ataxia telangiectasia. (From Callen JP [ed]: Color atlas of dermatology, ed 2, Philadelphia, 2000, WB Saunders.)

ICD-9CM CODES

334.8 Ataxia telangiectasia EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 1/40,000 live births. A-T is the most common cause of progressive cerebellar ataxia in childhood in most countries. It is estimated that 1% to 2% of the U.S. population may be carriers of A-T. PEAK INCIDENCE: Childhood PREDOMINANT SEX: Males=Females GENETICS: AR, chromosome 11q22-q23. Gene product is ATM, which encodes a protein kinase. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Children show normal early development until they start to walk, when gait and truncal ataxia become apparent. They soon develop polyneuropathy, progressive apraxia of eye movements and slurred speech, choreoathetosis, mild diabetes mellitus, delayed physical and sexual development, and signs of premature aging (graying of the hair).

•

Children with A-T experience deterioration of motor skills; by the second decade of life, most patients rely on wheelchairs for at least part of the day. Progressive oromotor difficulties also develop over time, placing patients at risk for aspiration.

•

Telangiectasias, which are characteristic of the disease but not always present, occur in the outer parts of the bulbar conjunctivae, over the surface of the ears and cheeks, on exposed parts of the neck, on the bridge of the nose, and in the flexor creases of the forearms.

•

Immunodeficiencies occur in 60% to 80% of individuals with A-T. Impaired humoral and cellular immunity lead to recurrent sinopulmonary infections in about 70% of children.

•

Cancer risk in individuals with A-T is 38%, of which leukemia and lymphoma account for about 95% of malignancies. As individuals begin to have longer life span, other malignancies are observed, such as melanoma, sarcomas, and cancers of the ovary, breast, stomach, brain, larynx, liver, and parotid gland. Multicenter trials are investigating the interaction between ATM and mutations in breast cancer susceptibility genes (BRCA 1 and 2).

•

Typically, individuals with A-T have normal intelligence. Deterioration of speech is typically noted after the age of 5 to 8 years.

•

Heterozygotes/carriers of the ATM gene are thought to have none of the classical manifestations of A-T.

DIAGNOSIS Diagnosis relies on the constellation of clinical findings, including ataxia and speech changes, as well as family

history and neuroimaging studies. A clinical diagnosis can now be confirmed by radiosensitivity testing (colony survival assay), immunoblotting, and mutation analysis. DIFFERENTIAL DIAGNOSIS (of early onset ataxias)

•

Friedreich's ataxia

•

Abetalipoproteinemia

•

Acquired vitamin E deficiency

•

Early-onset cerebellar ataxia with retained reflexes (EOCA)

•

Ataxia-ocular apraxia type 1 (AOA1)

•

Ataxia with metabolic abnormalities: associated with ceroid lipofuscinosis, xeroderma pigmentosa, Cockayne's syndrome, adrenoleukodystrophy, metachromatic leukodystrophy, mitochondrial disease, sialidosis, Niemann-Pick

WORKUP

•

Patients should be evaluated for immunoglobulin (IgA, IgG, IgE, and IgG subclasses) deficiency, and alpha fetoprotein, which is elevated in more than 95% of patients.

•

Cytogenetics show a 7;14 translocation in 5% to 15% of individuals with A-T. The result is a defective protein kinase. This delays accumulation of the tumor suppressor p53 in response to DNA damage, thereby increasing the risk of cancer. Cells are susceptible to damage by ionizing radiation or chemotherapeutic agents that cause double-stranded DNA breakages. Prenatal testing is available. Fibroblasts can be screened for abnormal sensitivity to ionizing radiation.

•

CT or MRI scans will show cerebellar atrophy, but may not be obvious in very young children.

•

Immunoblotting for ATM protein. This determines whether ATM protein is present in cells; approximately 90% of individuals will have no detectable ATM protein.

•

Pathology shows cerebellar degeneration, loss of pigmented neurons, and posterior column degeneration in the spinal cord.

TREATMENT

•

There is no proven treatment available to delay the progressive ataxia, dysarthria and oculomotor apraxia. Treatment remains supportive.

•

Surveillance for infections and neoplasms. Individuals with frequent and severe infections may benefit from intravenous immunoglobulin to supplement immune system.

•

Antioxidant treatment with Vitamin E is often given empirically, though it has not been formally tested.

•

Minimize radiation. Even diagnostic x-rays should be limited.

•

Physical and occupational therapy to maintain flexibility and minimize contractures.

DISPOSITION

•

The expected life span has increased considerably; most individuals now live beyond 25 years of age and some into the fourth and fifth decades.

REFERRAL

Immunology, neurology, physical and occupational therapy, genetic counselor

PEARLS & CONSIDERATIONS

•

Most common cause of hereditary ataxia

•

Defect in DNA repair

•

Predisposition to frequent infections, malignancies and sensitivity to ionizing radiation

SUGGESTED READINGS Butch AW, et al: Immunoassay to measure ataxia-telangiectasia mutated protein in cellular lysates. Clin Chem 2004; 50:2302-2308. Nowak-Wegrzyn A: Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr 2004; 144:505. Sun X, et al: Early diagnosis of ataxia-telangiectasia using radiosensitivitytesting. J Pediatr 2002; 140:724-731. Taylor AMR, Byrd PJ: Molecular pathology of ataxia telangiectasia. J Clin Pathol 2005; 58(b):1009-1015.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Atelectasis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Atelectasis is the collapse of lung volume.

ICD-9CM CODES

518.0 Atelectasis EPIDEMIOLOGY & DEMOGRAPHICS

•

Occurs frequently in patients receiving mechanical ventilation with higher Fio2

•

Dependent regions of the lung are more prone to atelectasis: they are partially compressed, they are not as well ventilated, and there is no spontaneous drainage of secretions with gravity

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Decreased or absent breath sounds

•

Abnormal chest percussion

•

Cough, dyspnea, decreased vocal fremitus and vocal resonance

•

Diminished chest expansion, tachypnea, tachycardia

ETIOLOGY

•

Mechanical ventilation with higher Fio2

•

Chronic bronchitis

•

Cystic fibrosis

•

Endobronchial neoplasms

•

Foreign bodies

•

Infections (e.g., TB, histoplasmosis)

•

Extrinsic bronchial compression from neoplasms, aneurysms of ascending aorta, enlarged left atrium

•

Sarcoidosis

•

Silicosis

•

Anterior chest wall injury, pneumothorax

•

Alveolar injury (e.g., toxic fumes, aspiration of gastric contents)

•

Pleural effusion, expanding bullae

•

Chest wall deformity (e.g., scoliosis)

•

Muscular weaknesses or abnormalities (e.g., neuromuscular disease)

•

Mucus plugs from asthma, allergic bronchopulmonary aspergillosis, postoperative state

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Neoplasm

•

Pneumonia

•

Encapsulated pleural effusion

•

Abnormalities of brachiocephalic vein and of the left pulmonary ligament

WORKUP

•

Chest x-ray ( Fig. 1-30 )

•

CT scan and fiberoptic bronchoscopy (selected patients)

FIGURE 1-30 Right middle and right lower lobe atelectasis that silhouettes the diaphram and the right heart border. (From Specht N [ed]: Practical guide to diagnostic imaging, St Louis, 1998, Mosby.)

IMAGING STUDIES

•

Chest x-ray will confirm diagnosis.

•

CT scan is useful in patients with suspected endobronchial neoplasm or extrinsic bronchial compression.

•

Fiberoptic bronchoscopy (selected patients) is useful for removal of foreign body or evaluation of endobronchial and peribronchial lesions.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Deep breathing, mobilization of the patient

•

Incentive spirometry

•

Tracheal suctioning

•

Humidification

•

Chest physiotherapy with percussion and postural drainage

ACUTE GENERAL RX

•

Positive-pressure breathing (CPAP by face mask, positive end-expiratory pressure [PEEP] for patients on mechanical ventilation)

•

Use of mucolytic agents (e.g., acetylcysteine [Mucomyst])

•

Recombinant human DNase (dornase alpha) in patients with cystic fibrosis

•

Bronchodilator therapy in selected patients

CHRONIC RX

•

Chest physiotherapy

•

Humidification of inspired air

•

Frequent nasotracheal suctioning

DISPOSITION

Prognosis varies with the underlying etiology. REFERRAL

•

Bronchoscopy for removal of foreign body or plugs unresponsive to conservative treatment

•

Surgical referral for removal of obstructing neoplasms

PEARLS & CONSIDERATIONS COMMENTS

Patients should be educated that frequent changes of position are helpful in clearing secretions. Sitting the patient upright in a chair is recommended to increase both volume and vital capacity relative to the supine position. AUTHOR: FRED F. FERRI, M.D. Atopic Dermatitis

BASIC INFORMATION DEFINITION

Atopic dermatitis is a genetically determined eczematous eruption that is pruritic, symmetric, and associated

with personal family history of allergic manifestations (atopy). SYNONYMS

Eczema Atopic neurodermatitis Atopic eczema

ICD-9CM CODES

691.8 Atopic dermatitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Incidence is between 5 and 25 cases/1000 persons.

•

Highest incidence is among children (5% to 10%). It accounts for 4% of acute care pediatric visits.

•

Onset of disease before age 5 yr in 85% of patients.

•

More than 50% of children with generalized atopic dermatitis develop asthma and allergic rhinitis by age 13 yr.

•

Concordance in monozygotic twins is 86%.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

There are no specific cutaneous signs for atopic dermatitis, and there is a wide spectrum of presentations ranging from minimal flexural eczema to erythroderma.

•

The primary lesions are a result of itching caused by severe and chronic pruritus. The repeated scratching modifies the skin surface, producing lichenification, dry and scaly skin, and redness.

•

The lesions are typically on the neck, face, upper trunk, and bends of elbows and knees (symmetric on flexural surfaces of extremities).

•

There is dryness, thickening of the involved areas, discoloration, blistering, and oozing.

•

Papular lesions are frequently found in the antecubital and popliteal fossae.

•

In children, red scaling plaques are often confined to the cheeks and the perioral and perinasal areas.

•

Inflammation in the flexural areas and lichenified skin is a very common presentation in children.

•

Constant scratching may result in areas of hypopigmentation or hyperpigmentation (more common in blacks).

•

In adults, redness and scaling in the dorsal aspect of the hands or about the fingers are the most common expression of atopic dermatitis; oozing and crusting may be present.

•

Secondary skin infections may be present (Staphylococcus aureus, dermatophytosis, herpes simplex).

ETIOLOGY

Unknown; elevated T-lymphocyte activation, defective cell immunity, and B cell IgE overproduction may play a

significant role.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Scabies

•

Psoriasis

•

Dermatitis herpetiform

•

Contact dermatitis

•

Photosensitivity

•

Seborrheic dermatitis

•

Candidiasis

•

Lichen simplex chronicus

•

Other: Wiskott-Aldrich syndrome, PKU, mycosis fungoides, ichthyosis, HIV dermatitis, nonnummular eczema, histiocytosis X

WORKUP

Diagnosis is based on the presence of three of the following major features and three minor features. MAJOR FEATURES: •

Pruritus

•

Personal or family history of atopy: asthma, allergic rhinitis, atopic dermatitis

•

Facial and extensor involvement in infants and children

•

Flexural lichenification in adults

MINOR FEATURES: •

Elevated IgE

•

Eczema-perifollicular accentuation

•

Recurrent conjunctivitis

•

Ichthyosis

•

Nipple dermatitis

•

Wool intolerance

•

Cutaneous S. aureus infections or herpes simplex infections

•

Food intolerance

•

Hand dermatitis (nonallergic irritant)

•

Facial pallor, facial erythema

•

Cheilitis

•

White dermographism

•

Early age of onset (after 2 mo of age)

LABORATORY TESTS

•

Lab tests are generally not helpful.

•

Elevated IgE levels are found in 80% to 90% of atopic dermatitis.

•

Blood eosinophilia correlates with disease severity.

TREATMENT NONPHARMACOLOGIC THERAPY

Avoidance of triggering factors: •

Sudden temperature changes, sweating, low humidity in the winter

•

Contact with irritating substance (e.g., wool, cosmetics, some soaps and detergents, tobacco)

•

Foods that provoke exacerbations (e.g., eggs, peanuts, fish, soy, wheat, milk)

•

Stressful situations

•

Allergens and dust

•

Excessive hand washing

•

Clip nails to decrease abrasion of skin

GENERAL RX

•

Emollients can be used to prevent dryness. Severely affected skin can be optimally hydrated by occlusion in addition to application of emollients.

•

Topical corticosteroids (e.g., 1% to 2.5% hydrocortisone) may be helpful and are generally considered first line therapy. Use intermediate-potency steroids (e.g., triamcinolone, fluocinolone) for more severe cases and limit potent corticosteroids (e.g., betamethasone, desoximetasone, clobetasol) to severe cases.

•

The topical immunomodulators pimecrolimus and tacrolimus are especially useful for treatment of the face and intertriginous sites, where steroid-induced atrophy may occur. However, due to concerns about carcinogenic potential, the FDA recommends limiting their use for short periods in patients who are intolerant or unresponsive to other treatments. Pimecrolimus cream (Elidel) 1% is applied bid and has antiinflammatory effects secondary to blockage of activated T-cell cytokine production. Tacrolimus (Protopic) ointment (0.03% or 0.1%) applied bid is a macrolide that suppresses humoral and cell-mediated immune responses.

•

Oral antihistamines (e.g., hydroxyzine, diphenhydramine) are effective in controlling pruritus and inducing sedation, restful sleep, and prevention of scratching during sleep. Doxepin and other tricyclic antidepressants also have antihistamine effect, induce sleep, and reduce pruritus.

•

Oral prednisone, IM triamcinolone, Goeckerman regimen, PUVA are generally reserved for severe cases.

•

Methotrexate, cyclosporine azathioprine, and systemic corticosteroids are sometimes tried for recalcitrant disease in adults.

DISPOSITION

•

Resolution occurs in approximately 40% of patients by adulthood.

•

Most patients have a course characterized by remissions and intermittent flares.

SUGGESTED READINGS Buys LM: Treatment options for atopic dermatitis. Am Fam Physician 2007; 75:523-528.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Atrial Fibrillation FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Atrial fibrillation is totally chaotic atrial activity caused by simultaneous discharge of multiple atrial foci. SYNONYMS

AF A-fib

ICD-9CM CODES

427.31 Atrial fibrillation EPIDEMIOLOGY & DEMOGRAPHICS

•

The prevalence of atrial fibrillation increases with age, from 2% in the general population, to 5% in patients older than 60 yr, to 9% of those aged 80 years or older.

•

Atrial fibrillation affects 2.3 million people in the U.S. and is a major cause of stroke (fivefold increased risk of stroke).

•

Chronic atrial fibrillation develops in 25% 5 years after paroxysmal atrial fibrillation.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Clinical presentation is variable: •

Most common complaint: palpitations

•

Fatigue, dizziness, light-headedness in some patients

•

A few completely asymptomatic patients

•

Cardiac auscultation revealing irregularly irregular rhythm

ETIOLOGY

•

Coronary artery disease

•

MS, MR, AS, AR

•

Thyrotoxicosis

•

Pulmonary embolism, COPD

•

Pericarditis

•

Myocarditis, cardiomyopathy

•

Tachycardia-bradycardia syndrome

•

Alcohol abuse

•

MI

•

WPW syndrome

•

Obesity (The excess risk of AF associated with obesity appears to be mediated by left atrial dilation.)

•

Other causes: left atrial myxoma, atrial septal defect, carbon monoxide poisoning, pheochromocytoma, idiopathic, hypoxia, hypokalemia, sepsis, pneumonia

•

Arterial stiffness as measured by an elevated pulse pressure (the difference between systolic and diastolic pressure) is a risk factor for incident AF

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Multifocal atrial tachycardia

•

Atrial flutter

•

Frequent atrial premature beats

WORKUP

New-onset atrial fibrillation: ECG, echocardiogram, Holter monitor (selected patients), and laboratory evaluation LABORATORY TESTS

•

TSH, free T4

•

Serum electrolytes

IMAGING STUDIES

•

ECG (see Fig. 1-31 for “Atrial flutter and atrial fibrillation”) 1.

Irregular, nonperiodic wave forms (best seen in V1) reflecting continuous atrial reentry

2.

Absence of P waves

3.

Conducted QRS complexes showing no periodicity

•

Echocardiography to evaluate left atrial size and detect valvular disorders

•

Holter monitor: useful only in selected patients to evaluate paroxysmal atrial fibrillation

FIGURE 1-31 Atrial flutter and fibrillation. Notice the sawtooth waves with atrial flutter (F) and the irregular fibrillatory waves with atrial fibrillation (f). (From Goldberger AL [ed]: Clinical electrocardiography, ed 5, St Louis, 1994, Mosby.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoidance of alcohol in patients with suspected excessive alcohol use

•

Avoidance of caffeine and nicotine

ACUTE GENERAL RX

New-onset atrial fibrillation •

If the patient is hemodynamically unstable, perform synchronized cardioversion following immediate conscious sedation with a rapid short-acting sedative (e.g., midazolam).

•

If the patient is hemodynamically stable, treatment options include the following:

1.

Diltiazem 0.25 mg/kg given over 2 min followed by a second dose of 0.35 mg/kg 15 min later if the rate is not slowed. May then follow with IV infusion 10 mg/hr (range 5 to 15 mg/hr). Onset of action following IV administration is usually within 3 min, with peak effect most often occurring within 10 min. After the ventricular rate is slowed, the patient can be changed to oral diltiazem 60 to 90 mg q 6 hr.

2.

Verapamil 2.5 to 5 mg IV initially, then 5 to 10 mg IV 10 min later if the rate is still not slowed. After the ventricular rate is slowed, the patient can be changed to oral verapamil 80 to 120 mg q6 to 8h.

3.

Esmolol, metoprolol, atenolol are beta blockers that are available in IV preparations that can be used in atrial fibrillation.

4.

Other medications useful for converting atrial fibrillation to sinus rhythm are ibutilide, flecainide, propafenone, disopyramide, amiodarone, and quinidine.

5.

Digoxin is not a very potent AV nodal blocking agent and cannot be relied on for acute control of the ventricular response. When used, give 0.5 mg IV loading dose (slow), then 0.25 mg IV 6 hr later. A third dose may be needed after 6 to 8 hr; daily dose varies from 0.125 to 0.25 mg (decrease dosage in patients with renal insufficiency and elderly patients). Digoxin should be avoided in Wolff-Parkinson-White patients with atrial fibrillation. Procainamide is the preferred pharmacologic agent in these patients.

•

IV heparin or SC low molecular weight heparin.

•

Cardioversion is indicated if the ventricular rate is >140 bpm and the patient is symptomatic (particularly in acute MI, chest pain, dyspnea, CHF) or when there is no conversion to normal sinus rhythm after 3 days of pharmacologic therapy. The likelihood of cardioversion-related clinical thromboembolism is low in patients with atrial fibrillation lasting2 days have a 5% to 7% risk of clinical thromboembolism if cardioversion is not preceded by several weeks of warfarin therapy. However, if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy. Anticoagulant therapy should be continued for at least 1 mo after cardioversion to minimize the incidence of adverse thromboembolic events following conversion from atrial fibrillation to sinus rhythm.

•

Anticoagulate with warfarin (unless patient has specific contraindications).

•

Long-term anticoagulation with warfarin (adjusted to maintain an INR of 2 to 3) is indicated in all patients with atrial fibrillation and associated cardiovascular disease, including the following: 1.

Rheumatic valvular disease (MS, MR, AI)

2.

Aortic stenosis

3.

Prostatic heart valves

4.

History of previous embolism

5.

Persistent atrial thrombus on transesophageal echocardiography

6.

CHF

7.

Cardiomyopathy with poor left ventricular function

8.

Nonrheumatic heart disease (e.g., hypertensive cardiovascular disease, coronary artery disease, ASD)

•

Anticoagulation with warfarin is generally not recommended in patients=60 yr with lone atrial fibrillation (no associated cardiovascular disease or diabetes). Aspirin at a dose of 325 mg/day is appropriate therapy in these patients.

•

Aspirin 325 mg/day may also be a suitable alternative to warfarin in patients 60 to 75 yr and no risk factors and in those who refuse warfarin or have contraindications to its use.

•

Medical cardioversion:

1.

Attempts at medical (pharmacologic) intervention should be considered only after proper anticoagulation because cardioversion can lead to systemic emboli. Following successful cardioversion, anticoagulation with warfarin should be continued for 4 wk.

2.

Useful agents for medical cardioversion are quinidine, flecainide, propafenone, amiodarone, ibutilide, sotalol, dofetilide, and procainamide. Procainamide (total dose of 15 mg/kg given IV at 15 to 20 mg/kg) will restore sinus rhythm in 60% of patients with AF of95% of patients without the use of long-term antiarrhythmic medication). Clear indications for its use remain undefined. Generally surgery is reserved for patients with rapid heart rate refractory to pharmacologic therapy or who cannot tolerate pharmacologic therapy.

•

Catheter-based radiofrequency ablation procedures designed to eliminate atrial fibrillation represent newer approaches to atrial fibrillation. Restoration and maintenance of sinus rhythm by catheter ablation without the use of drugs in patients with congestive heart failure and atrial fibrillation significantly improves cardiac function, symptoms, exercise capacity, and quality of life.

•

Pulmonary vein ablation for chronic atrial fibrillation: Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary vein ablation, independently of the effects of antiarrhythmic drug therapy, cardioversion, or both.

•

Implantable pacemakers and defibrillators that combine pacing and cardioversion therapies to both prevent and treat atrial defibrillation are likely to have an increasing role in the future management of atrial fibrillation.

PEARLS & CONSIDERATIONS COMMENTS

The American Academy of Family Physicians and the American College of Physicians provide the following recommendations for the management of newly detected atrial fibrillation: •

Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation. Rhythm control has not been shown to be superior to rate control (with chronic anticoagulation) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control. Rhythm control is appropriate when based on other special considerations, such as patient symptoms, exercise tolerance, and patient preference.

•

Patients with atrial fibrillation should receive chronic anticoagulation with adjusted-dose warfarin, unless they are at low risk of stroke or have a specific contraindication to the use of warfarin (thrombocytopenia, recent trauma or surgery, alcoholism).

•

For patients with atrial fibrillation, the following drugs are recommended for their demonstrated efficacy in rate control during exercise and while at rest: atenolol, metoprolol, diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is only effective for rate control at rest and therefore should only be used as a second-line agent for rate control in atrial fibrillation.

•

For those patients who elect to undergo acute cardioversion to achieve sinus rhythm in atrial fibrillation, both direct-current cardioversion and pharmacologic conversion are appropriate options.

•

Both transesophageal echocardiography with short-term prior anticoagulation followed by early acute cardioversion (in absence of intracardiac thrombus) with postcardioversion anticoagulation versus delayed cardioversion with pre- and postanticoagulation are appro-priate management strategies for those patients who elect to undergo cardioversion.

•

Most patients converted to sinus rhythm from atrial fibrillation should not be placed on rhythm maintenance therapy since the risks outweigh the benefits. In a selected group of patients whose quality of life is compromised by atrial fibrillation, the recommended pharmacologic agents for rhythm maintenance are amiodarone, disopyramide, propafenone, and sotalol (drugs listed in alphabetical order). The choice of agent depends on specific risk of side effects based on patient characteristics.

EVIDENCE

There is evidence for similar mortality and cardiovascular morbidity in older patients with atrial fibrillation treated with either a rate-controlling therapy or rhythm-controlling therapy. Five randomized controlled trials (RCTs) have recently found similar mortality rates between patients with rate-controlled atrial fibrillation and rhythm control.[[1]] The largest of these trials used a beta blocker, a calcium channel blocker, digoxin, or a combination of these for rate-control therapy. The rhythm-control therapies consisted of a wide range of antiarrhythmic drugs (most often amiodarone, followed by sotalol and propafenone), and 18% of that group underwent cardioversion. Patients included were at least 65 years old and had at least one other risk factor for stroke or death. After an average of 3.5 years follow-up there was no difference between the two groups in rates of death, disabling stroke, disabling encephalopathy, major bleeding, or cardiac arrest. It also found that more patients in the rhythm-control group required hospitalization and had adverse drug effects. These results may not apply to younger, healthier patients.[[2]]

However, a recent systematic review has questioned the validity of previous reviews and RCTs and suggests that benefits of long-term anticoagulation have yet to be established in patients with nonrheumatic

atrial fibrillation.[[3]] Digoxin is ineffective during exercise and may be more useful in patients with chronic atrial fibrillation when rate control during exercise is less important. Intravenous digoxin has been shown to reduce the ventricular rate in patients with acute atrial fibrillation in the short term. [326] [327] Digoxin was not shown to be more effective than placebo for converting patients in acute atrial fibrillation to sinus rhythm in three RCTs. [326] [327] [328] In patients with chronic atrial fibrillation, control of the ventricular rate during exercise with digoxin was poor unless a beta blocker or rate-limiting calcium channel blocker was added.[[7]] There is evidence that verapamil is effective at controlling rate at rest and during exercise. A systematic review included five RCTs comparing verapamil with placebo. It found that the heart rate was reduced significantly both at rest and with exercise, compared with placebo.[[8]] In selected patients rhythm control may be more appropriate, however studies of pharmacologic rhythm control have only produced limited evidence due to their small size and short follow-up. A meta-analysis of 60 RCTs found ibutilide, flecainide, dofetilide, propafenone, and amiodarone to be the most effective of the eight drugs evaluated.[[9]] Two RCTs that compared oral flecainide vs intravenous amiodarone in people with atrial fibrillation found that flecain-ide was associated with a higher rate of conversion to sinus rhythm at 8h. [332] [333] A study of 172 patients with nonvalvular atrial fibrillation treated with transesophageal echocardiographic guided early cardioversion found that short-term low molecular weight heparin treatment was as safe as standard unfractionated heparin for the prevention of thromboembolic events after cardioversion.[[12]]

Evidence-Based References 1. Cadwallader K, Jankowski TA: Other than anticoagulation, what is the best therapy for those with atrial fibrillation?. J Fam Pract 2004; 53:581-583. 2. AFFIRM Investigators: A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825-1833. 3. Taylor F, Cohen H, Ebrahim S: Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. BMJ 2001; 322:321-326.Reviewed in: Clinical Evidence 11:257-283, 2004. 4. DAAF trial group: Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebocontrolled multicentre trial in 239 patients. The Digitalis in Acute AF (DAAF) Trial Group. Eur Heart J 1997; 18:649-654.Reviewed in: Clinical Evidence 11:76-97, 2004. 5. Jordaens L, et al: Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo. Eur Heart J 1997; 18:643-648.Reviewed in: Clinical Evidence 11:76-97, 2004.

6. Falk RH, et al: Digoxin for converting recent-onset atrial fibrillation to sinus rhythm. Ann Intern Med 1987; 106:503-506.Reviewed in: Clinical Evidence 11:76-97, 2004. 7. Lip GYH, Kamath S, Freestone B: Atrial fibrillation (acute). Clinical Evidence, 11. London: BMJ Publishing Group; 2004:76-97.

8. Segal JB, et al: The evidence regarding the drugs used for ventricular rate control. J Fam Pract 2000; 49:47-59. 9. McNamara RL, et al: Management of atrial fibrillation: a review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003; 139:1018-1033. 10. Boriani G, et al: Conversion of recent-onset atrial fibrillation to sinus rhythm: effects of different drug protocols. Pacing Clin Electrophysiol 1998; 21:2470-2474.Reviewed in: Clinical Evidence 11:76-97, 2004. 11. Capucci A, et al: Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. Am J Cardiol 1992; 70:69-70.Reviewed in: Clinical Evidence 11:76-97, 2004. 12. Yigit Z, et al: The safety of low-molecular weight heparins for the prevention of thromboembolic events after cardioversion of atrial fibrillation. Jpn Heart J 2003; 44:369-377.

SUGGESTED READINGS Cooper JM, et al: Implantable devices for the treatment of atrial fibrillation. N Engl J Med 2002; 346:2062. Ezekowitz M, Falk RH: The increasing need for anticoagulation therapy to prevent stroke in patients with atrial fibrillation. Mayo Clin Proc 2004; 79(7):904. Hart RG: Atrial fibrillation and stroke prevention. N Engl J Med 2003; 349:1015. Hart RG, et al: Meta-analysis: antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007; 146:857. Hilek E, et al: Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349:1019. Hsu LF, et al: Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004; 351:23732383. Klein AL, et al: Use of transesophageal echocardiography to guide cardioversions in patients with atrial fibrillation. N Engl J Med 2001; 344:1411. Lip G, Tse H: Management of atrial fibrillation. Lancet 2007; 370:604. Mitchell GF, et al: Pulse pressure and risk of new-onset atrial fibrillation. JAMA 2007; 297:709. Oral H, et al: Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med 2006; 354:934. Page RL: Newly diagnosed atrial fibrillation. N Engl J Med 2004; 351:2408-2416. Singh B, et al: Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007; 357:987. Snow V, et al: Management of newly detected atrial fibrillation: a clinical practice guideline from the Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2003; 139:1009. SPORTIF Executive Steering Committee for the Sportif V Investigators: ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. JAMA 2005; 293:690-698. Wang TJ, et al: Obesity and the risk of new-onset atrial fibrillation. JAMA 2004; 292:2471-2477.

Zimetbaum P: Amiodarone for atrial fibrillation. N Engl J Med 2007; 356:935.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Atrial Flutter FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Atrial flutter is a rapid atrial rate of 280 to 340 bpm with varying degrees of intraventricular block. It is a macrorentrant tachycardia, most often involving right atrial tissue.

ICD-9CM CODES

427.32 Atrial flutter EPIDEMIOLOGY & DEMOGRAPHICS

•

Atrial flutter is the second most common atrial tachyarrhythmia after atrial fibrillation, with an estimated 200,000 new cases annually in the U.S.

•

Atrial flutter is common during the first week after open heart surgery.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Approximately 150 bpm

•

Symptoms of cardiac failure, light-headedness, and angina pectoris

ETIOLOGY

•

Atherosclerotic heart disease

•

MI

•

Thyrotoxicosis

•

Pulmonary embolism

•

Mitral valve disease

•

Cardiac surgery

•

COPD

•

Atrial flutter can also occur spontaneously or as a result of organization of atrial fibrillation from antiarrhythmic therapy

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Atrial fibrillation

•

Paroxysmal atrial tachycardia

WORKUP

•

ECG

•

Laboratory evaluation

LABORATORY TESTS

•

Thyroid function studies

•

Serum electrolytes

IMAGING STUDIES

ECG ( Fig. 1-31 ) •

Regular, “sawtooth,” or “F” wave pattern, best seen in II, III, and AVF and secondary to atrial depolarization

•

AV conduction block (2:1, 3:1, or varying)

•

The criteria of F waves in the frontal plane and a partially or completely regular ventricular response has a sensitivity of 90% and a specificity of 100% for atrial flutter

TREATMENT NONPHARMACOLOGIC THERAPY

•

Valsalva maneuver or carotid sinus massage usually slows the ventricular rate (increases grade of AV block) and may make flutter waves more evident.

•

DC cardioversion is the treatment of choice for acute management of atrial flutter. Electrical cardioversion is given at low energy levels (20 to 25 J). Sedation of a conscious patient is highly recommended before cardioversion is performed. The use of external defibrillators having biphasic waveforms decreases the amount of energy required for cardioversion and improves cardioversion success rate.

•

Overdrive pacing in the atrium may also terminate atrial flutter. This method is especially useful in patients who have recently undergone cardiac surgery and still have temporary atrial pacing wires.

ACUTE GENERAL RX

•

In absence of cardioversion, IV diltiazem or digitalization may be tried to slow the ventricular rate and convert flutter to fibrillation. Esmolol, verapamil, and adenosine may also be effective. In patients with atrial flutter it is essential to preadminister AV nodal blocking agents prior to using procainamide or ibutilide.

•

Atrial flutter is frequently associated with intermittent atrial fibrillation. It may be prudent to anticoagulate patients with atrial flutter and coexisting medical disorders (e.g., diabetes mellitus, hypertension, cardiac disease) before cardioversion. Anticoagulation should also be considered for all patients with atrial flutter who are older than 65 years of age.

CHRONIC RX

•

Chronic atrial flutter may respond to amiodarone.

•

Radiofrequency ablation to interrupt the atrial flutter is very effective for patients with chronic or recurring atrial flutter and is generally considered first-line therapy in those with recurrent episodes of atrial flutter.

DISPOSITION

More than 85% of patients convert to regular sinus rhythm following cardioversion with as little as 25 to 50 J. REFERRAL

For radiofrequency ablation in patients with chronic or recurring atrial flutter

PEARLS & CONSIDERATIONS COMMENTS

•

Lone atrial flutter has a stroke risk at least as high as lone atrial fibrillation and carries a higher risk for subsequent development of atrial fibrillation than in the general population.

•

Anticoagulation should be considered for all patients with atrial flutter who are older than 65 years of age.

SUGGESTED READINGS Halligan SC, et al: The natural history of long atrial flutter. Ann Int Med 2004; 140:265. Weinberg KM, et al: Criteria for the electrocardiographic diagnosis of atrial flutter improve diagnostic accuracy. Am J Med 2007; 120:814.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Atrial Myxoma CRAIG MCMACKIN, M.D., WEN-CHIH WU, M.D.

BASIC INFORMATION DEFINITION

Atrial myxoma is a benign neoplasm of mesenchymal origin and is the most common primary tumor of the heart. SYNONYMS

Cardiac myxoma

ICD-9CM CODES

212.7 Benign neoplasm, heart EPIDEMIOLOGY & DEMOGRAPHICS

•

Primary cardiac tumors are extremely rare, with an autopsy frequency of 0.001% to 0.03%. (The most frequent cardiac tumors are metastases.)

•

Benign atrial myxomas account for 75% of all primary tumors of the heart. (The remaining 25% are aggressive malignant angiosarcomas that usually occur in the ventricles.)

•

70% of sporadic cases occur in females.

•

Average age of incidence of sporadic cases is 30 to 60 years but can occur at any age.

•

Average age of incidence of familial cases is 25 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Patients with atrial myxomas characteristically present in one of three ways: •

Atrioventricular valve obstruction (e.g., mitral or tricuspid valve): dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema, dizziness, syncope, elevated jugular venous pressure, loud S1, secondary pulmonary hypertension, murmurs of regurgitation (holosystolic) or stenosis (rumbles), third heart sound “tumor plop,” atrial fibrillation

•

Systemic embolization: leading to cerebrovascular accidents, pulmonary embolism, paradoxical embolism

•

Constitutional symptoms: fever, weight loss, arthralgias, Raynaud's phenomenon

ETIOLOGY

•

Most cases (90%) of atrial myxomas are sporadic with no known cause.

•

In the remaining 10% of cases, a familial pattern occurs having an autosomal dominant transmission known as the Carney complex (myxomas of the heart, skin, and breast; skin pigmentation; endocrine tumors; and schwanomas).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Primary valvular diseases: mitral stenosis, mitral regurgitaiton, tricuspid stenosis, tricuspid regurgitation

•

Pulmonary hypertension

•

Endocarditis

•

Vasculitis

•

Atrial thrombus

•

Pulmonary embolism

•

Cerebrovascular accidents

•

Collagen-vascular disease

•

Carcinoid heart disease

•

Ebstein's anomaly

WORKUP

A high index of suspicion is needed because the clinical manifestations are nonspecific and similar to many common cardiovascular and pulmonary diseases. LABORATORY TESTS

Although not very specific, the following laboratory findings may be abnormal in patients with atrial myxomas: •

CBC: anemia, polycythemia, thrombocytopenia may occur

•

Erythrocyte sedimentation rate, C-reactive protein, and serum immunoglobulins are commonly elevated

•

ECG: left or right atrial enlargement, atrial fibrillation, premature ventricular depolarizations, or ventricular tachycardia

IMAGING STUDIES

•

Echocardiography: initial test of choice in suspected cases of atrial myxoma

•

Chest x-ray examination: altered cardiac contour and chamber enlargement

•

Transesophageal echocardiography: may better define cardiac masses not clearly visualized by transthoracic echocardiography

•

MRI: delineates size, shape, and tumor characterizations

•

Cardiac catheterization: may be required to rule out concomitant coronary artery disease in anticipation to surgical excision of the tumor

TREATMENT

ACUTE GENERAL Therapy

•

Surgical excision is the treatment of choice.

•

Surgery should be done promptly because systemic embolization and/or sudden death can occur while waiting for the procedure (see “Disposition”).

•

Treatment of constitutional and cardiac symptoms: diuresis, heart rate and blood pressure control, and fever control.

CHRONIC RX

Postoperative arrhythmias and conductions abnormalities were present in 26% of patients and can be treated according to convention. DISPOSITION

•

Surgical results have reported a 95% survival rate after a follow-up of 3 yr.

•

Careful follow-up is necessary since up to 5% of sporadic cases and 20% of familial cases of atrial myxoma may recur within the first 6 yr after surgery.

•

Sudden death in untreated patients may occur in up to 15%, resulting from coronary or systemic embolization, or by obstruction of the mitral or tricuspid valve.

REFERRAL

•

Consultation with a cardiologist is recommended.

•

Once the presence of cardiac tumor is confirmed, consultation with a cardiovascular surgeon is needed for prompt surgical excision.

PEARLS & CONSIDERATIONS

•

Approximately 75% of myxomas arise from the left atrium close to the fossa ovalis.

•

Approximately two thirds of patients present with cardiovascular symptoms, specifically dyspnea, often suggestive of valvular obstruction.

•

Nearly one third of patients have evidence of systemic embolization.

COMMENTS Annual echocardiograms should be performed to monitor for recurrence of atrial myxomas following surgical excision.

EVIDENCE

As far as research is concerned, there are simply too few cardiac tumors to merit major investigations. Most data are obtained through clinical series and case reports. SUGGESTED READINGS

Ipek G, et al: Surgical management of cardiac myxoma. J Card Surg 2005; 20(3):300. Swartz MF, et al: Atrial myxomas: pathologic types, tumor location, and presenting symptoms. J Card Surg 2006; 21(4):435. Vasquez A, et al: Atrial myxomas in the elderly: a case report and review of the literature. Am J Geriatr Cardiol 2004; 13(1):39.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Atrial Septal Defect FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Atrial septal defect (ASD) is an abnormal opening in the atrial septum that allows for blood flow between the atria. There are several forms ( Fig. 1-32 ): •

Ostium primum: defect low in the septum

•

Ostium secundum: occurs mainly in the region of the fossa ovalis

•

Sinus venous defect: less common form, involves the upper part of the septum

FIGURE 1-32 Location of the four types of atrial septal defect. SVC, Superior vena cava; RA, right atrium; IVC, inferior vena cava; RV, right ventricle; TVL, tricuspid valve leaflet. (From Noble J [ed]: Primary care medicine, ed 2, St Louis, 1996, Mosby.)

SYNONYMS

ASD

ICD-9CM CODES

429.71 Atrial septal defect EPIDEMIOLOGY & DEMOGRAPHICS

•

80% of cases of ASD involve persistence of ostium secundum.

•

Incidence is higher in females.

•

ASD accounts for 8% to 10% of congenital heart abnormalities.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pansystolic murmur best heard at apex secondary to mitral regurgitation (ostium primum defect)

•

Widely split S2

•

Visible and palpable pulmonary artery pulsations

•

Ejection systolic flow murmur

•

Prominent right ventricular impulse

•

Cyanosis and clubbing (severe cases)

•

Exertional dyspnea

•

Patients with small defects: generally asymptomatic

ETIOLOGY

Unknown

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Primary pulmonary hypertension

•

Pulmonary stenosis

•

Rheumatic heart disease

•

Mitral valve prolapse

•

Cor pulmonale

WORKUP

•

ECG

•

Chest x-ray examination

•

Echocardiography

•

Cardiac catheterization

IMAGING STUDIES

•

ECG 1.

Ostium primum defect: left axis deviation, RBBB, prolongation of PR interval

2.

Sinus venous defect: leftward deviation of P axis

3.

Ostium secundum defect: right axis deviation, right bundle-branch block

•

Chest x-ray: cardiomegaly, enlargement of right atrium and ventricle, increased pulmonary vascularity, small aortic knob

•

Echocardiography with saline bubble contrast and Doppler flow studies: may demonstrate the defect and the presence of shunting. Transesophageal echocardiography is much more sensitive than transthoracic echocardiography in identifying sinus venous defects and is preferred by some for the initial diagnostic evaluation

•

Cardiac catheterization: confirms the diagnosis in patients who are candidates for surgery. It is useful if the patient has some anatomic finding on echocardiography that is not completely clear or has significant elevation of pulmonary artery pressures

TREATMENT NONPHARMACO-LOGIC THERAPY

Avoidance of strenuous activity in symptomatic patients GENERAL RX

•

Children and infants: closure of ASD before age 10 yr is indicated if pulmonary:systemic flow ratio is >1.5:1.

•

Adults: closure is indicated in symptomatic patients with shunts >2:1.

•

Surgery should be avoided in patients with pulmonary hypertension with reversed shunting (Eisenmenger's syndrome) because of increased risk of right heart failure.

•

Transcatheter closure is advocated in children when feasible.

•

Prophylactic ß-blocker therapy to prevent atrial arrhythmias should be considered in adults with ASD.

•

Surgical closure is indicated in all patients with ostium primum defect and significant shunting unless patient has significant pulmonary vascular disease.

DISPOSITION

•

Mortality is high in patients with significant ostium primum defect.

•

Patients with small shunts have a normal life expectancy.

•

Surgical mortality varies with the age of the patient and the presence of cardiac failure and systolic pulmonary artery hypertension; mortality ranges from 35 yr of age at the time of ASD repair and continuing it for at least 6 mo will decrease the risk.

EVIDENCE

One randomized controlled trial of 400 patients over age 40 years, assessed whether surgical treatment of secundum ASDs improves their long-term outcome. After a median follow-up of 7.3 years, surgical closure was associated with lower rates of mortality and cardiovascular events.[[1]]

Evidence-Based Reference 1. Attie F, et al: Surgical treatment for secundum atrial septal defects in patients .40 years old. A randomized clinical trial. J Am Coll Cardiol 2001; 38:2035.

SUGGESTED READING Krasuski RA: When and how to fix a “hole in the heart”: approach to ASD and PFO. Cleve Clin J Med 2007; 74:137.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Attention Deficit Hyperactivity Disorder MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Attention deficit hyperactivity disorder (AD/HD) is a chronic disorder of attention/concentration and/or hyperactivity/impulsivity. Symptoms must be present in early childhood, last at least 6 mo, and cause functional impairment in multiple settings. SYNONYMS

Hyperactivity, attention deficit disorder (ADD)

ICD-9CM CODES ICD-9: 314.XX; ICD-10: F90.X EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: Diagnosis is usually first made in school-aged children (6 to 9 years). PREVALENCE: 3% to 9% of school-aged children and 2% to 5% of adults. PREDOMINANT SEX: Among children, male predominance with ratio of 3:1 to 9:1. Among adults, ratio is closer to 1:1. (Sex difference may reflect referral bias.) PREDOMINANT AGE: Some symptoms must occur before age 7. Symptoms (especially hyperactivity) tend to diminish with age. Greater than 70% continue to meet criteria in adolescence and an estimated 40% to 65% have some symptoms in adulthood. GENETICS: Strong polygenetic component. First-degree relatives of AD/HD patients have 5 times greater risk of AD/HD relative to controls. Studies suggest potential involvement of several genes including those associated with dopamine metabolism/transmission. RISK FACTORS: Possible environmental/epidemiologic risk factors include in utero tobacco/drug exposure or hypoxia, low birth weight, prematurity, pregnancy complications, lead exposure, family dysfunction, low SES. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Three types: 1.

Predominantly inattentive: difficulty organizing, planning, remembering, concentrating, starting/completing tasks; symptoms may not be present during preferred activities.

2.

Predominantly hyperactive-impulsive: edgy/restless, talkative, disruptive/intrusive, disinhibited, impatient.

3.

Combined.

•

Usually diagnosed in elementary school when achievement is compromised and behavioral problems are not tolerated. Children with academic underproductivity, problems with peer and family relations, or discipline issues are often referred for evaluation.

•

Adults with substance abuse or other addictions, multiple traffic violations, or frequent life failures should be screened.

•

Up to 50% may have associated disorders such as psychiatric diagnoses (oppositional defiant disorder, conduct disorder, depression, anxiety), learning disabilities, substance abuse, and criminal behavior.

ETIOLOGY

Strongest evidence exists for genetic inheritance. Other theories include abnormal metabolism of brain catecholamines, structural brain abnormalities, and environmental factors (see earlier).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Medical: visual/hearing impairment, seizure disorder, head injury, sleep disorder, medication interactions, mental retardation, developmental delay, thyroid abnormalities, lead toxicity.

•

Psychiatric: depression, bipolar disorder, anxiety, obsessive-compulsive disorder, conduct disorder, posttraumatic stress disorder, substance abuse, antisocial personality disorder, Tourette syndrome, tics.

•

Psychosocial: mismatch of learning environment with ability, family dysfunction, abuse/neglect.

WORKUP

•

Clinical interview should include assessment of symptoms and impact on work/school and relationships; developmental history; personal and family psychiatric history including substance abuse; social history including family dysfunction; medical history.

•

Thorough physical examination should be performed to investigate medical causes for symptoms, coexisting conditions, and contraindications to treatment.

•

Many patients will not display symptoms during an office visit and may under- or over-report symptoms. Therefore, information from collateral sources (parents, partners, teachers) is crucial to diagnosis.

•

Self-rating scales and standardized symptom-specific questionnaires from collateral sources can aid in diagnosis and in assessing response to treatment.

•

Laboratory or imaging studies should be undertaken only if indicated by history or physical examination.

•

Ancillary testing (e.g., IQ/achievement testing, language evaluation, and mental health assessment) may be indicated based on clinical findings and may require referral.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Data comparing the efficacy of behavioral or educational therapy versus pharmacologic management are limited. Prevailing opinion favors a multimodal approach in which nonpharmacologic therapies can be used to target comorbid conditions or behaviors that have not responded to medication.

•

Educational interventions are recommended, particularly in the setting of learning disabilities. Children with AD/HD are entitled to reasonable educational accommodations under a 504 Plan or the Individuals with Disabilities Education Act.

•

Behavioral interventions (e.g., goal setting and rewards systems) show short-term efficacy and are endorsed by most national organizations (e.g., American Academy of Pediatrics, American Medical Association). Time management and organizational skills appear useful.

•

Psychotherapy (cognitive behavioral, group, social skills, and parent training) may be beneficial, particularly when there is coexisting psychiatric disease.

•

Many support/advocacy groups provide education and other resources (e.g., Children and Adolescents with AD/HD, National ADD Association, American Academy of Child and Adolescent Psychiatry).

ACUTE GENERAL RX

•

Most studies on treatment of AD/HD performed in children. Limited data on adults.

•

Mainstay of treatment is drug therapy, particularly stimulants. Second-line therapies include antidepressants and alpha-agonists.

•

Stimulants:

•

•

1.

Release/block uptake of dopamine and norepinephrine.

2.

Include short- and long-acting methylphenidate (Ritalin, Concerta), dextroamphetamine/amphetamine combinations (Adderall).

3.

Do not cause euphoria or lead to addiction when taken as directed.

4.

Improve cognition, inattention, impulsiveness/hyperactivity, and driving skills. Limited impact on academic performance, learning, and emotional problems.

5.

Side effects are mild, reversible, and dose dependent. Include anorexia, weight loss, sleep disturbances, increased heart rate/blood pressure, nervousness/irritability, headache, onset or worsening of motor tics, reduction of growth velocity (but not adult height). Do not worsen seizures in patients on adequate anticonvulsant therapy. Rebound of symptoms can occur with withdrawal of medication.

6.

All equally effective; however, not all patients improve with stimulants. Patients who do not respond well to one stimulant may respond to another.

Atomoxetine (Strattera): 1.

Selective norepinephrine reuptake inhibitor.

2.

Efficacy/safety of long-term use has not been studied. Reports of behavioral abnormalities and increased suicidality in children.

3.

Side effects: gastrointestinal upset, sleep disturbance, decreased appetite, dizziness, sexual side effects in men.

4.

Monitor liver function as there have been reports of severe liver injury in adults and children.

Antidepressants (bupropion, imipramine, nortriptyline): 1.

May be useful in patients with coexisting psychiatric disorders.

2.

Studies comparing efficacy versus stimulants are inconclusive.

3.

Side effects: arrhythmias, anticholinergic effects, lowering of seizure threshold.

•

Use of medications, particularly stimulants (which are monitored under the Controlled Substance Act), require frequent monitoring.

•

Stimulants have been associated with cardiovascular events and mortality. Patients should be carefully evaluated for cardiovascular disease prior to initiation of therapy and be periodically monitored, including blood pressure checks, while they are treated.

DISPOSITION

•

While symptoms may change over time, for many patients, AD/HD represents a chronic condition that requires lifelong management.

•

Patients are at higher risk for academic underachievement, lower SES, work and relationship difficulties, high-risk behavior, and psychiatric comorbidities.

REFERRAL

•

Diagnosis complicated by difficult-to-treat comorbid psychiatric conditions, developmental disorders, or mental retardation.

•

Lack of adequate response to stimulants/atomoxetine.

PEARLS & CONSIDERATIONS The World Health Organization's Adult Self-Report Scale (ASRS) v1.1 has good sensitivity and adaptability to the primary care setting.

EVIDENCE

Systematic review found that methylphenidate plus behavioral treatment was superior to behavioral treatment alone. Symptoms and behaviors associated with ADHD and academic achievements were significantly improved with combination therapy, but no significant difference was noted in social skills or parent-child relationships. [[1]] A randomized controlled trial (RCT) found that children with ADHD had a significant improvement in measures of core symptoms when treated with intensive behavioral treatment plus medication vs. behavioral treatment alone.[[2]] A systematic review and several RCTs found that methylphenidate reduced core symptoms of ADHD in the short term. [358] [360] Another systematic review of longer-term studies found limited evidence that dextroamphetamine improved concentration and hyperactivity compared with placebo. The RCTs included in the review had methodological problems. [[4]] A crossover RCT compared slow-release dextroamphetamine with placebo in children with ADHD. Dextroamphetamine was associated with significant improvement on two rating scales.[[5]] RCTs found that atomoxetine was more effective than placebo in treating children with ADHD. [363] [364] [365]

Evidence-Based References 1. Lord J, Paisley S: The clinical effectiveness and cost-effectiveness of methylphenidate for hyperactivity in childhood, National Institute for Clinical Excellence, Version 2, August 2000. 2. Jensen PS, et al: A 14-month randomized clinical trial of treatment strategies for attentiondeficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry 1999; 56:1073. 3. Ramchandani P, Joughin C, Zwi M: Attention deficit hyperactivity disorder in children. Clin Evid 2003; 9:318. 4. Jadad AR, et al: Treatment of attention-deficit/hyperactivity disorder. Evidence report/technology assessment No 11, Rockville MD, Agency for Health Care Policy and Research and Quality, 1999. Reviewed in: Clinical Evidence 9:318, 2003. 5. James RS, et al: Double-blind, placebo-controlled study of single-dose amphetamine formulations in ADHD. J Am Acad Child Adolesc Psychiatry 2001; 40:1268. 6. Michelson D, et al: Atomoxetine ADHD study group. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, doseresponse study. Pediatrics 2001; 108:E83. 7. Spencer T, et al: Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry 2002; 63:1140. 8. Michelson D, et al: Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 2002; 159:1896.

SUGGESTED READINGS Culpetter L: Primary care treatment of attention-deficit/hyperactivity disorder. J Clin Psychiatry 2006; 67(8):51. Polayczyk G, et al: The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007; 164(6):942. Rappley MD: Attention deficit–hyperactivity disorder. N Engl J Med 2005; 352(2):165.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Autistic Spectrum Disorders MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Autistic spectrum disorders (ASD) encompass a spectrum of developmental disorders characterized by impairment in several behavioral domains. There is usually impairment in the development of language, communication, and reciprocal social interaction along with a restricted behavioral repertoire. Onset is typically before age 3 yr. SYNONYMS

Autism Early infantile autism Childhood autism Kanner's autism Pervasive developmental disorder

ICD-9CM CODES

F84.0 Autistic disorder (DSM-IV coded 299.0 Autistic disorder) EPIDEMIOLOGY & DEMOGRAPHICS

incidence (IN U.S.): 3 to 6/1000 of ASD (2 to 5/10,000 if restricted to autism alone) PEAK INCIDENCE: Before age 3 yr 3.3 to 10.6/100 (mean 6.6) PREDOMINANT SEX: Male:female ratio of 3.4 to 6.5:1.0 PREDOMINANT AGE: Lifelong GENETICS:

•

Unknown genetic component, though recent linkage analyses have identified chromosomal abnormalities in multiple genetic loci, including glutamate-related genes

•

3% risk for sibling of affected individual

•

60% to 92% concordance for classic autism in monozygotic twins, and 0% to 10% for dizygotic pairs

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Marked impairment in the understanding and use of both verbal and nonverbal communication (probably underlies the profound impairment in social interaction)

•

Stereotypic behavior or language

•

Sensory overload and avoidance of novel stimuli is typical.

ETIOLOGY

•

Majority of cases are not associated with a medical condition.

•

Significant increase in comorbid seizure disorder (25%) and developmental delay (45% to 60%).

•

Autism is sometimes associated with other neurologic conditions (e.g., encephalitis, tuberous sclerosis, phenylketonuria, fragile X, and others), suggesting that it may result from nonspecific neuronal injury.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Rett's syndrome: occurs in females, characterized by head growth deceleration, loss of previously acquired motor skills, and incoordination

•

Childhood disintegration disorder: normal development until age 2 yr, followed by regression

•

Childhood-onset schizophrenia: follows period of normal development

•

Asperger's syndrome: lacks the language developmental abnormalities of autism

•

Isolated symptoms of autism: when occurring in isolation, defined as disorders (i.e., selective mutism, expressive language disorder, mixed receptive-expressive language disorder, or stereotypic movement disorder)

WORKUP

•

Rule out underlying medical condition.

•

Diagnostic instruments based on questionnaires and observation noting scales (e.g., Autism Diagnostic Interview) may be helpful.

LABORATORY TESTS

•

PKU screen (usually done at birth in the U.S.)

•

Chromosome analysis to rule out fragile X in both boys and girls (carrier girls may exhibit mild symptoms)

•

IQ testing to help determine functional level of child

IMAGING STUDIES

•

EEG to diagnose coexisting seizure disorder (a normal EEG does not rule out a seizure disorder)

•

Head CT or MRI to rule out tuberous sclerosis

•

Consider BAER to rule out hearing deficit

TREATMENT NONPHARMACOLOGIC THERAPY

•

A behavioral training program that is consistent in both the home and school environments.

•

Educational program focused on language and social development.

•

A highly structured environment benefits most children.

•

Education for parents and teachers is of great value.

ACUTE GENERAL RX

•

Haloperidol or other high-potency neuroleptics are helpful in reducing aggression and stereotypy. Atypical neuroleptics, such as risperidone, also reduce aggression and irritability and improve overall behavioral symptoms.

•

Selective serotonin reuptake inhibitors may be useful in children with coexisting depression or with marked obsessive or ritualistic behaviors.

•

Buspirone reported to reduce aggression, hyperactivity and repetitive behaviors.

•

Valproic acid and carbamazepine are preferred for seizure control.

CHRONIC RX

•

Extended use of medications used for acute management

•

Pharmacotherapy is palliative only, not curative.

DISPOSITION

•

Most children (70%) will require some degree of assistance as adults, will not be able to work, and will not achieve proper social adjustment.

•

Some 10% (particularly if IQ is in the normal range and speech is achieved by age 5 yr) may have a reasonable outcome.

•

Children with Asperger's syndrome may have a very good outcome despite ongoing symptoms.

REFERRAL

Assistance may be needed in diagnosis, management, parental teaching, or intervention with the school system.

PEARLS & CONSIDERATIONS

•

Researchers are examining the relationship between childhood vaccination and the development of autism.

•

A center devoted to the study of autism: http://www.ucdmc.ucdavis.edu/mindinstitute/

.

EVIDENCE

Clomipramine may be superior to desipramine and to placebo for obsessive-compulsive and stereotyped motor behaviors in autistic disorder.[[1]] Small but significant reductions in hyperactivity ratings may be seen in response to stimulants such as methylphenidate and dextroamphetamine. [370] [371] Clonidine reduced irritability, hyperactivity, and impulsivity in the short term compared with placebo, and improved social relationships in two randomized controlled trials (RCTs). [372] [373] Clomipramine and haloperidol have been shown to be equally effective and more effective than placebo. However, 60% of those receiving clomipramine discontinued the trial early because of side effects, and haloperidol was better tolerated.[[6]] A long-term prospective study of autistic children who responded to initial haloperidol therapy found several factors increase the risk of dyskinesias, including cumulative dose and length of exposure to haloperidol, female sex, and perinatal complications. The most common dyskinesias were withdrawal dyskinesias, which developed in about one-third of patients; about half of these had more than one episode.[[7]] Risperidone was shown to be effective in children with autistic disorder who have serious behavioral disturbances, and the benefit was maintained at 6 mo in some.[[8]] Naltrexone appears to reduce hyperactivity in children with autism, but produces a more rapid clinical progression of the condition in children with Rett's syndrome. [377] [378] [379] A systematic review found no evidence to warrant recommendation of the use of pyridoxine and magnesium as a treatment for autism.[[12]] There is limited evidence for an improvement in aberrant behavior scores at 3 months in children with autism spectrum disorders treated with auditory integration training.[[13]] A 30-wk, double-blind RCT examining the effects of (8 g/70 kg/day) ascorbic acid on autistic children in residential school found a reduction in symptom severity with ascorbic acid treatment.[[14]] Many other therapies appear to be effective in autism according to anecdotal evidence and case reports, but the trials do not reach our criteria for evidence. We are unable to cite evidence that meets our criteria for other therapies that may be used successfully in autism.

Evidence-Based References 1. Gordon C, et al: A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry 1993; 50:44. 2. Quintana H, et al: Use of methylphenidate in the treatment of children with autistic disorder. J Autism Dev Disord 1995; 25:283. 3. Handen BL, Johnson CR, Lubetsky M: Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder. J Autism Dev Disord 2000; 30:245. 4. Jaselskis CA, et al: Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992; 12:322. 5. Fankhauser MP, et al: A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry 1992; 53:77. 6. Remington G, et al: Clomipramine versus haloperidol in the treatment of autistic disorder: a doubleblind, placebo-controlled, crossover study. J Clin Psychopharmacol 2001; 21:440. 7. Campbell M, et al: Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 1997; 36:835. 8. McCracken JT, et al: Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002; 347:314. 9. Campbell M, et al: Naltrexone in autistic children: behavioral symptoms and attentional learning. J Am Acad Child Adolesc Psychiatry 1993; 32:1283. 10. Kolmen BK: Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study. J Am Acad Child Adolesc Psychiatry 1995; 34:223. 11. Percy AK, et al: Rett's syndrome: controlled study of an oral opiate antagonist, naltrexone. Ann Neurol 1994; 35:464. 12. Nye C, Brice A: Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev 2005;CD003497, 13. Sinha Y, et al: Auditory integration training and other sound therapies for autism spectrum disorders. Cochrane Database Syst Rev 2004;CD003681, 14. Dolske MC, et al: A preliminary trial of ascorbic acid as a supplement therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry 1993; 17:765.

SUGGESTED READINGS Autism Genome Project Consortium: Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 2007; 39:319. Prevalence of Autism Spectrum Disorders—Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2002. MMWR Morb Mortal Wkly Rep 2007; 56(SS-1):1. Weiss LA, et al: Association between microdeletion and microduplication at 16p4.2 and autism. N Engl J Med 2008; 358:667-675.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

B Babesiosis GLENN G. FORT, M.D, M.P.H., DENNIS J. MIKOLICH, M.D, GEORGE O. ALONSO, M.D

BASIC INFORMATION DEFINITION

Babesiosis is a tick-transmitted protozoan disease of animals, caused by intraerythrocytic parasites of the genus Babesia. Humans are incidentally infected, resulting in a nonspecific febrile illness. The disease can be severe in immunocompromised hosts.

ICD-9CM CODES

088.82 Babesiosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Unknown PREVALENCE (IN U.S.): •

In areas of high endemicity, seropositivity ranging from 9% (Rhode Island) to 21% (Connecticut)

•

Highest number of reported cases in New York

PREDOMINANT SEX:Males (most likely through increased exposure to vectors during recreational or occupational activities) PREDOMINANT AGE: Severity apparently increasing with age >40 yr PEAK INCIDENCE:Spring and summer months, May through September GENETICS: None known CONGENITAL INFECTION: At least one case of probable vertical transmission NEONATAL INFECTION: At least two cases of perinatal transmission PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Incubation period 1 to 4 wk, or 6 to 9 wk in transfusion-associated disease

•

Gradual onset of irregular fever, chills, diaphoresis, headache, myalgia, arthralgia, fatigue, and dark urine

•

On physical examination: petechiae, frank or mild hepatosplenomegaly, and jaundice

•

Infection with B. divergens producing a more severe illness with a rapid onset of symptoms and increasing parasitemia progressing to massive intravascular hemolysis and renal failure

ETIOLOGY

•

Vector: Deer tick, Ixodes scapularis (also known as I. dammini) 1.

Feeds on rodents during the spring and summer while in its larval and nymphal stages and on deer as an adult

2.

During the warmer months in endemic areas, humans are readily infected while engaging in outdoor activities

•

B. microti, along with B. divergens and B. bovis, account for most human infections.

•

In the U.S., cases caused by B. microti are acquired on offshore islands of the northeastern coast, including Nantucket Island, Cape Cod, and Martha's Vineyard in Massachusetts; Block Island in Rhode Island; and Long Island, Fire Island, and Shelter Island in New York; as well as the nearby mainland including Connecticut and New Jersey.

•

Sporadic cases reported from California, Georgia, Maryland, Minnesota, Virginia, Wisconsin, and most recently the WA-1 strain from Washington State and the MO-1 strain from Missouri.

•

B. divergens and B. bovis are implicated in human disease in Europe, where the disease remains rare and predominantly associated with asplenia.

•

Majority of cases are asymptomatic.

•

May be transmissible by transfusion, through platelets and erythrocytes.

•

Mixed infections (B. microti and Borrelia burgdorferi, the causative agent of Lyme disease) are estimated to occur in 10% (Rhode Island and Connecticut) to 60% (New York) of cases.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Amebiasis

•

Ehrlichiosis

•

Hepatic abscess

•

Leptospirosis

•

Malaria

•

Salmonellosis, including typhoid fever

•

Acute viral hepatitis

•

Hemorrhagic fevers

WORKUP

Should be suspected in any febrile patient living or traveling in an endemic area, irrespective of exposure history to ticks or tick bites, especially if asplenic

LABORATORY TESTS

•

CBC to reveal mild to moderate pancytopenia

•

Abnormally elevated serum chemistries, including creatinine, liver function profile, lactate dehydrogenase, and direct and total bilirubin levels

•

Urinalysis to reveal proteinuria and hemoglobinuria

•

Examination of Giemsa- or Wright-stained thick and thin blood films for intraerythrocytic parasites

•

1.

In its classic, though infrequently seen, form a “tetrad” or “Maltese Cross” composed of four daughter cells attached by cytoplasmic strands is observed.

2.

More commonly, smaller forms composed of a single chromatin dot are eccentrically located within bluish cytoplasm.

3.

Parasitized erythrocytes may be multiply infected but not enlarged, or they may show evidence of pigment deposition, seen with Plasmodium species.

Diagnosis achieved serologically by indirect immunofluorescence assay (IFA) is specific for B. microti. 1.

Titer of =1:64 is indicative of seropositivity, whereas one =1:256 is considered diagnostic of acute infection.

2.

Assay is hampered by the inability to distinguish between exposed patients and those who are actively infected.

3.

Immunoglobulin M indirect immunofluorescent-antibody test may be highly sensitive and specific for diagnosis.

4.

Babesial DNA by polymerase chain reaction (PCR) has comparable sensitivity and specificity to microscopic analysis of thin blood smears.

TREATMENT NONPHARMACOLOGIC THERAPY

Supportive care with adequate hydration ACUTE GENERAL Rx

•

In patients with intact spleens: predominantly asymptomatic or if symptomatic, generally self-limited

•

Therapy reserved for the severely ill patient, especially if asplenic, elderly, or immunosuppressed

•

Combination of quinine sulfate 650 mg PO tid plus clindamycin 600 mg PO tid (1.2 g parenterally bid) taken for 7 to 10 days: effective but may not eliminate parasites

•

Combination of atovaquone 750 mg every 12 hr and azithromycin 500 mg on day 1 and 250 mg per day thereafter for 7 days appears to be as effective as a regimen of clindamycin and quinine with fewer adverse reactions

•

Exchange transfusions in addition to antimicrobial therapy: successful treatment for severe infections in asplenic patients associated with high levels of B. microti or B. divergens parasitemia

DISPOSITION

Prognosis is usually good and fatal outcomes are rare. REFERRAL

•

For prompt consultation with an infectious disease specialist if the diagnosis is acutely suspected, especially in the asplenic, elderly, or immunocompromised patient

•

For hospitalization for the severely ill patient who may require exchange transfusions in addition to antibiotic therapy

PEARLS & CONSIDERATIONS COMMENTS

•

Prevention of babesiosis in asplenic or immunocompromised hosts is best achieved by avoidance of areas where the vector is endemic, especially during the months of May through September.

•

If residence or travel in endemic areas is unavoidable, advise patients to perform daily cutaneous selfexamination, wear light-colored clothing (to facilitate removal of ticks), and apply tick repellent (diethyltoluamide and dimethylphthalate) to skin or clothing.

•

Advise a daily inspection for ticks in family pets (e.g., cats and dogs).

•

Infection with B. divergens, especially in the asplenic patient, is often fatal.

•

Concurrent babesiosis and Lyme disease has been documented—check for combined infection in severely ill patients.

•

Clindamycin and quinine has been successfully used to treat Babesiosis during the third trimester of pregnancy without incurring apparent adverse effect on the fetus.

EVIDENCE

Combination therapy with clindamycin and quinine is as effective as the atovaquone and azithromycin combination. Adverse effects from medication may be more common with clindamycin and quinine. Both combinations are effective in eradicating babesiosis parasites at 3 mo after the treatment course.[[1]] Silent infection may persist for months or years when left untreated. Treatment of babesiosis with clindamycin and quinine may reduce the duration of parasitemia.[[2]]

Evidence-Based References 1. Krause PJ, et al: Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med 2000; 343:1454. 2. Krause PJ, et al: Persistent parasitemia after acute babesiosis. N Engl J Med 1998; 339:160.

SUGGESTED READINGS Cable RG, Leiby DA: Risk and prevention of transfusion-transmitted babesiosis and other tick-borne diseases. Curr Opin Hematol 2003; 10(6):405. Gelfand JA, Callahan MV: Babesiosis: an update on epidemiology and treatment. Curr Infect Dis Rep 2003; 5(1):53. Krause PJ: Babesiosis diagnosis and treatment. Vector Borne Zoonotic Dis 2003; 3(1):45.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Baker' Cyst PETER PETROPOULOS, M.D

BASIC INFORMATION DEFINITION

Baker's cyst refers to a fluid-filled popliteal bursa located along the medial border of the popliteal fossa. SYNONYMS

Popliteal cyst

ICD-9CM CODES

727.51 Baker's cyst (knee) EPIDEMIOLOGY & DEMOGRAPHICS

•

Occurs at all ages.

•

Incidence is unknown.

•

Between 2% to 6% of all patients thought to have clinical DVT turn out to have symptomatic Baker's cysts.

•

Approximately 5% of MRIs of the knees reveal popliteal cysts.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pain in the popliteal space

•

Knee swelling

•

Leg edema

•

Prominence of the popliteal fossa

•

Decreased range of motion of the knee

•

Locking of the knee

•

Foucher's sign: The cyst becomes hard with knee extension and soft with knee flexion.

•

Neuropathic lancinating pains radiating from the knee down the back of the leg.

•

Deep vein thrombosis (DVT)

ETIOLOGY

•

Believed to represent fluid distention of the bursal sac separating the semimembranous tendon from the medial head of the gastrocnemius.

•

In children, Baker's cysts are thought to be secondary to trauma and irritation of the knee.

•

In adults, Baker's cysts are usually associated with pathologic changes of the knee joint: 1.

Rheumatoid arthritis

2.

Osteoarthritis of the knee

3.

Meniscal tears

4.

Patellofemoral chondromalacia

5.

Fracture

6.

Gout

7.

Pseudogout

8.

Infection (tuberculosis)

DIAGNOSIS Baker's cyst frequently mimics a DVT and is sometimes called pseudothrombo-phlebitis syndrome. DIFFERENTIAL DIAGNOSIS

•

DVT

•

Popliteal aneurysms

•

Abscess

•

Tumors

•

Lymphadenopathy

•

Varicosities

•

Ganglion

WORKUP

Anyone suspected of having a popliteal cyst should undergo imaging studies to exclude other causes. LABORATORY TESTS

Blood tests are not very specific in the diagnosis of Baker's cysts. IMAGING STUDIES

•

Plain x-ray (AP and lateral views) may show calcification in a solid tumor or in the posterior meniscal area.

•

Ultrasound is easy, cost effective, and excludes other causes of popliteal fossa pathology.

•

MRI of the knee identifies coexisting joint pathology (e.g., osteoarthritis, torn meniscus).

•

Noninvasive venous studies to rule out DVT.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Rest

•

Strenuous activity avoidance

•

Knee immobilization necessary in some cases

ACUTE GENERAL Rx

•

NSAIDs, ibuprofen 400 to 800 mg PO tid, or naproxen 250 to 500 mg PO bid can be used to treat Baker's cyst caused by RA, gout, and pseudogout.

•

Intraarticular injection or injection of the cyst with corticosteroids, triamcinolone acetonide 40 mg is sometimes tried.

CHRONIC Rx

Surgical procedures addressing the underlying cause include: 1.

Arthroscopic surgery to remove loose cartilaginous fragment

2.

Partial or total meniscectomy

3.

Open excision of the cyst ( Fig. 1-33

FIGURE 1-33 Removal of midline Baker's cyst. A, Skin incision. B, After being exposed, pedicle is clamped, ligated, divided, and inverted. (Redrawn and modified from Meyerding HW, Van Demark GE: JAMA 122:858, 1943.)

DISPOSITION

•

Baker's cyst may spontaneously resolve without treatment.

•

Complications of Baker's cysts are: 1.

Rupture

2.

DVT

3.

Nerve impingement

REFERRAL

Rheumatology or orthopedics if surgery is contemplated

PEARLS & CONSIDERATIONS

•

Popliteal cysts were first described in 1877 by Baker in connection with disease of the knee joint.

•

In the setting of meniscus injury, Baker's cysts commonly originate from the posterior horn of the medial meniscus with or without a tear.

COMMENTS

Baker's cyst and DVT can coexist. It is imperative to exclude the diagnosis of DVT before discharging the patient. SUGGESTED READINGS Fritshy D, et al: The popliteal cyst. Knee Surg Sports Traumatol Arthrosc 2006; 14(7):623. Handy JR: Popliteal cysts in adults: a review. Semin Arthritis Rheum 2001; 31(2):108. Torreggiani WC, et al: The imaging spectrum of Baker's (Popliteal) cysts. Clin Radiol 2002; 57(8):681.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Balanitis GLENN G. FORT, M.D, M.P.H., JOSEPH J. LIEBER, M.D., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Balanitis is an inflammation of the superficial tissues of the penile head ( Fig. 1-34 ).

FIGURE 1-34 Candida balanitis. The moist space between the skin surfaces of the uncircumcised penis is an ideal environment for Candida infection. This thick white exudate is typical of a severe acute infection. (From Habif TP: Clinical dermatology: a color guide to diagnosis and therapy, ed 3, St Louis, 1996, Mosby.)

ICD-9CM CODES

112.2 Balanitis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Unknown PREVALENCE (IN U.S.): Unknown PREDOMINANT SEX: Exclusive to males PEAK INCIDENCE: All ages, especially in sexually active men PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Itching and tenderness

•

Pain, dysuria, and local edema

•

Rarely, ulceration and lymph node enlargement

•

Severe ulcerations leading to superimposed bacterial infections

•

Inability to void: unusual, but a more distressing and serious complication

ETIOLOGY

•

Poor hygiene, causing erosion of tissue with erythema and promoting growth of Candida albicans

•

Sexual contact, urinary catheters, and trauma

•

Allergic reactions to condoms or medications

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Leukoplakiat

•

Reiter's syndrome

•

Lichen planus

•

Balanitis xerotica obliterans

•

Psoriasis

•

Carcinoma of the penis

•

Erythroplasia of Queyrat

•

Nodular scabies

WORKUP

•

Sexually active males: assessment for evidence of other sexually transmitted diseases

•

Biopsy if lesions do not heal

LABORATORY TESTS

•

VDRL

•

Serum glucose

•

Wet mount

•

KOH prep

•

Microbial culture

TREATMENT NONPHARMACOLOGIC THERAPY

•

Maintenance of meticulous hygiene

•

Retraction and bathing of prepuce several times a day

•

Warm sitz baths to ease edema and erythema

•

Consideration of circumcision, especially when symptoms are severe or recurrent

•

With Foley catheters, strict catheter care strongly advised

ACUTE GENERAL Rx

•

Analgesics, such as acetaminophen and/or codeine

•

Clotrimazole 1% cream applied topically twice daily to affected areas

•

Bacitracin or Neosporin ointment applied topically 4 times daily

•

With more severe bacterial superinfection: cephalexin 500 mg PO qid

•

Topical corticosteroids added 4 times daily if dermatitis severe

•

Patients with suspected urinary tract infections: trimethoprim-sulfa DS twice daily or ciprofloxacin 500 mg PO bid after obtaining appropriate cultures

DISPOSITION

Balanitis is often self-limited and usually responds to conservative therapy; if it does not improve, consider circinate balanitis (Reiter's Syndrome), nodular scabies, primary skin lesions including skin carcinoma.

PEARLS & CONSIDERATIONS Don't forget about nodular scabies involving the prepubic area—examine the region carefully for burrows and tracks of Sarcoptes scabiei. REFERRAL

•

For surgical evaluation for circumcision if symptoms are recurrent, especially if phimosis or meatitis occurs (note: Severe phimosis with an inability to void may require prompt slit drainage.)

•

For biopsy to rule out other diagnosis such as premalignant or malignant lesions if lesions are not healing

SUGGESTED READINGS Buechner SA: Common skin disorders of the penis. BJU Int 2002; 90(5):498. Bunker CB: Topics in penile dermatology. Clin Exp Dermatol 2001; 26(6):469. Huntley JS, et al: Troubles with the foreskin: one hundred consecutive referrals to paediatric surgeons. J R Soc Med 2003; 96(9):449. Pandher BS, et al: Treatment of balanitis xerotica obliterans with topical tacrolimus. J Urol 2003; 170(3):923. Thiruchelvan M, et al: Emergency dorsal slit for balanitis with retention. J R Soc Med 2004; 97(4):206.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Barrett's Esophagus HARLAN G. RICH, M.D.

BASIC INFORMATION DEFINITION

Barrett's esophagus occurs when the squamous lining of the lower esophagus is replaced by metaplastic, intestinalized columnar epithelium. The condition is associated with an increased risk of adenocarcinoma of the esophagus. SYNONYMS

Intestinal metaplasia of lower esophagus

ICD-9CM CODES

530.85 Barrett's esophagus EPIDEMIOLOGY & DEMOGRAPHICS

•

4:1 ratio of men to women

•

Mean age of onset is 40 yr with a mean age of diagnosis of 55 to 60 yr

•

Occurs more frequently in Caucasians and Hispanics than in African Americans with a ratio of 10 to 20:1

•

Mean prevalence of 5% to 15% in patients undergoing endoscopy (EGD) for symptoms of GERD

•

Prevalence in asymptomatic cohorts ranges from 5% to 25%

CLINICAL PRESENTATION

Symptoms: •

Chronic heartburn

•

Dysphagia for solid food

•

May be an incidental finding on EGD in patients without reflux symptoms

•

Less frequent: chest pain, hematemesis, or melena

Physical findings: •

Nonspecific; can be completely normal

•

Epigastric tenderness on palpation

ETIOLOGY

•

Metaplasia is thought to result from re-epithelialization of esophageal tissue injured secondary to chronic GERD.

•

Patients with Barrett's tend to have more severe esophageal motility disturbances (decreased lower esophageal sphincter pressure, ineffective peristalsis) and greater esophageal acid exposure on 24-hour pH monitoring.

•

Intraesophageal bile reflux may also play a role in the pathogenesis.

•

Familial clustering of GERD and Barrett's suggests a genetic predisposition, but no gene has yet been identified.

•

Progression from metaplasia to carcinoma is associated with changes in gene structure and expression.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

GERD, uncomplicated

•

Erosive esophagitis

•

Gastritis

•

Peptic ulcer disease

•

Angina

•

Malignancy

•

Stricture or Schatzki's ring

WORKUP

•

EGD with biopsy for diagnosis.

•

Diagnosis requires the presence of intestinal metaplasia in columnar epithelium proximal to the gastroesophageal junction. Longer segment Barrett's is more readily diagnosed.

•

Intestinal metaplasia of the gastric cardia is not Barrett's and does not have the same risk of malignancy.

•

Imaging studies are nonspecific and insensitive for the diagnosis.

•

The Practice Parameters Committee of the American College of Gastroenterology (ACG) has recommended that patients with chronic GERD symptoms be considered for EGD to exclude Barrett's. General population screening is not currently recommended. Although screening has become standard of practice in some communities, the effectiveness of screening using current techniques is controversial because it may not improve mortality from adenocarcinoma or be cost effective.

•

Screening for H. pylori infection in patients with GERD and Barrett's esophagus is not recommended.

TREATMENT Goal is to control GERD symptoms and maintain healed mucosa. NONPHARMACOLOGIC THERAPY

•

Lifestyle modifications, elevating head of bed, avoiding chocolate, tobacco, caffeine, mints, and certain drugs (see “Gastroesophageal Reflux Disease”).

•

Chronic acid suppression is often necessary to control symptoms and promote healing.

ACUTE GENERAL Rx

•

Proton pump inhibitors (PPIs) are most effective.

•

Adequate control of GERD symptoms in patients with Barrett's may or may not completely control intraesoph-ageal acid exposure. Some studies suggest that normalization of intraesophageal acid exposure may either lead to regression of Barrett's or reduce the risk of dysplasia.

•

If asymptomatic and incidentally found to have Barrett's esophagus, medication use may be considered.

CHRONIC Rx

•

Thermal ablation techniques, photodynamic therapy, and endoscopic mucosal resection are all possible approaches in patients with Barrett's and high-grade dysplasia, either in conjunction with aggressive surveillance or as an alternate to surgery in poor operative candidates. All these options run the risk of residual intestinal metaplasia. As only a minority of patients with Barrett's progress to high-grade dysplasia or carcinoma, these techniques cannot be currently recommended in patients with Barrett's alone. Studies will need to show that they reduce or eliminate the need for surveillance endoscopy and/or the risk of cancer, and that they are cost effective.

•

Antireflux surgery may be considered for management of GERD and associated sequelae. Patients should still have EGD surveillance of their Barrett's. Surgical resection is offered for multifocal high-grade dysplasia or carcinoma.

DISPOSITION

•

Overall, 30 to 50×increased risk of adenocarcinoma of the esophagus.

•

Corresponds to 500 cancers per yr per 100,000 persons with Barrett's.

•

Frequency of monitoring is controversial; no studies have proven that surveillance increases life expectancy.

•

ACG recommends that patients with Barrett's undergo surveillance EGD and systematic four-quadrant biopsy at intervals determined by the presence and grade of dysplasia. All mucosal abnormalities should be biopsied. Patients who have had two EGDs showing no dysplasia should have follow-up every 3 years. Patients with low-grade dysplasia should have extensive mucosal sampling and follow-up every year. Patients with high-grade dysplasia should have expert confirmation and extensive mucosal sampling. Consider intensive surveillance every 3 months for patients with focal high-grade dysplasia. Patients with multifocal high-grade dysplasia or carcinoma should be considered for resection, or ablation if not an operative candidate.

•

Patients should be treated aggressively for GERD before surveillance.

REFERRAL

•

For EGD with biopsy in patients with chronic GERD who have not had previous EGD.

•

For surveillance in those with biopsy-proven Barrett's.

•

For those with high-grade dysplasia, refer for intensive surveillance or esophageal resection; ablative therapy may be considered as part of a research protocol or if not an operative candidate.

SUGGESTED READINGS Bonino JA, Sharma P: Barrett's esophagus. Curr Opin Gastroenterol 2006; 22:406.

Dellon ES, Shaheen NJ: Does screening for Barrett's esophagus and adenocarcinoma of the esophagus prolong survival?. J Clin Oncol 2005; 23:4478. Shaheen NJ: Advances in Barrett's esophagus and esophageal adenocarcinoma. Gastroenterology 2005; 128:1554. Sharma P, et al: A critical review of the diagnosis and management of Barrett's esophagus: the AGA Chicago workshop. Gastroenterology 2004; 127:310. Spechler SJ, Barr B: Review article: screening and surveillance of Barrett's esophagus: what is a cost-effective framework?. Aliment Pharmacol Ther 2004; 19(Suppl 1):49.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Bartter's Syndrome JONATHAN BURNS, M.A., M.D.

BASIC INFORMATION DEFINITION

Bartter's syndrome is a group of renal tubular disorders characterized by metabolic alkalosis, hypokalemia, hyperplasia of the juxtaglomerular apparatus, hyperreninemic hyperaldosteronism, and hypercalciuria. SYNONYMS

Hypokalemic alkalosis with hypercalciuria

ICD-9CM CODES

255.13 Bartter's Syndrome EPIDEMIOLOGY & DEMOGRAPHICS

Classic Bartter's syndrome can present with symptoms at 2 years of age or younger. Neonatal Bartter's syndrome can be diagnosed at birth. The true incidence in the U.S. is not known. Incidence is similar in males and in females. CLINICAL PRESENTATION

•

Neonatal Bartter's syndrome involves maternal polyhydramnios, frequent preterm delivery, fetal polyuria, and FTT.

•

Classic Bartter's syndrome may include a history of maternal polyhydramnios and premature delivery. The following features are characteristic: Polyuria. Polydipsia. Hypokalemia. Metabolic alkalosis. Hypercalciuria. Plasma magnesium is normal or mildly reduced. Patients are normotensive. Patients do not have edema.

ETIOLOGY

•

Disorder of chloride reabsorption in the thick ascending loop of Henle.

•

A couple of defects manifest the same phenotype.

•

Tubular pathophysiology is identical to loop diuretic mechanism of action.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Diuretic abuse

•

Surreptitious vomiting

•

Gitelman's syndrome

•

Autosomal dominant hypocalcemia

•

Hyperprostaglandin E syndrome

WORKUP

•

Classic Bartter's syndrome is usually a diagnosis of exclusion.

•

Vomiting associated with a low urine chloride and scarring of the dorsum of the hand and dental erosions suggests bulimia nervosa.

•

Diuretic abuse can only be excluded by a urinary assay for diuretics.

LABORATORY TESTS

•

Serum sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus.

•

Urine calcium, chloride, assay for diuretics as above.

•

Serum pH can be confirmed by performing ABG.

IMAGING STUDIES

•

Renal ultrasonography may show nephrocalcinosis, hydronephrosis, and hydroureter in neonatal Bartter's syndrome.

•

Classic signs of hypokalemia may be present on ECG.

TREATMENT NONPHARMACOLOGIC THERAPY

None ACUTE GENERAL Rx

Neonatal Bartter's syndrome requires correction of electrolyte imbalance and volume depletion. CHRONIC Rx

•

Usual treatment includes oral potassium and magnesium supplementation though achievement of normal serum potassium and magnesium levels is often difficult.

•

Potassium-sparing diuretics such as spironolactone/amiloride have also been used effectively in the treatment of Bartter's.

REFERRAL

Consultation with nephrology facilitates diagnosis and management of this condition.

PEARLS & CONSIDERATIONS COMMENTS

•

Just as Bartter's looks like loop diuretic use from the point of view of laboratory testing, Gitelman's syndrome appears identical to thiazide use.

•

High urine calcium is the best way to distinguish Bartter's from Gitelman's syndrome.

•

Serum magnesium differences have been described but are likely to be low in both syndromes and are probably not useful in distinguishing these syndromes.

PREVENTION

None PATIENT/FAMILY EDUCATION

•

Foods with high potassium content should be emphasized in dietary education.

•

Patients with Bartter's syndrome are more vulnerable to volume depletion due to potassium derangement during exercise and exposure.

SUGGESTED READINGS Hebert SC: Bartter syndrome. Curr Opin Nephrol Hypertens 2003; 12(b):527-532. Kurtz I: Molecular pathogenesis of Bartter's and Gitelman's syndromes. Kidney Int 1998; 54:1396.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Basal Cell Carcinoma GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JOSEPH GRILLO, M.D.

BASIC INFORMATION DEFINITION

Basal cell carcinoma (BCC) is a malignant tumor of the skin arising from basal cells of the lower epidermis and adnexal structures. It may be classified as one of six types (nodular, superficial, pigmented, cystic, sclerosing or morpheaform, and nevoid). The most common type is nodular (21%); the least common is morpheaform (1%); a mixed pattern is present in approximately 40% of cases. Basal cell carcinoma advances by direct expansion and destroys normal tissue. SYNONYMS

BCC

ICD-9CM CODES

179.9 Basal cell carcinoma, site unspecified 173.3 Basal cell carcinoma, face 173.4 Basal cell carcinoma, neck, scalp 173.5 Basal cell carcinoma, trunk 173.6 Basal cell carcinoma of the limb 173.7 Basal cell carcinoma, lower limb EPIDEMIOLOGY & DEMOGRAPHICS

•

Most common cutaneous neoplasm

•

85% appear on the head and neck region

•

Most common site: nose (30%)

•

Increased incidence with age>40 yr

•

Increased incidence in men

•

Risk factors: fair skin, increased sun exposure, use of tanning salons with ultraviolet A or B radiation, history of irradiation (e.g., Hodgkin's disease), personal or family history of skin cancer, impaired immune system

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Variable with the histologic type: •

Nodular: dome-shaped, painless lesion that may become multilobular and frequently ulcerates (rodent ulcer); prominent telangiectatic vessels are noted on the surface; border is translucent, elevated, pearly white ( Fig. 1-35 ); some nodular basal cell carcinomas may contain pigmentation, giving an appearance similar to a melanoma.

•

Superficial: circumscribed scaling black appearance with a thin raised pearly white border; a crust and erosions may be present; occurs most frequently on the trunk and extremities.

•

Morpheaform: flat or slightly raised yellowish or white appearance (similar to localized scleroderma); appearance similar to scars, surface has a waxy consistency.

FIGURE 1-35 Basal cell carcinoma. Note rolled translucent border and central ulceration in typical facial location. (From Noble J et al: Textbook of primary care medicine, ed 3, St Louis, 2001, Mosby.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Keratoacanthoma

•

Melanoma (pigmented basal cell carcinoma)

•

Xeroderma pigmentosa

•

Basal cell nevus syndrome

•

Molluscum contagiosum

•

Sebaceous hyperplasia

•

Psoriasis

WORKUP

Biopsy to confirm diagnosis

TREATMENT Variable with tumor size, location, and cell type: •

Excision surgery: preferred method for large tumors with well-defined borders on the legs, cheeks, forehead, and trunk.

•

Mohs' micrographic surgery: preferred for lesions in high-risk areas (e.g., nose, eyelid), very large primary tumors, recurrent basal cell carcinomas, and tumors with poorly defined clinical margins.

•

Electrodesiccation and curettage: useful for small (40% risk within 5 yr of treatment).

•

A lesion is considered low risk if it is30%) and the greatest recurrence rate.

EVIDENCE

Surgical treatment of primary facial basal cell carcinomas results in a significantly lower treatment failure rate at 4 yr compared with radiotherapy, in addition to a significantly superior cosmetic result.[[1]] In the treatment of primary superficial and nodular BCCs of the head and neck, both surgery and cryotherapy give equivalent recurrence rates at 12 mo, but cosmetic results favor surgery. [[1]] Radiotherapy treatment of primary basal cell carcinoma results in significantly fewer recurrences at 1 yr vs. cryotherapy. Such short-term results, however, should be interpreted with caution. Cosmetic results, at 1 yr, do not significantly differ between the two groups.[[1]] A randomized phase III study compared imiquimod or vehicle cream once daily 5 or 7 times per wk for 6 wk on superficial basal cell carcinoma. Combined clinical and histological assessments produced clearance rates for the 5 and 7 times per week imiquimod groups of 75% and 73%, respectively. The researchers concluded that imiquimod appears to be safe and effective for the treatment of BCC compared with vehicle cream.[[2]]

Evidence-Based References 1. Bath FJ, et al: Interventions for basal cell carcinoma of the skin. Cochrane Database Sys Rev 2003;

2. Geisse J, et al: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 2004; 50:722.

AUTHOR: FRED F. FERRI, M.D. Beçet's Disease

BASIC INFORMATION DEFINITION

Behçet's disease is a chronic, relapsing, inflammatory disorder characterized by the presence of recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions (Figs. 1-36 and 1-37 [5] [4]).

FIGURE 1-37 Behçet's syndrome. Painful aphthous inner lower lip ulcer in a 30-year-old Chinese woman with relapsing oral and genital ulcers and uveitis. She did well on low-dose prednisone plus colchicine. (From Canoso J: Rheumatology in primary care, Philadelphia, 1997, WB Saunders.)

FIGURE 1-36 Behçet's syndrome. Painful prepuceal ulcer in a male with superficial thrombophlebitis, oral ulcers, and bowel vasculitis. (From Canoso J: Rheumatology in primary care, Philadelphia, 1997, WB Saunders.)

SYNONYMS

Behçet's syndrome

ICD-9CM CODES

136.1 Behçet's syndrome EPIDEMIOLOGY & DEMOGRAPHICS

Behçet's disease is observed in two different geographic locations. •

•

One region consists of Japan, Korea, Turkey, and the Mediterranean basin. 1.

Prevalence ranges from 1:7000 to 1:10,000.

2.

Turkey has the highest prevalence at 80 to 370 cases per 100,000.

The second region consists of North America and Northern Europe. 1.

Prevalence ranges from 1:20,000 to 1:100,000.

2.

Prevalence of Behçet's disease in the U.S. is 0.12 to 0.33 cases per 100,000.

•

In these regions the prevalence of HLA-B51 is higher in patients with Behçet's disease.

•

Males=females.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Behçet's disease typically affects individuals in the third to fourth decade of life and primarily presents with painful aphthous oral ulcers. The ulcers occur in crops measuring 2 to 10 mm in size and are found on the mucous membrane of the cheek, gingiva, tongue, pharynx, and soft palate

•

Genital ulcers are similar to the oral ulcers

•

Decreased vision secondary to uveitis, keratitis, or vitreous hemorrhage, or occlusion of the retinal artery or vein may occur

•

Skin findings include nodular lesions, which are histologically equally divided to erythema nodosum-like lesions, superficial thrombophlebitis, and acne lesions, which are also presented at sites uncommon for ordinary acne (arms and legs)

•

Arthritis and arthralgias

•

CNS: meningeal findings including headache, fever, and stiff neck can occur. Cerebellar ataxia and pseudobulbar palsy occur with involvement of the brainstem

•

Vasculitis leading to both arterial and venous inflammation or occlusion can result in signs and symptoms of a myocardial infarction, intermittent claudication, deep vein thrombosis, hemoptysis, and aneurysm formation

ETIOLOGY

The etiology of Behçet's disease is unknown. An immune-related vasculitis is thought to lead to many of the manifestations of Behçet's disease. What triggers the immune response and activation is not yet known.

DIAGNOSIS According to the International Study Group for Behçet's disease, the diagnosis of Behçet's disease is established when recurrent oral ulceration is present along with at least two of the following in the absence of other systemic diseases: •

Recurrent genital ulceration

•

Eye lesions

•

Skin lesions

•

Positive pathergy test (enlarging papules at sterile needle injection sites)

DIFFERENTIAL DIAGNOSIS

•

Ulcerative colitis

•

Crohn's disease

•

Lichen planus

•

Pemphigoid

•

Herpes simplex infection

•

Benign aphthous stomatitis

•

SLE

•

Reiter's syndrome

•

Ankylosing spondylitis

•

AIDS

•

Hypereosinophilic syndrome.

•

Sweet's syndrome

WORKUP

The diagnosis of Behçet's disease is a clinical diagnosis. Laboratory tests and x-ray imaging may be helpful in working up the complications of Behçet's disease or excluding other diseases in the differential. LABORATORY TESTS

There are no diagnostic laboratory tests for Behçet's disease. IMAGING STUDIES

CT scan, MRI, and angiography are useful for detecting CNS and vascular lesions.

TREATMENT Treatment is directed at the patient's clinical presentation (e.g., mucocutaneous lesions, ocular lesions, arthritis, GI, CNS, or vascular lesions). NONPHARMACOLOGIC THERAPY

Supportive care ACUTE GENERAL Rx

•

•

•

•

•

•

Oral and genital ulcers 1.

Topical corticosteroids (e.g., triamcinolone acetonide ointment applied tid)

2.

Tetracycline tablets 250 mg dissolved in 5 cc water and applied to the ulcer for 2 to 3 min

3.

Colchicine 0.5 to 1.5 mg/kg/day PO

4.

Thalidomide 100 to 300 mg PO daily

5.

Dapsone 100 mg PO daily

6.

Pentoxifylline 300 mg/day PO

7.

Azathioprine 1 to 2.5 mg/kg/day PO

8.

Methotrexate 7.5 to 25 mg/wk PO or IV

Ocular lesions 1.

Anterior uveitis is treated by an ophthalmologist with topical corticosteroids (e.g., betamethasone drops 1 to 2 drops tid). Topical injection with dexamethasone 1 to 1.5 mg has also been tried

2.

Infliximab 5 mg/kg single dose

CNS disease 1.

Chlorambucil 0.1 mg/kg/day is used in the treatment of posterior uveitis, retinal vasculitis, or CNS disease. Patients not responding to chlorambucil can be tried on cyclosporine 5 to 7 mg/kg/day.

2.

In CNS vasculitis, cyclophosphamide 2 to 3 mg/kg/day is used. Prednisone can be used as an alternative.

Arthritis 1.

NSAIDs (e.g., ibuprofen 400 to 800 mg tid PO or indomethacin 50 to 75 mg/day PO)

2.

Sulfasalazine 1 to 3 g/day PO is an alternative treatment

GI lesions 1.

Sulfasalazine 1 to 3 g/day PO

2.

Prednisone 40 to 60 mg/day PO

Vascular lesions 1.

Prednisone 40 to 60 mg/day PO

2.

Cytotoxic agents as mentioned previously

3.

Heparin 5000 to 20,000 U/day followed by oral warfarin

CHRONIC Rx

•

Chronic therapy is usually continued for approximately 1 yr after remission.

•

Surgery may be indicated in patients with complications of bowel perforation, vascular occlusive disease, and aneurysm formation.

DISPOSITION

•

The aphthous oral ulcers last 1 to 2 wk, recurring more frequently than genital ulcers.

•

Approximately 25% of patients with ocular lesions become blind.

•

The disease course is unpredictable.

•

Complications include: 1.

Meningitis

2.

Cerebrovascular accident (stroke)

3.

Aneurysm rupture

4.

Peripheral lower-extremity ischemia

5.

Mesenteric ischemia

6.

Myocardial infarction

REFERRAL

If the diagnosis of Behçet's disease is suspected, a referral to both rheumatology and ophthalmology is indicated because the disease is so rare.

PEARLS & CONSIDERATIONS COMMENTS

•

The pathergy test refers to the formation of a papule or pustule of 2 mm or more in size after oblique insertion of a sterile 20- or 25-gauge needle into the skin.

•

Due to rarity of this disease, data from controlled, prospective, randomized clinical trials are lacking.

SUGGESTED READINGS Al-Otaibi LM, Porter SR, Poate TW: Behcet's disease: a review. J Dent Res 2005; 84(3):209. Bonfioli AA, Orefice F: Behcet's disease. Semin Ophthalmol 2005; 20(3):199. Evereklioglu C: Managing the symptoms of Behcet's disease. Expert Opin Pharmacother 2004; 5(2):317. Kurokawa MS, Yoshikawa H, Suzuki N: Behcet's disease. Semin Respir Crit Care Med 2004; 25(5):557. Yazici H: Behçet's syndrome: an update. Curr Rheumatol Rep 2003;195.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Bell's Palsy RICHARD ISAACSON, M.D.

BASIC INFORMATION DEFINITION

Bell's palsy is an idiopathic, isolated, usually unilateral facial weakness in the distribution of the seventh cranial nerve ( 1% are bilateral). SYNONYMS

Idiopathic facial paralysis

ICD-9CM CODES

351.0 Bell's palsy EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE:20 to 30 cases/100,000; occurs at any age, median age 45 RISK FACTORS: •

Pregnancy (especially third trimester/first postpartum week)

•

Diabetes (5% to 10% of patients)

•

Travel to area endemic for Lyme disease

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Unilateral paralysis of the upper and lower facial muscles (asymmetric eye closure, brow, and smile).

•

Ipsilateral loss of taste

•

Ipsilateral ear pain, usually 2 to 3 days before presentation

•

Increased or decreased unilateral eye tearing

•

Hyperacusis

•

Subjective ipsilateral facial numbness

•

In about 8% of cases, other cranial neuropathies may occur

ETIOLOGY

•

Most cases are idiopathic although the cause is often viral (herpes simplex).

•

Herpes zoster can cause Bell's palsy in association with herpetic blisters affecting the outer ear canal or the area behind the ear (Ramsay-Hunt syndrome).

•

Bell's palsy can also be one of the manifestations of Lyme disease and less commonly has been associated with hepatitis and post-smallpox vaccination.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Neoplasms affecting the base of the skull or the parotid gland

•

Infectious process (meningitis, otitis media, osteomyelitis of the skull base)

•

Brainstem stroke

•

Multiple sclerosis

•

Head trauma/temporal bone fracture

•

Other: sarcoidosis, Guillain-Barré, carcinomatous or leukemic meningitis, leprosy, Melkersson-Rosenthal syndrome

WORKUP

Bell's palsy is a clinical diagnosis. A focused history and neurologic examination confirms the diagnosis. LABORATORY TESTS

•

Consider CBC, fasting glucose, VDRL, ESR, ACE in selected patients.

•

Lyme titer in endemic areas.

IMAGING STUDIES

•

Contrast-enhanced MRI to exclude neoplasms is indicated only in patients with atypical features or course.

•

Chest x-ray may be useful to exclude sarcoidosis or rule out TB in selected patients before treating with steroids.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Reassure patient that the prognosis is usually good and the disease is most likely a result of a virus attacking the nerve, not a stroke.

•

Avoid corneal drying by patching the eye. Lacri-Lube ophthalmic ointment at night and artificial tears during the day are also useful to prevent excessive drying.

ACUTE GENERAL Rx

•

A short course of oral prednisone is commonly used and may improve the chances of complete recovery at 3 and 9 mo.

•

If used, prednisone therapy should be started within 24 to 48 hr of symptom onset. Optimal steroid dose is unknown.

•

Combination therapy with acyclovir and prednisone is not effective in improving clinical recovery.

•

Surgical decompression remains controversial and data from randomized trials are lacking to compare medical vs. surgical therapy.

•

There are some data that suggest that methylcobalamin (active form of vitamin B12) and hyperbaric oxygen may be of benefit, but these have not yet received widespread acceptance.

•

Botulinum toxin may be helpful for treatment of synkinesis and hemifacial spasm, two late sequelae of Bell's palsy.

CHRONIC Rx

Patients should be monitored for evidence of corneal abrasion and ulceration. Physical therapy including moist heat and massage may be beneficial. DISPOSITION

•

71% of patients should recover completely. Prognosis is better for those with less severity of symptoms at onset and clinical improvement within 3 wk. Diabetes may confer a worse prognosis.

•

Recovery begins within 3 wk in 85% of patients. The remainder have some improvement within 3 to 6 months.

•

Recurrence occurs in 5% of cases.

REFERRAL

•

Persistent eye irritation or redness requires referral to ophthalmology.

•

Neurology referral is recommended if diagnosis is unclear or if clinical course is atypical.

PEARLS & CONSIDERATIONS Assure that both upper and lower aspects of the face are involved (as this suggests a peripheral lesion). Lower facial asymmetry alone is more likely central (e.g., stroke) and further workup is necessary.

EVIDENCE

There is no unequivocal evidence favoring the use of corticosteroids, either alone or in combination with acyclovir, for patients with Bell's palsy. The available evidence from randomized controlled trials is conflicting and meta-analysis of the data from these trials suggests that steroids are probably beneficial. [28] [29] The available evidence suggests that acyclovir given alone or in combination with steroids offers any additional benefit.[[3]]

Evidence-Based References 1. Grogan PM: Practice parameter: steroids, acyclovir, and surgery for Bell's Palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 57(7):830. 2. Salinas RA, et al: Corticosteroids for Bell's palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 2004; 4:CD001942 3. Sullivan FM, et al: Early treatment with prednisone or acyclovir in Bell's palsy. N Eng J Med 2009; 357:1598-1607.

SUGGESTED READINGS Alberton DL, Zed PJ: Bell's palsy: a review of treatment using antiviral agents. Ann Pharmacother 2006; 40(10):1838.Epub ahead of print. Austin JR, et al: Idiopathic facial nerve paralysis: a randomized double blind controlled study of placebo versus prednisone. Larynoscope 1993; 103:1326. Benatar M, Edlow JA: The spectrum of cranial neuropathy in patients with Bell's palsy. Arch Intern Med 2004; 164:2283. Gilden D: Bell's palsy. N Engl J Med 2004; 351:1323. Holland NJ, Weiner GM: Recent developments in Bell's palsy. BMJ 2004; 329:553. Kanazawa A, et al: Prognosis for Bell's palsy: a comparison of diabetic and nondiabetic patients. Acta Otolaryngol 2007; 127(8):888. Sipe J, Dunn L: Acyclovir for Bell's palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 2004; 3:CD001869 Tigmstra JD, Khatkhate N: Bell's palsy: diagnosis and management. Am Fam Physician 2004; 76:997-1002.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Bipolar Disorder VICTOR I. REUS, M.D.

BASIC INFORMATION DEFINITION

Bipolar disorder is an episodic, recurrent, and frequently progressive condition in which the afflicted individual experiences at least one episode of mania, characterized by at least 1 week of continuous symptoms of elevated, expansive, or irritable mood in association with three or four of the following: •

Decreased need for sleep

•

Grandiosity

•

Pressured speech

•

Subjective or objective flight of ideas

•

Distractibility

•

Increased level of goal-directed activity

•

Problematic behavior

Most individuals with bipolar disorder will also experience one or more episodes of major depression over their lifetime or have symptoms of a depressive episode commingled with those of mania (mixed episode). SYNONYMS

Manic-depression Cycloid psychosis

ICD-9CM CODES

296.4-6 Circular manic, circular depressed, circular type mixed EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE:0.016% to 0.021% PREVALENCE (IN U.S.):0.7% to 1.6%; bipolar spectrum disorders 2.8% to 6.5% PREDOMINANT SEX:Equal distribution among male and female PREDOMINANT AGE:Lifelong condition with symptoms present 50% of the time and depression 3 times more

frequent than mania PEAK INCIDENCE:Onset of symptoms between ages 15 and 19 yr GENETICS: •

Concordance rates for monozygotic twins: 0.7 to 0.8; for dizygotic twins: 0.2

•

Risk of affective disorder in offspring with one affected parent with bipolar disorder: 27% to 29%; with two affected parents: 50% to 74%

•

Heritability estimate of 0.85

•

Although no specific causal mutations have been identified, candidate gene loci have been reported on chromosomes 4, 5, 8, 18, and 21, as well as others; a recent whole genome association study of 2000 patients and 3000 controls found a signal at 16p12, but this was not supported in a replication sample.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Mania associated with psychomotor activation that is usually goal directed but not necessarily productive; increase in goal-directed activity and excessive involvement in activities leading to unexpected adverse outcomes

•

Elevated, euphoric, and frequently labile mood

•

Decreased need for sleep

•

Flight of ideas with rapid, loud, pressured speech

•

Psychosis may occur, with delusions, hallucinations, and formal thought disorder

•

Depressive episodes resembling major depressive disorder (see “Depression, Major”); however, atypical features (hypersomnia, weight gain) may be present

•

Mixed states, characterized by activation, irritability, and dysphoria also possible

ETIOLOGY

•

Hypotheses: 1.

Abnormalities of receptor and membrane function and of circadian regulation

2.

Alteration of cAMP, MAP kinase, protein kinase C, and glycogen synthase kinase-3 signal transduction pathways

3.

Alteration in cell survival pathways

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Secondary manias caused by medical disorders (e.g., hyperthyroidism, AIDS, TBI, stroke, Cushing's syndrome) or drug treatment (stimulants, steroids) are frequent.

•

First onset of mania after age 50 yr is suggestive of secondary mania.

•

Less severe, and possibly distinct, conditions of bipolar type II and cyclothymia are possible.

•

Comorbidity with substance abuse or dependency is common and may confound diagnostic assessment and treatment.

•

Cross-sectional examination of acutely manic patient can be confused with schizophrenia or a paranoid psychosis.

WORKUP

•

History

•

Physical examination

•

Mental status examination

•

Mood disorder questionnaire (MDQ)

LABORATORY TESTS

Because of high rate of secondary manias, initial evaluation to confirm health of all major organ systems (routine chemistries, complete blood count, urinalysis, sedimentation rate) IMAGING STUDIES

•

Consider brain imaging if late onset or if neurologic exam is abnormal.

•

Neuroimaging may show evidence of ventricular enlargement or increased white matter hyperintensities; changes in amygdala, frontal cortex, and striatal volume have also been reported.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Cognitive-behavioral and family-focused psychoeducational psychotherapy to help patients cope with consequences of the disease, improve adherence with medications, and identify possible environmental triggers

•

Bright light therapy in the northern latitudes in individuals exhibiting a seasonal pattern of winter depression

•

Lifestyle “regularization”

ACUTE GENERAL Rx

•

First-line agents for acute mania: lithium 1500 to 1800 mg/day (0.8 to 1.2 meq/L), valproate 1000 to 1500 mg/day (50 to 125 mg/ml), carbamazepine 600 to 800 mg/day (4 to 12 µg/ml), oxcarbazepine 900 to 2400 mg/day, olanzapine 10 to 20 mg/day, risperidone 2 to 4 mg/day, quetiapine 350 to 800 mg/day, ziprasidone 80 to 120 mg/day, and aripiprazole 10 to 30 mg/day.

•

Useful adjuncts to acute treatment: Benzodiazepines: lorazepam 1 to 2 mg/q4h, clonazepam 1 to 2 mg/q4h.

•

Traditional antidepressants are effective in bipolar depression but can induce manic episodes and exacerbate mania in mixed episodes.

•

Lamotrigine can have acute antidepressant benefit; monotherapy with quetiapine or a combination of olanzapine and fluoxetine are secondary options in bipolar depression.

CHRONIC Rx

•

Goal of long-term treatment: prevention of relapse or episode recurrence

•

Best agents for prophylaxis of mania: lithium, valproate, and olanzapine (carbamazepine/oxcarbazepine possibly beneficial)

•

Best agents for prophylaxis of depression: lamotrigine and lithium

•

Role of atypical antipsychotics in maintenance unclear; combination therapy with a mood stabilizer is more effective than monotherapy

•

Long-term use of antidepressants: frequently destabilizes patient and leads to more frequent relapses

DISPOSITION

•

Course is variable.

•

More than 90% of patients having a single manic episode are likely to experience others.

•

Uncontrolled manic or depressive episodes can lead to additional episodes (“illness begets illness”).

•

Lithium treatment is shown to specifically decrease suicidal risk.

•

Psychosocioeconomic consequences of both mania and depression can be severe and disabling.

REFERRAL

•

If use of antidepressant contemplated

•

If patient is severely manic, rapid cycling, or suicidal or is in a bipolar, mixed episode

PEARLS & CONSIDERATIONS COMMENTS

•

All patients presenting with depression should be asked about past personal and family history of mania and hypomania; 70% of bipolar patients have previously been misdiagnosed.

•

Denial of illness is common in mania and often necessitates more assertive therapeutic interventions.

•

Prompt recognition of the earliest signs of mania in a given individual (e.g., decreased need for sleep, increased rate of speech) allows earlier intervention and a better likelihood of preventing a full episode.

•

Bipolar disorder in children frequently manifests as behavioral disinhibition and impulsive aggression.

•

Life charting helps identify environmental triggers and drug efficacy.

PATIENT/FAMILY EDUCATION

Information available at www.NMHA.org

and www.dbsalliance.org

.

EVIDENCE

Lithium and valproate are effective in the treatment of acute mania. [39] [40] Systematic reviews of randomized clinical trials (RCTs) of lithium and valproate have found that both drugs are significantly more effective than placebo in therapeutic response measured after 3 to 4 weeks. Lithium is also effective in the long-term prevention of recurrence of mania,[[3]] as shown in a systematic review of RCTs comparing lithium to placebo and assessing relapse over 2 years. Lamotrigine also delayed time to treatment of depression, as well as mania, in a pooled analysis of two RCTs.[[4]] A beneficial effect of helping people to recognize early warning signs of recurrence in bipolar disorder on rate of recurrence and risk of hospitalization has also been shown in a review of eleven RCTs.[[5]]

Evidence-Based References 1. Poolsup N, et al: Systematic overview of lithium treatment in acute mania. J Clin Pharm Ther 2000; 25:139.Reviewed in: Clin Evid 13:1158, 2005. 2. Macritchie K, et al: Valproate for acute mood episodes in bipolar disorder. Cochrane Database Syst Rev 2003; 1:CD004052 3. Burgess S, et al: Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev 2001; 3:CD003013 4. Goodwin GM, et al: A pooled analysis of 2 placebo-controlled 18-month trials of Lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry 2004; 65(b):432-441. 5. Morriss RK, et al: Interventions for helping people recognize early signs of recurrence in bipolar disorder. Cochrane Database Syst Rev 2007; 1:CD004854,

SUGGESTED READINGS Arora M, et al: Mania in the medically ill. Curr Psychiatry Rep 2007; 9(b):232-235. Cousins DA, et al: The armamentarium of treatments for bipolar disorder: a review of the literature. Int J Neuropsychopharmacol 2007; 10(b):411-431. Farmer A, et al: The genetics of bipolar affective disorder. Curr Opin Psychiatry 2007; 20(b):8-12. Goodwin FK, Redfield JK: Manic-depressive illness: bipolar disorders and recurrent depression, ed 2. New York, Oxford University Press, 2007. Keck PE: Long-term management strategies to achieve optimal function in patients with bipolar disorder. J Clin Psychiatry 2006; 67(12):e17. McClellan J, et al: Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2007; 46(1):107.

Miklowitz DJ: A review of evidence-based psychosocial interventions for bipolar disorder. J Clin Psychiatry 2006; 67(b):28-33. Rouget BW, et al: Efficacy of psychoeducational approaches on bipolar disorders: a review of the literature. J Affect Disor 2007; 98(b):11-27. Sachs GS, et al: Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007; 356(b):1711-1722. Scherk H, et al: Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 2007; 64(b):442-455. Vieta E, et al: Evolving trends in the long-term treatment of bipolar disorder. World J Biol Psychiatry 2007; 8(b):4-11.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Bite Wounds FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

A bite wound can be animal or human, accidental or intentional.

ICD-9CM CODES

879.8 Bite wound, unspecified site EPIDEMIOLOGY & DEMOGRAPHICS

•

Bite wounds account for 1% of emergency department visits.

•

More than 1 million bites occur in humans annually in the U.S.

•

Dog bites account for 85% to 90% of all bites and result in 10 to 20 fatalities yearly in the U.S.; cat bites, 10% to 20%. Typically the animal is owned by the victim.

•

Infection rates are highest for cat bites (30% to 50%), followed by human bites (15% to 30%) and dog bites (5%).

•

The extremities are involved in 75% of bites.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The appearance of the bite wound is variable (e.g., puncture wound, tear, avulsion).

•

Cellulitis, lymphangitis, and focal adenopathy may be present in infected bite wounds.

•

Patient may experience fever and chills.

ETIOLOGY

•

Increased risk of infection: human and cat bites, closed fist injuries, wounds involving joints, puncture wounds, face and lip bites, bites with skull penetration, bites in immunocompromised hosts

•

Most frequent infecting organisms: 1.

Pasteurella spp.: responsible for majority of infections within 24 hr of dog (P. canis) and cat (P. multocida, P. septica) bites

2.

Capnocytophaga canimorsus (formerly DF-2 bacillus): a gram-negative organism responsible for late infection, usually following dog bites

3.

Gram-negative organisms (Pseudomonas, Haemophilus): often found in human bites

4.

Streptococcus spp., Staphylococcus aureus

5.

Eikenella corrodens in human bites

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Bite from a rabid animal (often the attack is unprovoked)

•

Factitious injury

WORKUP

•

Determination of the time elapsed since the patient was bitten, status of rabies immunization of the animal, and underlying medical conditions that might predispose the patient to infection (e.g., DM, immunodeficiency)

•

Documentation of bite site, notification of appropriate authorities (e.g., police department, animal officer)

LABORATORY TESTS

•

Generally not necessary

•

Hct if there has been significant blood loss

•

Wound cultures (aerobic and anaerobic) if there is evidence of sepsis or victim is immunocompromised patient; cultures should be obtained before irrigation of the wound but after superficial cleaning

IMAGING STUDIES

X-rays are indicated when bony penetration is suspected or if there is suspicion of fracture or significant trauma; x-rays are also useful for detecting presence of foreign bodies (when suspected).

TREATMENT NONPHARMACOLOGIC THERAPY

•

Local care with debridement, vigorous cleansing, and saline irrigation of the wound; debridement of devitalized tissue

•

High-pressure irrigation to clean bite wound and ensure removal of contaminants (e.g., use saline solution with a 30- to 35-ml syringe equipped with a 20-gauge needle or catheter with tip of syringe placed 2 to 3 cm above the wound)

•

Avoid blunt probing of wounds (increased risk of infection)

•

If the animal is suspected to be rabid: infiltrate wound edges with 1% procaine hydrochloride, swab wound surface vigorously with cotton swabs and 1% benzalkoronium solution or other soap, and rinse wound with normal saline

ACUTE GENERAL Rx

•

Avoid suturing of hand wounds and any wounds that appear infected

•

Puncture wounds should be left open

•

Give antirabies therapy and tetanus immune globulin (250 to 500 units IMin limb controlateral to toxoid) and toxoid (adult or child older than 5 years: 0.5 ml DT given IM, child less than 5 years 0.5 ml DPT IM) as needed

•

Use empiric antibiotic therapy in high-risk wounds (e.g., cat bite, hand bites, face bites, genital area bites, bites with joint or bone penetration, human bites, immunocompromised host): amoxicillin-clavulanate 875 to 1000 mg bid for 7 days or cefuroxime 500 mg bid for 7 days

•

In hospitalized patients, IV antibiotics of choice are cefoxitin 1 to 2 g q6h, ampicillin-sulbactam 1.5 to 3 g q6h, ticarcillin-clavulanate 3 g q6h, or ceftriaxone 1 to 2 g q24h

•

Prophylactic therapy for persons bitten by others with HIV and hepatitis B (see Section V)

DISPOSITION

•

Prognosis is favorable with proper treatment.

•

Important prognostic factors are type and depth of wound, which compartments are entered, and pathogenicity of inoculated bacteria.

•

Punctures that are difficult to irrigate adequately, carnivore bites over vital structures (arteries, nerves, joints), and tissue crushing that cannot be debrided have a worse prognosis.

•

In general, human bites have a higher complication and infection rate than do animal bites.

•

Nearly 50% of the anaerobic gram-negative bacilli isolated from human bite wounds may be penicillin resistant and beta-lactamase positive.

REFERRAL

•

Hospitalization and IV antibiotic therapy for infected human bites; bites with injury to joints, nerves, or tendons; or any animal bites unresponsive to oral therapy.

•

In the outpatient setting, bite wounds should be reevaluated within 48 hr to assess for signs of infection.

SUGGESTED READINGS Broder J, et al: Human bites. Am J Med 2004; 22:10.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Bites and Stings, Arachnids GAIL O'BRIEN, M.D.

BASIC INFORMATION DEFINITION

There are two major classes of arthropods: insects and arachnida. This chapter will focus on the class arachnida. Arachnid bites consist of bites caused by: •

Spiders

•

Scorpions

•

Ticks

ICD-9CM CODES

E905.1 Venomous spiders (black widow spider, brown spider, tarantula) E905.2 Scorpion 989.5

Bites of venomous snakes, lizards, and spiders; tick paralysis

E906.4 Bite of nonvenomous arthropod; insect bite NOS EPIDEMIOLOGY & DEMOGRAPHICS

•

Spiders: ubiquitous; only three types potentially significantly harmful: 1.

Sydney funnel web spider—Australia

2.

Black widow—worldwide (not Alaska)

3.

Brown recluse—most common (South Central U.S.)

•

Scorpions: various warm climates: Africa, Central South America, Middle East, India; in U.S.: Texas, New Mexico, California, Nevada

•

Ticks: woodlands

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Spiders:

•

Sydney funnel web—atrataxin toxin 1.

•

•

Piloerection, muscle spasms leading to tachycardia, HTN, increased intracranial pressure, coma

Black widow—females toxic 1.

Initial reaction: local swelling, redness (two fang marks) leading to local piloerection, edema, urticaria, diaphoresis, lymphangitis

2.

Pain in limb leading to rest of body (chest pain, abdominal pain)

Brown recluse 1.

Minor sting or burn.

2.

Wound may become pruritic and red with a blanched center with vesicle. Can necrose, especially in fatty areas. Leaves eschar, which sloughs and leaves ulcer, can take months to heal.

3.

Systemic symptoms: headache, fever, chills, GI upset, hemolysis, renal tubular necrosis, disseminated intravascular coagulation (DIC) possible.

Scorpions: •

Sting leading to sympathetic and parasympathetic stimulation: HTN, bradycardia, vasoconstriction, pulmonary edema, reduced coronary blood flow, priapism, inhibition of insulin

•

Also possible: tachycardia, arrhythmia, vasodilation, bronchial relaxation, excessive salivation, vomiting, sweating, bronchoconstriction

Ticks: U.S., Europe, Asia •

Very small (36 hours to transmit disease.

•

Lyme disease—most common 1.

Early: erythema migrans 60% to 80% of cases

2.

7 to 10 days: mild to moderate constitutional symptoms—disseminated—secondary skin lesions, fever, adenopathy, constitutional symptoms, facial palsy, peripheral neuropathy, lymphocytic meningitis, meningoencephalitis, cardiac manifestations (heart block)

3.

Late: chronic arthritis, dermatitis, neuropathy, keratitis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Cellulitis Urticaria Other tick-borne illnesses: •

Babesiosis

•

Tick-borne relapsing fever

•

Tularemia

•

Rocky Mountain spotted fever

•

Ehrlichiosis

•

Colorado tick fever

•

Tick paralysis

•

Community-acquired cutaneous MRSA

WORKUP

Physical examination: thorough skin examination may reveal fang marks, attached ticks, black eschar.

TREATMENT ACUTE GENERAL Rx

Spiders: •

Sydney funnel web 1.

•

Pressure, immobilization immediately, supportive care, antivenin

Black widow 1.

Treatment based on severity of symptoms. Bite is rarely fatal.

2.

All should get on oxygen, IV, cardiac monitor, tetanus prophylaxis.

3.

Symptomatic/supportive therapy.

4.

10% calcium gluconate for muscle cramps (controversial).

5.

Antivenin only for more severe reactions. Antivenin carries risk of anaphylaxis.

•

Dose: one vial in 100 ml 0.9% saline over 20 to 30 minutes.

•

Skin test before use.

•

Give antihistamines with use.

•

Brown recluse 1.

Pain management, tetanus, supportive treatment.

2.

No consensus regarding best treatment. Some evidence for hyperbaric oxygen.

Scorpions: •

Fluids, supportive care, species-specific antivenin (equine based, risk of serum sickness)—controversial.

Ticks:

•

Prophylactic: tick >36 hours: single dose of doxycycline 200 mg

•

Early localized disease 1.

Treatment of choice in children: amoxicillin×14 days.

2.

Doxycycline preferred in patients with possible concurrent ehrlichiosis.

3.

Early disseminated: treatment depends on manifestation.

4.

Late disease: may require longer-term/IV therapy. Controversial for neurologic disease. (See “Lyme Disease” for further details.)

DISPOSITION

•

For patients with systemic reactions, send home with emergency epinephrine kit.

•

If severe or anaphylactic reaction, admit and observe for 48 hours for cardiac, renal, or neurologic problems.

REFERRAL

For patients with systemic reactions, refer to allergist for immunotherapy; 95% to 98% effective in preventing anaphylaxis.

PEARLS & CONSIDERATIONS Identification of spider should not be based on patient history (many look-alikes); spider should be brought into medical facility to be identified. SUGGESTED READINGS Bolgiano EB, Sexton J: Tick-borne illnesses. Rosen's emergency medicine, ed 6. Philadelphia, Mosby, 2006. Hayes P: Current concepts: how can we prevent Lyme disease?. N Engl J Med 2003; 348(24):2424. Otten E: Venomous animal injuries. Rosen's emergency medicine, ed 6. Philadelphia, Mosby, 2006.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Bites and Stings, Insect JENNIFER JEREMIAH, M.D.

BASIC INFORMATION DEFINITION

Most stinging insects belong to the Hymenoptera order and include yellow jackets (most common cause of reactions), hornets, bumble bees, sweat bees, wasps, harvester ants, fire ants, and the Africanized honey bee “killer bee.” Brown recluse spiders, although they are not insects, are another common cause of bites (see Bites and Stings, Arachnids). The usual effect of a sting is intense local pain, some immediate erythema, and often a small area of edema by injecting venom. Allergic reactions can be either local or generalized leading to anaphylactic shock. The majority of reactions occur within the first 6 hr after the sting or bite, but a delayed presentation may occur up to 24 hr. SYNONYMS

Venom allergy

ICD-9CM CODES

989.5 Stings (bees, wasps) 989.5 Bites (fire ant, brown recluse spider) EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE (OF BEE STINGS AND INSECT BITES): •

Unknown

•

Between 0.4% and 4% of the population is allergic to the venom of one or more stinging insects

•

Most anaphylactic reactions occur during summer months in those most likely to be exposed including children, males, outdoor workers

•

About one half of fatal reactions occur without prior allergic response

•

Bites by fire ants and brown recluse spiders are less likely to cause systemic disease

INCIDENCE (IN U.S.):About 45 people die each year from insect sting anaphylaxis; anaphylaxis occurs more often within 10 to 30 min of a sting. Delayed reactions are rare occurring only in 40 yr

•

Male:female ratio of 2:1

OSTEOGENIC SARCOMA: •

Average age at onset: 10 to 20 yr

•

Males > females

•

Parosteal sarcoma in older patients

CHONDROSARCOMA: •

Age at onset: 40 to 60 yr

•

Male:female ratio of 2:1

EWING'S SARCOMA:Age at onset: 10 to 15 yr PHYSICAL FINDINGS & clinical presentation

MULTIPLE MYELOMA: •

May present as a systemic process or, less commonly, as a “solitary” lesion

•

Early manifestations: anorexia, weight loss, and bone pain; majority of cases present initially with back pain that often leads to the detection of a destructive skeletal lesion

•

Other organ systems eventually become involved, resulting in more bone pain, anemia, renal insufficiency, and/or bacterial infections, usually as a result of the dysproteinemia typical of this disorder

•

Possible secondary amyloidosis, leading to cardiac failure or nephrotic syndrome

OSTEOSARCOMA: •

Most originating in the metaphysis

•

50% to 60% around the knee

•

Possible pain and swelling, but otherwise healthy patient

•

Osteosarcoma in conjunction with Paget's disease, manifested primarily as a sudden increase in bone pain

CHONDROSARCOMA: •

Tumor most commonly involving the pelvis, upper femur, and shoulder girdle

•

Painful swelling

EWING'S SARCOMA: •

Painful soft tissue mass often present

•

Possibly increased local heat

•

Midshaft of a long bone usually affected (in contrast to other tumors)

•

Weight loss, fever, and lethargy

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Osteomyelitis

•

Metastatic bone disease

LABORATORY TESTS

•

Slightly elevated alkaline phosphatase in osteosarcoma

•

In Ewing's sarcoma: reflective of systemic reaction; include anemia, an increase in WBC count, and an elevated sedimentation rate

•

In multiple myeloma: 1.

Bence Jones protein in the urine

2.

Anemia and elevated sedimentation rate

3.

Characteristic dysproteinemia on serum protein electrophoresis

4.

Diagnostic feature: peak in the electrophoretic pattern suggestive of a monoclonal gammopathy

5.

Rouleaux formation in the peripheral blood smear

6.

Often, presence of hypercalcemia, but alkaline phosphatase levels usually normal

IMAGING STUDIES

•

Classic osteogenic sarcoma penetrates the cortex early in many cases. 1.

A blastic (dense), lytic (lucent), or mixed response may be seen in the affected bone.

2.

An aggressive perpendicular sunburst pattern may be present as a result of periosteal reaction, and peripheral Codman's triangles are often noted.

3.

Margins of the tumor are poorly defined.

•

Speckled calcifications in a destructive radiolucent lesion are usually suggestive of chondrosarcoma.

•

Ewing's sarcoma is characterized radiographically by mottled, irregular destructive changes with periosteal new bone formation. The latter may be multilayered, producing the typical “onion skin” appearance.

•

Typical roentgenographic finding in multiple myeloma is the “punched out” lesion with sharply demarcated edges. 1.

Multiple lesions are usual.

2.

Diffuse osteoporosis may be the only finding in many cases.

3.

Pathologic fractures are common.

TREATMENT The evaluation and treatment of malignant bone tumors are complicated. Diagnostic studies and treatment should be supervised by an orthopedic cancer specialist and oncologist. DISPOSITION

•

In the past 20 yr, dramatic improvements have been made in the treatment protocols for osteosarcoma with the use of adjuvant multidrug regimens and limb-sparing surgery.

•

Prognosis of multiple myeloma remains poor despite new therapies.

•

Prognosis for Ewing's sarcoma has improved with a combination of chemotherapy, local resection, and radiation therapy.

•

Chondrosarcomas are not sensitive to chemotherapy or radiation, and prognosis will depend on the grade of the tumor and the ability to obtain an adequate resection.

PEARLS & CONSIDERATIONS Early diagnosis is important because most tumors have not metastasized at the time of initial presentation. SUGGESTED READINGS Dormans JP, Moroz L: Infection and tumors of the spine in children. J Bone Joint Surg 2007; 89A:79. Futani H, et al: Long-term follow-up after limb salvage in skeletally immature children with a primary malignant tumor of the distal end of the femur. J Bone Joint Surg 2006; 88A:595. Hoffmann C, et al: Functional results and quality of life after treatment of pelvic sarcomas involving the acetabulum. J Bone Joint Surg 2006; 88A:575. Lewis VO: What's new in musculoskeletal oncology?. J Bone Joint Surg 2007; 89:1399. Plate AM, et al: Malignant tumors of the hand and wrist. J Am Acad Orthop Surg 2006; 14:680. Staals EL, et al: Dedifferentiated chondrosarcomas arising in preexisting osteochondromas. J Bone Joint Surg 2007; 89A:987.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Borderline Personality Disorder MICHELE MONTANDON, M.D.,, MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in interpersonal relationships, self-image, affect regulation, and impulse control that causes significant subjective distress or impairment of functioning. The individual must meet five or more of the following criteria: 1.

Frantic efforts to avoid real or imagined abandonment

2.

Unstable and intense personal relationships characterized by alternating between extremes of idealization and devaluation

3.

Identity disturbance characterized by an unstable self-image

4.

Impulsivity in at least two areas that are potentially self-damaging (e.g., overspending, sex, substance abuse, binge eating, reckless driving)

5.

Recurrent suicidal behavior, gestures, threats, or self-mutilating behavior

6.

Affective instability due to a marked reactivity of mood

7.

Chronic feelings of emptiness

8.

Inappropriate, intense anger, or difficulty controlling anger

9.

Transient, stress-related paranoid ideation or severe dissociative symptoms

ICD-9CM CODES

301.83 Borderline personality EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE:Affects about 1% to 2% of the general population and up to 10% of psychiatric outpatients PREDOMINANT SEX: Female (3:1) PREDOMINANT AGE: 20s GENETICS: Five times as likely if BPD is present in first-degree relative. An increased prevalence of mood disorders and substance abuse disorders is also found in first-degree relatives of persons with BPD. RISK FACTORS: Association with childhood physical, sexual, or emotional abuse and/or neglect

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

There are no specific physical findings associated with BPD.

•

Mental status examination may reveal affective lability.

Clinical presentation may reveal the following: •

Patients experience a pervasive sense of loneliness and emptiness. In addition to affective instability, persons with BPD often demonstrate an underlying negative affect with dysphoria.

•

Intense emotions with difficulty returning to emotional baseline.

•

All-or-nothing, either-or cognitive style that is represented by a phenomenon known as “splitting,” in which patient sees situations or people as all good or all bad.

•

Difficulty in maintaining commitment to long-term goals; history of numerous stormy relationships and multiple jobs.

•

Reacts with rage, panic, despair to actual or perceived abandonment; may present with suicidality or selfmutilating behavior in response to recent stressor.

•

Attempts to block the experience of pain, which may induce feelings of derealization, depersonalization, changes in consciousness, and/or brief psychotic reactions with delusions and hallucinations.

•

Substance use, gambling, overspending, eating binges, and/or self-mutilation as a way to escape intensely painful affect.

•

Some patients may display psychotic symptoms.

ETIOLOGY

•

Interaction of psychosocial adversity plus genetic factors

•

Hypotheses: 1.

Genetic: increased risk if first-degree relative with BPD.

2.

Biologic: abnormalities in limbic system and other areas of the brain cause emotional dysregulation. Serotonergic functioning appears to be disturbed.

3.

Environmental: history of childhood abuse or neglect.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Histrionic and narcissistic personality disorders share some common features.

•

Dysthymia and other depressive disorders: requires a stability of affective symptoms not seen in BPD.

•

Bipolar disorder: mood changes in BPD are often triggered by stressors and are less sustained than in bipolar disorder.

•

Substance abuse or dependence: often induces impulsive, emotionally labile behavior.

•

Posttraumatic stress disorder: individuals with BPD often have history of trauma but do not avoid the feared stimulus or reexperience the trauma as do individuals with PTSD.

•

Mild cases of schizophrenia may superficially resemble BPD.

WORKUP

•

History (often helpful to gather collateral information from family and friends)

•

Physical examination

•

Mental status examination

LABORATORY TESTS

•

Toxicology screen. Substance use is common and can mimic features of personality disorders.

•

Screen for HIV and other sexually transmitted illnesses. Patients with personality disorders often exhibit poor impulse control.

IMAGING STUDIES

Structural and functional MRI demonstrate abnormalities in the amygdala and hippocampus. PET scans reveal altered metabolism in prefrontal cortex. Imaging is not recommended as part of routine evaluation.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Few randomized trials have assessed psychosocial interventions for BPD.

•

Dialectical behavior therapy (DBT), a variation of cognitive behavior therapy (CBT), and transferencefocused psychotherapy, a type of psychodynamic therapy, have the most empirical support from randomized trials. The goal of DBT is to help patients control impulses and angry outbursts and to develop social skills, and the focus of transference-focused psychotherapy is on examining the affect-laden themes that emerge in the relationship between patient and therapist.

ACUTE GENERAL Rx

Low-dose antipsychotics to control impulsivity, brief psychotic episodes. CHRONIC Rx

•

Medications have low to moderate effectiveness and are most effective in improving symptoms of impulsivity, mood instability, and self-destructive behavior. Effectiveness of medications for BPD has only been studied within the first 3 mo of treatment.

•

SSRIs if concurrent mood disorder. Higher doses of antidepressants may be required than for patients with major depression alone.

•

Low-dose antipsychotics.

•

Mood stabilizers (lithium, valproate, carbamazepine, topiramate).

•

In preliminary studies, daily omega-3 fatty acids improve symptoms of irritability.

DISPOSITION

•

Course is variable. The most unstable period is typically in early adulthood; the majority of patients achieve greater stability in social/occupational functioning later in life but often continue to have difficulty maintaining intimate relationships.

•

There is no evidence of progression to schizophrenia, but patients have a high incidence of episodes of major depressive disorder and other Axis I disorders. This highlights the importance of evaluating for Axis I pathology in patients with BPD to identify potentially treatable illness.

REFERRAL

•

Referral to mental health specialty care advised to confirm diagnosis and assist in management.

•

Referral recommended if: Use of pharmacotherapy contemplated Patient is severely impaired in daily function or suicidal

PEARLS & CONSIDERATIONS COMMENTS

Guidelines for physician management of patients with BPD: •

Consider frequent, brief, scheduled visits for needy, demanding, or somaticizing patients with BPD.

•

Validate the patient's feelings while stating the expectation of behavior control.

•

Be matter-of-fact; avoid expressing extreme emotions.

•

Be alert to the risk of suicide and assess suicide risk often.

•

Convey a demeanor of competence but openly acknowledge minor errors.

•

Have a low threshold for seeking psychiatric consultation.

PREVENTION

There are no known ways to prevent BPD and other personality disorders. Attempts may be made to prevent the deleterious consequences of personality disorders: •

Suicidality should be actively and consistently monitored.

•

Benzodiazepines, narcotic analgesics, and other drugs with potential for dependency should be used rarely and with great caution. Nearly all personality disorders are marked by impaired impulse control and consequent risk of addictive behavior.

•

Patients with personality disorder who have children should be asked frequently and in detail about their parenting practices. Their low frustration tolerance, externalization of blame for psychological distress, and impaired impulse control put the children of these patients at risk for neglect or abuse.

PATIENT/FAMILY EDUCATION

National Alliance for the Mentally Ill (NAMI), http://www.nami.org , provides patient information, on-line chat groups, and information on support groups throughout the U.S. for people with borderline personality disorder and their families. SUGGESTED READINGS American Psychiatric Association practice guidelines for the treatment of patients with BPD: http://www.psych.org/psych_pract/treatg/pg/borderline_revisebook_index.cfm . Clarkin JF, et al: Evaluating three treatments for BPD: a multiwave study. Am J Psychiatry 2007; 164:922. Conklin C, Westin D: Borderline personality disorder in clinical practice. Am J Psychiatry 2005; 162:867. Zanarini MC, et al: Prediction of the 10-year course of borderline personality disorder. Am J Psychiatry 2006; 163(5):827.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Botulism GLENN G. FORT, M.D., M.P.H.,, DENNIS J. MIKOLICH, M.D.,, MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Botulism is an illness caused by a neurotoxin produced by Clostridium botulinum. Three types of disease can occur: foodborne botulism, wound botulism, and infant intestinal botulism. Recent concern has increased about a possible fourth type of disease: inhalational botulism, which does not occur naturally, but may occur as a result of bioterrorism. SYNONYMS

Clostridium botulinum food poisoning Botulinum toxin food poisoning Wound botulism Infantile botulism

ICD-9CM CODE

005.1 Botulism EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.):Approximately 24 cases/yr of foodborne illness, 3 cases/yr of wound botulism, and 71 cases/yr of infant botulism PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms usually begin 12 to 36 hr following ingestion.

•

Severity of illness is related to the quantity of toxin ingested.

•

Significant findings:

•

1.

Cranial nerve palsies, with ocular and bulbar manifestations being most frequent (diplopia, ophthalmoplegia, ptosis, dysphagia, dysarthria, fixed and dilated pupils, and dry mouth)

2.

Usually bilateral nerve involvement that may progress to a descending flaccid paralysis

3.

Typically, absence of sensory findings; sensorium intact

4.

GI symptoms (nausea, vomiting, diarrhea, or cramps)

5.

Usually no fever

Wound botulism 1.

Occurs mostly in injecting drug users (subcutaneous heroin injection—“skin popping”) or with traumatic injury.

2.

Presentation is similar to that of foodborne disease, except for a longer incubation period and the absence of GI symptoms.

3.

Wound infection is not always apparent, but injection sites frequently reveal cellulitis, draining pus, or abscess formation.

ETIOLOGY

•

Cause is one of several types of neurotoxins (usually A, B, or E) produced by C. botulinum, an anaerobic, gram-positive bacillus. Spore production guarantees survival of the organism in extreme conditions. Botulinum toxin is the most powerful neurotoxin known.

•

Disease results from absorption of toxin into the circulation from a mucosal surface or wound. Botulinum toxin does not penetrate intact skin.

•

In foodborne variety, disease is caused by ingestion of preformed toxin. Although rapidly inactivated by heat, the toxin can survive the proteolytic environment of the stomach.

•

In wound botulism, toxin is elaborated by organisms that contaminate a wound. Most cases reported are from California.

•

In infant botulism, toxin is produced by organisms in the GI tract.

•

Inhalational botulism has been demonstrated experimentally in primates. This manufactured form results from aerosolized toxin, and has been attempted by bioterrorists.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Myasthenia gravis

•

Guillain-Barré syndrome

•

Tick paralysis

•

CVA

WORKUP

•

Search made for toxin and the organism (see “Laboratory Tests”)

•

Electrophysiologic studies (EMG) may aid in the diagnosis

LABORATORY TESTS

•

Samples of food and stool are cultured for the organism.

•

Food, serum, and stool are sent for toxin assay.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Supportive care with intubation if respiratory failure occurs

•

Debridement of the wound in wound botulism

ACUTE GENERAL Rx

•

Give trivalent equine serum botulinum antitoxin as early as possible. Once a clinical diagnosis is made, antitoxin should be administered before laboratory confirmation. 1.

Give one vial by IM injection and one vial IV.

2.

The antitoxin is available from the Centers for Disease Control and Prevention [(404) 639-2206 or (404) 639-2888]; it is derived from horse serum, so there is a significant incidence of serum sickness. A human-derived antitoxin immunoglobin is now available for infants less than 1 yr of age (BIG-IV).

3.

Skin testing (conjunctival instillation and observation for 15 min), and possible desensitization, is recommended before treatment.

•

Give wound botulism patients penicillin 2 million U IV q4h.

•

Babies with infantile intestinal botulism may benefit from a cathartic to mechanically clear the number of C. botulinum vegetative forms and spores residing in the gastrointestinal tract.

CHRONIC Rx

•

Supportive

•

Rehabilitation/physical therapy

DISPOSITION

•

Highest mortality in the first case in an outbreak, with subsequent cases receiving rapid treatment

•

Complete recovery for most individuals (this may take several weeks in severely affected individuals)

REFERRAL

Immediate for all cases to an ER and an infectious disease consultant

PEARLS & CONSIDERATIONS COMMENTS

•

Routine cooking inactivates the toxin, but spores are resistant to environmental factors. At room temperature, spores can germinate and produce toxin.

•

Most outbreaks are associated with home-canned foods, especially vegetables.

•

Patients must be closely monitored for progression to respiratory paralysis.

•

There is increasing concern over the potential use of botulinum toxin as a biologic weapon, either by the enteric route or by aerosolization.

•

Notify public health authorities immediately to alert other health care services of possible additional cases and to initiate investigation into cause and scope of outbreak.

•

Recent botulism food recalls have involved canned chili, cut green beans, and olives.

SUGGESTED READINGS Amon SS, et al: Botulinum toxin as a biological weapon. JAMA 2001; 285(8):1059. Arnon SS, et al: Human botulism immune globulin for the treatment of infant botulism. N Engl J Med 2006; 354(5):462. Bleck TP: Clostridium botulinum (botulism). In: Mandell GL, Bennett JE, Dolin R, ed. Principles and practice of infectious diseases, ed 5. New York: Churchill Livingstone; 2000. Cherington M: Botulism: update and review. Semin Neurol 2004; 24:155. Sobel J: Botulism. Clin Infect Dis 2005; 41(8):1167.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Brain Neoplasm NICOLE J. ULLRICH, M.D., PH.D.

BASIC INFORMATION DEFINITION

Brain neoplasms are a diverse group of primary (nonmetastatic) tumors arising from one of many different cell types within the central nervous system (CNS). Specific tumors' subtypes and prognosis depend on the tumor cell of origin and pattern of growth. SYNONYMS

Brain tumors Primary tumors of the central nervous system

ICD-9CM CODES

225.0 Brain neoplasm (benign) 239.2 Brain neoplasm (unspecified) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Approximately 8 cases/100,000 persons/yr. In 2002, the Central Brian Tumor Registry data estimated approximately 41,130 new cases of both malignant and benign brain tumors in the U.S. in 2004. Primary brain neoplasms account for~2% of all cancers,~20% of all cancers in children >15 yr. Most common cause of cancer death in children up to 15 yr. PREDOMINANT SEX:Male:female=3:2; except for meningiomas: female:male = 3:1. PREDOMINANT AGE:Male: 75+ yr; female: 65 to 74 yr. GENETICS: Most primary CNS neoplasms are sporadic; 5% are associated with hereditary syndromes that predispose to neoplasia. The most common of these include:

•

Li-Fraumeni syndrome: p53 mutation on chromosome 17q13, gliomas

•

Von Hippel-Lindau: VHL, chromosome 3p25, hemangioblastoma

•

Tuberous sclerosis: TSC1/TSC2 (chromosome 9q34/16p13), subependymal giant cell astrocytoma

•

Neurofibromatosis type 1: NF1, chromosome 17q11, neurofibroma, optic nerve glioma, meningioma

•

Neurofibromatosis type 2: NF2, chromosome 22q12, schwannoma, meningioma, ependymoma

•

Retinoblastoma: pRB, chromosome 13q, retinoblastoma

•

Gorlin's syndrome: chromosome 9q31, desmoplastic medulloblastoma

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

In general, the location, size, and rate of growth will determine the symptoms and signs. Even within a tumor subtype, clinical presentation may vary. Brain tumors can produce signs and symptoms related to local invasion, compression of adjacent structures, and increased intracranial pressure.

•

Headache is a common problem; this may be a presenting symptom in 20% and develops later in 60%. The headache can be localizing or may result from increased intracranial pressure, and may worsen with change in body position, such as bending over, or coughing/sneezing/Valsalva-type maneuvers. Concerning features of headaches include nausea and vomiting, change in typical headache pattern, worsening with position, and vertex location. Headaches with brain tumors tend to be worse during the night and may awaken the patient. The nocturnal pattern may be related to increased pCO 2 levels during sleep, which acts as a potent vasodilator.

•

Seizures occur in 33% of patients, and are among the most common symptoms, particularly with brain metastases and low-grade gliomas. The type of seizure and clinical presentation depends on location. Seizures are more common in low-grade compared to high-grade gliomas. Tumor-related seizures are often repetitive and stereotypical in a given patient. It is thought that patients who present with seizures typically have smaller tumors at time of diagnosis compared to those who present with other symptoms, because the onset of seizures prompts an imaging study, leading to an earlier diagnosis.

•

Symptoms and signs of hydrocephalus and raised intracranial pressure (headache, vomiting [particularly in children], clouding of consciousness, papilledema). Extremity weakness or sensory changes are common complaints in patients with brain tumors. These symptoms often respond to high-dose steroids, meaning that the weakness is caused by edema more likely than direct tumor involvement.

•

Patients may also present with subtle behavioral changes or cognitive and visual-spatial dysfunction. These symptoms are often recognized in retrospect and may be quite subtle. The pattern of these symptoms can be confused with depression.

ETIOLOGY

•

Most cases are idiopathic, though specific chromosomal abnormalities have been implicated in some tumor types.

•

Exposure to ionizing radiation has been implicated in meningiomas, gliomas, and nerve sheath tumors. No convincing evidence has shown a link with trauma, occupation, diet, or electromagnetic fields.

DIAGNOSIS

•

Most common tumors in children: astrocytoma, medulloblastoma, ependymoma

•

Most common adult tumors: glioblastoma multiforma, anaplastic astrocytoma, meningioma

DIFFERENTIAL DIAGNOSIS

•

Stroke

•

Abscess/parasitic cyst

•

Demyelinating disease—multiple sclerosis, postinfectious encephalomyelitis

•

Metastatic tumors

•

Primary CNS lymphoma

LABORATORY TESTS

•

Cerebrospinal fluid (CSF) analysis for measurement of tumor markers and cytology may yield tumor cells for histology.

•

Lumbar puncture must never be performed if there is concern for increased intracranial pressure.

IMAGING STUDIES ( Fig. 1-39 )

•

MRI with gadolinium enhancement is highly sensitive, though CT scan is useful if calcification or hemorrhage suspected. MRI imaging permits visualization of the tumor as well as the relationship to the surrounding tissue. Enhancing tumor can be distinguished from surrounding edema. Low-grade tumors often present as an infiltrating lesion without mass effect. MRI is superior to CT scan to evaluate the meninges, subarachnoid space, and posterior fossa, and for defining relationship to major intracranial vessels.

•

MR spectroscopy is increasingly being used as a diagnostic tool to define metabolic composition of an area of interest and may be useful to contrast areas of tumor progression from radiation necrosis. Nacetylaspartate is often decreased in brain tumors, whereas choline, a component of cell membranes, is increased due to high cellular turnover.

•

PET scan is helpful to distinguish neoplastic lesions (with high rate of metabolism) from other lesions such as demyelination or radiation necrosis (with a much lower metabolic rate). Such lesions take up greater amounts of glucose than surrounding tissues or tumors with slower metabolic rates. May be useful to help map functional areas of the brain before surgery or radiation.

•

Functional MRI is now used as an adjunct to perioperative planning for patients whose lesion is in vital regions, such as those responsible for speech, language, and motor control.

FIGURE 1-39 Glioblastoma multiforme. Axial (A) and coronal (B) postcontrast enhanced T1-weighted image showing a large homogenously contrast-enhancing mass in the right medial temporal lobe with extension across the midline. (From Specht N [ed]: Practical guide to diagnostic imaging, St Louis, 1998, Mosby.)

PATHOLOGY

•

Ultimately, only a histologic examination can provide the exact diagnosis. Information may also be gleaned from additional features such as proliferative index, immunohistochemical stains, and electron microscopy.

•

The present classification schema for gliomas is based on pathologic and microscopic criteria.

•

Molecular classification: Different subtypes of gliomas have distinct gene-expression profiles, which can be distinguished from one another and from normal tissue; these differences typically involve pathways of cell proliferation, energy metabolism, and signal transduction. In adults, global expression profiling identified differences in 360 genes between low-grade and high-grade tumors. Epidermal growth factor receptor gene (EGFR) amplification is the most frequent genetic change in adult high-grade glioma and is considered a negative prognostic marker. Mutation of the P53 and PTEN pathways are also relatively frequent.

•

Genetic analysis of tumors is rapidly becoming important for genetic classification and stratification of treatments and for predicting outcome.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Maximal surgical removal or debulking is the initial treatment of choice. Outcome is often dependent on extent of resection.

•

Biopsy alone is performed if the tumor is located in eloquent regions of brain or is inaccessible; this is essential for histopathologic diagnosis. Biopsy can be performed under CT or MRI guidance using stereotactic localization.

•

If the tumor is benign (e.g., meningioma, acoustic neuroma), no further therapy is usually required.

ACUTE GENERAL Rx

•

Steroids are used to reduce edema and may also be used perioperatively or during radiation therapy.

•

Antiseizure medications have been used perioperatively and to control seizures resulting from focal lesions. Prophylactic use of anticonvulsants is not typically recommended without clear history of seizures.

CHRONIC Rx

•

Current standard-of-care therapies include surgery, radiation, and palliative chemotherapy, which have significant side effects and limited efficacy.

•

Chemotherapy (combination or single agent) may be used before, during, or after surgery and radiation therapy. (In children, chemotherapy is often used to delay radiation therapy.) Radiosensitizers may help increase the therapeutic effect of radiation therapy.

•

Radiation is useful for certain types of tumors: Conventional radiation uses external beams over a period of weeks, whereas stereotactic radiosurgery delivers a single, high dose of radiation to a well-defined area (usually 25%) and associated coronary atherosclerosis (angina, ECG changes, reversible defects on thallium scan) may benefit from surgical revascularization.

DISPOSITION

•

Annual mortality is 20% in patients with moderate heart failure, and it exceeds 50% in patients with severe heart failure.

•

The implantation of a cardioverterdefibrillator in patients with severe, nonischemic dilated cardiomyopathy already being treated with ACE inhibitors and ß-blockers significantly reduces the risk of sudden death from arrhythmia.

REFERRAL

Consider heart transplant for young patients (>60 yr old) who are no longer responsive to medical therapy. Dilated cardiomyopathy is the cause of 45% of heart transplantations.

PEARLS & CONSIDERATIONS COMMENTS

•

Patients should be encouraged to restrict or eliminate alcohol and decrease sodium intake.

•

Vulnerability to cardiomyopathy among chronic alcohol abusers is partially genetic and is related to the presence of angiotensin-converting-enzyme (ACE) DD genotype.

•

Idiopathic dilated cardiomyopathy is often familial, and apparently, healthy relatives may have latent, early, or undiagnosed established disease. Echocardiographic evaluation of family members is recommended.

SUGGESTED READINGS Kadish A, et al: Prophylactic defibrillator implantation in patients with non-ischemic dilated cardiomyopathy. N Engl J Med 2004; 350:2151. Mahon NG, et al: Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease. Ann Intern Med 2005; 143:108.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cardiomyopathy, Hypertrophic FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cardiomyopathies are a group of diseases primarily involving the myocardium and characterized by myocardial dysfunction that is not the result of hypertension, coronary atherosclerosis, valvular dysfunction, or pericardial abnormalities. In hypertrophic cardiomyopathy (HCM) there is marked hypertrophy of the myocardium and disproportionally greater thickening of the intraventricular septum than that of the free wall of the left ventricle (asymmetric septal hypertrophy [ASH]). SYNONYMS

Idiopathic hypertrophic subaortic stenosis (IHSS) Hypertrophic obstructive cardiomyopathy (HOCM) ASH HCM

ICD-9CM CODES

425.4

Cardiomyopathy, hypertrophic nonobstructive

425.1

Cardiomyopathy, hypertrophic obstructive

746.84 Cardiomyopathy, hypertrophic congenital EPIDEMIOLOGY & DEMOGRAPHICS

•

The disease occurs in two major forms: 1.

A familial form, usually diagnosed in young patients and gene mapped to chromosome 14q. It is caused by a missense mutation in 1 of at least 10 genes that encode the proteins of the cardiac sarcomere (0% of cases of hypertrophic cardiomyopathy are familial).

2.

A sporadic form, usually found in elderly patients.

•

The prevalence of phenotypically expressed HCM in the adult general population is 0.2% (most common genetic cardiovascular disease) and manifests with massive hypertrophy involving primarily the ventricular septum.

•

To date, more than 200 different hypertrophic cardiomyopathy–causing mutations have been reported.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

•

Hypertrophic cardiomyopathy may be suspected on the basis of abnormalities found on physical examination. Classic findings include: 1.

Harsh, systolic, diamond-shaped murmur at the left sternal border or apex that increases with Valsalva maneuver and decreases with squatting

2.

Paradoxic splitting of S2 (if left ventricular obstruction is present)

3.

S4

4.

Double or triple apical impulse

Increased obstruction can occur with: 1.

Drugs: digitalis, ß-adrenergic stimulators (isoproterenol, dopamine, epinephrine), nitroglycerin, vasodilators, diuretics, alcohol

2.

Hypovolemia

3.

Tachycardia

4.

Valsalva maneuver

5.

Standing position

Decreased obstruction is seen with: 1.

Drugs: ß-adrenergic blockers, calcium channel blockers, disopyramide, a-adrenergic stimulators

2.

Volume expansion

3.

Bradycardia

4.

Hand grip exercise

5.

Squatting position

Clinical manifestations are as follows: 1.

Dyspnea

2.

Syncope (usually seen with exercise)

3.

Angina (decreased angina in recumbent position)

4.

Palpitations

ETIOLOGY

•

Autosomal dominant trait with variable penetrance caused by mutations in any of 1 to 10 genes, each encoding proteins of cardiac sarcomere

•

Sporadic occurrence

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Coronary atherosclerosis

•

Valvular dysfunction

•

Pericardial abnormalities

•

Chronic pulmonary disease

•

Psychogenic dyspnea

WORKUP

•

The diagnosis can be confirmed by two-dimensional echocardiography. Continuous-wave Doppler echocardiography can be used to diagnose obstruction.

•

ECG is abnormal in 75% to 95% of patients: left ventricular hypertrophy, abnormal Q waves in anterolateral and inferior leads.

•

24-hr Holter monitor to screen for potential lethal arrhythmias (principal cause of syncope or sudden death in obstructive cardiomyopathy) should be performed initially and annually.

•

Exercise testing is indicated and can also provide prognostic information and should also be considered on an annual basis.

IMAGING STUDIES

•

Chest x-ray: may be normal or may show cardiomegaly.

•

Two-dimensional echocardiography is used to establish the diagnosis. Findings include: ventricular hypertrophy, ratio of septum thickness to left ventricular wall thickness >1.3:1, increased ejection fraction.

•

Magnetic resonance imaging may be of diagnostic value when echocardiographic studies are technically inadequate. MRI is also useful in identifying segmental LVH undetectable by echocardiography.

TREATMENT NONPHARMACOLOGIC THERAPY

Advise avoidance of alcohol; alcohol use (even in small amounts) results in increased obstruction of the left ventricular outflow tract. Patients should also be advised on avoidance of dehydration and strenuous exertion. GENERAL Rx

•

Therapy for hypertrophic cardiomyopathy is directed at blocking the effect of catecholamines that can exacerbate dynamic left ventricular outflow tract obstruction and avoidance of certain agents (e.g., vasodilator or diuretic agents), which can worsen the obstruction.

•

Propranolol 160 to 240 mg/day. The beneficial effects of ß-blockers on symptoms (principally dyspnea and chest pain) and exercise tolerance appear to be largely a result of a decrease in the heart rate with consequent prolongation of diastole and increased passive ventricular filling. By reducing the inotropic response, ß-blockers may also lessen myocardial oxygen demand and decrease the outflow gradient during exercise, when sympathetic tone is increased.

•

Verapamil also decreases left ventricular outflow obstruction by improving filling and probably reducing myocardial ischemia. It is used mainly as a second line agent in patients who cannot tolerate ß-blockers. It should be used with caution in patients with symptomatic obstruction. Administration in the hospital setting is recommended in these patients.

•

IV saline infusion in addition to propranolol or verapamil is indicated in patients with CHF.

•

Disopyramide is a useful antiarrhythmic because it is also a negative inotrope resulting in further decrease in outflow gradient.

•

Use antibiotic prophylaxis for surgical procedures.

•

Avoid use of digitalis, diuretics, nitrates, and vasodilators.

•

Encouraging results have been reported on the use of DDD pacing for hemodynamic and symptomatic benefit in patients with drug-resistant hypertrophic obstructive cardiomyopathy. Implantation of a dualchamber pacemaker has not been shown to result in significant improvement in objective measures of exercise capacity.

•

Implantable cardiac defibrillators (ICD) are a safe and effective therapy in HCM patients prone to ventricular arrhythmias. Their use is strongly warranted for patients with prior cardiac arrest or sustained spontaneous ventricular tachycardia. The use of ICD to prevent sudden death in HCM has been advocated by some cardiologists not only for patients with HCM who are at high risk but also in others with a single risk factor.

DISPOSITION

HCM is not a static disease. Some adults may experience subtle regression in wall thickness while others (approximately 5% to 10%) paradoxically evolve into an end stage resembling dilated cardiomyopathy and characterized by cavity enlargement, LV wall thinning, and diastolic dysfunction. Patients with HCM are at increased risk of sudden death, especially if there is onset of symptoms during childhood. Left ventricular outflow at rest is also a strong, independent predictor of severe symptoms of heart failure and of death. Adult patients can be considered low risk if they have no symptoms or mild symptoms and also if they have none of the following: •

A family history of premature death caused by hypertrophic cardiomyopathy

•

Nonsustained ventricular tachycardia during Holter monitoring

•

A marked outflow tract gradient

•

Substantial hypertrophy (>20 mm)

•

Marked left atrial enlargement

•

Abnormal blood pressure response during exercise

REFERRAL

•

Surgical treatment (myotomy-myectomy involving resection of the basal septum) is reserved for patients who have both a large outflow gradient (=50 mm Hg) and severe symptoms of heart failure that are unresponsive to medical therapy. The risk of sudden death from arrhythmias is not altered by surgery. When this operation is performed by experienced surgeons in tertiary referral centers the operative mortality is >2% and many patients are able to achieve near normal exercise capacity postoperatively.

•

Nonsurgical reduction of interventricular septum represents a controversial therapeutic approach that can be used in patients with HCM refractory to pharmacologic treatment. This technique involves the injection of ethanol in the septal perforator branch of the left anterior descending coronary artery, producing a controlled myocardial infarction of the interventricular septum and thereby reducing the left ventricular outflow tract gradient. This method may lead to improvement in both subjective and objective measures of exercise capacity but is associated with a high incidence of heart block, often requiring permanent pacing in about one fourth of patients.

PEARLS & CONSIDERATIONS COMMENTS

•

Screening of first-degree relatives with two-dimensional echocardiography and electrocardiography is indicated, particularly if adverse HCM-related events have occurred in the family. Annual screening is recommended for all adolescents from age 12 to 18. Periodic screening of all first-degree adult family members at 5-year intervals is recommended since hypertrophy may not be detected until the sixth decade of life. It is advisable to have a trained clinical genetic counselor see the patient and obtain consent before genetic testing.

•

Future screening techniques may involve identification of mutations in the gene encoding the sarcomeric proteins. The most common sarcomeric subtype is MYBPC3-HCM affecting 1 in 5 patients. Clinical predictors of positive genotype, such as the presence of an implantable cardioverter-defibrillator, age at diagnosis, degree of left ventricular wall hypertrophy, and family history of HCM, may aid in patient selection for genetic testing and increase the yield of cardiac sarcomere gene screening.

•

Mortality rate in HCM is approximately 1% to 2%.

•

It is important to remember that HCM is predominantly a non-obstructive disease (75% of patients do not have a sizable resting outflow tract gradient).

•

Patients should be instructed on need for bacterial endocarditis prophylaxis.

•

Section III describes an algorithm for the management of symptoms and risk in patients with hypertrophic cardiomyopathy.

SUGGESTED READINGS Maron BJ: Hypertrophic cardiomyopathy, a systematic review. JAMA 2002; 287:1308. Maron BJ, et al: Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298(4):405. Maron MS, et al: Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003; 348:295. Nishimura RA, Holmes DR: Hypertrophic obstructive cardiomyopathy. N Engl J Med 2004; 350:1320. Shamim W, et al: Nonsurgical reduction of the interventricular septum in patients with hypertrophic cardiomyopathy. N Engl J Med 2002; 347:1326. VanDriest SL, et al: Yield of genetic testing in hypertrophic cardiomyopathy. Mayo Clin Proc 2005; 80(6):739.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cardiomyopathy, Restrictive RAMI ELTIBI, M.D., WEN-CHIH WU, M.D.

BASIC INFORMATION DEFINITION

Cardiomyopathies are a group of diseases primarily involving the myocardium and characterized by myocardial dysfunction that is not the result of hypertension, coronary atherosclerosis, valvular dysfunction, or pericardial abnormalities. Restrictive cardiomyopathies are characterized by decreased ventricular compliance, usually secondary to infiltration of the myocardium. These patients have impaired ventricular filling and reduced diastolic volume, normal systolic function, and normal or near-normal myocardial thickness.

ICD-9CM CODES

425.4 Other primary cardiomyopathies EPIDEMIOLOGY & DEMOGRAPHICS

•

Relatively uncommon cardiomyopathy that is most frequently caused by amyloidosis ( Fig. 1-44 ), myocardial fibrosis (after open heart surgery), and radiation.

•

Many patients classified as having “idiopathic” restrictive cardiomiopathy may have mutations in the gene for cardiac troponin I, and restrictive cardiomyopathy may represent an overlap with hypertrophic cardiomyopathy in many familial cases.

FIGURE 1-44 A necropsy specimen of an amyloid heart demonstrating the thickened ventricular septum (VS), atrial septum (AS), and free wall of the left ventricle (LV) and right ventricle (RV), and the dilated left atrium (LA). RA, Right atrium. (Courtesy Dr. William Edwards, Mayo Clinic, Rochester, MN. In Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders.)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Restrictive cardiomyopathy presents with symptoms of progressive left-sided and right-sided heart failure: •

Edema, ascites, hepatomegaly, distended neck veins

•

Fatigue, weakness (secondary to low output)

•

Kussmaul's sign: may be present

•

Regurgitant murmurs

•

Possible prominent apical impulse

ETIOLOGY

•

Infiltrative and storage disorders (glycogen storage disease, amyloidosis, sarcoidosis, hemochromatosis)

•

Scleroderma

•

Radiation

•

Endocardial fibroelastosis

•

Endomyocardial fibrosis

•

Idiopathic

•

Toxic effects of anthracycline

•

Carcinoid heart disease, metastatic cancers

•

Diabetic cardiomyopathy

•

Eosinophilic cardiomyopathy (Löffler's endocarditis)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Coronary atherosclerosis

•

Valvular dysfunction

•

Pericardial abnormalities

•

Chronic lung disease

•

Psychogenic dyspnea

WORKUP

•

Chest x-ray, ECG, echocardiogram

•

Cardiac catheterization, MRI (selected cases)

IMAGING STUDIES

•

•

Chest x-ray: 1.

Moderate cardiomegaly

2.

Possible evidence of CHF (pulmonary vascular congestion, pleural effusion)

ECG: 1.

Low voltage with ST-T wave changes

2.

Possible frequent arrhythmias, left axis deviation, and atrial fibrillation

•

Echocardiogram: increased wall thickness and thickened cardiac valves (especially in patients with amyloidosis)

•

Cardiac catheterization to distinguish restrictive cardiomyopathy from constrictive pericarditis 1.

Constrictive pericarditis: usually involves both ventricles and produces a plateau of elevated filling pressures

2.

Restrictive cardiomyopathy: impairs the left ventricle more than the right (PCWP > RAP, PASP >50 mm Hg)

TREATMENT

•

MRI may also be useful to distinguish restrictive cardiomyopathy from constrictive pericarditis (thickness of the pericardium >5 mm in the latter)

TREATMENT NONPHARMACOLOGIC THERAPY

Control CHF by restricting salt. ACUTE GENERAL Rx

•

Cardiomyopathy caused by hemochromatosis may respond to repeated phlebotomies to decrease iron deposition in the heart.

•

Sarcoidosis may respond to corticosteroid therapy.

•

Corticosteroid and cytotoxic drugs may improve survival in patients with eosinophilic cardiomyopathy.

•

There is no effective therapy for other causes of restrictive cardiomyopathy.

CHRONIC Rx

Death usually results from CHF or arrhythmias; therefore therapy should be aimed at controlling CHF by restricting salt, administering diuretics, and treating potentially fatal arrhythmias. DISPOSITION

Prognosis varies with the etiology of the cardiomyopathy. REFERRAL

Cardiac transplantation can be considered in patients with refractory symptoms and idiopathic or familial restrictive cardiomyopathies. AUTHOR: FRED F. FERRI, M.D. Carotid Sinus Syndrome

BASIC INFORMATION DEFINITION

Light-headedness, dizziness, presyncope, or syncope in a patient with carotid sinus hypersensitivity is defined as carotid sinus syndrome (CSS). Carotid sinus hypersensitivity is the exaggerated response to carotid stimulation resulting in bradycardia, hypotension, or both. SYNONYMS

Carotid sinus syncope CSS

Carotid sinus hypersensitivity

ICD-9CM CODES

337.0 Idiopathic peripheral autonomic neuropathy 780.2 Syncope or collapse EPIDEMIOLOGY & DEMOGRAPHICS

•

Carotid sinus hypersensitivity accounts for 10% to 20% of presyncopal and syncopal episodes.

•

Carotid sinus hypersensitivity is frequently associated with atherosclerosis and diabetes mellitus.

•

The incidence increases with age, with an average age of 61 to 74 yr.

•

Men are affected more often than women (2:1).

•

Carotid sinus syndrome is rarely found in patients younger than 50 yr of age.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usually associated with sudden neck movements or tight-fitting collars

•

Usually associated with prodrome of nausea, warmth, pallor, or diaphoresis

•

Light-headedness or presyncopal symptoms

•

Syncope

Properly performed carotid sinus massage (CSM) at the bedside is diagnostic. This maneuver can elicit three types of responses in patients with carotid sinus hypersensitivity (see “Diagnosis”). 1.

CSM should be performed in the supine and upright positions while monitoring the patient's blood pressure by cuff and heart rate by ECG.

2.

CSM should be performed on only one artery at a time.

3.

CSM should be applied for approximately 5 to 10 seconds and repeated on the opposite side if no effect is produced.

4.

Contraindications to CSM include the presence of carotid artery bruits, documented carotid artery stenosis >70%, history of stroke or transient ischemic attack >3 months, history of myocardial infarction >6 months, history of serious cardiac arrhythmias, or prior carotid endarterectomy.

5.

Complications of visual disturbance and transient paresis from CSM occur in less than 1% of patients.

ETIOLOGY

•

Idiopathic

•

Head and neck tumors (e.g., thyroid)

•

Significant lymphadenopathy

•

Carotid body tumors

•

Prior neck surgery

DIAGNOSIS

•

Screening must be performed by doctors experienced with the maneuver and monitoring of the patient.

•

The diagnosis of CSS is made when carotid sinus hypersensitivity is demonstrated by CSM and no other cause of syncope is identified.

•

CSM can elicit three types of responses that are diagnostic of carotid sinus hypersensitivity: 1.

Cardioinhibitory type: CSM producing (1) asystole for at least 3 seconds in the absence of symptoms or (2) reproduction of symptoms occurring with a decline in heart rate of 30% to 40% or asystole of up to 2 seconds in duration. Symptoms should not recur when CSM is repeated after atropine infusion.

2.

Vasodepressor type: CSM producing (1) a decrease in systolic blood pressure of 50 mm Hg in absence of symptoms, or 30 mm Hg in the presence of neurologic symptoms; (2) no evidence of asystole; and (3) neurologic symptoms that persist after infusion of atropine.

3.

Mixed type: CSM producing both types of responses.

DIFFERENTIAL DIAGNOSIS

All causes of syncope WORKUP

•

It is a diagnosis of exclusion.

•

Exclude other causes of syncope or presyncope: history and physical examination. Other tests should be ordered depending on the clinical setting.

TREATMENT NONPHARMACOLOGIC THERAPY

Avoid applying neck pressure from tight collars, shaving, or rapid head turning. ACUTE GENERAL Rx

Treatment will vary according to the type of carotid hypersensitivity response and symptoms present (see “Chronic Rx”). CHRONIC Rx

Therapy is divided into three classes: medical, surgical (carotid denervation), and cardiac pacing. Surgical therapy has been largely abandoned except in cases of compressing tumors or masses that are responsible for CSS. For infrequent and mildly symptomatic carotid sinus hypersensitivity of either the cardioinhibitory or vasodepressor type, treatment is generally not necessary. For symptomatic patients with a cardioinhibitory response to CSM:

•

A dual-chamber permanent pacemaker is a class I indication.

For symptomatic patients with a vasodepressor response to CSM: •

Sympathomimetics: midodrine 2.5 to 10 mg tid

•

Serotonin reuptake inhibitors

•

Fludrocortisone

•

Elastic knee-high or thigh-high stockings

•

Carotid sinus denervation

For symptomatic patients with CSS with a mixed response to CSM: •

Combination of dual-chamber permanent pacemaker, atropine, and agents used to treat vasodepressor response.

DISPOSITION

•

Up to 50% of the patients will have recurrent symptoms.

•

No increased mortality of patients with idiopathic CSS when compared with the general population.

REFERRAL

Cardiology referral is indicated if a pacemaker is considered.

PEARLS & CONSIDERATIONS The most common type is cardioinhibitory, followed by mixed and vasodepressor responses. COMMENTS

Prognosis depends on the underlying cause. SUGGESTED READINGS AHA/ACCF scientific statement on the evaluation of syncope. J Am Coll Cardiol 2006; 47(2):473. Brignole M, et al: Task Force on Syncope, European Society of Cardiology, Guidelines on management (diagnosis and treatment) of syncope—update 2004. Europace 2004; 6:467. Grubb BP: Clinical practice: neurocardiogenic syncope. N Engl J Med 2005; 352:1004. Kerr SR, et al: Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls. Arch Intern Med 2006; 166(5):515.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Carpal Tunnel Syndrome LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Carpal tunnel syndrome is an entrapment neuropathy involving the median nerve at the wrist ( Fig. 1-45 ). It is the most common entrapment neuropathy in the upper extremity.

FIGURE 1-45 Distribution of pain and/or paresthesias (dark-shaded area) when the median nerve is compressed by swelling in the wrist (carpal tunnel). (From Arnett FC: Rheumatoid arthritis. In Andreoli TE [ed]: Cecil essentials of medicine, ed 4, Philadelphia, 1997, WB Saunders.)

ICD-9CM CODES

354.0 Carpal tunnel syndrome EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENT AGE: 30 to 60 yr (bilateral up to 50%) PREVALENT SEX: Females are affected two to five times as often as males PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Nocturnal pain

•

Occasional median nerve sensory impairment (often only index and long fingers)

•

Positive Tinel's sign at wrist (tapping over the median nerve on the flexor surface of the wrist produces a tingling sensation radiating from the wrist to the hand)

•

Positive Phalen's test (reproduction of symptoms after 1 min of gentle, unforced wrist flexion)

•

Carpal compression test: Pressure with the examiner's thumb over the patient's carpal tunnel for 30 sec elicits symptoms

•

Thenar atrophy in long-standing cases

ETIOLOGY

•

Idiopathic in most cases

•

Space-occupying lesions in carpal tunnel (tenosynovitis, ganglia, aberrant muscles)

•

Often associated with hypothyroidism, hormonal changes of pregnancy

•

Job-related mechanical overuse may be a risk factor

•

Traumatic injuries to wrist

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Cervical radiculopathy

•

Chronic tendinitis

•

Vascular occlusion

•

Reflex sympathetic dystrophy

•

Osteoarthritis

•

Other arthritides

•

Other entrapment neuropathies

IMAGING STUDIES

Routine roentgenograms may be helpful in establishing cause or ruling out other conditions. ELECTRODIAGNOSTIC STUDIES

Nerve conduction velocity tests and electromyography are useful in establishing the diagnosis and ruling out other syndromes.

TREATMENT ACUTE GENERAL Rx

•

Elimination of repetitive trauma

•

Occupational splints or braces

•

NSAIDs

•

Injection of carpal canal on ulnar side of palmaris longus tendon at wrist flexor crease (avoiding median nerve)

•

Low-dose oral corticosteroids (e.g., prednisolone 20 mg qd for 2 wk, followed by 10 mg qd for 2 more wk) are also effective for symptom relief in selected patients

•

Stretching exercises

DISPOSITION

Prognosis is variable. Some cases resolve spontaneously. Relief from local injection appears transient and symptoms recur in the majority of cases following injection. Carpal tunnel syndrome is common in the third trimester of pregnancy, but symptoms subside after delivery in most cases, often dramatically. Symptoms may recur with subsequent pregnancies. Surgery is not recommended in pregnant patients because of the likelihood of spontaneous recovery. REFERRAL

Surgical referral in cases of failed medical management or signs of motor weakness. Results of surgery usually excellent with return to full activity in 4 to 6 weeks.

PEARLS & CONSIDERATIONS

•

Carpal tunnel syndrome may occur in conjunction with cervical nerve root compression, a situation sometimes termed “double-crush syndrome.” It has been suggested that compression at a more proximal level may decrease the ability of the nerve to tolerate distal compression.

•

Whether computer keyboard use is a risk factor is controversial.

EVIDENCE

Local corticosteroid injections have been shown to be effective for the treatment of carpal tunnel syndrome in the short term. [37] [38] A single injection of methylprednisolone is no more effective than an oral anti-inflammatory plus nocturnal neutral wrist splints in relieving symptoms at 2 weeks.[[1]] A single local methylprednisolone injection reduces symptoms at 8 and 12 weeks compared with oral prednisolone given for 10 days. [[3]] Full time use of a neutral-angle wrist splint has not been shown to be superior to nighttime only use for improving mean symptom severity score [[4]] Ultrasound plus nocturnal wrist splints and chiropractic manipulation were compared with nocturnal wrist splints and NSAIDs in an RCT of patients with carpal tunnel syndrome. After 9 weeks there was no significant difference in symptom severity between the groups.[[5]] Vitamin B6 does not significantly improve overall symptoms compared with placebo.[[6]]

Evidence-Based References 1. Marshall S, Tardif G, Ashworth N: Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database Syst Rev 2002; 4:CD001554, 2. O'Gradiagh D, Merry P: Corticosteroid injection for the treatment of carpal tunnel syndrome. Ann Rheum Dis 2000; 59:918. 3. Wong SM, et al: Local vs systemic corticosteroids in the treatment of carpal tunnel syndrome. Neurology 2001; 56:1565.Reviewed in: Clin Evid 10:1271, 2003. 4. Walker WC, et al: Neutral wrist splinting in carpal tunnel syndrome: a comparison of night-only versus full-time wear instructions. Arch Phys Med Rehabil 2000; 81:424.Reviewed in: Clin Evid 10:1271, 2003.

5. Davis PT, et al: Comparative efficacy of conservative medical and chiropractic treatments for carpal tunnel syndrome: a randomized clinical trial. J Manipulative Physiol Ther 1998; 21:317.Reviewed in: Clin Evid 10:1271, 2003. 6. Gerritsen AAM, et al: Conservative treatment options for carpal tunnel syndrome: a systematic review of randomised controlled trials. J Neurol 2002; 249:272.Reviewed in: Clin Evid 10;1271, 2003.

SUGGESTED READINGS

Atroshi I, et al: Carpal tunnel syndrome and keyboard use at work: a population-based study. Arthritis Rheum 2007; 56:3620. Burke FD, et al: Primary care management of patients with carpal tunnel syndrome referred to surgeons: are non-operative interventions effectively utilized?. Postgrad Med J 2007; 83:498. Cranford CS, et al: Carpal tunnel syndrome. J Am Acad Orthop Surg 2007; 15:537. Dias JJ, Burke FD, et al: Carpal Tunnel Syndrome and work. J Hand Surg 2004; 29:329. Geoghegan JM, Clark DI, et al: Risk factors in carpal tunnel syndrome. J Hand Surg 2004; 29:315. Gerritsen AM, et al: Splinting vs surgery in the treatment of carpal tunnel syndrome. JAMA 2002; 288:1245. Goodyear-Smith F, Arroll B: What can family physicians offer patients with carpal tunnel syndrome other than surgery? A systematic review of nonsurgical management. Ann Fam Med 2004; 2:267. Hui AC, Wong SM, et al: Long-term outcome of carpal tunnel syndrome after conservative treatment. Int J Clin Pract 2004; 58:337. Katz JN, Simmons BP: Carpal tunnel syndrome. N Engl J Med 2002; 346:1807. Lee DH, Claussen GC, Oh S: Clinical nerve conduction and needle electromyography studies. J Am Acad Orthop Surg 2004; 12:276. Piszzini DB, et al: A systematic review of conservative treatment of carpal tunnel syndrome. Clin Rehabil 2007; 21:299. Rich JT, et al: Carpal tunnel syndrome due to tophaceous gout. Orthopedics 2004; 27:862. Vjera AJ: Management of carpal tunnel syndrome. Am Fam Physician 2003; 68:265.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cataracts MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

Cataracts are the clouding and opacification of the normally clear crystalline lens of the eye. The opacity may occur in the cortex, the nucleus of the lens, or the posterior subcapsular region, but it is usually in a combination of areas. SYNONYMS

Congenital cataracts (e.g., from rubella) Metabolic cataracts (e.g., caused by diabetes) Collagen-vascular disease cataracts (caused by lupus) Hereditary cataracts Age-related senile cataracts Traumatic cataracts Toxic or drug-induced cataracts (e.g., caused by steroids) Lenticular opacities

ICD-9CM CODES

366 Cataract EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Highest cause of treatable blindness; cataract removal is the most frequent surgical procedure in patients >65 yr old (1.3 million operations/yr, with an annual cost of approximately $3 billion). By year 2020 expect over 30 million Americans to have cataracts. Of Americans >40, 20.5 million (17.2%) have cataracts. Of these, 5% have had surgery.

PEAK INCIDENCE: •

In early life: congenital and hereditary causes predominant; consider drug related and trauma

•

In older age group: senile cataracts (after 40 yr of age)

PREDOMINANT AGE: Elderly; some stage of cataract development is present in >50% of persons 65 to 74 yr old and in 65% of those >75 yr old. Lens clouding begins at 39 to 40 yr old and then usually progresses either slowly or rapidly depending on individual and health. GENETICS: Hereditary with such syndromes as galactosemia, homocystinuria, diabetes PHYSICAL FINDINGS & CLINICAL PRESENTATION

Cloudiness and opacification of the crystalline lens of the eye ( Fig. 1-46 )

FIGURE 1-46 The central location of a posterior subcapsular cataract (1). (From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

•

Heredity

•

Trauma

•

Toxins

•

Age related

•

Drug related

•

Congenital

•

Inflammatory

•

Diabetes

•

Collagen vascular disease

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Corneal lesions

•

Retinal lesions, detached retina, tumors

•

Vitreous disease, chronic inflammation

WORKUP

•

Complete eye examination, including slit lamp examination, funduscopic examination, and brightness acuity testing

•

Complete physical exam for other underlying causes

LABORATORY TESTS

•

Rarely, urinary amino acid screening and CNS imaging studies with congenital cataracts

•

Fasting glucose in young adults with cataracts

•

Diabetes, collagen vascular, other metabolic diseases in younger patients

•

Genetic and hereditary evaluation

TREATMENT There is no evidence that antioxidants or drugs will slow down or help cataracts. NONPHARMACOLOGIC THERAPY

•

Wait until vision is compromised before doing surgery.

•

Surgery is indicated when corrected visual acuity in the affected eye is >20/30 in the absence of other ocular disease; however, surgery may be justified when visual acuity is better in specific situations (especially disabling glare, monocular diplopia). Surgery indicated when vision in one eye is greatly different from the other and affects patient's life.

ACUTE GENERAL Rx

None necessary except when acute glaucoma or inflammation occurs CHRONIC Rx

•

Change glasses as cataracts develop.

•

Myopia is common, and glasses can be adjusted until surgery is contemplated.

DISPOSITION

Refer if sight compromised or inflamed red eye. REFERRAL

Refer to ophthalmologist for evaluation extraction when vision is compromised (see “Nonpharmacologic Therapy”).

PEARLS & CONSIDERATIONS Patients want to know five things about cataracts: 1.

Chance for vision improvement

2.

When vision will improve

3.

Risk from surgery

4.

Effect of surgery

5.

Types of complications

EVIDENCE

Phacoemulsification has been shown to give a better visual outcome than extracapsular extraction with sutures.[[1]] Extracapsular surgery with posterior chamber lens implant gives acceptable visual outcomes at 1 to 2 years after surgery.[[1]] Extracapsular cataract extraction with a posterior chamber lens implant provides a better visual outcome and quality of life, with fewer complications, than intracapsular extraction with aphakic glasses.[[1]] Lensectomy and lens aspiration with primary capsulotomy are both effective treatments in children with bilateral, symmetrical, congential cataracts, but lens aspiration is associated with a significantly greater risk of secondary opacification.[[2]] Multifocal or bifocal intraocular lenses are very promising and successful in properly selected and qualifying patients.

Evidence-Based References 1. Snellingen T, et al: Surgical interventions for age-related cataract. Reviewed. Cochrane Library, 3, Chichester, UK, John Wiley, 2004. 2. Long V, Chen S: Surgical interventions for bilateral congenital cataract. Reviewed. Cochrane Library, 3, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Congdon N, et al: Prevalence of cataract and pseudophakia/aphakia among adults in the US. Arch Ophthalmol 2004; 122(4):487. Solomon R, Donninfeld ED: Recent advances and future frontiers in treating age-related cataracts. JAMA 2003; 290:248.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cat-Scratch Disease GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., GEORGE O. ALONSO, M.D.

BASIC INFORMATION DEFINITION

Cat-scratch disease (CSD) is a syndrome consisting of gradually enlarging regional lymphadenopathy occurring after contact with a feline. Atypical presentations are characterized by a variety of neurologic manifestations as well as granulomatous involvement of the eye, liver, spleen, and bone. The disease is usually self-limiting, and recovery is complete; however, patients with atypical presentations, especially if immunocompromised, may suffer significant morbidity and mortality. SYNONYMS

Cat-scratch fever Benign inoculation lymphoreticulosis Nonbacterial regional lymphadenitis

ICD-9CM CODES

078.3 Cat-scratch disease EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: Unknown INCIDENCE (IN U.S.): •

Unknown

•

Majority of reported cases in children

PEAK INCIDENCE: August through January GENETICS: Unknown PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Classic, most common finding: regional lymphadenopathy occurring within 2 wk of a scratch or contact with felines; usually a new kitten in the household

•

Tender, swollen lymph nodes most commonly found in the head and neck, followed by the axilla and the epitrochlear, inguinal, and femoral areas

•

Erythematous overlying skin, showing signs of suppuration from involved lymph nodes

•

On careful examination; evidence of cutaneous inoculation in the form of a nonpruritic, slightly tender pustule or papule ( Fig. 1-47 )

•

Fever in most patients

•

Malaise and headache in fewer than a third of patients

•

Atypical presentations in fewer than 15% of cases 1.

Usually in association with lymph-adenopathy and a low-grade or frank fever (>101° F, >38.3° C)

2.

Include granulomatous involvement of the conjunctiva (Parinaud's oculoglandular syndrome) and focal masses in the liver, spleen, and mesenteric nodes

•

CNS involvement: neuroretinitis, encephalopathy, encephalitis, transverse myelitis, seizure activity, and coma

•

Osteomyelitis in adults and children

FIGURE 1-47 Primary lesion of cat-scratch disease is a tender papule occurring 3 to 10 days after a scratch. (From Noble J [ed]: Primary care medicine, ed 2, St Louis, 1996, Mosby.)

ETIOLOGY

•

Major cause: Bartonella (Rochalimaea) henselae

•

Mode of transmission: predominantly by direct inoculation through the scratch, bite, or lick of a cat, especially a kitten

•

Limited evidence in support of an arthropod (flea) as an alternative vector of infection arising from bacteremic felines

•

Rarely, associated with dogs, monkeys, and inanimate objects with which a feline has been in recent contact

•

Approximately 2 wk after introduction of the bacteria into the host, regional lymphatic tissues displaying granulomatous infiltration associated with gradual hypertrophy

•

Possible dissemination to distant sites (e.g., liver, spleen, and bone), usually characterized by focal masses or discrete parenchymal lesions

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Granulomas of this syndrome must be differentiated from those associated with: •

tularemia

•

tuberculosis or other myobacterial infections

•

brucellosis

•

sarcoidosis

•

sporotrichosis or other fungal diseases

•

toxoplasmosis

•

lymphogranuloma venerum

•

benign and malignant tumors such as lymphoma

WORKUP

Diagnosis should be considered in patients who present with a predominant complaint of gradually enlarging regional (focal) lymphadenopathy, often with fever and a recent history of having contact with a cat. A primary ulcer at the site of the cat scratch may or may not be present at the time lymphadenopathy becomes manifest. LABORATORY TESTS

•

CSD skin test is no longer used for clinical purposes.

•

Biopsied lymph node histology consistent with CSD.

•

Enhanced culture techniques and serologies augment establishment of the diagnosis. An IFA Bartonella serology is commercially available. A PCR is used in research settings.

•

Histopathologically, Warthin-Starry silver stain has been used to identify the bacillus.

•

Routine laboratory findings: 1.

Mild leukocytosis or leukopenia

2.

Infrequent eosinophilia

3.

Elevated ESR or CRP

•

Abnormalities of bilirubin excretion and elevated hepatic transaminases are usually secondary to hepatic obstruction by granuloma, mass, or lymph node.

•

In patients with neurologic manifestations, lumbar puncture usually reveals normal CSF, although there may be a mild pleocytosis and modest elevation in protein.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Warm compresses to the affected nodes

•

In cases of encephalitis or coma: supportive care

ACUTE GENERAL Rx

•

There is no consensus over therapy, especially as the disease is self-limited in a majority of cases.

•

It would be prudent to treat severely ill patients, especially if immunocompromised, with antibiotic therapy, because these patients tend to suffer dissemination of infection and increased morbidity.

•

Bartonella is usually sensitive to a 5-day course of azithromycin, or alternatively aminoglycosides, tetracycline, and the quinolones can be used.

•

When the isolate is proven by culture, the patient should receive antibiotic therapy as directed by the obtained susceptibilities.

•

Antipyretics and NSAIDs may also be used.

DISPOSITION

Overall prognosis is good. REFERRAL

•

To an appropriate subspecialist to evaluate specific lesions

•

For diagnostic aspiration or excision in presence of regional lymphadenopathy, bone lesions, and mesenteric lymph nodes and organs

•

To ophthalmologist for ocular granulomas 1.

Usually diagnosed clinically

2.

Rarely require excision

PEARLS & CONSIDERATIONS COMMENTS

•

A presentation of this syndrome, especially in patients with HIV infection or impaired cellular immunity, may be fever of unknown origin.

•

Hepatic and splenic granulomas, coronary valve infections may offer few physical clues to diagnosis, emphasizing the need for a complete history.

•

CSD should be considered in the differential diagnosis of school-aged children presenting with status epilepticus.

•

Chronically immunocompromised patients considering the acquisition of a young feline should be made aware of the possible risk of infection.

•

No signs of illness may be apparent in bacteremic kittens.

SUGGESTED READINGS Arvand M, Schäd SG: Isolation of Bartonella henselae DNA from the peripheral blood of a patient with cat scratch disease up to 4 months after the cat scratch injury. J Clin Microbiol 2006; 44(6):2288. Batts S, Demers DM: Spectrum and treatment of cat-scratch disease. Pediatr Infect Dis J 2004; 23(12):1161. Koehler JE, et al: Prevalence of Bartonella infection among human immunodeficiency virus-infected patients with fever. Clin Infect Dis 2003; 37(4):559. Manfredi R, Sabbatani S, Chiodo F: Bartonellosis: light and shoadows in diagnostic and therapeutic issues. Clin Microbiol Infect 2005; 11(3):167. Tsuneoka H, Isukahara M: Analysis of data in 30 patients with cat scratch disease without lymphadenopathy. J Infect Chemother 2006; 12(4):224.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cavernous Sinus Thrombosis WEN-Y WU-CHEN, M.D.

BASIC INFORMATION DEFINITION

Cavernous sinus thrombosis (CST) is a late complication of face or paranasal sinuses infection, resulting in thrombosis of the cavernous sinus and inflammation of its surrounding anatomic structures, including cranial nerves III, IV, V (ophthalmic and maxillary branch), and VI, and the internal carotid artery. SYNONYMS

Intracranial venous sinus thrombosis or thrombophlebitis

ICD-9CM CODES

325 Phlebitis and thrombophlebitis of intracranial venous sinus EPIDEMIOLOGY & DEMOGRAPHICS

•

Cavernous sinus thrombosis is rare in the postantibiotic era.

•

Before antibiotics the mortality rate was 80% to 100%.

•

With antibiotics and early diagnosis, mortality rates have fallen to >20%.

•

Reported morbidity rates have also declined from between 50% and 70% to only 22% with advances in imaging modalities, and aggressive medical care.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Can be either an acute and fulminant disease or an indolent and subacute presentation.

•

Most common signs are related to the anatomic structures affected within the cavernous sinus, notably cranial nerves III to VI, as well as symptoms resulting from impaired venous drainage from the orbit and the eye.

•

A classic presentation is abrupt onset of unilateral periorbital edema, headache, photophobia, and proptosis. Headache is usually the presenting complaint and may precede fever and periorbital edema by several days. Elderly patients may present only with alteration in mental status without antecedent headache.

Other common signs and symptoms include:

•

Ptosis

•

Chemosis

•

Cranial nerve palsies (III, IV, V, VI) 1.

Sixth nerve palsy is the most common.

2.

Hypoesthesia or hyperesthesia of the ophthalmic and maxillary branch of the fifth nerve are common. Periorbital sensory loss and impaired corneal reflex may be noted.

Papilledema, retinal hemorrhages, and decreased visual acuity and blindness may occur from venous congestion within the retina. •

Pupil may be dilated and sluggishly reactive.

•

Fever, tachycardia, sepsis may be present.

•

Headache with nuchal rigidity and changes in mental status may occur.

Infection can spread to the contralateral cavernous sinus through the intercavernous sinuses within 24 to 48 hr of initial presentation. ETIOLOGY

•

CST most commonly results from contiguous spread of an infection from the sinuses (sphenoid, ethmoid, or frontal) or the middle third region of the face. Nasal furuncles are the most common facial infection to produce this complication. Less common primary sites of infection include dental abscess, tonsils, soft palate, middle ear, or orbit (orbital cellulitis).

•

It also can result from hematogenous spread of infection to the cavernous sinus via the superior and inferior ophthalmic veins. This venous system has a predisposition to impaired drainage because it is valveless, where the direction of blood flow depends on the venous pressure gradient.

•

Staphylococcus aureus is the most common infectious microbe, found in 60% to 70% of the cases.

•

Streptococcus is the second leading cause.

•

Gram-negative rods and anaerobes may also lead to cavernous sinus thrombosis.

•

Rarely, Aspergillus fumigatus and mucormycosis cause CST.

DIAGNOSIS

•

The diagnosis of cavernous sinus thrombosis is made by clinical suspicion and confirmed by appropriate imaging studies.

•

Proptosis, ptosis, chemosis, and cranial nerve palsy beginning in one eye and progressing to the other eye establish the diagnosis.

DIFFERENTIAL DIAGNOSIS

•

Orbital or periorbital cellulitis

•

Internal carotid artery aneurysm or fistula

•

CVA

•

Migraine headache

•

Allergic blepharitis

•

Thyroid ophthalmopathy

•

Orbital neoplasm

•

Meningitis

•

Epidural and subdural infections

•

Epidural and subdural hematoma

•

Subarachnoid hemorrhage

•

Acute angle-closure glaucoma

•

Trauma

WORKUP

Cavernous sinus thrombosis is a clinical diagnosis with laboratory tests and imaging studies confirming the clinical impression. LABORATORY TESTS

•

CBC, ESR, blood cultures, and sinus cultures help establish and identify an infectious primary source.

•

Lumbar puncture (LP) is necessary in distinguishing CST from more localized processes (e.g., sinusitis, orbital cellulites). LP reveals inflammatory cells in 75% of cases. The CSF profile is typically that of a parameningeal focus (high WBC, normal glucose, normal protein, culture negative) but may be similar to that of a bacterial meningitis.

IMAGING STUDIES

•

Historically, sinus films are helpful in the diagnosis of sphenoid sinusitis. Opacification, sclerosis, and airfluid levels are typical findings.

•

Noncontrast CT can demonstrate an increase density in the region of the cavernous sinus. Contrastenhanced CT scan may reveal underlying sinusitis, thickening of the superior ophthalmic vein, and irregular filling defects within the cavernous sinus; however, findings may be normal early in the disease course.

•

MRI with gadolinium including MR angiography is more sensitive than CT scan and is the imaging study of choice to diagnose cavernous sinus thrombosis. Findings may include deformity of the internal carotid artery within the cavernous sinus, and an obvious signal hyperintensity within thrombosed vascular sinuses on all pulse sequences.

•

Cerebral angiography can be performed, but it is invasive and not very sensitive.

•

Orbital venography is difficult to perform, but it is excellent in diagnosing occlusion of the cavernous sinus.

TREATMENT NONPHARMACOLOGIC THERAPY

Recognizing the primary source of infection (i.e., facial cellulitis, middle ear, and sinus infections) and treating

the primary source expeditiously is the best way to prevent cavernous sinus thrombosis. ACUTE GENERAL Rx

•

Appropriate therapy should take into account the primary source of infection as well as possible associated complications such as brain abscess, meningitis, or subdural empyema.

•

Broad-spectrum intravenous antibiotics are used as empiric therapy until a definite pathogen is found. Treatment should include a penicillinase-resistant penicillin at maximum dose plus a third- or fourthgeneration cephalosporin: 1.

Nafcillin (or oxacillin) 2 g IV q4h plus either ceftriaxone (2 g q12h) or cefipime (2 g q6h).

2.

Metronidazole 500 mg IV q6h should be added if anaerobic bacterial infection is suspected (dental or sinus infection).

•

Vancomycin (1 g q12h with normal renal function) may be substituted for nafcillin if significant concern exists for infection by methicillin-resistant Staphylococcus aureus or resistant Streptococcus pneumoniae.

•

Anticoagulation with heparin is controversial. Cerebral infarction or intracranial hemorrhage should first be ruled out by noncontrast CT scan before initiating heparin therapy. Current recommendation is for early heparinization in patients with unilateral cavernous sinus thrombosis to prevent clot propagation and to reduce the incidence of septic emboli. Coumadin therapy should be avoided in the acute phase of the illness, but should ultimately be instituted to achieve an INR of 2 to 3, and continued until the infection, symptoms, and signs of cavernous thrombosis have resolved or significantly improved.

•

Steroid therapy is also controversial but may prove helpful in reducing cranial nerve dysfunction or when progression to pituitary insufficiency occurs. Corticosteroids should only be instituted after appropriate antibiotic coverage. Dexamethasone 10 mg q6h is the treatment of choice.

CHRONIC Rx

•

Emergent surgical drainage with sphenoidotomy is indicated if the primary site of infection is thought to be the sphenoid sinus.

•

All patients with CST are usually treated with prolonged courses (3 to 4 wk) of IV antibiotics. If there is evidence of complications such as intracranial suppuration, 6 to 8 wk of total therapy may be warranted.

•

All patients should be monitored for signs of complicated infection, continued sepsis, or septic emboli while antibiotic therapy is being administered.

DISPOSITION

•

Cavernous sinus thrombosis can be a life-threatening, rapidly progressive infectious disease with high morbidity and mortality rates (30%) despite antibiotic use. Morbidity and mortality are increased in cases of sphenoid sinus infection.

•

Complications of untreated CST include extension of thrombus to other dural venous sinuses, carotid thrombosis with concomitant strokes, subdural empyema, brain abscess, or meningitis. Septic embolization may also occur to the lungs, resulting in ARDS, pulmonary abscess, empyema, and pneumothorax.

•

30% of treated patients develop long-term sequelae, which include cranial nerve palsies, blindness, pituitary insufficiency, and hemiparesis.

REFERRAL

If the diagnosis is suspected, this should be considered a medical emergency. Depending on the primary site of infection, appropriate consultation should be made (i.e., ENT, ophthalmology, and infectious disease).

PEARLS & CONSIDERATIONS COMMENTS

Realizing the cavernous sinus lies just above and lateral to the sphenoid sinus and drains the middle portion of the face via the superior and inferior ophthalmic veins and knowing that cranial nerves III, IV, V, and VI pass alongside or through the cavernous sinus make the clinical findings and diagnosis easier to understand.

EVIDENCE

We were unable to cite any evidence that meets our criteria regarding the use of antibiotics in cavernous sinus thrombosis. A systematic review concluded that heparin treatment appeared safe and was associated with an important reduction in the risk of death or dependency, which did not reach statistical significance in cases of cerebral sinus thrombosis.[[1]]

Evidence-Based References 1. Stam J, de Bruijn SFTM, DeVeber G: Anticoagulation for cerebral sinus thrombosis. Cochrane Library, 3, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Bhatia K, Jones NS: Septic cavernous sinus thrombosis secondary to sinusitis: are anticoagulants indicated? A review of the literature. J Laryngol Otol 2002; 116(b):667-676. Ferro JM, et al: Cerebral vein and dural sinus thrombosis in elderly patients. Stroke 2005; 36:1927. Hoshino CH, et al: Septic cavernous sinus thrombosis complicated by narrowing of the internal carotid artery, subarachnoid abcess and multiple pulmonary septic emboli. Intern Med 2007; 46:317. Lee JH, et al: Cavernous sinus syndrome: clinical features and differential diagnosis with MR imaging. AJR 2003; 181:583.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Celiac Disease FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Celiac disease is a chronic disease characterized by malabsorption and diarrhea precipitated by ingestion of food products containing gluten. SYNONYMS

Gluten-sensitive enteropathy Celiac sprue Nontropical sprue

ICD-9CM CODES

579.0 Celiac disease EPIDEMIOLOGY & DEMOGRAPHICS

•

The prevalence of celiac disease is 1% in the general population in North America and Western Europe and 5% in high-risk groups such as first-degree relatives of persons with the disease.

•

Incidence is highest during infancy and the initial 36 mo (secondary to the introduction of foods containing gluten), in the third decade (frequently associated with pregnancy and severe anemia during pregnancy), and in the seventh decade.

•

There is a slight female predominance.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination may be entirely within normal limits.

•

Weight loss, dyspepsia, short stature, and failure to thrive may be noted in children and infants.

•

Weight loss, fatigue, and diarrhea are common in adults.

•

Abdominal pain, nausea, and vomiting are unusual.

•

Pallor as a result of iron deficiency anemia is common.

•

Atypical forms of the disease are being increasingly recognized and include osteoporosis, short stature, anemia, infertility, and neurologic problems. Manifestations of calcium deficiency, such as tetany and seizures, are rare and can be exacerbated by coexistent magnesium deficiency.

•

Angular cheilitis, aphthous ulcers, atopic dermatitis, and dermatitis herpetiformis are frequently associated with celiac disease.

ETIOLOGY

•

Celiac sprue is considered an autoimmune-type disease with tissue transglutaminase (tTG) suggested as a major autoantigen. It results from an inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed individuals who carry either HLA-DQ2 or HLA-DQ8 genes. There is sensitivity to gliadin, a protein fraction of gluten found in wheat, rye, and barley.

•

Timing of introduction of gluten into the infant diet is associated with the appearance of celiac disease in children at risk. Children initially exposed to gluten in the first 3 mo of life have a fivefold increased risk.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

IBD

•

Laxative abuse

•

Intestinal parasitic infestations

•

Other: irritable bowel syndrome, tropical sprue, chronic pancreatitis, Zollinger-Ellison syndrome, cystic fibrosis (children), lymphoma, eosinophilic gastroenteritis, short bowel syndrome, Whipple's disease

LABORATORY TESTS

•

Iron deficiency anemia (microcytic anemia, low ferritin level)

•

Folic acid deficiency

•

Vitamin B12 deficiency, hypomagnesemia, hypocalcemia

•

IgA antiendomysium antibodies (EMA) are a good screening test for celiac disease, except in the case of patients with IgA deficiency. IgA tissue transglutaminase (TTG) antibody by ELISA is a newer and very accurate serologic test for celiac sprue.

•

Biopsy of the small bowel is helpful in confirming a suspected diagnosis when positive, but a negative result does not rule out the diagnosis. It may be reasonable in children with significant elevations of TTG levels (>100U) to first try a gluten-free diet and consider biopsy in those who do not improve with diet.

•

Human leukocyte antigen DQ2DQ8 testing is highly sensitive (90% to 95%) for celiac disease but not very specific. Its greatest diagnostic value is in its negative predictive value, making it useful when negative in ruling out the disease.

IMAGING STUDIES

Capsule endoscopy can be used to evaluate the small-intestinal mucosa, especially if future innovations will allow mucosal biopsy.

TREATMENT NONPHARMACOLOGIC THERAPY

Patients should be instructed on gluten-free diet (avoidance of wheat, rye, and barley). Recent studies show that oats do not damage the mucosa in celiac disease. GENERAL Rx

•

Correct nutritional deficiencies with iron, folic acid, calcium, vitamin B12 as needed.

•

Prednisone 20 to 60 mg qd gradually tapered is useful in refractory cases.

•

Lifelong gluten-free diet is necessary.

DISPOSITION

•

Prognosis is good with adherence to gluten-free diet. Rapid improvement is usually seen within a few days of treatment.

•

Serial antigliadin or antiendomysial antibody tests can be used to monitor the patient's adherence to a gluten-free diet.

•

Repeat small bowel biopsy following treatment generally reveals significant improvement. It is also useful to evaluate for increased risk of small bowel T-cell lymphoma in these patients, especially in untreated patients.

PEARLS & CONSIDERATIONS COMMENTS

•

Some experts recommend a repeat biopsy only in selected patients who have an unsatisfactory response to a strict gluten-free diet.

•

Celiac disease should be considered in patients with unexplained metabolic bone disease, osteoporosis, or hypocalcemia, especially because GI symptoms may be absent or mild. Clinicians should also consider testing children and young adults for celiac disease if unexplained weight loss, abdominal pain or distention, or chronic diarrhea is present.

•

The prevalence of celiac disease in patients with dyspepsia is twice that of the general population. Screening for celiac disease should be considered in all patients with persistent dyspepsia.

•

Celiac disease is associated with an increased risk for non-Hodgkin's lymphoma, especially of T-cell type and primarily localized in the gut. Lymphoma is 4 to 40 times more common and death from lymphoma is 11 to 70 times more common in patients with celiac disease.

SUGGESTED READINGS Alaedini A, Green PH: Narrative review: celiac disease: understanding a complex autoimmune disorder. Ann Intern Med 2005; 142:289-298. Green PH, Cellier C: Celiac disease. N Engl J Med 2007; 357:1731-1743. Hadithi M, et al: Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Am Intern

Med 2007; 147:294-302. Norris JM, et al: Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA 2005; 293:2343-2351.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cellulitis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cellulitis is a superficial inflammatory condition of the skin. It is characterized by erythema, warmth, and tenderness of the area involved. SYNONYMS

Erysipelas (cellulitis generally secondary to group A ß-hemolytic streptococci)

ICD-9CM CODES

682.9 Cellulitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Occurs most frequently in diabetics, immunocompromised hosts, and patients with venous and lymphatic compromise.

•

Frequently found near skin breaks (trauma, surgical wounds, ulcerations, tinea infections). Edema, animal or human bites, subadjacent osteomyelitis, and bacteremia are potential sources of cellulitis.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Variable with the causative organism •

Erysipelas: superficial-spreading, warm, erythematous lesion distinguished by its indurated and elevated margin; lymphatic involvement and vesicle formation are common.

•

Staphylococcal cellulitis: area involved is erythematous, hot, and swollen; differentiated from erysipelas by nonelevated, poorly demarcated margin; local tenderness and regional adenopathy are common; up to 85% of cases occur on the legs and feet.

•

H. influenzae cellulitis: area involved is a blue-red/purple-red color; occurs mainly in children; generally involves the face in children and the neck or upper chest in adults.

•

Vibrio vulnificus: larger hemorrhagic bullae, cellulitis, lymphadenitis, myositis; often found in critically ill patients in septic shock.

ETIOLOGY

•

Group A ß-hemolytic streptococci (may follow a streptococcal infection of the upper respiratory tract)

•

Staphylococcal cellulitis

•

H. influenzae

•

Vibrio vulnificus: higher incidence in patients with liver disease (75%) and in immunocompromised hosts (corticosteroid use, diabetes mellitus, leukemia, renal failure)

•

Erysipelothrix rhusiopathiae: common in people handling poultry, fish, or meat

•

Aeromonas hydrophila: generally occurring in contaminated open wound in fresh water

•

Fungi (Cryptococcus neoformans): immunocompromised granulopenic patients

•

Gram-negative rods (Serratia, Enterobacter, Proteus, Pseudomonas): immunocompromised or granulopenic patients

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Necrotizing fasciitis

•

DVT

•

Peripheral vascular insufficiency

•

Paget's disease of the breast

•

Thrombophlebitis

•

Acute gout

•

Psoriasis

•

Candida intertrigo

•

Pseudogout

•

Osteomyelitis

•

Insect bite

•

Fixed drug eruption

•

Lymphedema

•

Rare causes: Vaccinia vaccination, Kawasaki disease, pyoderma gangrenosa, Sweet's syndrome, carcinoma erysipeloides, anaerobic myonecrosis, erythromelalgia, eosinophilic cellulitis (Well's syndrome), familial Mediterranean Fever

LABORATORY TESTS

•

Gram stain and culture (aerobic and anaerobic) 1.

Aspirated material from: a.

Advancing edge of cellulitis

b.

Any vesicles

2.

Swab of any drainage material

3.

Punch biopsy (in selected patients)

•

Blood cultures in hospitalized patients, in patients who have cellulitis superimposed on lymphedema, in patients with buccal or periorbital cellulitis, and in patients suspected of having a salt-water or fresh-water source of infection. Bacteremia is uncommon in cellulitis (positive blood cultures in only 4% of patients)

•

ALOS titer (in suspected streptococcal disease)

Despite the previous measures, the cause of cellulitis remains unidentified in most patients. IMAGING STUDIES

CT or MRI in patients with suspected necrotizing fasciitis (deep-seated infection of the subcutaneous tissue that results in the progressive destruction of fascia and fat).

TREATMENT NONPHARMACOLOGIC THERAPY

Immobilization and elevation of the involved limb. Cool sterile saline dressings to remove purulence from any open lesion. Support stockings in patients with peripheral edema. ACUTE GENERAL Rx

Erysipelas •

PO: dicloxacillin 500 mg PO q6h

•

IV: cefazolin 1 g q6 to 8h or nafcillin 1.0 or 1.5 g IV q4 to 6h

note: Use erythromycin, clindamycin, or vancomycin in patients allergic to penicillin. Staphylococcus cellulitis •

PO: dicloxacillin 250 to 500 mg qid

•

IV: nafcillin, 1 to 2 g q4 to 6h

•

Cephalosporins (cephalothin, cephalexin, cephradine) also provide adequate antistaphylococcal coverage except for MRSA

•

Use vancomycin 1.0 to 2.0 g IV qd or linezolid 0.6 g IV q12h in patients allergic to penicillin or cephalosporins and in patients with methicillin-resistant S. aureus (MRSA). Daptomycin (Cubicin), a cyclic lipopeptide can be used as an alternative to vancomycin for complicated skin and skin structure infections. Usual dose is 4 mg/kg IV given over 30 min every 24 hr

H. influenzae cellulitis •

PO: cefixime or cefuroxime

•

IV: cefuroxime or ceftriaxone

Vibrio vulnificus •

Doxycycline 100 mg IV or PO bid +/- third-generation cephalosporin. Ciprofloxacin is an alternative antibiotic

•

IV support and admission into ICU (mortality rate >50% in septic shock)

Erysipelothrix •

Penicillin

Aeromonas hydrophila •

Aminoglycosides

•

Chloramphenicol

•

Complicated skin and skin structure infections in hospitalized patients can be treated with daptomycin (cubicin) 4 mg/kg IV every 24 hr

DISPOSITION

Prognosis is good with prompt treatment. REFERRAL

For surgical debridement in addition to antibiotics in patients with suspected necrotizing fasciitis SUGGESTED READINGS Swartz MN: Cellulitis. N Engl J Med 2004; 350:904. Falagas M, Vergidis PI: Narrative review: diseases that masquerade as infectious cellulitis. Ann Intern Med 2005; 142:47.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cerebral Palsy MAITREYI MAZUMDAR, M.P.H.

BASIC INFORMATION DEFINITION

Cerebral palsy (CP) is a group of disorders of the central nervous system characterized by aberrant control of movement or posture, present since early in life and not the result of a progressive or degenerative disease. SYNONYMS

Little's disease Congenital static encephalopathy Congenital spastic paralysis

ICD-9CM CODES

343 Infantile cerebral palsy EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 2 to 2.5 per 1000 live births PREDOMINANT SEX: Male = female PREDOMINANT AGE: Diagnosis made at 3 to 5 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Monoplegia, diplegia, quadriplegia, hemiplegia

•

Often hypotonic in newborn period, followed by development of hypertonia

•

Spasticity

•

Athetosis

•

Delay in motor milestones

•

Hyperreflexia

•

Seizures

•

Mental retardation

ETIOLOGY

Mulitfactorial, including low birthweight, congenital malformation, asphyxia, multiple gestations, intrauterine exposure to infection, neonatal stroke, and hyperbilirubinemia

DIAGNOSIS A motor deficit is always present. The usual presenting complaint is that child is not reaching motor milestones at the appropriate age. Medical history establishes that the child is not losing function. This history, combined with a neurologic examination establishing that motor deficit is due to a cerebral abnormality, establishes the diagnosis of CP. Serial examinations may be necessary if the history is unreliable. DIFFERENTIAL DIAGNOSIS

Other causes of neonatal hypotonia include: muscular dystrophies, spinal muscular atrophy, Down's syndrome, spinal cord injuries WORKUP

•

Laboratory tests are not necessary to establish the diagnosis.

•

Workup is helpful for assessment of recurrence risk, implementation of prevention programs, and medicolegal purposes.

LABORATORY TESTS

•

Metabolic and genetic testing should be considered if on follow-up the child has (1) evidence of deterioration or episodes of metabolic decompensation, (2) no etiology determined by neuroimaging, (3) family history of childhood neurologic disorder associated with CP, (4) developmental malformation on neuroimaging.

•

If previous stroke seen on neuroimaging, consider evaluation for coagulopathy.

•

An EEG should be obtained when a child with CP has a history suggestive of seizures.

•

Children with CP should be screened for ophthalmologic and hearing impairments, speech and language disorders. Nutrition, growth, and swallowing function should be monitored.

IMAGING STUDIES

•

Neuroimaging is recommended if the etiology has not been established previously; for example, by perinatal imaging.

•

MRI, when available, is preferred to CT scanning because of higher yield in suggesting an etiology, and timing of the insult leading to CP.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Physical therapy, occupational therapy, and speech therapy.

•

Orthotics and casting are used to increase musculotendinous length.

ACUTE GENERAL Rx

If present, treatment of seizures CHRONIC Rx

•

Treatment of seizures, as directed by seizure type.

•

Medical treatment of spasticity includes baclofen (oral and intrathecal) and botulinum toxin A.

•

Surgical treatments of spasticity include dorsal rhizotomy, tendon lengthening, and osteotomy.

DISPOSITION

Most children with cerebral palsy live at home. Those children with severely impaired mobility or other disabilities often live in chronic-care nursing facilities. REFERRAL

If the child has difficulty with spasticity, physical medicine and rehabilitation referrals are especially helpful.

PEARLS & CONSIDERATIONS In full-term infants, history of traumatic delivery is usually not present.

EVIDENCE

Intensive (weekly) neurodevelopmental therapy has been demonstrated to lead to improved motor and functional outcomes after 6 months when compared with monthly therapy in children under age 18 months.[[1]] Speech and language therapy might help children with cerebral palsy communicate more effectively,[[2]] but more research is needed. Continuous administration of intrathecal baclofen has been shown to improve motor function in a small series of children with spasticity due to cerebral palsy.[[3]] Studies have shown that children who receive botulinum toxin or selective dorsal rhizotomy have improvement in some objective measures of spasticity, but the effect of these therapies on functional ability is still unclear. [79] [80] [81]

Evidence-Based References 1. Mayo NE: The effect of physical therapy for children with motor delay and cerebral palsy. A randomized clinical trial. Am J Phys Med Rehabil 1991; 70(b):258-267. 2. Pennington L, et al: Speech and language therapy to improve the communication skills of children with cerebral palsy. Cochrane Database Syst Rev 2004; 2: 3. Van Schaeybroeck P, et al: Intrathecal baclofen for intractable cerebral spasticity: a prospective placebo-controlled, double-blind study. Neurosurgery 2000; 46(3):603-609.discussion 609–612 4. Ade-Hall RA, Moore AP: Botulinum toxin type A in the treatment of lower limb spasticity in cerebral palsy. Cochrane Database Syst Rev 2000; 1: 5. Wasiak J, Hoare B, Wallen M: Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database Syst Rev 2004; 4: 6. Graubert C, et al: Changes in gait at 1 year post-selective dorsal rhizotomy: results of a prospective randomized study. J Pediatr Orthop 2000; 20(b):496-500.

SUGGESTED READINGS Ashwal S, et al: Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2004; 62(6):851. Nelson KB: The epidemiology of cerebral palsy in term infants. Ment Retard Dev Disabil Res Rev 2002; 8(3):146.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cervical Cancer GIL FARKASH, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Cervical cancer is penetration of the basement membrane and infiltration of the stroma of the uterine cervix by malignant cells.

ICD-9CM CODES

180 Malignant neoplasm of cervix uteri EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: There are approximately 15,000 new cases annually, with 4000 to 5000 associated deaths. The U.S. has an age-adjusted mortality of 2.6 cases/100,000 persons for cervical cancer. PREDOMINANCE: Higher incidence rates occur in developing countries. Among the U.S. population, Hispanics have a higher incidence than African Americans, who likewise have a higher incidence than whites. RISK FACTORS: Smoking, early age at first intercourse, multiple sexual partners, immunocompromised state, nonbarrier methods of birth control, infection with high-risk HPV (types 16 and 18), and multiparity. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Unusual vaginal bleeding, particularly postcoital

•

Vaginal discharge and/or odor

•

Advanced cases may present with lower extremity edema or renal failure

•

In early stages there may be little or no obvious cervical lesion, more advanced cases may present with large, bulky, friable lesions encompassing the majority of the vagina ( Fig. 1-48 )

FIGURE 1-48 Carcinoma of cervix (gross specimen). (From Mishell D [ed]: Comprehensive gynecology, ed 3, St Louis, 1997, Mosby.)

ETIOLOGY

•

Dysplastic cells progress to invasive carcinoma.

•

Thought to be linked to the presence of HPV types 16, 18, 45, and 56 via interaction of E6 oncoproteins on p53 gene product.

•

There may be an association with past infection with Chlamydia trachomatis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Cervical polyp or prolapsed uterine fibroid

•

Preinvasive cervical lesions

•

Neoplasia metastatic from a separate primary

WORKUP

•

Thorough history and physical examination.

•

Pelvic examination with careful rectovaginal examination.

•

As compared with PAP testing, HPV testing has a greater sensitivity for the detection of cervical intraepithelial neoplasia. The addition of an HPV test to the PAP test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.

•

Colposcopy with directed biopsy and endocervical curettage.

•

Clinically staged, not surgically staged.

LABORATORY TESTS

•

CBC, chemistry profile

•

Squamous cell carcinoma (SCC) antigen in research setting

•

Carcinoembryonic antigen (CEA)

IMAGING STUDIES

•

Chest x-ray examination

•

IVP

•

Depending on stage, may need cystoscopy, sigmoidoscopy or BE, CT scan or MRI, lymphangiography

TREATMENT NONPHARMACOLOGIC THERAPY

•

FIGO stage Ia: cone biopsy or simple hysterectomy

•

FIGO stage Ib or IIa: type III radical hysterectomy and pelvic lymphadenectomy or pelvic radiation therapy

•

Advanced or bulky disease: multimodality therapy (radiation, chemotherapy, and/or surgery); platinum use before radiation therapy

ACUTE GENERAL Rx

Cervical cancer may present with massive and acute vaginal bleeding requiring volume and blood replacement, vaginal packing or other hemostatic modalities, and/or high-dose local radiotherapy. CHRONIC Rx

•

Physical examination with Pap smear every 3 mo for 2 yr, every 6 mo during the third to fifth year, and annually thereafter

•

Chest x-ray examination annually

DISPOSITION

Five-year survival varies by stage:

•

Stage I 60% to 90%

•

Stage II 40% to 80%

•

Stage III >60%

•

Stage IV >15%

Early detection by Pap smear imperative to long-term improvements in survival. REFERRAL

Gynecologic oncologist for all invasive disease

PEARLS & CONSIDERATIONS Gardasil is a vaccine indicated in girls and women 9 to 26 yr of age for the prevention of cervical cancer caused by human papilloma virus types 6, 11, 16, and 18.

EVIDENCE

There is little evidence that is available and that meets rigorous criteria for the management of cervical malignancy/dysplasia. Concomitant chemotherapy and radiotherapy appears to improve overall survival and progression-free survival in patients with locally advanced cervical cancer. Local and distant recurrence rates are also reduced with chemoradiation.[[1]]

Evidence-Based References 1. Green J, et al: Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix. Cochrane Database Sys Rev 2001;

SUGGESTED READINGS Long HJ, et al: Prevention, diagnoisis, and treatment of cervical cancer. Mayo Clin Proc 2007; 82(b):15661574. Mayrand MH, et al: Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Eng J Med 2007; 357:1579-1588. McCreath S: Cervical cancer: current management of early/late disease. Surg Oncol Clin N Am 2005; 14(2):249. Naucler P, et al: Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Eng J Med 2007; 357:1589-1597.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cervical Disk Syndromes LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Cervical disk syndromes refer to diseases of the cervical spine resulting from disk disorder, either herniation or degenerative change (spondylosis). When posterior osteophytes compress the anterior spinal cord, lower extremity symptoms may result, a condition termed cervical spondylotic myelopathy.

ICD-9CM CODES

722.4

Degenerative intervertebral cervical disk

722.71 Degenerative cervical disk with myelopathy EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 10% of general adult population (symptoms in 50% of population at some time in their life) PREDOMINANT SEX: Male = female PREDOMINANT AGE: 30 to 60 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Neck pain, radicular symptoms, or myelopathy, either alone or in combination

•

Limited neck movement

•

Pain with neck motion, especially extension

•

Referred unilateral interscapular pain, resulting in a local trigger point

•

Radicular arm pain (usually unilateral), numbness, and tingling possible, most commonly involving the C6 (C5-C6 disk) or C7 (C6-C7 disk) nerve root

•

Weakness and reflex changes (C6—biceps, C7—triceps)

•

Myelopathy possibly resulting in gait disturbance, weakness, and even spasticity

•

Sensory examination usually not helpful

ETIOLOGY

Unknown

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Rotator cuff tendinitis

•

Carpal tunnel syndrome

•

Thoracic outlet syndrome

•

Brachial neuritis

A differential diagnosis for evaluation of neck pain is described in Section II. WORKUP

In most cases, the diagnosis can be established on a clinical basis alone. Section III, “Cervical Disk Syndrome,” describes an algorithm for a workup of suspected cases. IMAGING STUDIES

•

Plain roentgenograms within the first few weeks 1.

Usually normal in soft disk herniation

2.

With chronic degenerative disk disease, usually loss of height of the disk space, anterior and posterior osteophyte formation, and encroachment on the intervertebral foramen by osteophytes

•

Myelography, CT scanning, and MRI indicated in patients whose symptoms do not resolve or when other spinal pathology suspected

•

Electrodiagnostic studies to confirm the diagnosis or rule out peripheral nerve disorders

TREATMENT NONPHARMACOLOGIC THERAPY

•

Rest and cervical collar if needed

•

Local modalities such as heat

•

Physical therapy ( Fig. 1-49 )

•

Avoid extreme range of motion exercises in degenerative disk disease

FIGURE 1-49 Isometric neck exercises. A, The hand is placed against the side of the head slightly above the ear, and pressure is gradually increased while resisting with the neck muscles and keeping the head in the same position. The position is held 5 sec, relaxed, and repeated five times. B, The exercise is performed on the other side and then from the back and front (C). The exercise should be performed three to four times daily. (From Mercier LR [ed]: Practical orthopedics, ed 4, St Louis, 1995, Mosby.)

ACUTE GENERAL Rx

•

NSAIDs

•

“Muscle relaxants” for their sedative effect

•

Analgesics as needed

•

Epidural steroid injection for radicular pain

DISPOSITION

•

Usually improve with time

•

Surgical intervention in >5%

REFERRAL

Orthopedic or neurosurgical consultation for intractable pain or neurologic deficit

PEARLS & CONSIDERATIONS Myelopathy from cervical spondylosis is the most common cause of acquired spastic paralysis in the adult and is usually progressive. Whether to intervene surgically is a complicated decision. COMMENTS

•

Pain relief with physical therapy seems anecdotal and short-lived; any overall improvement usually parallels what would have probably occurred naturally.

•

Sometimes carpal tunnel syndrome and cervical radiculopathy occur together; this is termed the doublecrush syndrome and results from nerve compression at two separate levels. Proximal compression may decrease the ability of the nerve to tolerate a second, more distal compression.

•

Surgical intervention is indicated primarily for relief of radicular pain caused by nerve root compression or for the treatment of myelopathy; it is generally not helpful when chief complaint is neck pain alone.

•

In many cases of cervical spondylosis with myelopathy, the lower-extremity symptoms are much more disabling than the neck symptoms, a situation that can cause some difficulty in determining their etiology.

SUGGESTED READINGS Gorski JM, Schwartz LH: Shoulder impingement presenting as neck pain. J Bone Joint Surg 2003; 85A:635. King JT, et al: Preference-based quality of life measurement in patients with cervical spondylotic myelopathy. Spine 2004; 29:1271. Rao RD, et al: Operative treatment of cervical spondylotic myelopathy. J Bone Joint Surg 2006; 88A:1619. Rao RD, et al: Degenerative cervical spondylosis: clinical syndromes, pathogenesis, and management. J Bone Joint Surg 2007; 89A:1360. Rhee JM, Yoou T, Riew KD: Cervical radiculopathy. J Am Acad Orthop Surg 2007; 15:486.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cervical Dysplasia DENNIS M. WEPPNER, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Cervical dysplasia refers to atypical development of immature squamous epithelium that does not penetrate the basement epithelial membrane. Characteristics include increased cellularity, nuclear abnormalities, and increased nuclear to cytoplasm ratio. A progressive polarized loss of squamous differentiation exists beginning adjacent to the basement membrane and progressing to the most advanced stage (severe dysplasia), which encompasses the complete squamous epithelial layer thickness ( Fig. 1-50 ).

FIGURE 1-50 Diagram of cervical epithelium showing various terminologies used to characterize progressive degrees of cervical epithelium. (From Mishell D [ed]: Comprehensive gynecology, ed 3, St Louis, 1997, Mosby.)

BETHESDA 2001 UPDATED CLASSIFICATION: Interpretation/result (including specimen adequacy)

•

Negative for intraepithelial lesion or malignancy

•

Organisms (i.e., Trichomonas vaginalis, Candida sp., bacterial vaginosis), reactive cellular changes (inflammation), atrophy

•

Epithelial cell abnormalities: atypical squamous cells (ASC), of undetermined significance (ASC-US), cannot exclude HSIL (ASC-H), LSIL (CIN 1 and HPV), HSIL (CIN 2 & 3, CIS), squamous cell carcinoma

•

Glandular cell abnormalities: atypical glandular cells (AGC): (specify endocervical, endometrial, or NOS), atypical glandular cells, favor neoplastic (specify endocervical, endometrial, or NOS) endocervical adenocarcinoma in situ (AIS), adenocarcinoma

•

Other: endometrial cells in a woman 40 yr of age

SYNONYMS

Class III or class IV Pap smear Cervical intraepithelial neoplasia (CIN) Low-grade or high-grade squamous intraepithelial lesion (LGSIL or HGSIL)

ICD-9CM CODES

622.1 Dysplasia of cervix (uteri) EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: •

Age 35 yr

•

Abnormal Pap smear rate revealing dysplasia approximates 2% to 5%, depending on population risk factors and false-negative rate variance

•

False-negative rate approaching 40%

•

Average age-adjusted incidence of severe dysplasia 35 cases/100,000 persons

PREVALENCE: •

Dysplasia: peak age, 26 yr (3600 cases/100,000 persons)

•

CIS: peak age, 32 yr (1100 cases/100,000 persons)

•

Invasive cancer: peak age, >60 yr (800 cases/100,000 persons)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Cervical lesions associated with dysplasia usually are not visible to the naked eye; therefore physical findings are best viewed by colposcopy of a 3% acetic acid–prepared cervix.

•

Patients evaluated by colposcopy are identified by abnormal cervical cytology screening from Pap smear screening.

•

Colposcopic findings: 1.

Leukoplakia (white lesion seen by the unaided eye that may represent condyloma, dysplasia, or cancer)

2.

Acetowhite epithelium with or without associated punctation, mosaicism, abnormal vessels

3.

Abnormal transformation zone (abnormal iodine uptake, “cuffed” gland openings)

ETIOLOGY

•

Not clearly elucidated

•

May be caused by abnormal reserve cell hyperplasia resulting in atypical metaplasia and dysplastic epithelium

•

Strongly associated and initiated by oncogenic HPV infection (high-risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, 56, and 58; low-risk HPV types 6, 11, 42, 43, and 44)

•

Risk factors: 1.

Any heterosexual coitus

2.

Coitus during puberty (Transformation-zone metaplasia peak)

3.

DES exposure

4.

Multiple sexual partners

5.

Lack of prior Pap smear screening

6.

History of STD

7.

Other genital tract neoplasia

8.

HIV

9.

TB

10. Substance abuse 11. “High-risk” male partner (HPV) 12. Low socioeconomic status 13. Early first pregnancy 14. Tobacco use 15. HPV

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Metaplasia

•

Hyperkeratosis

•

Condyloma

•

Microinvasive carcinoma

•

Glandular epithelial abnormalities

•

Adenocarcinoma in situ

•

VIN

•

VAIN

•

Metastatic tumor involvement of the cervix

WORKUP

Periodic history and physical examination (including cytologic screening), depending on age, risk factors, and history of preinvasive cervical lesions •

Consider screening for sexually transmitted disease (GC, Chlamydia, VDRL, HIV, HPV)

•

Abnormal cytology (HSIL/LSIL, initial ASC/ASC-US/ASC-H in high-risk patients, recurrent in lowrisk/postmenopausal patients) and grossly evident suspicious lesions; refer for colposcopy and possible directed biopsy/ECC (examination should include cervix, vagina, vulva, and anus)

•

For glandular cell abnormalities (AGC): refer for colposcopy and possible directed biopsy/ECC, and consider endometrial sampling

•

In pregnancy: abnormal cytology followed by colposcopy in the first trimester and at 28 to 32 wk; only highgrade lesions suspect for cancer biopsied; ECC contraindicated

LABORATORY TESTS

•

GC, Chlamydia to rule out STD

•

Pap cytology screening (requires appropriate sampling, preparation, cytologist interpretation and reporting)

•

Colposcopy and directed biopsy, ECC for indications (see “Workup”)

•

HPV-DNA typing if identified abnormal cytology

IMAGING STUDIES

•

Cervicography

•

Computer-enhanced Pap cytology screening (e.g., PAPNET)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Superficial ablative techniques (cryosurgery, CO 2 laser, and electrocoagulation diathermy) considered for colposcopy-identified dysplasia (moderate to severe dysplasia or CIS) and negative ECC; mild dysplasia followed conservatively in a compliant patient

•

Cone biopsy (LEEP, CO2 laser, “cold knife” cone biopsy) considered for colposcopy-identified dysplasia (moderate to severe dysplasia or CIS) and positive ECC or if there is a two-grade or more discrepancy between the Pap smear, colposcopy, and biopsy or ECC findings

•

Hysterectomy if patient has completed child bearing and has persistent or recurrent severe dysplasia or CIS

•

In pregnancy: treatment for cervical dysplasia deferred until after delivery

ACUTE GENERAL Rx

Topical 5-fluorouracil (5-FU) is rarely used for recurrent cervicovaginal lesions. CHRONIC Rx

•

Because of the risk for persistent and recurrent dysplasia, long-term follow-up is individualized based on patient risk factors, Pap smear and colposcopy results, treatment history, and presence of high-risk HPV (e.g., Pap smear q3 to 4 mo/yr, then q6 mo/1 yr, then annually [if all normal], or repeat colposcopy examination and treat as indicated).

•

Mild dysplasia with negative ECC should be followed conservatively in a compliant patient as a majority of these lesions regress.

DISPOSITION

•

Because of the large numbers of women in high-risk groups, the prevalence of HPV, and the high falsenegative Pap smear rate, routine Pap smear screening should be strongly encouraged for all women, especially those with a history of cervical dysplasia. The addition of an HPV test to the PAP test reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening.

•

Success rates for treatment approach 80% to 90%.

•

Detection of persistence of recurrence requires careful follow-up.

•

Cervical treatment possibly results in infertility (cervical stenosis or incompetence), which requires careful consideration and discretion for use of LEEP and cone biopsy.

•

Appropriate counseling and informed consent needed when considering any form of management of cervical dysplasia.

REFERRAL

•

Patients with abnormal Pap cytology should not be followed by repeat Pap smear screening.

•

Patients with identified abnormal cytology should be evaluated by a skilled colposcopist (defined as documented didactic and preceptorship training including 50 cases of identified pathology, ongoing colposcopy activity with a minimum of 2 cases/wk, QA log, and periodic CME).

•

If treatment is required, patient should be referred to a gynecologist or gynecologic oncologist skilled in the diagnosis and treatment of preinvasive cervical disease.

PEARLS & CONSIDERATIONS COMMENTS

•

Patient education material available from American College of Obstetricians and Gynecologists.

•

Gardasil is a vaccine indicated in girls and women 9 to 26 yr of age for the prevention of CIN caused by human papillomavirus (HPV) types 6, 11, 16, and 18.

EVIDENCE

There is little evidence that is available and that meets our criteria for the management of cervical malignancy/dysplasia. The available evidence suggests that there is no obviously superior surgical technique for the treatment of cervical intraepithelial neoplasia. [[1]]

Evidence-Based References 1. Martin-Hirsch PL, Paraskevaidis E, Kitchener H: Surgery for cervical intraepithelial neoplasia. Cochrane Database Sys Rev 1999;

SUGGESTED READINGS Apgar BS, Brotzman G: Management of cervical cytologic abnormalities. Am Fam Physician 2004; 70(10):1905. Naucler P, et al: Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Eng J Med 2007; 357:1589-1597. Schlecht NF, et al: Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA 2001; 286:3106. Solomon D, et al: The 2001 Bethesda system terminology for reporting results of cervical cytology. JAMA 2002; 287:2114. Stoler MH: New Bethesda terminology and evidence-based management guidelines for cervical cytology findings. JAMA 2002; 287:2140. Wright TC, et al: 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cervical Polyps GEORGE T. DANAKAS, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

A cervical polyp is a growth protruding from the cervix or endocervical canal. Polyps that arise from the endocervical canal are called endocervical polyps. If they arise from the ectocervix, they are called cervical polyps.

ICD-9CM COdes

622.7 Mucous polyp of cervix EPIDEMIOLOGY & DEMOGRAPHICS

Cervical polyps are common. Found in approximately 4% of all gynecologic patients. Most commonly present in perimenopausal and multigravid women between the ages of 30 and 50 yr. Endocervical polyps are more common than cervical polyps and are almost always benign ( Fig. 1-51 ). Malignant degeneration is extremely rare.

FIGURE 1-51 A, Fibroid polyp protruding through the external cervical os. B, Small endocervical polyp. (From Symonds EM, Macpherson MBA: Color atlas of obstetrics and gynecology, St Louis, 1994, Mosby.)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Polyps may be single or multiple and vary in size from being extremely small (a few mm) to large (4 cm). They are soft, smooth, reddish-purple to cherry-red in color. They bleed easily when touched. Very large polyps can cause some cervical dilation. There may be vaginal discharge associated with cervical polyps if the polyp has become infected. ETIOLOGY

•

Most unknown

•

Inflammatory

•

Traumatic

•

Pregnancy

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Endometrial polyp

•

Prolapsed myoma

•

Retained products of conception

•

Squamous papilloma

•

Sarcoma

•

Cervical malignancy

WORKUP

Polyps are most commonly asymptomatic and are usually found at the time of annual gynecologic pelvic examination. Polyps are also found in women who present for evaluation of intermenstrual or postcoital bleeding and for profuse vaginal discharge. Polyps are painless. Unless a patient has a bleeding abnormality that necessitates her being evaluated by a physician, polyps would go undiagnosed until her next Pap smear was obtained.

TREATMENT NONPHARMACOLOGIC THERAPY

Simple surgical excision can be done in the office. The physician should be prepared for bleeding, which can easily be controlled with silver nitrate or Monsel's solution. Most commonly, a polyp is excised by grasping it at the stalk and twisting it off. Polyps can also be excised by electrocautery or, in the case of very large polyps, in an outpatient surgical suite. Sexual intercourse and tampon usage are to be avoided until the patient's follow-up visit. Also, douching is not to be performed.

ACUTE GENERAL Rx

Generally, no medication is needed. CHRONIC Rx

Patient is followed up in 2 wk for recheck of the surgical excision site unless there is active bleeding, in which case she would be seen immediately. The cervix should be checked at the patient's routine gynecologic visits. DISPOSITION

Because these are almost always benign, usually no further treatment is needed. Annual gynecologic examinations should be performed to check for any regrowths. REFERRAL

To a gynecologist for removal of polyps

PEARLS & CONSIDERATIONS COMMENTS

A Pap smear should be obtained before removing the polyp. If an abnormal Pap smear is obtained, more than likely the cause will be secondary to the polyp. If a colposcopic evaluation is needed, this should also be performed. During pregnancy, the cervix is highly vascularized. If the polyps are stable and benign-appearing, they should just be observed during the pregnancy and removed only if they are causing bleeding. SUGGESTED READINGS Endo H, et al: Cervical polyp with eccrine syringofibroadenoma-like features. Histopathology 2003; 42(3):301. Rupke S: Family practice forum: clinical medicine. Evaluation and management of cervical polyps. Hosp Pract 1998; 33(6):81. Scott PM: Procedures in family practice. Performing cervical polypectomy. JAAPA 1999; 12(6):81. Spiewankiewicz B: Hysteroscopy in cases of cervical polyps. Eur J Gynaecol Oncol 2003; 24(1):67.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cervicitis GEORGE T. DANAKAS, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Cervicitis is an infection of the cervix. It may result from direct infection of the cervix, or it may be secondary to uterine or vaginal infection. SYNONYMS

Endocervicitis Ectocervicitis Mucopurulent cervicitis

ICD-9CM CODES

616.0

Cervicitis

098.15 Acute gonococcal cervicitis 079.8

Chlamydia infection

EPIDEMIOLOGY & DEMOGRAPHICS

Cervicitis accounts for 20% to 25% of patients presenting with abnormal vaginal discharge, and this affects women only. It is most common in adolescents, but it can be found in any sexually active woman. Practicing unsafe sex with multiple sexual partners increases the risk of developing cervicitis, as well as other sexually transmitted diseases. PHYSICAL FINDINGS & clinical presentation

Cervicitis is usually asymptomatic or associated with mild symptoms. Copious purulent or mucopurelence in vaginal discharge ( Fig. 1-52 ), pelvic pain, and dyspareunia may be present if cervicitis is severe. The cervix can be erythematous and tender on palpation during bimanual examination. The cervix may also bleed easily when obtaining cultures or a Pap smear. May have postcoital bleeding.

FIGURE 1-52 Colposcopy of a woman with mucopurulent cervicitis and purulent discharge from endocervical os. (Courtesy Dr. David Soper, Richmond, VA. From Mandell GL [ed]: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, ed 5, New York, 2000, Churchill Livingstone.)

ETIOLOGY

•

Chlamydia

•

Trichomonas

•

Neisseria gonorrhoeae

•

Herpes simplex

•

Trichomonas vaginalis

•

Human papillomavirus

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Carcinoma of the cervix

•

Cervical erosion

•

Cervical metaplasia

WORKUP

The patient usually presents with a vaginal discharge or history of postcoital bleeding. Otherwise the patient is asymptomatic and diagnosed during routine examination. On examination there is gross visualization of yellow, mucopurulent material on the cotton swab. LABORATORY TESTS

On a smear there will be ten or more polymorphonuclear leukocytes per microscopic field. Positive Gram stain is found. Cultures should be obtained for Chlamydia and N. gonorrhoeae. Use a wet mount to look for trichomonads. Obtain a Pap smear.

TREATMENT NONPHARMACOLOGIC THERAPY

Cervicitis is treated in an outpatient setting. Cryosurgery is an option for treatment of cervicitis with negative cultures and negative biopsies. Safe sex should be practiced with the use of condoms. Partners should be treated in all cases of infection proven by culture. ACUTE GENERAL Rx

Because Chlamydia and N. gonorrhoeae make up >50% of the cause of infectious cervicitis, if it is suspected, treat without waiting for culture results. Administer ceftriaxone 125-mg IM single dose followed by doxycycline 100 mg PO bid for 7 days. If the patient is pregnant, treat with azithromycin (Zithromax) 1-g single dose instead of using doxycycline, which is contraindicated in pregnant or nursing mothers. Alternative treatments include: erythromycin base 500 mg PO qid for 7 days, erythromycin ethylsuccinate 800 mg PO qid for 7 days, ofloxacin 300 mg PO bid for 7 days, or levofloxacin 500 mg PO qd for 7 days. If Trichomonas is the etiologic agent, treat with metronidazole 2-g single dose. For herpes, treat with acyclovir 200 mg PO five times daily for 7 days. DISPOSITION

Cervicitis responds well to antibiotics. Possible complications to watch for are a subsequent PID and infertility (found in 5% to 10% of patients). Repeat cultures should be performed after treatment. Sexual relations can be resumed after negative cultures. REFERRAL

If subsequent PID develops, consider hospital admission for IV antibiotics.

PEARLS & CONSIDERATIONS COMMENTS

Patient educational material can be obtained from local health clinics and clinics for sexually transmitted diseases.

SUGGESTED READINGS Centers for Disease Control and Prevention: 2006 sexually transmitted diseases treatment guidelines. MMWR Morb Mortal Wkly Rep 2006; 55(RR-11): Marrazzo JM: Mucopurulent cervicitis: no longer ignored, but still misunderstood. Infect Dis Clin of N Am 2005; 19(2):333. Simpson T: Urethritis and cervicitis in adolescents. Adolesc Med Clin 2004; 15(2):253.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Chagas' Disease GEORGE O. ALONSO, M.D., GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Chagas' disease is an infection caused by the protozoan parasite Trypanosoma cruzi. This is a vector-borne disease transmitted by reduviid bugs from multiple wild and domesticated animal reservoirs. The disease is characterized by an acute nonspecific febrile illness that may be followed, after a variable latency period, by chronic cardiac, GI, and neurologic sequelae. SYNONYMS

American trypanosomiasis

ICD-9CM CODES

086.2 Chagas' disease EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Four cases of autochthonous transmission in California and Texas

•

In the last 2 decades, six cases of laboratory-acquired infection, three cases of transfusion-associated transmission, and nine cases of imported disease reported to the Centers for Disease Control and Prevention (none of the imported cases involving returning tourists)

PREVALENCE (IN U.S.): Based on regional seroprevalence studies in Hispanic blood donors, it is estimated that between 50,000 and 100,000 persons infected with T. cruzi are currently residing in the U.S. PREDOMINANT SEX: Male = female PREDOMINANT AGE: •

In highly endemic areas, mean age of acute infection: approximately 4 yr

•

Variable age distribution for both types of chronic disease, depending on geography

•

Mean age of onset: usually between 35 and 45 yr

PEAK INCIDENCE: Unknown

GENETICS: Congenital infection: Congenital transmission has been documented with attendant high fetal mortality and morbidity in surviving infants. Neonatal infection: In rural areas, within substandard housing, transmission is likely to occur. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Inflammatory lesion that develops about 1 wk after contamination of a break in the skin with infected insect feces (chagoma) 1.

Area of induration and erythema

2.

Usually accompanied by local lymphadenopathy

•

Presence of Roma—a's sign, which consists of unilateral painless palpebral and periocular edema, when conjunctiva is portal of entry

•

Constitutional symptoms of fever, fatigue, and anorexia, along with edema of the face and lower extremities, generalized lymphadenopathy, and mild hepatosplenomegaly after the appearance of local signs of disease

•

Myocarditis in a small portion of patients, sometimes with resultant CHF

•

Uncommonly, CNS disease, such as meningoencephalitis, which carries a poor prognosis

•

Symptoms and signs of disease persisting for weeks to months, followed by spontaneous resolution of the acute illness; patient then in the indeterminate phase of the disease (asymptomatic with attendant subpatent parasitemia and reactive antibodies to T. cruzi antigens)

•

Chronic disease may become manifest years to decades after the initial infection: 1.

ETIOLOGY

Most common organ involved: heart, followed by GI tract, and to a much lesser extent the CNS a.

Cardiac involvement takes the form of arrhythmias or cardiomyopathy, but rarely both.

b.

Cardiomyopathy is bilateral but predominantly affects the right ventricle and is often accompanied by apical aneurysms and mural thrombi.

c.

Arrhythmias are a consequence of involvement of the bundle of His and have been implicated as the leading cause of sudden death in adults in highly endemic areas.

d.

Right-sided heart failure, thromboembolization, and rhythm disturbances associated with symptoms of dizziness and syncope are characteristic.

2.

Patients with megaesophagus: dysphasia, odynophagia, chronic cough, and regurgitation, frequently resulting in aspiration pneumonitis

3.

Megacolon: abdominal pain and chronic constipation, which, when severe, may lead to obstruction and perforation

4.

CNS symptoms: most often secondary to embolization from the heart or varying degrees of peripheral neuropathy

•

•

•

T. cruzi 1.

Found only in the Americas, ranging from the southern U.S. to southern Argentina

2.

Transmitted to humans by various species of bloodsucking reduviid (“kissing”) insects, primarily those of the genera Triatoma, Panstrongylus, and Rhodnius

3.

Usually found in burrows and trees where infected insects transmit the parasite to natural reservoirs (e.g., opossums and armadillos)

4.

Intrusion into enzootic areas for farmland, allowing insects to take up residence in rural dwellings, thus including humans and domestic animals in the cycle of transmission

5.

Initial infection of insects by ingesting blood from animals or humans that have circulating flagellated trypanosomes (trypomastigotes)

6.

Multiplication in the insect midgut as epimastigotes, then differentiation into metacyclic trypomastigotes discharged with the feces during subsequent blood meals

7.

Transmission to the second mammalian host through contamination of mucous membranes, conjunctivae, or wounds with insect feces containing infected forms

In the vertebrate host 1.

Movement of parasites into various cell types, intracellular transformation into amastigotes, and thereafter differentiation into trypomastigotes

2.

Following rupture of the cell membrane, parasitic invasion of local tissues or hematogenous spread to distant sites, maintaining a parasitemia infective for vectors

In addition to insect vectors, T. cruzi is transmitted through blood transfusions, transplacentally, and, occasionally, secondary to laboratory accidents

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Acute disease •

Early African trypanosomiasis

•

New World cutaneous and mucocutaneous leishmaniasis

Chronic disease •

Idiopathic cardiomyopathy

•

Idiopathic achalasia

•

Congenital or acquired megacolon

WORKUP

Principal considerations in diagnosis: •

A history of residence where transmission is known to occur

•

Recent receipt of a blood product while in an endemic area

•

Occupational exposure in a laboratory

LABORATORY TESTS

For acute diagnosis:

•

Demonstration of T. cruzi in wet preparations of blood, buffy coat, or Giemsa-stained smears

•

Xenodiagnosis, a technique involving laboratory-reared insect vectors fed on subjects with suspected infection thereafter examined for parasites, and culture of body fluids in liquid media to establish diagnosis

•

1.

Hampered by the length of time required for completion

2.

Of limited use in clinical decision making with regard to drug therapy

3.

Although xenodiagnosis and broth culture are considered to be more sensitive than microscopic examination of body fluids, sensitivities may not exceed 50%

Recent advances in serologic testing include immunoblot assay, in situ indirect fluorescent antibody, PCRbased techniques, and an immunochromatographic assay (Chagas Stat Pak)

For chronic T. cruzi infection: •

Traditional serologic tests including: complement fixation (CF), indirect immunofluorescence (IIF), indirect hemagglutination, and enzyme-linked immunosorbent assay (ELISA)

•

Serologic tests have variable sensitivity and specificity and frequent false-positive results

•

Saliva ELISA may be useful as a screening diagnostic test in epidemiologic studies of chronic trypanosomiasis infection in endemic areas

TREATMENT NONPHARMACOLOGIC THERAPY

•

Chronic chagasic heart disease: mainly supportive

•

Megaesophagus: symptoms usually amenable to dietary measures or pneumonic dilation of the esophagogastric junction

•

Chagasic megacolon: in its early stages responsive to a high-fiber diet, laxatives, and enemas

ACUTE GENERAL Rx

Nifurtimox (Lampit, Bayer 2502): •

Only drug available in the U.S. for the treatment of acute, congenital, or laboratory-acquired infection

•

Recommended oral dosage for adults: 8 to 10 mg/kg/day given in 4 divided daily doses and continued for 90 to 120 days

•

Parasitologic cure in approximately 50% of those treated; should be begun as early as possible

Benznidazole, a nitroimidazole derivative: •

Has demonstrated similar efficacy as nifurtimox in limited trials

•

Recommended oral dosage: 5 mg/kg/day for 60 days

CHRONIC Rx

•

In patients with indeterminate phase or chronic disease: Some evidence of benefit in a recent uncontrolled trial with benznidazole in patients with chagasic cardiomyopathy

•

In patients exhibiting bradyarrhythmias: pacemakers

•

In individuals with congestive heart failure:

•

1.

Treat with standard modalities for dilated, right-sided, cardiomyopathic disease.

2.

Cardiac transplant is an option for end-stage cardiomyopathy; however, reactivation rate found to be low and amenable to therapy without subsequent infection of the allograft.

3.

Myotomy or esophageal resection is reserved for patients with advanced disease.

In advanced chagasic megacolon associated with chronic fecal impaction, perforation, or, less commonly, volvulus: surgical resection

DISPOSITION

Based on few prospective studies, most patients infected with T. cruzi will not develop symptomatic Chagas' disease. REFERRAL

•

For consultation with an infectious disease specialist or communication with the Centers for Disease Control and Prevention when the disease is acutely suspected

•

To a cardiologist for pacemaker implantation for patients with brady-arrhythmias

•

To a surgeon for symptomatic disease with chagasic megaesophagus or megacolon

PEARLS & CONSIDERATIONS COMMENTS

•

In recipients of solid organ or bone marrow transplants, patients with AIDS, or those receiving chemotherapy, there may be reactivation of indeterminate phase disease.

•

Mortality predictors associated with chagasic cardiomyopathy include CHF, QT-interval dispersion, left ventricular (LV) end-systolic dimension, the presence of pathological Q waves, frequent PVCs, and isolated LAFB on ECG.

•

Chagasic esophageal disease has an increased incidence of esophageal malignancy.

•

The use of pyrethroid-impregnated curtains may represent an option for the reduction or elimination of Chagas' disease transmission in certain endemic areas.

SUGGESTED READINGS Garcia S, et al: Treatment with benznidazole during the chronic phase of experimental Chagas' disease decreases cardiac alterations. Antimicrob Agents Chemother 2005; 49(4):1521. Golgher D, Gazzinelli RT: Innate and acquired immunity in the pathogenesis of Chagas disease. Autoimmunity 2004; 37(5):399. Kirchhoff LV, et al: Transfusion-associated Chagas disease (American trypanosomiasis) in Mexico: implications for transfusion medicine in the United States. Transfusion 2006; 46(2):298. Viotti R, et al: Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med 2006; 144(10):724.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Chancroid MARIA A. CORIGLIANO, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Chancroid is a sexually transmitted disease characterized by painful genital ulceration and inflammatory inguinal adenopathy. SYNONYMS

Soft chancre Ulcus molle

ICD-9CM CODES

099.0 Chancroid EPIDEMIOLOGY & DEMOGRAPHICS

•

Exact incidence is unknown.

•

Occurs more frequently in men (male:female ratio of 10:1).

•

Clinical infection is rare in women.

•

There is a higher incidence in uncircumcised men and in tropical and subtropical regions.

•

Incubation period is 4 to 7 days but may take up to 3 wk.

•

High incidence of HIV infection associated with chancroid.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

One to three extremely painful ulcers ( Fig. 1-53 ), accompanied by tender inguinal lymphadenopathy (especially if fluctuant)

•

May present with inguinal bubo and several ulcers

•

In women: initial lesion in the fourchette, labia minora, urethra, cervix, or anus; inflammatory pustule or papule that ruptures, leaving a shallow, nonindurated ulceration, usually 1- to 2-cm diameter with ragged, undermined edges

•

Unilateral lymphadenopathy develops 1 wk later in 50% of patients

FIGURE 1-53 Chancroid. Note shaggy, ragged-edged ulcer with edema and exudative base. (Courtesy Beverly Sanders, M.D. From Goldstein B [ed]: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

ETIOLOGY

Haemophilus ducreyi, a bacillus

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other genitoulcerative diseases such as syphilis, herpes, LGV, granuloma inguinale

•

A clinical algorithm for the initial management of genital ulcer disease is described in Section III

WORKUP

Diagnosis based on history and physical examination is often inadequate. Must rule out syphilis in women because of the consequences of inappropriate therapy in pregnant women. Base initial diagnosis and treatment

recommendations on clinical impression of appearance of ulcer and most likely diagnosis for population. Definitive diagnosis is made by isolation of organism from ulcers by culture or Gram stain. LABORATORY TESTS

Darkfield microscopy, RPR, HSV cultures, H. ducreyi culture, HIV testing recommended

TREATMENT NONPHARMACOLOGIC THERAPY

Fluctuant nodes should be aspirated through healthy adjacent skin to prevent formation of draining sinus. I&D not recommended, delays healing. Use warm compresses to remove necrotic material. ACUTE GENERAL Rx

•

Azithromycin 1 g PO (single dose) or

•

Ceftriaxone 250 mg IM (single dose) or

•

Ciprofloxacin 500 mg PO bid for 3 days or

•

Erythromycin 500 mg PO qid for 7 days NOTE: Ciprofloxacin is contraindicated in patients who are pregnant, lactating, or >18 yr.

•

HIV-infected patients may need more prolonged therapy

DISPOSITION

•

All sexual partners should be treated with a 10-day course of one of the previous regimens (see “Acute General Rx”).

•

Patients should be reexamined 3 to 7 days after initiation of therapy. Ulcers should improve symptomatically within 3 days and objectively within 7 days after initiation of successful therapy.

PEARLS & CONSIDERATIONS COMMENTS

In the U.S. HSV-1 and syphilis are the most common causes of genital ulcers, followed by chancroid, LGV, and granuloma inguinale.

EVIDENCE

Despite the absence of an extensive clinical trial data base, these therapies have gained acceptance and are in accordance with CDC guidelines. The Centers for Disease Control and Prevention recommend oral azithromycin, intramuscular ceftriaxone sodium, oral ciprofloxacin, or oral erythromycin as first line therapies for treatment of chancroid caused by H. ducreyi. All regimens are effective for treating chancroid in patients that are HIV-negative and HIV-positive. Azithromycin and ceftriaxone are offered as single dose therapies.

Evidence-Based Reference Centers for Disease Control and Prevention, 2006. Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines. MMRW 2006; 55(RR-11):1.

SUGGESTED READINGS Sehgal VN, Srivastave G: Chancroid: contemporary appraisal. Int J Dermatol 2003; 42(3):182. Lewis DA: Chancroid: clinical manifestations, diagnosis and management. Sex Transm Infect 2003; 79(1):68.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Charcot-Marie-Tooth Disease LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Charcot-Marie-Tooth disease is a heterogeneous group of noninflammatory inherited peripheral neuropathies. It is the most common inherited neuromuscular disorder. (See also “Neuropathy, Inherited Peripheral”.) SYNONYMS

Peroneal muscular atrophy Hereditary motor and sensory neuropathy (HMSN) Idiopathic dominantly inherited hypertrophic polyneuropathy

ICD-9CM CODES

356.1 Charcot-Marie-Tooth disease, paralysis, or syndrome EPIDEMIOLOGY & DEMOGRAPHICS

PREDOMINANT AGE: Onset usually 10 to 20 yr but can be delayed to 50 to 60 yr PREDOMINANT SEX: Male:female ratio of 3:1 PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Variable presentation from family to family, but affected individuals in a family tend to have similar symptomatology

•

Usually, gradual onset, with slowly progressive disorder

•

Foot deformity producing a high arch (cavus) and hammertoes

•

Atrophy of the lower legs producing a storklike appearance (muscle wasting does not involve the upper legs) ( Fig. 1-54 )

•

Nerve enlargement

•

Sensory loss or other neurologic signs, although the sensory involvement is usually mild

•

Scoliosis

•

Decreased proprioception that often interferes with balance and gait

•

Painful paresthesias

•

In late cases, possible involvement of hands

•

Absence of DTRs in many cases

•

Poorly healing foot ulcers in some patients

FIGURE 1-54 Patient with Charcot-Marie-Tooth disease showing marked wasting of calf muscles and intrinsic foot muscles. (From Dubowitz V: Muscle disorders in childhood, London, 1995, WB Saunders. In Goetz CG: Textbook of clinical neurology, Philadelphia, 1999, WB Saunders.)

ETIOLOGY

Chronic segmental demyelination of peripheral nerves with hypertrophic changes caused by remyelination

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other inherited neuropathies

•

Toxic, metabolic, and nutritional polyneuropathies

WORKUP

•

The early onset, slow progression, and familial nature of the disorder are usually sufficient to establish diagnosis.

•

Electrophysiologic studies are often diagnostic and may also be helpful in defining various subtypes of this group of neuropathies.

•

Occasionally, muscle and nerve (sural) biopsy may be required.

TREATMENT ACUTE GENERAL Rx

•

Genetic counseling

•

Supportive physical therapy and occupational therapy

•

Prevention of injury to limbs with diminished sensibility

•

Bracing

CHRONIC Rx

Occasionally, surgery to add stability and restore a plantigrade foot DISPOSITION

•

Disability is usually mild and compatible with a long life.

•

10% to 20% of patients are asymptomatic.

•

A small number of cases are nonambulators by the sixth or seventh decade.

•

The condition is usually not life threatening.

REFERRAL

•

For orthopedic consultation for bracing and treatment of deformity

•

For genetic counseling

PEARLS & CONSIDERATIONS COMMENTS

Patient information on Charcot-Marie-Tooth disease is available from the Muscular Dystrophy Association, 3300 East Sunrise Drive, Tucson, Arizona 85718; phone: 1-800-572-1717. SUGGESTED READINGS Chetlin RD, Gutmann L, et al: Resistance training exercise and creatine in patients with Charcot-Marie-Tooth disease. Muscle Nerve 2004; 30:69. Gemignani F, Marbini A: Charcot-Marie-Tooth disease (CMT) distinctive phenotypic and genotypic features in CMT type 2. J Neurol Sci 2001; 184:1.

Karol LA, Elerson E: Scoliosis in patients with Charcot-Marie-Tooth disease. J Bone Joint Surg 2007; 89A:1504. Nave KA, et al: Mechanisms of disease: inherited demyelinating neuropathies—from basic to clinical research. Nat Clin Pract Neurol 2007; 3:453. Pareyson D: Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies. Neurol Sci 2004; 25:72. Parman Y: Hereditary neuropathies. Curr Opin Neurol 2007; 20:542.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Charcot's Joint LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Charcot's joint is a chronic, progressive joint degeneration, often devastating, seen most commonly in peripheral weight-bearing joints and vertebrae, which develops as a result of the loss of normal sensory innervation of the joint. It was described by Charcot as a result of tabes dorsalis. SYNONYMS

Neuropathic arthropathy

ICD-9CM CODES

094.0 Charcot's arthropathy EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: •

1 case/750 patients with diabetes mellitus; 5 cases/100 of those with peripheral neuropathy (foot is most commonly involved)

•

20% to 40% of patients with syringomyelia (shoulder most commonly involved)

•

5% to 10% of patients with tabes dorsalis; usually >60 yr (spine, hip, and knee most commonly involved)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Neuropathic joint disease is relatively painless, often in spite of considerable destruction •

Often, diffusely warm, swollen, and occasionally erythematous involved joint, the latter suggesting sepsis

•

Possible progression of joint instability; palpable osseous debris; crepitus common

•

Often, frank dislocation, leading to bony deformity, especially in more superficial joints

ETIOLOGY

The most widely accepted theory is the “neurotraumatic” theory: •

Impairment and loss of joint sensitivity decreases the protective mechanism about the joint.

•

Rapid destruction occurs.

•

Chronic inflammation and repetitive effusions develop, eventually contributing to joint instability and incongruity.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Osteomyelitis, cellulitis, abscess

•

Infectious arthritis

•

Osteoarthritis

•

Rheumatoid and other inflammatory arthritides

WORKUP

•

An underlying neurologic disorder must always be present.

•

Diabetes mellitus with peripheral neuropathy is the most common cause ( Fig. 1-55 ).

•

Syringomyelia, tabes dorsalis, Charcot-Marie-Tooth disease, congenital indifference to pain, alcoholism, and spinal dysraphism can all lead to the disorder.

FIGURE 1-55 Diabetes mellitus and neuropathic arthritis. Note lateral displacement of metatarsals (left) and fragmentation and osseous debris (right). (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders.)

LABORATORY TESTS

In questionable cases, aspiration, sometimes including biopsy, to rule out sepsis IMAGING STUDIES

Plain roentgenography •

Sufficient to establish diagnosis in most cases, especially if etiology is known

•

Findings: variable degrees of destruction and dislocation

TREATMENT

ACUTE GENERAL Rx

•

Protection of effusions, sprains, and fractures until all hyperemic response has resolved

•

Braces, special shoes with molded inserts, and elevation of the extremity

•

Patient education with avoidance of weight bearing when lower extremity joints are involved

•

Surgery: only limited value

DISPOSITION

Once the full-blown neuropathic joint has developed, treatment is difficult. SUGGESTED READINGS Choski P, et al: Charcot arthropathy: an often overlooked complication of diabetes mellitus. J Ark Med Soc 2007; 103:229. Guyton GP, Saltzman CL: The diabetic foot: basic mechanisms of disease. Instr Course Lect 2002; 51:169. Herbst SA, Jones KB, Saltzman CL: Pattern of diabetic neuropathic arthropathy associated with peripheral bone mineral density. J Bone Joint Surg 2004; 86:378. Neves FS, et al: Syringomyelia, neuropathic arthropathy and rheumatoid arthritis as diagnostic dilemmas in two different cases: confounding factor and true coexistence. Clin Rheumatol 2007; 26:98. Pakarinen TK, et al: Charcot arthropathy of the diabetic foot: current concepts and review of 36 cases. Scand J Surg 2002; 91:195. Pinzur MS: Current concepts review: Charcot arthropathy of the foot and ankle. Foot Ankle Int 2007; 28:952. Slater RA, et al: The diabetic Charcot foot. 1st Med Assoc J 2004; 6:280.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Chlamydia Genital Infections MARIA A. CORIGLIANO, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Genital infection with Chlamydia trachomatis may result in urethritis, epididymitis, cervicitis, and acute salpingitis, but often it is asymptomatic in women (see “Pelvic Inflammatory Disease”). In men, urethritis, mucopurulent discharge, dysuria, urethral pruritus.

ICD-9CM CODES

597.80 Urethritis 604.0

Epididymitis

616.0

Cervicitis

381.51 Acute salpingitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Chlamydia trachomatis is the most common cause of sexually transmitted disease in the U.S. More than 4 million infections occur annually, although the exact number is unknown because reporting is not required in all states. Occurrence is common worldwide and has been increasing steadily over the last 2 decades in the U.S., Canada, Australia, and Europe.

•

Most women with endocervical or urethral infections are asymptomatic.

•

Up to 45% of cases of gonococcal infection may have concomitant chlamydial infection.

•

Infertility or ectopic pregnancy can result as a complication from symptomatic or asymptomatic chronic infections of the endometrium and fallopian tubes.

•

Conjunctival and pneumonic infection of the newborn may result from infection in pregnancy.

•

In men 15% to 55% of cases are of C. trachomatis. Complications of nongonococcal urethritis in men infected with C. trachomatis include epididymitis and Reiter's syndrome.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Clinical manifestations may be similar to those of gonorrhea: mucopurulent endocervical discharge, with edema, erythema, and easily induced endocervical bleeding caused by inflammation of endocervical columnar epithelium. Less frequent manifestations may include bartholinitis, urethral syndrome with dysuria and pyuria, perihepatitis (Fitz-Hugh–Curtis syndrome). ETIOLOGY

•

Chlamydia trachomatis, serotypes D through K

•

Obligate, intracellular bacteria

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Gonorrhea, nongonococcal urethritis (nonchlamydial etiologies) WORKUP

Diagnosis based on laboratory demonstration of evidence of infection in intraurethral or endocervical swab by various tests. The intracellular organism is less readily recovered from the discharge. LABORATORY TESTS

•

Cell culture is the reference method for diagnosis (single culture sensitivity 80% to 90%), but it is labor intensive and takes 48 to 96 hr; it is not suited for large screening programs.

•

Nonculture methods: Direct fluorescent antibody (DFA) tests Enzyme immunoassay (EIA) DNA probes Polymerase chain reaction (PCR)

•

With the exception of PCR, the other tests are probably less specific than cell culture and may yield falsepositive results.

•

Because this is an intracellular organism, purulent discharge is not an appropriate specimen. An adequate sample of infected cells must be obtained.

•

10 WBCs per high-power field.

TREATMENT ACUTE GENERAL Rx

Nongonococcal urethritis, urethritis, cervicitis, conjunctivitis (except for LGV): •

Azithromycin 1 g PO × 1 or

•

Doxycycline 100 mg PO bid for 7 days

•

Alternatives 1.

Erythromycin base 500 mg PO qid for 7 days or

2.

Erythromycin ethylsuccinate 800 mg PO qid for 7 days or

3.

Ofloxacin 300 mg PO bid for 7 days

4.

Levofloxacin 500 mg PO qd for 7 days

Infection in pregnancy:

•

Erythromycin base 500 mg PO qid for 7 days or

•

Amoxicillin 500 mg PO tid for 7 days

Alternatives: 1.

Erythromycin base 250 mg PO qid for 7 days or

2.

Erythromycin ethylsuccinate 800 mg PO qid for 7 days or

3.

Erythromycin ethylsuccinate 400 mg PO qid for 14 days or

4.

Azithromycin 1 g PO (single dose)

NOTE: Doxycycline and ofloxacin are contraindicated in pregnancy. Safety and efficacy of azithromycin are not established in pregnancy and lactation, although preliminary data indicate that it may be safe and effective. Erythromycin estolate is contraindicated in pregnancy because of drug-related hepatotoxicity. FOLLOW-UP: Reculture after therapy completion and refer partners for evaluation and treatment. RECURRENT AND PERSISTENT URETHRITIS: Retreat noncompliant patients with the above regimens. If patient was initially compliant, recommended regimens: metronidazole 2 g PO in single dose plus erythromycin base 500 mg PO qid for 7 days or erythromycin ethylsuccinate 800 mg PO qid for 7 days. DISPOSITION

See “Gonorrhea.” REFFERAL

Refer to infectious disease specialist if persistant infection or to gynecologist if salpingitis is suspected.

EVIDENCE

Doxycycline is effective in the treatment of genital chlamydial infections in men and nonpregnant women. Small randomized controlled trials (RCTs) with short-term follow-up have found microbiological cure rates of at least 95%. [[1]] Another systematic review found no significant difference between azithromycin and doxycycline in terms of microbiological cure rates in males and nonpregnant females with genital chlamydial infections.[[2]] In small, short-term RCTs including men and nonpregnant women with genital chlamydial infection, cure rates achieved with erythromycin ranged from 77% to 100%.[[1]] No significant difference was found in two unblinded RCTs between azithromycin and amoxicillin in terms of microbiological cure in pregnant women with chlamydial infections.[[3]]

Evidence-Based References 1. Low N: Chlamydia (uncomplicated, genital). Clin Evid 2004; 12:2203. 2. Lau CY, Qureshi AK: Azithromycin versus doxycycline for genital chlamydial infections: a metaanalysis of randomized clinical trials. Sex Transm Dis 2002; 29:497.Reviewed in: Clin Evid 12:2200, 2004. 3. Jacobson GF: A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy. Am J Obstet Gynecol 2001; 184:1352.Reviewed in: Clin Evid 12:2200, 2004.

SUGGESTED READINGS Centers for Disease Control and Prevention: 2006 sexually transmitted diseases treatment guidelines. MMWR Morb Mortal Wkly Rep 2006; 55(RR-11): Spiliopoulou , et al: Chlamydia trachomatis: time for screening?. Clin Microbiol Infect 2005; 11(9):687.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cholangitis STEVEN M. OPAL, M.D., MICHELE HALPERN, M.D.

BASIC INFORMATION DEFINITION

Cholangitis refers to an inflammation and/or infection of the hepatic and common bile ducts associated with obstruction of the common bile duct. SYNONYMS

Biliary sepsis Ascending cholangitis Suppurative cholangitis

ICD-9CM CODES

576.1 Cholangitis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Complicates approximately 1% of cases of cholelithiasis PEAK INCIDENCE: Seventh decade PREVALENCE (IN U.S.): 2 cases/1000 hospital admissions PREDOMINANT SEX: •

Females, for cholangitis secondary to gallstones

•

Males, for cholangitis secondary to malignant obstruction and HIV infection

PREDOMINANT AGE: Seventh decade and older; unusual >50 yr of age PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usually acute onset of fever, chills, abdominal pain, tenderness over the RUQ of the abdomen, and jaundice (Charcot's triad)

•

All signs and symptoms in only 50% to 85% of patients

•

Often, dark coloration of the urine resulting from bilirubinuria

•

Complications: 1.

Bacteremia (50%) and septic shock

2.

Hepatic abscess and pancreatitis

ETIOLOGY

Obstruction of the common bile duct causing rapid proliferation of bacteria in the biliary tree •

Most common cause of common bile duct obstruction: stones, usually migrated from the gallbladder

•

Other causes: prior biliary tract surgery with secondary stenosis, tumor (usually arising from the pancreas or biliary tree), and parasitic infections from Ascaris lumbricoides or Fasciola hepatica

•

Iatrogenic after contamination of an obstructed biliary tree by endoscopic retrograde cholangiopancreatoscopy (ERCP) or percutaneous transhepatic cholangiography (PTC)

•

Primary sclerosing cholangitis (PSC)

•

HIV-associated sclerosing cholangitis: associated with infection by CMV, Cryptosporidium, Microsporidia, and Mycobacterium avium complex

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Biliary colic

•

Acute cholecystitis

•

Liver abscess

•

Peptic ulcer disease (PUD)

•

Pancreatitis

•

Intestinal obstruction

•

Right kidney stone

•

Hepatitis

•

Pyelonephritis

WORKUP

•

Blood cultures

•

CBC

•

Liver function tests

LABORATORY TESTS

•

Usually, elevated WBC count with a predominance of polymorphonuclear forms

•

Elevated alkaline phosphatase and bilirubin in chronic obstruction

•

Elevated transaminases in acute obstruction

•

Positive blood cultures in 50% of cases, typically with enteric gram-negative aerobes (e.g., E. coli, Klebsiella pneumoniae), enterococci, or anaerobes

IMAGING STUDIES

•

•

•

Ultrasound: 1.

Allows visualization of the gallbladder and bile ducts to differentiate extrahepatic obstruction from intrahepatic cholestasis

2.

Insensitive but specific for visualization of common duct stones

CT scan: 1.

Less accurate for gallstones

2.

More sensitive than ultrasound for visualization of the distal part of the common bile duct

3.

Also allows better definition of neoplasm

ERCP: 1.

Confirms obstruction and its level

2.

Allows collection of specimens for culture and cytology

3.

Indicated for diagnosis if ultrasound and CT scan are inconclusive

4.

May be indicated in therapy (see “Treatment”)

TREATMENT NONPHARMACOLOGIC THERAPY

Biliary decompression •

May be urgent in severely ill patients or those unresponsive to medical therapy within 12 to 24 hr

•

May also be performed semielectively in patients who respond

•

Options: 1.

ERCP with or without sphincterotomy or placement of a draining stent

2.

Percutaneous transhepatic biliary drainage for the acutely ill patient who is a poor surgical candidate

3.

Surgical exploration of the common bile duct

ACUTE GENERAL Rx

•

Nothing by mouth

•

Intravenous hydration

•

Broad-spectrum antibiotics directed at gram-negative enteric organisms, anaerobes, and enterococcus: if infection is nosocomial, post-ERCP, or the patient is in shock, broaden antibiotic coverage.

CHRONIC Rx

Repeated decompression may be necessary, particularly when obstruction is related to neoplasm. DISPOSITION

Excellent prognosis if obstruction is amenable to definitive surgical therapy; otherwise relapses are common. REFERRAL

•

To biliary endoscopist if obstruction is from stones or a stent needs to be placed

•

To interventional radiologist if external drainage is necessary

•

To a general surgeon in all other cases

•

To an infectious disease specialist if blood cultures are positive or the patient is in shock or otherwise severely ill

PEARLS & CONSIDERATIONS

•

Cholangitis is a life threatening form of intra-abdominal sepsis, though it may appear to be rather innocuous at its onset.

•

Antibiotics alone will not resolve cholangitis in the presence of biliary obstruction because high intrabiliary pressures prevent antibiotic delivery. Decompression and drainage of the biliary tract to alleviate the obstruction with antimicrobial therapy is the therapy of choice.

SUGGESTED READINGS Kumar R, et al: Endoscopic biliary drainage for severe acute cholangitis in biliary obstruction as a result of malignant and benign diseases. J Gastroenterol Hepatol 2004; 19(9):994. Ozden I, et al: Endoscopic and radiologic interventions as the leading causes of severe cholangitis in a tertiary referral center. Am J Surg 2005; 189(6):702. Yarze JC, Herlihy KJ, Scalia SV: Cholangiohepatoma presenting with recurrent cholangitis. Dig Dis Sci 2005; 50(3):552.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cholecystitis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cholecystitis is an acute or chronic inflammation of the gallbladder generally secondary to gallstones (>95% of cases). SYNONYMS

Gallbladder attack

ICD-9CM CODES

575.0 Acute cholecystitis 574.0 Calculus of the gallbladder with acute cholecystitis 575.1 Cholecystitis without mention of calculus EPIDEMIOLOGY & DEMOGRAPHICS

•

Acute cholecystitis occurs most commonly in females during the fifth and sixth decades.

•

The incidence of gallstones is 0.6% in the general population and much higher in certain ethnic groups (>75% of Native Americans by age 60 yr).

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pain and tenderness in the right hypochondrium or epigastrium; pain possibly radiating to the infrascapular region

•

Palpation of the right upper quadrant (RUQ) eliciting marked tenderness and stoppage of inspired breath (Murphy's sign)

•

Guarding

•

Fever (33%)

•

Jaundice (25% to 50% of patients)

•

Palpable gallbladder (20% of cases)

•

Nausea and vomiting (>70% of patients)

•

Fever and chills (>25% of patients)

•

Medical history often revealing ingestion of large, fatty meals before onset of pain in the epigastrium and RUQ

ETIOLOGY

•

Gallstones (>95% of cases)

•

Ischemic damage to the gallbladder, critically ill patient (acalculous cholecystitis)

•

Infectious agents, especially in patients with AIDS (CMV, Cryptosporidium)

•

Strictures of the bile duct

•

Neoplasms, primary or metastatic

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hepatic: hepatitis, abscess, hepatic congestion, neoplasm, trauma

•

Biliary: neoplasm, stricture

•

Gastric: pelvic ulcer disease (PUD), neoplasm, alcoholic gastritis, hiatal hernia

•

Pancreatic: pancreatitis, neoplasm, stone in the pancreatic duct or ampulla

•

Renal: calculi, infection, inflammation, neoplasm, ruptured kidney

•

Pulmonary: pneumonia, pulmonary infarction, right-sided pleurisy

•

Intestinal: retrocecal appendicitis, intestinal obstruction, high fecal impaction

•

Cardiac: myocardial ischemia (particularly involving the inferior wall), pericarditis

•

Cutaneous: herpes zoster

•

Trauma

•

Fitz-Hugh–Curtis syndrome (perihepatitis)

•

Subphrenic abscess

•

Dissecting aneurysm

•

Nerve root irritation caused by osteoarthritis of the spine

WORKUP

Workup consists of detailed history and physical examination coupled with laboratory evaluation and imaging

studies. No single clinical finding or laboratory test is sufficient to establish or exclude cholecystitis without further testing. LABORATORY TESTS

•

Leukocytosis (12,000 to 20,000) is present in >70% of patients.

•

Elevated alkaline phosphatase, ALT, AST, bilirubin; bilirubin elevation >4 mg/dl is unusual and suggests presence of choledocholithiasis.

•

Elevated amylase may be present (consider pancreatitis if serum amylase elevation exceeds 500 U).

IMAGING STUDIES

•

Ultrasound of the gallbladder is the preferred initial test; it will demonstrate the presence of stones and also dilated gallbladder with thickened wall and surrounding edema in patients with acute cholecystitis.

•

Nuclear imaging (HIDA scan) is useful for diagnosis of cholecystitis: sensitivity and specificity exceed 90% for acute cholecystis. This test is only reliable when bilirubin is >5 mg/dl. A positive test will demonstrate obstruction of the cystic or common hepatic duct; the test will not demonstrate the presence of stones.

•

CT scan of abdomen is useful in cases of suspected abscess, neoplasm, or pancreatitis.

•

Plain film of the abdomen generally is not useful, because >25% of stones are radiopaque.

TREATMENT NONPHARMACOLOGIC THERAPY

Provide IV hydration; withhold oral feedings. ACUTE GENERAL Rx

•

Cholecystectomy (laparoscopic is preferred, open cholecystectomy is acceptable); conservative management with IV fluids and antibiotics (ampicillin-sulbactam [Unasyn] 3 g IV q6h or piperacillintazobactam [Zosyn] 4.5 g IV q8h) may be justified in some high-risk patients to convert an emergency procedure into an elective one with a lower mortality.

•

Endoscopic retrograde cholangiopancreatoscopy (ERCP) with sphincterectomy and stone extraction can be performed in conjunction with laparoscopic cholecystectomy for patients with choledochal lithiasis; approximately 7% to 15% of patients with cholelithiasis also have stones in the common bile duct.

•

IV fluids, broad-spectrum antibiotics, pain management (meperidine prn) should be used.

DISPOSITION

•

Prognosis is good; elective laparoscopic cholecystectomy can be performed as outpatient procedure.

•

Hospital stay (when necessary) varies from overnight with laparoscopic cholecystectomy to 4 to 7 days with open cholecystectomy.

•

Complication rate is approximately 1% (hemorrhage and bile leak) for laparoscopic cholecystectomy and >0.5% (infection) with open cholecystectomy.

REFERRAL

Hospitalization and surgical referral in all patients with acute cholecystitis

PEARLS & CONSIDERATIONS COMMENTS

•

Patients should be instructed that stones may recur in bile ducts.

•

Gallbladder aspiration in which all fluid visualized by ultrasound is aspirated represents a nonsurgical treatment when patients who are at high operative risk develop acute cholecystitis. Salvage cholecystectomy is reserved for nonresponders.

SUGGESTED READINGS Cuschieri A: Management of patients with gallstones and ductal calculi. Lancet 2002; 360:739. Trowbridge RL, et al: Does this patient have acute cholecystitis?. JAMA 2003; 289:80.

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Cholelithiasis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cholelithiasis is the presence of stones in the gallbladder. SYNONYMS

Gallstones

ICD-9CM CODES

574.2 Calculus of the gallbladder without mention of cholecystitis 574.0 Calculus of the gallbladder with acute cholecystitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Gallstone disease can be found in 12% of the U.S. population. Of these, 2% to 3% (500,000 to 600,000) are treated with cholecystectomies each year.

•

Annual medical expenditures for gallbladder surgeries in the U.S. exceed $5 billion.

•

Incidence of gallbladder disease increases with age. Highest incidence is in the fifth and sixth decades. Predisposing factors for gallstones are female sex, pregnancy, age >40 yr, family history of gallstones, obesity, ileal disease, oral contraceptives, diabetes mellitus, rapid weight loss, estrogen replacement therapy.

•

Patients with gallstones have a 20% chance of developing biliary colic or its complications at the end of a 20-yr period.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination is entirely normal unless patient is having biliary colic; 80% of gallstones are asymptomatic.

•

Typical symptoms of obstruction of the cystic duct include intermittent, severe, cramping pain affecting the right upper quadrant (RUQ).

•

Pain occurs mostly at night and may radiate to the back or right shoulder. It can last from a few minutes to several hours.

ETIOLOGY

•

75% of gallstones contain cholesterol and are usually associated with obesity, female sex, diabetes mellitus; mixed stones are most common (80%), pure cholesterol stones account for only 10% of stones.

•

25% of gallstones are pigment stones (bilirubin, calcium, and variable organic material) associated with hemolysis and cirrhosis. These tend to be black pigment stones that are refractory to medical therapy.

•

50% of mixed-type stones are radiopaque.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Pelvic ulcer disease (PUD)

•

GERD

•

IBD

•

Pancreatitis

•

Neoplasms

•

Nonnuclear dyspepsia

•

Inferior wall MI

•

Hepatic abscess

LABORATORY TESTS

Generally normal unless patient has biliary obstruction (elevated alkaline phosphatase, bilirubin). IMAGING STUDIES

•

Ultrasound of the gallbladder will detect small stones and biliary sludge (sensitivity, 95%; specificity, 90%); the presence of dilated gallbladder with thickened wall is suggestive of acute cholecystitis.

•

Nuclear imaging (HIDA scan) can confirm acute cholecystitis (>90% accuracy) if gallbladder does not visualize within 4 hr of injection and the radioisotope is excreted in the common bile duct.

•

Common bile duct stones can be detected noninvasively by magnetic resonance cholangiopancreatography (MRCP) or invasively via endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiography.

TREATMENT NONPHARMACOLOGIC THERAPY

Lifestyle changes (avoidance of diets high in polyunsaturated fats, weight loss in obese patients—however, avoid rapid weight loss) ACUTE GENERAL Rx

•

The management of gallstones is affected by the clinical presentation.

•

Asymptomatic patients do not require therapeutic intervention.

•

Surgical intervention is generally the ideal approach for symptomatic patients. Laparoscopic cholecystectomy is generally preferred over open cholecystectomy because of the shorter recovery period and lower mortality. Between 5% and 26% of patients undergoing elective laparoscopic cholecystectomy will require conversion to an open procedure. Most common reason is inability to clearly identify the biliary anatomy.

•

Laparoscopic cholecystectomy after endoscopic sphincterectomy is recommended for patients with common bile duct stones and residual gallbladder stones. Where possible, single-stage laparoscopic treatments with removal of duct stones and cholecystectomy during the same procedure are preferable.

•

Patients who are not appropriate candidates for surgery because of coexisting illness or patients who refuse surgery can be treated with oral bile salts: ursodiol (Actigall) 8 to 10 mg/kg/day in 2 to 3 divided doses for 16 to 20 mo, or chenodiol (Chenix) 250 mg bid initially, increasing gradually to a dose of 60 mg/kg/day. Candidates for oral bile salts are patients with cholesterol stones (radiolucent, noncalcified stones), with a diameter of =15 mm and having three or fewer stones. Candidates for medical therapy must have a functioning gallbladder and must have absence of calcifications on CT scans.

•

Direct solvent dissolution with methyl tert-butyl ether (MTBE) is rarely used. Administration of the solvent is either through percutaneous transhepatic placement of a catheter into the gallbladder or endoscopic retrograde catheter placement with subsequent continuous infusion and aspiration of the solvent either manually or by automatic pump system.

•

Extracorporeal shock wave lithotripsy (ESWL) is another form of medical therapy. It can be used in patients with stone diameter of =3 cm and having three or fewer stones.

DISPOSITION

•

Recurrence rate after bile acid treatment is approximately 50% in 5 yr. Periodic ultrasound is necessary to assess the effectiveness of treatment.

•

Gallstones recur after dissolution therapy with MTBE in >40% of patients within 5 yr.

•

Following extracorporeal shock wave lithotripsy, stones recur in approximately 20% of patients after 4 yr.

•

Patients with at least one gallstone >5 mm in diameter have a greater than fourfold increased risk of presenting with acute biliary pancreatitis. A policy of watchful waiting in such cases is generally unwarranted.

•

A potential serious complication of gallstones is acute cholangitis. ERCP and endoscopic sphincterectomy (EC) followed by interval laparoscopic cholecystectomy is effective in acute cholangitis.

SUGGESTED READINGS Bellows CF, et al: Management of gallstones. Am Fam Physician 2005; 72:637. Moon JH, et al: The detection of bile duct stones in suspected biliary pancreatitis: comparison of MRCP, ERCP, and intraductal US. Am J Gastroenterol 2005; 100:1051.

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Cholera GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Cholera is an acute diarrheal illness caused by Vibrio cholerae. SYNONYMS

None

ICD-9CM CODES

001.0 Cholera EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Previously, approximately 50 cases per yr, mostly in travelers returning from endemic areas. From 1995 to 2000, 61 cases reported, 37 (61%) of which acquired outside the U.S. PEAK INCIDENCE: •

None in the U.S.

•

Summer and fall in endemic areas

PREDOMINANT SEX: None PREDOMINANT AGE: In nonendemic areas, attack rates are equal in all age groups. In epidemic areas, children over the age of 2 yr are most commonly infected. Neonatal infection: illness is uncommon before the age of 2 yr, likely because of passive immunity. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Infection may result in asymptomatic illness or a mild diarrhea. The classic illness is described as the abrupt onset of voluminous watery diarrhea, which may lead to severe dehydration, acidosis, shock, and death. Vomiting may occur early in the illness, but fever and abdominal pain are usually absent. The typical “rice water” stools are pale with flecks of mucus and contain no blood. Muscle cramps may be prominent, and are the result of loss of fluid and electrolytes. Untreated illness results in hypovolemic shock, and death may occur in hours to days. With adequate fluid and electrolyte repletion, cholera is a self-limited illness that resolves in a few days. The use of antimicrobials can shorten the course of illness.

ETIOLOGY

The organism responsible for this illness is one of several strains of V. cholerae. Most infections result from the 01 serotype, the El Tor biotype. In the U.S., one outbreak occurred from the ingestion of illegally imported crab, and sporadic infection has been associated with the consumption of contaminated shellfish in Gulf Coast states. Most cases are seen in returning travelers. Transmission during epidemics is the result of the ingestion of contaminated water and, in some instances, contaminated food.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Mild illness may mimic gastroenteritis resulting from a variety of etiologies.

•

Sudden, voluminous diarrhea causing marked dehydration is uncommon in other illnesses.

WORKUP

Stool should be sent for culture and microscopy. Treatment should not be delayed while awaiting culture results. LABORATORY TESTS

•

WBC may be elevated, and hemoglobin may be increased as a result of hemoconcentration.

•

Elevated bun and creatinine suggests prerenal azotemia. Hypoglycemia may occur. Stool cultures on appropriate media may grow the organism. Wet mount of stool under dark field or phase contrast microscopy shows organisms with characteristic darting motility.

TREATMENT NONPHARMACOLOGIC THERAPY

The mainstay of therapy is adequate fluid and electrolyte replacement. This can usually be achieved using oral rehydration solutions containing salts and glucose. Some patients may require intravenous fluid and electrolyte replacement. ACUTE GENERAL Rx

•

•

Antimicrobial therapy can decrease shedding of fluid and organisms and can shorten the course of illness: 1.

Doxycycline 100 mg po bid for 5 days or

2.

SMX-TMP, one DS tablet po bid for 5 days or

3.

Azithromycin two 500 mg tablets po as a single dose

Resistance to SMX-TMP is increasing in travel-associated infections.

CHRONIC Rx

It is likely that asymptomatic chronic carriers exist; however, because they are difficult to identify, and their role in transmission of disease appears to be rather limited, there is no recommendation for treatment of these

individuals. DISPOSITION

The mortality of adequately hydrated patients is less than 1%. REFERRAL

If more than mild illness occurs

PEARLS & CONSIDERATIONS COMMENTS

•

There is currently no indication for vaccination of travelers to endemic areas. The risk of infection is small, protection from available vaccines is limited, and side effects are prominent and frequent.

•

Doxycycline should not be used to treat children or pregnant women.

•

A recent study indicates a single dose treatment strategy with azithromycin is significantly better than ciprofloxacin for the management of cholera.

EVIDENCE

Rice-based oral rehydration solution has been shown to be significantly more effective than standard oral rehydration solution for the reduction of stool volume in patients with cholera. [140] [141] Tetracycline has been shown to significantly reduce stool volume and duration of diarrhea compared with placebo in patients with severe cholera secondary to infection with Vibrio cholerae O139 Bengal. [[3]] Clinical improvement and eradication of V. cholerae has been found to be similar with tetracycline and ciprofloxacin.[[4]]

Evidence-Based References 1. Rabbani GH, et al: Antidiarrheal effects of L-histidine-supplemented rice-based oral rehydration solution in the treatment of male adults with severe cholera in Bangladesh: a double-blind, randomized trial. J Infect Dis 2005; 191(b):1507-1514. 2. Garcia L, et al: The vaccine candidate Vibrio cholerae 638 is protective against cholera in healthy volunteers. Infect Immun 2005; 73(b):3018-3024. 3. Thiagarajah JR, Verkman AS: New drug targets for cholera therapy. Trends Pharmacol Sci 2005; 26(b):172-175. 4. Lucas ME, et al: Effectiveness of mass oral cholera vaccination in Beira, Mozambique. N Engl J Med 2005; 352(b):757-767.

SUGGESTED READINGS Hill DR, et al: Oral cholera vaccines: use in clinical practice. Lancet Infect Dis 2006; 6(6):361. Saha D, et al: Single dose azithromycin for the treatment of cholera in adults. N Engl J Med 2006; 354(23):2452.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Chronic Fatigue Syndrome FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Chronic fatigue syndrome (CFS) is characterized by four or more of the following symptoms, present concurrently for at least 6 mo: •

Impaired memory or concentration

•

Sore throat

•

Tender cervical or axillary lymph nodes

•

Muscle pain

•

Multijoint pain

•

New headaches

•

Unrefreshing sleep

•

Postexertion malaise

SYNONYMS

Yuppie flu CFS Chronic Epstein-Barr syndrome

ICD-9CM CODES

780.7 Chronic fatigue syndrome 300.8 Neurasthenia EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE IN U.S.: 100 to 300 cases/100,000 persons PREDOMINANT AGE: Young adulthood and middle age PREDOMINANT SEX: Female > male

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

There are no physical findings specific for CFS.

•

The physical examination may be useful to identify fibromyalgia and other rheumatologic conditions that may coexist with CFS.

ETIOLOGY

•

The etiology of CFS is unknown.

•

Many experts suspect that a viral illness may trigger certain immune responses leading to the various symptoms. Most patients often report the onset of their symptoms with a flulike illness.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Psychosocial depression, dysthymia, anxiety-related disorders, and other psychiatric diseases

•

Infectious diseases (SBE, Lyme disease, fungal diseases, mononucleosis, HIV, chronic hepatitis B or C, TB, chronic parasitic infections)

•

Autoimmune diseases: SLE, myasthenia gravis, multiple sclerosis, thyroiditis, RA

•

Endocrine abnormalities: hypothyroidism, hypopituitarism, adrenal insufficiency, Cushing's syndrome, diabetes mellitus, hyperparathyroidism, pregnancy, reactive hypoglycemia

•

Occult malignant disease

•

Substance abuse

•

Systemic disorders: chronic renal failure, COPD, cardiovascular disease, anemia, electrolyte abnormalities, liver disease

•

Other: inadequate rest, sleep apnea, narcolepsy, fibromyalgia, sarcoidosis, medications, toxic agent exposure, Wegener's granulomatosis

LABORATORY TESTS

•

•

No specific laboratory tests exist for diagnosing CFS. Initial laboratory tests are useful to exclude other conditions that may mimic or may be associated with CFS. 1.

Screening laboratory tests: CBC, ESR, ALT, total protein, albumin, globulin, alkaline phosphatase, calcium, phosphorus, glucose, BUN, creatinine, electrolytes, TSH, and urinalysis are useful.

2.

Serologic tests for Epstein-Barr virus, Candida albicans, human herpesvirus 6, and other studies for immune cellular abnormalities are not useful; these tests are expensive and generally not recommended.

Other tests may be indicated depending on the history and physical examination (e.g., ANA, RF in patients presenting with joint complaints or abnormalities on physical examination, Lyme titer in areas where Lyme disease is endemic).

IMAGING STUDIES

Generally not recommended unless history and physical examination indicate specific abnormalities (e.g., chest x-ray in any patient suspected of TB or sarcoidosis)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Patients should be reassured that the illness is not fatal and that most patients improve over time.

•

An initially supervised exercise program to preserve and increase strength is beneficial for most patients and can improve symptoms.

GENERAL Rx

Therapy is generally palliative. The following medications may be helpful: •

Antidepressants: The choice of antidepressant varies with the desired side effects. Patients with difficulty sleeping or fibromyalgia-like symptoms may benefit from low-dose tricyclics (doxepin 10 mg hs or amitriptyline 25 mg qhs). When sedation is not desirable, low-dose SSRIs (paroxetine 20 mg qd) often help alleviate fatigue and associated symptoms.

•

NSAIDs can be used to relieve muscle and joint pain and headaches.

“Alternative” medications (herbs, multivitamins, nutritional supplements) are very popular with many CFS patients but are generally not very helpful.

PEARLS & CONSIDERATIONS COMMENTS

•

In CFS the symptoms are serious enough to reduce daily activities by >50% and in absence of any other medically identifiable disorders.

•

Moderate to complete recovery at 1 yr occurs in 22% to 60% of patients with CFS.

EVIDENCE

Graded aerobic exercise has been shown to result in improvements in fatigue and physical functioning in patients with CFS.[[1]] A randomized controlled trial compared graded exercise plus fluoxetine, graded exercise plus placebo, general advice to exercise plus fluoxetine, and general advice to exercise plus placebo. After 26 weeks, significantly fewer patients in the active exercise groups experienced fatigue.[[2]] Cognitive behavioral therapy appears to be an effective treatment for adult outpatients with chronic fatigue syndrome (CFS). Physical functioning is significantly improved, and the treatment is highly acceptable to patients.[[3]] There is insufficient evidence for the benefit of corticosteroids, nicotinamide adenine dinucleotide (NADH), immunoglobulins, prolonged rest, or antidepressants in the treatment of CFS.[[4]]

Evidence-Based References 1. Edmonds M, McGuire H, Price J: Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev 2004; 3:CD003200, 2. Wearden AJ, et al: Randomised, double-blind, placebo controlled treatment trial of fluoxetine and a graded exercise programme for chronic fatigue syndrome. Br J Psychiatry 1998; 172:485-490. 3. Price JR, Couper J: Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev 2000; 2:CD001027, 4. Reid S, et al: Chronic fatigue syndrome. Clinical Evidence, 12. London: BMJ Publishing Group; 2003.

SUGGESTED READINGS Hickie I, et al: Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ 2006; 333:575.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Chronic Inflammatory Demyelinating Polyradiculoneuropathy GENNA GEKHT, M.D.

BASIC INFORMATION DEFINITION

A chronic demyelinating disease of the spinal nerve roots and peripheral nerves that is characterized by weakness and sensory deficits. SYNONYMS

CIDP RELATED DISORDERS

•

Multifocal motor neuropathy with conduction block

•

Lewis-Sumner syndrome

•

Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy

ICD-9CM CODES

357.8 Inflammatory and toxic neuropathy, other (use for chronic inflammatory demyelinating polyradiculoneuropathy) EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 1.0 to 1.9 per 100,000 PREDOMINANT SEX: Male predominance PREDOMINANT AGE: Most common in the fifth to seventh decade, although may also occur in children PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Onset is over weeks, months, or years.

•

Symptoms may be both sensory (paresthesias, neuropathic pain, and numbness of the hands and feet) and motor (weakness).

•

Postural instability, gait abnormalities, and proximal muscle weakness may become prominent late in the disease.

•

Sensory findings on examination include impaired vibration and joint position sense more commonly than impaired light touch, pinprick, and temperature sensation.

•

Muscle weakness is usually distal and symmetric, although may occasionally be asymmetric and more proximal than distal.

•

Reflexes are usually reduced or absent.

•

Cranial nerve abnormalities as well as bowel and bladder dysfunction are highly unusual.

•

Autonomic dysfunction is rare, but may occur.

ETIOLOGY

CIDP occurs as a primary (idiopathic) form and may also occur in association with a number of systemic disorders.

•

The idiopathic variety is most common and an autoimmune process is likely.

•

The most common systemic disorder associated with CIDP is a monoclonal gammopathy.

•

Occasionally an underlying plasma cell dyscrasia such as Waldenstrom's macroglobulinemia, multiple myeloma, or osteosclerotic myeloma may be identified.

•

An association with diabetes mellitus has been recognized more recently.

•

CIDP may occasionally occur in the context of human immunodeficiency virus (HIV) and hepatitis B or C virus infection.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Guillain-Barré syndrome (GBS)—the difference being that GBS evolves over a maximum of 4 wk and CIDP usually progresses over at least 8 wk.

•

Diabetic neuropathy—the distinction can be made with electrodiagnostic studies, which show axonal physiology in diabetic neuropathy.

•

Mononeuritis multiplex.

•

Monoclonal gammopathy of undetermined significance, plasma cell dyscrasia, osteosclerotic myeloma, and HIV infection are not so much part of the differential diagnosis, but may coexist and so should always be sought.

WORKUP

Nerve conduction studies and electromyography—these should show evidence of primary demyelination (with or without secondary axonal loss). Nerve biopsy may occasionally be required. LABORATORY TESTS

•

Lumbar puncture 1.

Shows increased CSF protein (especially helpful if >100 mg/dl)

2.

There is little or no pleocytosis (80,000 deaths/yr.

•

COPD is the fourth leading cause of death in the U.S. and is expected to become the third leading cause of death by 2020.

•

Highest incidence is in males >40 yr.

•

16 million office visits, 500,000 hospitalizations, and >$18 billion in direct health care costs annually can be attributed to COPD.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Blue bloaters (chronic bronchitis): peripheral cyanosis, productive cough, tachypnea, tachycardia.

•

Pink puffers (emphysema): dyspnea, pursed-lip breathing with use of accessory muscles for respiration, decreased breath sounds.

•

Possible wheezing in both patients with chronic bronchitis and emphysema.

•

Features of both chronic bronchitis and emphysema in many patients with COPD.

•

Acute exacerbation of COPD is mainly a clinical diagnosis and generally manifests with worsening dyspnea, increase in sputum purulence, and increase in sputum volume.

ETIOLOGY

•

Tobacco exposure

•

Occupational exposure to pulmonary toxins (e.g., cadmium)

•

Atmospheric pollution

•

Alpha-1-antitrypsin deficiency (rare; >1% of COPD patients)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

CHF

•

Asthma

•

Respiratory infections

•

Bronchiectasis

•

Cystic fibrosis

•

Neoplasm

•

Pulmonary embolism

•

Sleep apnea, obstructive

•

Hypothyroidism

WORKUP

Chest x-ray, pulmonary function testing, blood gases (in selected patients with acute exacerbation) LABORATORY TESTS

•

CBC may reveal leukocytosis with “shift to the left” during acute exacerbation.

•

Sputum may be purulent with bacterial respiratory tract infections. Sputum staining and cultures are usually reserved for cases that are refractory to antibiotic therapy.

•

ABGs: normocapnia, mild to moderate hypoxemia may be present.

•

Pulmonary function testing (PFT): the primary physiologic abnormality in COPD is an accelerated decline in forced expiratory volume in one second (FEV1) from the normal rate in adults over 30 years of age of approximately 30 ml/yr to nearly 60 ml/yr. PFTs results in COPD reveal abnormal diffusing capacity, increased total lung capacity and/or residual volume, fixed reduction in FEV1 in patients with emphysema; normal diffusing capacity, reduced FEV 1 in patients with chronic bronchitis. Patients with COPD can generally be distinguished from asthmatics by their incomplete response to albuterol (change in FEV1 10% on WBC count Mononeuropathy or polyneuropathy Migratory pulmonary infiltrates Paranasal sinus abnormalities Extravascular eosinophils on biopsy

The presence of any four or more of the six criteria yields a sensitivity of 85% and a specificity of 99.7%. For patients with vasculitis, the presence of asthma and eosinophilia was 90% sensitive and 99% specific for CSS. DIFFERENTIAL DIAGNOSIS

•

Polyarteritis nodosa (PAN)

•

Wegener's granulomatosis (WG)

•

Sarcoidosis

•

Loeffler syndrome

•

Henoch-Schönlein purpura

•

Allergic bronchopulmonary aspergillosis

•

Rheumatoid arthritis

•

Leukocytoclastic vasculitis

Although similar and at times grouped with patients with PAN or WG, CSS differs in that: •

CSS vasculitis involves not only small-sized arteries, but also veins and venules.

•

CSS, unlike PAN, predominantly involves the lung. Other organs affected include heart, GI, CNS, kidney, and skin.

•

Kidney involvement is much less common in CSS than in WG. Pulmonary lesions in WG usually involve the upper respiratory tract, vs. peripheral lung parenchyma in CSS.

•

CSS shows necrotizing vasculitis along with a granulomatous extravascular reaction infiltrated by eosinophils.

In contrast to CSS, the eosinophilia in Loeffler syndrome is usually refractory to steroid therapy, systemic vasculitis and granulomas are absent on biopsy, and endomyocardial fibrosis is a typical finding. WORKUP

History and physical exam, accompanied by laboratory tests, are suggestive. Tissue biopsy is confirmatory. LABORATORY TESTS

•

CBC with differential: eosinophilia.

•

Erythrocyte sedimentation rate is usually elevated.

•

BUN/creatinine may be elevated, suggesting renal involvement.

•

Urinalysis may show hematuria and proteinuria.

•

24-hour urine for protein if greater than 1 g/day is a poor prognostic factor.

•

ANCA is found in up to 70% of patients, usually with a perinuclear staining pattern.

•

Stools may be positive for occult blood (enteric involvement during eosinophilic phase).

•

AST, ALT, and CPK may indicate liver or muscle (skeletal or cardiac) involvement.

•

RF and ANA may be positive.

•

Biopsy confirms the diagnosis. Surgical lung biopsy is the gold standard. Transbronchial biopsy is rarely helpful. Necrotizing vasculitis and extravascular necrotizing granulomas, usually with eosinophilic infiltrates, are suggestive of CSS. The presence of eosinophils in extravascular tissues is most specific for CSS.

IMAGING STUDIES

•

Chest x-ray is abnormal in 37% to 77% of the cases: asymmetrical patchy migratory infiltrates, interstitial lung disease, or nodular infiltrates ( Fig. 1-57 ). Small pleural effusions are found in 29% of cases.

•

Lung lesions in CSS are noncavitating, as opposed to WG.

•

Paranasal sinus films may reveal sinus opacification.

•

Angiography is sometimes done in patients with mesenteric ischemia or renal involvement.

FIGURE 1-57 Allergic angiitis and granulomatosis. PA chest radiograph demonstrates peripheral air-space consolidation in the right lung and a nodule (arrow) in the left upper lobe in this asthmatic patient. (From McLoud TC [ed]: Thoracic radiology: the requisites, St Louis, 1998, Mosby.)

TREATMENT NONPHARMACOLOGIC THERAPY

Oxygen therapy in severe asthmatic exacerbations

PHARMACOLOGIC THERAPY

The following five factors suggest poor prognosis (five-factor score) and determines the aggressiveness of the immune suppressive therapy: 1.

Proteinuria >1 g/day

2.

Creatininemia >1.58 mg/dl

3.

Cardiomyopathy

4.

GI tract involvement

5.

CNS involvement

ACUTE GENERAL Rx

•

Corticosteroids are the treatment of choice if no poor prognostic factors are present. Prednisone 1 mg/kg/day is the starting dose and is continued for 6 to12 wk or until the disease has resolved. After clinically evident vasculitis resolves, prednisone is tapered progressively to 10 mg/day at 1 year.

•

A drop in the eosinophil count and the ESR documents a response. ANCA does not reliably correspond with disease activity.

CHRONIC Rx

•

In patients with one or more poor prognostic factors, addition of an immunosuppressant (cyclophosphamide) is a first-line therapy with corticosteroids.

•

In patients who do not respond to corticosteroid treatment or in CSS relapse, cyclophosphamide therapy is indicated as a second-line therapy.

•

Azathioprine or high-dose intravenous IG has shown benefit in patients with severe disease and in patients unresponsive to corticosteroids. Corticosteroids in combination with interferon-alpha have also been used in refractory cases.

•

Patients with persistent symptoms of asthma will require long-term corticosteroids even if vasculitis is no longer present.

DISPOSITION

•

Clinical remissions are obtained in more than 90% of patients after treatment.

•

Relapse occurs in 26%.

•

With treatment, long-term prognosis is good, with a 5-year survival rate of 90% and 50% at 7 years. Despite successful treatment of vasculitis, asthma generally remains persistent, and ischemic damage to peripheral nerves can be permanent.

•

The 5-year survival of untreated CSS is 25%.

•

Death usually occurs from progressive refractory vasculitis, myocardial involvement (approximately 50% of deaths), or severe GI involvement (mesenteric ischemia, pancreatitis).

REFERRAL

•

A pulmonary referral for diagnosis and management is appropriate.

•

Patients should be followed very closely at a rheumatology clinic. Patients usually need long-term immunosuppressive medications.

PEARLS & CONSIDERATIONS

COMMENTS

•

First described by Churg and Strauss in 1951 after reviewing a number of autopsy cases previously classified as polyarteritis nodosa.

•

CSS is distinguished from other vasculitides by the nearly universal presence of asthma that typically precedes all other symptoms.

•

The asthma associated with CSS is distinct from common allergic asthma in that it typically has a late onset and a degree of eosinophilia that is much greater than typically seen in allergic asthma. Patients typically have no family history of allergies or asthma.

•

Up to 77% of patients in the prodromal phase of CSS require oral steroids for asthma control.

•

Nearly 50% of patients will experience improvement or dramatic remission of asthma symptoms shortly before or at the start of the vasculitic phase.

•

Patients often experience constitutional symptoms of weight loss, fever, and malaise before specific organ involvement is clinically evident.

•

Peripheral nerve involvement due to vasculitis of the vasa vasorum commonly manifests as mononeuritis multiplex. Patients may present with sudden foot or wrist drop, along with sensory deficits in the distribution of one or more distal nerves.

•

Most patients with GI involvement are symptomatic. Gastroenteritis, acute abdomen, cholecystitis, hemorrhage, bowel perforation, and mesenteric ischemia have all been reported in patients with CSS.

•

Cutaneous involvement is seen in 40% to 70% of cases of CSS, and manifests as palpable purpura, petechiae, and/or cutaneous nodules.

•

Most patients with CSS respond to corticosteroid treatment and do not require cytotoxic therapy.

•

Symptoms of CSS typically appear as oral corticosteroids are being decreased or discontinued for the treatment of asthma, and not triggered by leukotriene receptor-1 antagonists as previously reported.

•

Reports of CSS developing in severe asthmatics after vaccination or desensitization therapy have led some authors to conclude that massive or nonspecific immunologic stimulation should be used with caution in patients with unstable asthma.

SUGGESTED READINGS Masi A, et al: American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome. Arthritis Rheum 1990; 33:1094. Sable-Fourtassou R, et al: Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 2005; 143:632. Pagnoux C, et al: Churg Strauss syndrome. Curr Opin Rheumatol 2007; 19(b):25-32. Kallenberg CG: Churg-Strauss syndrome: just one disease entity?. Arthritis Rheum 2005; 52(b):2589-2593.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cirrhosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cirrhosis is defined histologically as the presence of fibrosis and regenerative nodules in the liver. It can be classified as micronodular, macronodular, and mixed; however, each form may be seen in the same patient at different stages of the disease. Cirrhosis manifests clinically with portal hypertension, hepatic encephalopathy, and variceal bleeding.

ICD-9CM CODES

571.5 Cirrhosis of the liver 571.2 Cirrhosis of the liver secondary to alcohol EPIDEMIOLOGY & DEMOGRAPHICS

•

Cirrhosis is the eleventh leading cause of death in the U.S. (death rate 9 deaths/100,000 persons/yr).

•

Alcohol abuse and viral hepatitis are the major causes of cirrhosis in the U.S.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

SKIN: Jaundice, palmar erythema (alcohol abuse), spider angiomata, ecchymosis (thrombocytopenia or coagulation factor deficiency), dilated superficial periumbilical vein (caput medusae), increased pigmentation (hemochromatosis), xanthomas (primary biliary cirrhosis), needle tracks (viral hepatitis) EYES: Kayser-Fleischer rings (corneal copper deposition seen in Wilson's disease; best diagnosed with slit lamp examination), scleral icterus BREATH: Fetor hepaticus (musty odor of breath and urine found in cirrhosis with hepatic failure) CHEST: Possible gynecomastia in men ABDOMEN: Tender hepatomegaly (congestive hepatomegaly), small, nodular liver (cirrhosis), palpable, nontender gallbladder (neoplastic extrahepatic biliary obstruction), palpable spleen (portal hypertension), venous hum auscultated over periumbilical veins (portal hypertension), ascites (portal hypertension, hypoalbuminemia)

RECTAL EXAMINATION: Hemorrhoids (portal hypertension), guaiac-positive stools (alcoholic gastritis, bleeding esophageal varices, pelvic ulcer disease (PUD), bleeding hemorrhoids) GENITALIA: Testicular atrophy in males (chronic liver disease, hemochromatosis) EXTREMITIES: Pedal edema (hypoalbuminemia, failure of right side of the heart), arthropathy (hemochromatosis) NEUROLOGIC: Flapping tremor, asterixis (hepatic encephalopathy), choreoathetosis, dysarthria (Wilson's disease) ETIOLOGY

•

Alcohol abuse

•

Secondary biliary cirrhosis, obstruction of the common bile duct (stone, stricture, pancreatitis, neoplasm, sclerosing cholangitis)

•

Drugs (e.g., acetaminophen, isoniazid, methotrexate, methyldopa)

•

Hepatic congestion (e.g., CHF, constrictive pericarditis, tricuspid insufficiency, thrombosis of the hepatic vein, obstruction of the vena cava)

•

Primary biliary cirrhosis

•

Hemochromatosis

•

Chronic hepatitis B or C

•

Wilson's disease

•

Alpha-1-antitrypsin deficiency

•

Infiltrative diseases (amyloidosis, glycogen storage diseases, hemochromatosis)

•

Nutritional: jejunoileal bypass

•

Others: parasitic infections (schistosomiasis), idiopathic portal hypertension, congenital hepatic fibrosis, systemic mastocytosis, autoimmune hepatitis, hepatic steatosis, IBD

DIAGNOSIS WORKUP

In addition to an assessment of liver function, the evaluation of patients with cirrhosis should also include an assessment of renal and circulatory function. Diagnostic workup is aimed primarily at identifying the most likely cause of cirrhosis. The history is extremely important:

•

Alcohol abuse: alcoholic liver disease

•

History of hepatitis B (chronic active hepatitis, primary hepatic neoplasm, or hepatitis C)

•

History of IBD (primary sclerosing cholangitis)

•

History of pruritus, hyperlipoproteinemia, and xanthomas in a middle-aged or elderly female (primary biliary cirrhosis)

•

Impotence, diabetes mellitus, hyperpigmentation, arthritis (hemochromatosis)

•

Neurologic disturbances (Wilson's disease, hepatolenticular degeneration)

•

Family history of “liver disease” (hemochromatosis [positive family history in 25% of patients], alpha-1antitrypsin deficiency)

•

History of recurrent episodes of RUQ pain (biliary tract disease)

•

History of blood transfusions, IV drug abuse (hepatitis C)

•

History of hepatotoxic drug exposure

•

Coexistence of other diseases with immune or autoimmune features (ITP, myasthenia gravis, thyroiditis, autoimmune hepatitis)

LABORATORY TESTS

•

Decreased Hgb and Hct, elevated MCV, increased BUN and creatinine (the BUN may also be “normal” or low if the patient has severely diminished liver function), decreased sodium (dilutional hyponatremia), decreased potassium (as a result of secondary aldosteronism or urinary losses). Evaluation of renal function should also include measurement of urinary sodium and urinary protein from a 24-hr urine collection.

•

Decreased glucose in a patient with liver disease indicating severe liver damage

•

Other laboratory abnormalities: 1.

Alcoholic hepatitis and cirrhosis: there may be mild elevation of ALT and AST, usually ALT (ratio >2:3).

2.

Extrahepatic obstruction: there may be moderate elevations of ALT and AST to levels 500 IU) of ALT and AST.

4.

Transaminases may be normal despite significant liver disease in patients with jejunoileal bypass operations or hemochromatosis or after methotrexate administration.

5.

Alkaline phosphatase elevation can occur with extrahepatic obstruction, primary biliary cirrhosis, and primary sclerosing cholangitis.

6.

Serum LDH is significantly elevated in metastatic disease of the liver; lesser elevations are seen with hepatitis, cirrhosis, extrahepatic obstruction, and congestive hepatomegaly.

7.

Serum -glutamyl transpeptidase (GGTP) is elevated in alcoholic liver disease and may also be elevated with cholestatic disease (primary biliary cirrhosis, primary sclerosing cholangitis).

8.

Serum bilirubin may be elevated; urinary bilirubin can be present in hepatitis, hepatocellular jaundice, and biliary obstruction.

9.

Serum albumin: significant liver disease results in hypoalbuminemia.

10. Prothrombin time: an elevated PT in patients with liver disease indicates severe liver damage and poor prognosis. 11. Presence of hepatitis B surface antigen implies acute or chronic hepatitis B. 12. Presence of antimitochondrial antibody suggests primary biliary cirrhosis, chronic hepatitis.

13. Elevated serum copper, decreased serum ceruloplasmin, and elevated 24-hr urine may be diagnostic of Wilson's disease. 14. Protein immunoelectrophoresis may reveal decreased a-1 globulins (alpha-1-antitrypsin deficiency), increased IgA (alcoholic cirrhosis), increased IgM (primary biliary cirrhosis), increased IgG (chronic hepatitis, cryptogenic cirrhosis). 15. An elevated serum ferritin and increased transferrin saturation are suggestive of hemochromatosis. 16. An elevated blood ammonia suggests hepatocellular dysfunction; serial values, however, are generally not useful in following patients with hepatic encephalopathy because there is poor correlation between blood ammonia level and degree of hepatic encephalopathy. 17. Serum cholesterol is elevated in cholestatic disorders. 18. Antinuclear antibodies (ANA) may be found in autoimmune hepatitis. 19. Alpha fetoprotein: levels >1000 pg/ml are highly suggestive of primary liver cell carcinoma. 20. Hepatitis C viral testing identifies patients with chronic hepatitis C infection. 21. Elevated level of serum globulin (especially -globulins), positive ANA test may occur with autoimmune hepatitis. IMAGING STUDIES

•

Ultrasonography is the procedure of choice for detection of gallstones and dilation of common bile ducts.

•

CT scan is useful for detecting mass lesions in liver and pancreas, assessing hepatic fat content, identifying idiopathic hemochromatosis, early diagnosing of Budd-Chiari syndrome, dilation of intrahepatic bile ducts, and detection of varices and splenomegaly.

•

Technetium-99m sulfur colloid scanning is useful for diagnosing cirrhosis (there is a shift of colloid uptake to the spleen, bone marrow), identifying hepatic adenomas (cold defect is noted), diagnosing Budd-Chiari syndrome (there is increased uptake by the caudate lobe).

•

ERCP is the procedure of choice for diagnosing periampullary carcinoma, common duct stones; it is also useful in diagnosing primary sclerosing cholangitis.

•

Percutaneous transhepatic cholangiography (PTC) is useful when evaluating patients with cholestatic jaundice and dilated intrahepatic ducts by ultrasonography; presence of intrahepatic strictures and focal dilation is suggestive of PSC.

•

Percutaneous liver biopsy is useful in evaluating hepatic filling defects, diagnosing hepatocellular disease or hepatomegaly, evaluating persistently abnormal liver function tests, and diagnosing hemachromatosis, primary biliary cirrhosis, Wilson's disease, glycogen storage diseases, chronic hepatitis, autoimmune hepatitis, infiltrative diseases, alcoholic liver disease, drug-induced liver disease, and primary or secondary carcinoma.

TREATMENT NONPHARMACOLOGIC THERAPY

Avoid any hepatotoxins (e.g., ethanol, acetaminophen); improve nutritional status. GENERAL Rx

•

Remove excess body iron with phlebotomy and deferoxamine in patients with hemochromatosis.

•

Remove copper deposits with d-penicillamine in patients with Wilson's disease.

•

Long-term ursodiol therapy will slow the progression of primary biliary cirrhosis. It is, however, ineffective in primary sclerosing cholangitis.

•

Glucocorticoids (prednisone 20 to 30 mg/day initially or combination therapy or prednisone and azathioprine) is useful in autoimmune hepatitis.

•

Liver transplantation may be indicated in otherwise healthy patients (age >65 yr) with sclerosing cholangitis, chronic hepatitis cirrhosis, or primary biliary cirrhosis with prognostic information suggesting >20% chance of survival without transplantation; contraindications to liver transplantation are AIDS, most metastatic malignancies, active substance abuse, uncontrolled sepsis, uncontrolled cardiac or pulmonary disease.

•

Treatment of complications of portal hypertension (ascites, esophagogastric varices, hepatic encephalopathy, and hepatorenal syndrome).

DISPOSITION

•

Prognosis varies with the etiology of the patient's cirrhosis and whether there is ongoing hepatic injury. Mortality rate exceeds 80% in patients with hepatorenal syndrome.

•

If advanced cirrhosis is present and transplantation is not feasible, survival is 1 to 2 yr.

PEARLS & CONSIDERATIONS COMMENTS

Thrombocytopenia and advanced Child-Pugh cases are associated with the presence of varices. These factors are useful to identify cirrhotic patients who benefit most from referral for endoscopic screening for varices.

EVIDENCE

Both neomycin plus sorbitol and lactulose plus placebo are effective in the treatment of patients with cirrhosis and chronic portal-systemic en-cephalopathy, but lactulose is more effective at reducing stool mean pH.[[1]] Antibiotic prophylaxis significantly reduces the incidence of bacterial infections and associated mortality in cirrhotic patients with gastrointestinal bleeding.[[2]] In people with cirrhosis, beta-blockers are more effective than placebo in preventing a first episode of variceal bleeding and in reducing the incidence of bleeding episodes. [210] [211] When treating acute bleeding esophageal varices, treatment with somatostatin analogs does not significantly decrease mortality compared with placebo, but it is associated with fewer transfusions and a lower number of patients with failed hemostasis.[[5]] Current evidence does not support the use of emergency sclerotherapy over vasoactive agents as first line treatment of bleeding varices in cirrhotic patients.[[6]]

In patients with cirrhosis and a recent esophageal variceal bleed, treatment with a beta-blocker with or without a nitrate is as effective as endoscopic banding of varices in preventing rebleeding or death.[[7]]

Evidence-Based References 1. Conn HO, et al: Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 1997; 72:573. 2. Soares-Weiser K, et al: Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database Syst Rev 2002; 2:CD002907, 3. Pagliaro L, et al: Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of nonsurgical treatment. Ann Intern Med 1992; 117:59. 4. Pascal JP, Cales P: Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med 1987; 317:856. 5. Gotzsche PC: Somatostatin analogues for acute bleeding oesophageal varices. Cochrane Database Syst Rev 2002; 1:CD000193, 6. D'Amico G, et al: Emergency sclerotherapy versus medical interventions for bleeding oesophageal varices in cirrhotic patients. Cochrane Database Syst Rev 2002; 1:CD002233, 7. Patch D, et al: A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis. Gastroenterology 2002; 123:1013.

SUGGESTED READINGS Gines P, et al: Management of cirrhosis and ascites. N Engl J Med 2004; 350:1645. Heidelbaugh JJ, Bruderly M: Cirrhosis and chronic liver failure. Am Fam Physic 2006; 74:756-767.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cirrhosis, Primary Biliary JENNIFER ROH HUR, M.D.

BASIC INFORMATION DEFINITION

Primary biliary cirrhosis (PBC) is a chronic, variably progressive disease most often affecting women and characterized by destruction of the small intrahepatic bile ducts leading to portal inflammation, fibrosis, cirrhosis, and ultimately liver failure. SYNONYMS

Biliary cirrhosis Nonsupparative destructive cholangitis Autoimmune cholangiopathy

ICD-9CM CODES

571.6 Biliary cirrhosis EPIDEMIOLOGY & DEMOGRAPHICS

•

PBC affects all races and accounts for 0.6% to 2% of deaths from cirrhosis worldwide.

•

Approximately 95% of patients are female.

•

Annual incidence rates 0.7 to 49 cases per million.

•

Prevalence highest in the U.K., Scandinavia, and the U.S. and varies tremendously by geographic areas, ranging from 67 to 402 cases per million.

•

Although there are no clearly identified genetic factors affecting the occurrence of PBC, there is a clear familial occurrence. Prevalence among first-degree relatives is 5% to 6%, and 1% to 6% of all patients have at least one affected family member. The concordance rate among monozygotic twins is 63%.

•

Onset typically occurs between the ages of 30 and 65, and it is uncommon before age 25.

•

Up to 84% of patients with PBC have at least one other autoimmune disorder, such as thyroiditis, Sjögren's syndrome, rheumatoid arthritis (RA), Raynaud's phenomenon, or scleroderma. A variant form of PBC exists as an overlap syndrome with autoimmune hepatitis (AIH) and is referred to as autoimmune cholangiopathy (AIC).

ETIOLOGY

•

Although the cause of PBC is still unknown, it is felt to be due to an environmental insult that modifies mitochondrial proteins triggering persistent T lymphocyte–mediated attack on intralobular bile duct epithelial cells in genetically susceptible individuals.

•

Possible risk factors being examined include cigarette smoking, urinary tract infections (UTIs), Raynaud's phenomenon, autoimmune thyroid disease, history of tonsillectomy or cholecystectomy, multiple pregnancies, autoimmune thyroid disease, and family history of PBC, Sjögren's syndrome, and systemic lupus erythematosus (SLE).

•

Recent studies have identified a peptide, an enzyme complex subunit (PDC-E2) in the mitochondrial membrane, as a major autoantigen in the early pathogenesis of PBC. Patients with PBC have a tenfold increased concentration of cytotoxic CD8+ lymphocytes recognizing this peptide in their livers as compared with their blood, and autoantibodies against mitochondria (AMA), especially the PDC-E2 subunit, are the serologic hallmark of this disease. In addition, bile duct epithelial cells handle PDC-E2 in a unique way that exposes them to immune-mediated attack by PDC-E2–oriented cytotoxic T cells. Future therapies may be specific immunomodulation directed at these peptides.

•

In addition to the T lymphocyte–mediated direct destruction of small bile ducts, secondary damage to hepatocytes may result from the accumulation of noxious substances such as bile acids.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Clinical stages: •

Asymptomatic

•

Symptomatic

•

Cirrhotic

•

Hepatic Failure

Symptoms: •

48% to 60% of patients may be asymptomatic; 40% to 100% of these patients will go on to develop symptoms.

•

Fatigue (78% of patients) and pruritus (20 to 70% of patients) are the usual presenting symptoms.

•

Pruritus is worse at night, under constricting, coarse garments; in association with dry skin; and in hot, humid weather. The cause is unknown; it is no longer felt to be a result of the retention of bile acids in skin. Pruritus may first occur during pregnancy but is distinguished from pruritus of pregnancy because it persists into the postpartum period and beyond.

•

Other common symptoms include hepatomegaly, jaundice, unexplained right upper quadrant pain (10%), splenomegaly, manifestations of portal hypertension, sicca symptoms, and scleroderma-like lesions.

•

Musculoskeletal complaints caused by inflammatory arthropathy in 40% to 70% of patients: 5% to 10% develop chronic RA; 10% develop “arthritis of PBC.”

•

Steatorrhea may be seen in advanced disease.

Physical:

•

Variable: dependent on stage of disease at time of presentation. Patients at early stage may be completely normal.

•

25% to 50% have hypopigmentation of skin.

•

Excoriations may be present.

•

Hepatomegaly (70%) and splenomegaly (initially 35%) may be present in more advanced disease.

•

Xanthomas and jaundice appear in advanced disease. Kayser-Fleischer rings are rare and result from copper retention.

•

Late physical findings mirror those of cirrhosis: spider nevi, temporal and proximal limb wasting, ascites, and edema.

DIAGNOSIS

•

Based on three criteria: Positive serum antimitochondrial antibodies (AMA), titer >1:40 Increased liver function tests (especially alkaline phosphatase) for >6 months Characteristic liver histology: asymmetric destruction of the bile ducts within the portal triads

•

Two criteria indicate a probable diagnosis and all three criteria are required for a definite diagnosis.

DIFFERENTIAL DIAGNOSIS

•

Drug-induced cholestasis Other etiologies of chronic liver disease and cirrhosis:

•

Alcoholic cirrhosis

•

Viral hepatitis (chronic)

•

Primary sclerosing cholangitis

•

Autoimmune chronic active hepatitis

•

PBC-AIH overlap syndrome—reported in almost 10% of adults with AIH or PBC; transition from stable PBC to AIH and vice versa also seen

•

Chemical/toxin-induced cirrhosis

•

Other hereditary or familial disorders (e.g., CF, µ-1-antitrypsin deficiency)

WORKUP

•

History, physical examination, laboratory evaluation, and liver biopsy

LABORATORY TESTS

•

Antimitochondrial antibodies (AMA) found in 95% of patients with PBC and are 98% specific.

•

Antinuclear antibodies (ANA) found in approximately 50%. Unlike AMA, these may correlate with disease severity and prognosis. Presence of anti-gp 210 antinuclear protein antibody seems to predict hepatic failure type progression, whereas an anticentromere pattern appears to be a risk factor for the development of portal hypertension.

•

Markedly elevated alkaline phosphatase (of hepatic origin).

•

Elevated GGTP.

•

Elevated serum IgM levels or elevated IgG levels in AMA-negative PBC.

•

Bilirubin normal early; increases with disease progression (direct and indirect) in 60% of patients. Elevated serum bilirubin is a poor prognostic sign.

•

Normal or slightly elevated aminotransferases, rarely more than 5× the upper limit of normal, for more than 6 months. Degree of elevation has no prognostic significance.

•

Markedly elevated serum lipids in more than 50% of patients. Total cholesterol may exceed 1000 mg/dl. No increased risk of death from atherosclerosis seen, possibly because of very high HDL levels and low serum levels of Lp(a) lipoprotein.

•

Elevated ceruloplasmin.

•

Percutaneous liver biopsy confirms or rules out the diagnosis, allows staging, and indicates response to therapy.

•

Histology is not uniform and so histologic stage is based on the most advanced lesion present. Stage I—lymphocytic infiltration of the epithelial cells of the small bile ducts with granuloma-like lesions, limited to portal triads. Stage II—extension of inflammatory cells to periportal parenchyma, invasion by foamy macrophages, and development of biliary piecemeal necrosis. Stage III—fibrous septa link portal triads. Stage IV—frank cirrhosis. Hyaline deposits and accumulation of stainable copper are also seen.

IMAGING STUDIES

If history, physical examination, blood tests, and liver biopsy are all consistent with PBC, neither imaging nor cholangiography is necessary. PROGNOSIS

•

Median survival is 9 years.

•

Mean time of progression from Stage I or II disease to cirrhosis with no medical treatment is 4 to 6 years.

•

Neither presence nor titer of antimitochondrial antibodies predicts survival, disease progression, or response to therapy.

•

Unclear if presence of symptoms at time of diagnosis affects survival.

•

Prognostic laboratory measures: serum bilirubin is most important, but also albumin and prothrombin time.

•

Poor prognosis with jaundice, advanced histologic stage, advanced age, edema, coagulopathy, and ascites.

•

Presence of cirrhosis confers increased risk for hepatocellular carcinoma.

TREATMENT

•

Treatment is given according to the clinical stage of the disease.

•

Asymptomatic stage—follow bilirubin every 3 to 4 months, and if begins to rise, start ursodeoxycholic acid (UDCA).

•

No generally accepted treatment of underlying disease process.

•

Treatment focuses on management of complications (pruritus, metabolic bone diseases, hyperlipidemia) because liver transplantation is the only definitive treatment for this disease.

•

20% of patients will not respond to medical therapy and proceed to liver transplantation.

ACUTE GENERAL Rx

•

Goals of treatment: resolution of pruritus, decrease of alkaline phosphatase levels to >50% above normal, and improvement in liver biopsy histology.

•

Ursodiol (12 to 15 mg/kg/day, divided or as one bedtime dose) significantly reduces ascites, jaundice, and levels of bilirubin and liver transaminases. Data are mixed as to whether ursodiol reduces mortality, need for liver transplantation, pruritus, fatigue, quality of life, liver histology, or portal blood pressures. Safe and well tolerated. Some reported side effects include weight gain, hair loss, diarrhea, and flatulence. May see decreased efficacy after 10 years. Ineffective and may actually worsen disease if started in advanced stages.

•

Colchicine (0.6 mg twice daily) and methotrexate (15 mg/wk) yield less impressive results but may be helpful. Patients with PBC on methotrexate need to be monitored for the development of interstitial pneumonitis, which resolves with discontinuation of the drug.

•

Prednisone, azathioprine, penicillamine, and cyclosporine are no longer used because of limited efficacy and significant toxicity.

•

Experiments are ongoing to examine the use of budesonide in combination with ursodeoxycholic acid.

•

For the pruritus of PBC, cholestyramine resin (8 to 24 g daily) reduces pruritus in most patients. Antihistamines at bedtime help nighttime symptoms. Rifampin (150 mg twice daily) is effective for those who do not respond to or tolerate resins. Naloxone and naltrexone are third-line agents and plasmapheresis is helpful when all other therapies fail.

CHRONIC Rx

•

Diet low in neutral triglycerides and high in medium-chain triglycerides decreases steatorrhea and improves nutritional status.

•

Treatment for acute bacterial cystitis, which occurs with greater frequency in these patients.

•

Treatment for osteoporosis, including calcium and vitamin D, should be undertaken, although only liver transplantation results in improvement. Bisphosphonates may be helpful.

•

Vitamin A, K, E deficiencies can be clinically important in advanced cases and respond to oral replacement.

•

Esophageal variceal bleeding often happens earlier in the course of PBC than with other progressive liver diseases. These are best treated with endoscopic rubber-band ligation or TIPS shunt.

•

Liver transplantation is the definitive cure and appropriate referral should be sought. Indications for transplant include unacceptable quality of life owing to pruritus and a Mayo (MELD) score of >10.

•

Liver transplant recipients with PBC are more likely to develop chronic rejection and less likely to be weaned from immunosuppressive therapy. After transplant, antimitochondrial antibody levels persist and histologic changes of PBC are seen in up to 50% of liver transplant patients in 10 yr.

•

With appropriate immunosuppression and despite histologic changes, patients who undergo transplant for PBC clinically do very well. Survival at 1 yr is 85% to 90%, and 70% survive at least 10 yr after transplantation; survival rates thereafter resemble age/sex-matched healthy persons.

•

Other associated illnesses that should be detected and treated include hyperlipidemia (without increased risk of ASHD), Hashimoto's thyroiditis (20% of patients), interstitial pneumonitis, celiac disease, sarcoidosis, asymptomatic renal tubular acidosis (from copper deposition in the kidneys), hemolytic anemia, autoimmune thrombocytopenia, and coexisting autoimmune disease including Sjögren's syndrome, sicca syndrome, and scleroderma.

DISPOSITION

Definitive treatment requires liver transplantation; survival is 7 to 16 yr, dependent on symptoms at time of diagnosis. REFERRAL

Gastroenterology and or hepatology referral for treatment, evaluation for liver transplantation, and potentially treatment of refractory variceal bleeding

PEARLS & CONSIDERATIONS

•

Antimitochondrial antibodies are practically pathognomonic for PBC.

•

Ursodiol can be an effective and well-tolerated treatment if started early in the course of the disease.

•

Associated illnesses need to be detected and treated.

•

Liver transplantation is the definitive treatment for PBC.

SUGGESTED READINGS Gluud C, Christensen E: Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2001; 4: Kaplan M, Gershwin ME: Primary biliary cirrhosis (review). N Engl J Med 2005; 353:1261-1273. Levy C, Lindor KD: Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia in primary biliary cirrhosis. Clin Liver Dis 2003; 7(4):901. MacQuillan GC, Neuberger J: Liver transplantation for primary biliary cirrhosis. Clin Liver Dis 2003; 7(4):941.ix Selmi C, et al: Epidemiology and pathogenesis of primary biliary cirrhosis. J Clin Gastroenterol 2004; 38(3):264.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Claudication MEL ANDERSON, M.D.

BASIC INFORMATION DEFINITION

Claudication refers to leg pain brought on by exertion and relieved with rest. SYNONYMS

Intermittent claudication

ICD-9CM CODES

443.9

Peripheral vascular disease, unspecified

440.21 Intermittent claudication due to atherosclerosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 3 to 8 cases/1000 persons PREVALENCE: 2% to 4% in the general population RISK FACTORS: Major risk factors of tobacco, hypertension, diabetes, and hypercholesterolemia increase the risk of developing claudication. Cigarette smoking is the major determinant of disease progression. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Diminished pulses, cool skin temperature

•

Bruits over the distal aorta, iliac or femoral arteries

•

Pallor of the distal extremities on elevation

•

Rubor with prolonged capillary refill on dependency

•

Trophic changes of hair loss and muscle atrophy noted

•

Nonhealing ulcers, necrotic tissue, and gangrene possible

ETIOLOGY

Primary cause of claudication is atherosclerosis.

DIAGNOSIS History and physical findings make the diagnosis of claudication. Noninvasive studies help confirm the diagnosis. DIFFERENTIAL DIAGNOSIS

•

Spinal stenosis (neurogenic claudication)

•

Muscle cramps

•

Degenerative osteoarthritic joint disease, particularly of the lumbar spine and hips

•

Compartment syndrome

WORKUP

•

Ankle-brachial index (ABI): the ratio of ankle pressure to brachial pressure is usually about 1. 1.

In claudication, the ABI ranges from 0.5 to 0.8.

2.

In patients with rest pain or impending limb loss, ABI =0.3.

•

Segmental systolic pressures usually are measured from the high thigh, above the knee, below the knee, and the ankle. Normally there should not be >20 mm Hg difference in pressures between adjacent segments. If the gradient is >20 mm Hg, significant narrowing is suspected in the intervening segment.

•

Both ABI and segmental pressures can be done before and after exercise.

IMAGING STUDIES

•

Duplex ultrasound can be used to locate the occluded areas and assess the patency of the distal arterial system or prior vein grafts.

•

MRA and spiral CT angiography are further imaging techniques available.

•

Angiography remains the gold standard for imaging peripheral arterial occlusion.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Tobacco cessation is vital.

•

Diet to control diabetes, blood pressure and cholesterol should be followed.

•

Walking 30 to 60 min/day for 5 days at about 2 mi/hr is recommended.

•

New prospective data point to intermittent pneumatic compression (IPC) as a promising adjunctive therapy.

ACUTE GENERAL Rx

Acute revascularization is usually reserved for patients with impending ischemic limb loss. CHRONIC Rx

•

Antiplatelet agents like aspirin or clopidogrel.

•

Risk factor modification: pharmacologic treatment for hyperlipidemia, hypertension, and diabetes in particular.

•

Pentoxifylline 400 mg tid or cilostazol 100 mg bid for 3 mo should be tried. If there is no improvement in symptoms, the medicine should be discontinued.

•

Revascularization is indicated in patients with refractory rest pain or lifestyle altering pain, nonhealing ulcers, or gangrene and in a select group of patients with functional disability. Common procedures: 1.

Aortoiliofemoral reconstruction or bypass, or infrainguinal bypass (e.g., femoropopliteal, femorotibial).

2.

Angioplasty, often with stenting, is used primarily on short, discrete stenotic lesions in the iliac or femoropopliteal artery.

COMPLEMENTARY & ALTERNATIVE MEDICINE

•

A systematic review found that over 12 to 24 wk, Gingko biloba increased pain-free walking distance by 33 meters compared to placebo.

•

Systematic reviews have shown that chelation therapy is no better than placebo.

DISPOSITION

•

Intermittent claudication progressing to an ischemic leg or limb loss is unusual, especially if maintaining the conservative treatment of exercise and abstaining from tobacco.

•

The 5-yr risk for developing ischemic ulceration in patients treated for diabetes and with ABI >0.5 was 30% compared with only 5% in patients with neither characteristic.

REFERRAL

Consultation with an interventionalist is recommended in the patient with threatened limb loss, rest pain, nonhealing ulcers, functional disability from pain, and gangrene.

PEARLS & CONSIDERATIONS

•

About 70% of patients with peripheral vascular disease will have concomitant coronary artery disease.

•

Beta blockers may worsen claudication symptoms in some patients, although their underuse is associated with excess cardiovascular mortality.

•

Patients with peripheral vascular disease may benefit from secondary cardiovascular prevention with clopidogrel versus aspirin more so than other high-risk patients (CAPRIE trial).

COMMENTS

•

Claudication is a marker for generalized atherosclerosis. This group of patients has a higher risk of death from cardiovascular events than from limb loss.

•

The ABI is more closely associated with leg function in persons with peripheral arterial disease than is intermittent claudication or other leg symptoms.

SUGGESTED READINGS Abramson B, Huckell V: Canadian Cardiovascular Society Consensus Conference: peripheral arterial disease—executive summary. Can J Cardiol 2005; 21(b):997-1006.

ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease: www.acc.org/qualityandscience/clinical/topic/topic.htm (select Peripheral Arterial Disease). Clagett G, et al: Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126(suppl 3):609S-626S. Kakkos S, et al: Improvement of the walking ability in intermittent claudication due to superficial femoral artery occlusion with supervised exercise and pneumatic foot and calf compression: a randomized controlled trial. Eur J Endovasc Surg 2005; 302(b):164-175. Simon RW, et al: Intermittent claudication. BMJ 2007; 334:746. White C: Clinical practice: intermittent claudication. N Engl J Med 2007; 356:1241-1250.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cocaine Overdose SAJEEV HANDA, M.D.

BASIC INFORMATION DEFINITION

Cocaine is an alkaloid derived from the coca plant Erythroxylon coca, native to South America, which contains approximately 0.5% to 1% cocaine. The drug produces physiologic and behavioral effects when administered orally, intranasally, intravenously, or via inhalation following smoking. Cocaine has potent pharmacologic effects on dopamine, norepinephrine, and serotonin neurons in the central nervous system (CNS) involving alteration and blockade of cellular membrane transport and prevention of reuptake. SYNONYMS

Cocaine hydrochloride: topical solution (FDA approved as a topical anesthetic) Freebase: aqueous solution of cocaine hydrochloride converted to a more volatile base state by the addition of alkali, thereby extracting the cocaine base in a residue or precipitate Crack: potent, purified smokable form; produces effects similar to those of intravenous administration Street names include Bernice, Bernies, C, Cadillac or Champagne of drugs, Carrie, Cecil, Charlie, Coke, Dust, Dynamite, Flake, Gin, Girl, Gold dust, Green gold, Jet, Powder, Star dust, Paradise, Pimp's drug, Snowflake, Stardust, White girl Liquid lady = alcohol + cocaine Speedball = heroin + cocaine Street measures: hit (2 to 200 mg), snort, line, dose, spoon (approximately 1 g)

ICD-9CM CODES

304.2 Cocainism EPIDEMIOLOGY & DEMOGRAPHICS

The 1993 National Household Survey on Drug Abuse estimated that 4.5 million Americans used cocaine in 1992, with 1.3 million reporting use at least monthly. By 1998 this had not significantly changed.

Between 1993 and 1994, intravenous cocaine and heroin abusers accounted for a major new group of persons with human immunodeficiency virus (HIV) in several metropolitan areas. In 1999 an estimated 25 million Americans admitted that they used cocaine at least once, 3.7 million the previous year, and 1.5 million were current users. It is the most frequent cause of drug-related deaths reported by medical examiners and is increasing more sharply in women than in men. PHYSICAL FINDINGS & CLINICAL PRESENTATION

PHASE I: •

CNS: euphoria, agitation, headache, vertigo, twitching, bruxism, nonintentional tremor

•

Nausea, vomiting, fever, hypertension, tachycardia

PHASE II: •

CNS: lethargy, hyperreactive deep tendon reflexes, seizures (status epilepticus)

•

Sympathetic overdrive: tachycardia, hypertension, hyperthermia

•

Incontinence

PHASE III: •

CNS: flaccid paralysis, coma, fixed dilated pupils, loss of reflexes

•

Pulmonary edema

•

Cardiopulmonary arrest

Psychologic dependence manifests with habituation, paranoia, hallucinations (cocaine “bugs”). Central nervous system: cerebral ischemia and infarction, cerebral arterial spasm, cerebral vasculitis, cerebral vascular thrombosis, subarachnoid hemorrhage, intraparenchymal hemorrhage, seizures, cerebral atrophy, movement disorders. Cardiac: acute myocardial ischemia and infarction, arrhythmias and sudden death, dilated cardiomyopathy and myocarditis, infective endocarditis, aortic rupture. Pulmonary: (secondary to smoking crack cocaine) inhalation injuries: cartilage and nasal septal perforation, oropharyngeal ulcers; immunologically mediated diseases: hypersensitivity pneumonitis, bronchiolitis obliterans; pulmonary vascular lesions and hemorrhage, pulmonary infarction, pulmonary edema secondary to left ventricular failure, pneumomediastinum, and pneumothorax. Gastrointestinal: gastroduodenal ulceration and perforation; intestinal infarction or perforation, colitis. Renal: acute renal failure secondary to rhabdomyolysis and myoglobinuria; renal infarction; focal segmental glomerulosclerosis. Obstetric: placental abruption, low infant weight, prematurity, and microcephaly. Psychiatric: anxiety, depression, paranoia, delirium, psychosis, and suicide. ETIOLOGY

Cocaine may be absorbed through different routes with varying degrees of speed •

Nasal insufflation/snorting: 2.5 min

•

Smoking: >30 sec

•

Oral: 2 to 5 min

•

Mucosal: >20 min

•

Intravenous injection: >30 sec

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Methamphetamine (“speed”) abuse

•

Methylenedioxyamphetamine (“ecstasy”) abuse

•

Cathione (“khat”) abuse

•

Lysergic acid diethylamide (LSD) abuse

WORKUP

Physical examination and laboratory evaluation LABORATORY TESTS

•

Toxicology screen (urine): cocaine is metabolized within 2 hr by the liver to major metabolites, benzoylecgonine and ecgonine methylester, which are excreted in the urine. Metabolites can be identified in urine within 5 min of IV use and up to 48 hr after oral ingestion.

•

Blood: CBC, electrolytes, glucose, BUN, creatinine, calcium.

•

ABG analysis.

•

ECG.

•

Serum creatinine kinase and troponin concentration.

TREATMENT There is no specific antidote and, at present, no drug therapy is uniquely effective in treating cocaine abuse and dependence. In addition, adulterants, contaminants, and other drugs may be admixed with street cocaine. Amantadine may provide effective treatment for cocaine-dependent patients with severe cocaine withdrawal symptoms, as well as the other dopamine agonist bromocriptine (1.5 mg po tid), which may alleviate some of the symptoms of craving associated with acute cocaine withdrawal. ACUTE GENERAL Rx

Acute cocaine toxicity requires following advanced poisoning treatment and life support. A suspected “bodypacker” should have an abdominal radiograph to detect the continued presence of cocaine-containing condoms in the intestinal tract. If present, gentle catharsis with charcoal and mineral oil should be performed with ICU admission and monitoring. SPECIFIC TREATMENT

INHALATION: Wash nasal passages AGITATION: •

Check STAT glucose.

•

Diazepam 15 to 20 mg po or 2 to 10 mg IM or IV for severe agitation.

HYPERTHERMIA: •

Check rectal temperature, CK, electrolytes.

•

Monitor with continuous rectal probe; bring temperature down to 101° F within 30 to 45 min.

RHABDOMYOLYSIS: •

Vigorous hydration with urine output at least 2 ml/kg

•

Mannitol or bicarbonate for rhabdomyolysis resistant to hydration

SEIZURE MANAGEMENT (STATUS EPILEPTICUS): •

Diazepam 5 to 10 mg IV over 2 to 3 min, may be repeated every 10 to 15 min.

•

Lorazepam 2 to 3 mg IV over 2 to 3 min, may be repeated.

•

Phenytoin loading dose 15 to 18 mg/kg IV at a rate not to exceed 25 to 50 mg/min under cardiac monitoring.

•

Phenobarbital loading dose 10 to 15 mg/kg IV at a rate of 25 mg/min; an additional 5 mg/kg may be given in 30 to 45 min if seizures are not controlled.

•

Refractory seizures, consider: Pancuronium 0.1 mg/kg IV Halothane general anesthesia Both require EEG monitoring to determine brain seizure activity.

HYPERTENSION: Cocaine-induced hypertension usually responds to benzodiazepines. If this fails: •

Consider arterial line for continuous BP monitoring

•

Avoid the use of calcium channel blockers because they may potentiate the incidence of seizures and death, especially in body packers.

•

The use of beta blockers may exacerbate cocaine-induced vasoconstriction

•

Phentolamine (unopposed adrenergic effects) or nitroglycerin may be required.

•

If diastolic pressure >120 mm Hg: hydralazine hydrochloride 25 mg IM or IV; may repeat q1h

•

If hypertension uncontrolled or hypertensive encephalopathy is present: sodium nitroprusside initially at 0.5 µg/kg/min not to exceed 10 µg/kg/min

CHEST PAIN:

•

CXR, ECG, cardiac enzymes.

•

Benzodiazepines for agitation.

•

ASA and nitroglycerin for ischemic pain.

•

PTCA possibly better than thrombolysis for cocaine-associated MI.

•

The use of beta-adrenergic blockers remains controversial because of the unopposed alpha-adrenergic effects of cocaine.

•

The combination of nitroprusside and a beta-adrenergic blocking agent or phentolamine alone or in addition to a beta-adrenergic blocking agent may successfully treat myocardial ischemia and hypertension.

VENTRICULAR ARRHYTHMIAS: •

Antiarrhythmia agents should be used with caution during the early period after cocaine exposure as a result of their proarrhythmic and proconvulsant effects.

•

Propranolol 1 mg/min IV for up to 6 mg.

•

Lidocaine 1.5 mg/kg IV bolus followed by IV infusion (controversial: may be proarrhythmic and proconvulsant).

•

Termination of ventricular arrhythmias may be resistant to lidocaine and even cardioversion.

•

NaHCO32 is under investigation in cocaine-mediated conduction abnormalities and rhythm disturbances.

DISPOSITION

Although many patients who use cocaine may not require any treatment because of the short half-life of the drug, others may require specific treatment for possible cocaine-related complications. REFERRAL

Consider psychotherapy or behavioral therapy once stable.

PEARLS & CONSIDERATIONS

•

Cocaine-induced vasoconstriction may be exacerbated by the use of selective and nonselective betaadrenergic blocking agents.

•

The use of lidocaine in treating ventricular arrhythmias may precipitate seizures and further arrhythmias.

SUGGESTED READINGS Jones JH, Wier WB: Cocaine associated chest pain. Med Clin North Am 2005; 89(6):1323. Lange RA, Hillis LD: Cardiovascular complications of cocaine use. N Engl J Med 2001; 345:351. Mokhlesi B, Corbridge T: Adult toxicology in critical care: part II: Specific poisonings. Clin Chest Med 2003; 123(3):897.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Coccidioidomycosis GEORGE O. ALONSO, M.D., GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Coccidioidomycosis is an infectious disease caused by the fungus Coccidioides immitis. It is usually asymptomatic and characterized by a primary pulmonary focus with infrequent progression to chronic pulmonary disease and dissemination to other organs. SYNONYMS

San Joaquin Valley fever

ICD-9CM CODES

114.0 Coccidioides pneumonia 114.1 Cutaneous or extrapulmonary (primary) coccidioidomycosis 114.3 Disseminated or prostate coccidioidomycosis 114.5 Pulmonary coccidioidomycosis 114.2 Coccidioidal meningitis 114.4 Chronic coccidioidomycosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Estimated annual infection rate 100,000 persons, predominantly in southwest U.S. PEAK INCIDENCE: Unknown PREVALENCE: Unknown PREDOMINANT SEX: Males, between the ages of 25 to 55 yr Clinical disease more severe than in older children and adults PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Asymptomatic infections or illness consistent with a nonspecific upper respiratory tract infection in at least 60%.

•

Symptoms of primary infection—cough, malaise, fever, chills, night sweats, anorexia, weakness, and arthralgias (desert rheumatism)—in remaining 40% within 3 wk of exposure.

•

Erythema nodosum and erythema multiforme more common in women.

•

Scattered rales and dullness on percussion.

•

Spontaneous improvement within 2 wk of illness, with complete recovery usual.

•

Pulmonary nodules and cavities in >10% of those patients with primary infection; half of these patients asymptomatic.

•

In a small portion of these patients: a progressive pneumonitis, often with a fatal outcome.

•

Immunocompromised or diabetic patients may progress to chronic pulmonary disease.

•

Over many years, granulomas rupture, leading to new cavity formation and continued fibrosis, often accompanied by hemoptysis.

•

Disseminated or extrapulmonary disease in approximately 0.5% of acutely infected patients.

•

1.

Early signs of probable dissemination: fever, malaise, hilar adenopathy, and elevated ESR persisting in the setting of primary infection.

2.

Most organs are susceptible to dissemination, with heart and GI tract generally spared.

Musculoskeletal involvement: bone lesions often unifocal, ribs, long bones, and vertebral lesions are common. 1.

Joint lesions predominantly unifocal, most commonly involving the ankle and knee, and often accompanying adjacent sites of osteomyelitis.

•

Meningeal involvement: headache, fever, weakness, confusion, lethargy, cranial nerve defects, seizures; meningeal signs often minimal or absent.

•

Cutaneous involvement: variable lesions—pustules, papules, plaques, nodules, ulcers, abscesses, or verrucous proliferative lesions. 1.

Dissemination and fatal outcomes most common in men, pregnant women, neonates, immunocompromised hosts, and individuals of dark-skinned races, especially those of African, Filipino, Mexican, and Native American ancestry.

ETIOLOGY

•

Coccidioides immitis is endemic to North and South America.

•

In the U.S., endemic areas coincide with the Lower Sonoran Life Zone, with semiarid climate, sparse flora, and alkaline soil in Arizona, California, New Mexico, and Texas.

•

Fungus exists in the mycelial phase in soil, having barrel-shaped hyphae (arthroconidia). Arthrospores are aerosolized and deposit in the alveoli, then fungus converts to thick-walled spherule.

•

Internal spherical spores (endospores) are released through spherule rupture and mature into new spherules (parasitic cycle).

•

Fungus incites a granulomatous reaction in host tissue, usually with caseation necrosis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

•

Acute pulmonary coccidioidomycoses: 1.

Community-acquired pneumonias caused by Mycoplasma and Chlamydia

2.

Granulomatous diseases, such as Mycobacterium tuberculosis and sarcoidosis

3.

Other fungal diseases, such as Blastomyces dermatitidis and Histoplasma capsulatum

Coccidioidomas: true neoplasms

WORKUP

Suspected in patients with a history of residence or travel in an endemic area, especially during periods favorable to spore dispersion (e.g., dust storms and drought followed by heavy rains) LABORATORY TESTS

•

CBC to reveal eosinophilia, especially with erythema nodosum

•

Routine chemistries: usually normal but may reveal hyponatremia

•

Elevated serum levels of IgE; associated with progressive disease

•

CSF cell counts and chemistry: pleocytosis with mononuclear cell predominance associated with hypoglycorrhachia and elevated protein level

•

Definitive diagnosis based on demonstration of the organism by culture from body fluids or tissues

•

•

1.

Greatest yield with pus, sputum, synovial fluid, and soft tissue aspirations, varying with the degree of dissemination

2.

Possible positive cultures of blood, gastric aspirate, pleural effusion, peritoneal fluid, and CSF, but less frequently obtained

Serologic evaluations 1.

Latex agglutination and complement fixation

2.

Elevated serum complement-fixing antibody (CFA) titers =1:32 strongly correlated with disseminated disease, except with meningitis where lower titers seen

3.

In meningeal disease: CFA detected in CSF except with high serum CFA titers secondary to concurrent extraneural disease

4.

Enzyme-linked immunosorbent assay (ELISA) against a 33-kDa spherule antigen to detect and monitor CNS disease

Skin test: coccidioidin, the mycelial phase antigen, and spherulin, the parasitic phase antigen 1.

Positive (>5 mm) 1 mo following onset of symptomatic primary infection

2.

Useful in assessing prior infection

3.

Negative skin test with primary infection: latent or future dissemination

IMAGING STUDIES

Chest x-ray examination: •

Reveals unilateral infiltrates, hilar adenopathy, or pleural effusion in primary infection

•

Shows areas of fibrosis containing usually solitary, thin-walled cavities that persist as residua of primary infection

•

Possible coccidioidoma, a coinlike lesion representing a healed area of previous pneumonitis

TREATMENT NONPHARMACOLOGIC THERAPY

•

Supportive care in mild symptomatic disease

•

In patients with extrapulmonary manifestations involving draining skin, joint, and soft tissue infection: local wound care to avoid possible bacterial superinfection

ACUTE GENERAL Rx

•

In general, drug therapy is not required for patients with asymptomatic pulmonary disease and most patients with mild symptomatic primary infection.

•

Chemotherapy is indicated under the following circumstances: 1.

Severe symptomatic primary infection

2.

High serum CFA titers

3.

Persistent symptoms >6 wk

4.

Prostration

5.

Progressive pulmonary involvement

6.

Pregnancy

7.

Infancy

8.

Debilitation

9.

Concurrent illness (e.g., diabetes, asthma, COPD, malignancy)

10. Acquired or induced immunosuppression 11. Racial group with known predisposition for disseminated disease •

•

Fluconazole 1.

Most commonly, oral therapy with 400 mg/day up to 1.2 g/day appears to be the drug of choice for meningeal and deep-seated mycotic infections.

2.

In patients with AIDS, fluconazole may be considered the drug of choice for initial and maintenance therapy.

3.

All patients with coccidioidal meningitis should continue azole therapy indefinitely.

Itraconazole 1.

400 to 600 mg/day achieves 90% response rate in bone, joint, soft tissue, lymphatic, and genitourinary infections.

2.

Itraconazole may be more efficacious than fluconazole in the treatment of skeletal (bone) infections.

•

Posaconazole is a new triazole that has recently been approved for use for systemic mycoses such as coccidioidomycosis; its relative efficacy compared to other agents will need additional clinical study.

•

For pulmonary infections, treatment with either fluconazole or itraconazole, given for 6 to 12 wk, appears to be equal in efficacy.

•

Amphotericin B is the classic therapy for disseminated extraneural disease, dose 1 to 1.5 mg/kg/day, qd for the first week and every other day, for a total dose of 1 to 2.5 g or until clinical and serologic remission is accomplished.

•

•

1.

Local instillation into body cavities such as sinuses, fistulae, and abscesses has been adjunct to therapy.

2.

Liposomal amphotericin B is probably equally effective, but further studies are needed.

3.

Duration of therapy for extraneural disease is undefined but probably about 1 yr.

With meningeal disease: 1.

Intrathecal amphotericin B remains the traditional treatment modality, given alone or preceding the use of oral agents.

2.

Begin in doses of 0.01 to 0.025 mg/day, gradually increasing the dose as tolerated, to 0.5 mg/day with the patient in Trendelenburg's position.

3.

If given via Ommaya reservoir, as in ventriculitis, dose may be increased to 1.5 mg/day if tolerated.

4.

Concomitant parenteral therapy with amphotericin B is used for simultaneous extraneural disease as standard doses and with purely meningeal disease in smaller doses, although not strictly indicated.

5.

Intrathecal therapy is usually given three times a week for at least 3 mo, then discontinued or gradually tapered until once every 6 wk through 1 yr of therapy.

6.

Patients need routine monitoring of CSF, CFA, cell count, and chemistries for at least 2 yr following cessation of therapy.

For osteomyelitis, soft tissue closed-space infections, and pulmonary fibrocavitary disease: surgical debridement, drainage, or resection, respectively, in addition to oral azole therapy or parenteral administration of amphotericin B.

CHRONIC Rx

For chronically immunocompromised patients, lifelong therapy with oral azoles or amphotericin B DISPOSITION

•

Prognosis for primary symptomatic infection is good.

•

Immunocompromised patients are most likely to have disseminated disease and higher morbidity and mortality.

REFERRAL

•

To surgeon for the evaluation of chronic hemoptysis, enlarging cavitary lesions despite chemotherapy and intrapleural rupture, osteomyelitis, and other synovial or soft tissue closed space infections

•

For neurosurgical consultation in patients with meningeal disease to establish the delivery route of intrathecal drug therapy

PEARLS & CONSIDERATIONS COMMENTS

•

Infected body fluids contained within a closed moist environment (e.g., sputum in a specimen cup) provide the opportunity for the fungus to revert to its hyphal form whereby spores may be made airborne on opening of the container. This is a biohazard for laboratory personnel. Purulent drainage into a cast, allowing conversion of fungus to the saprophytic phase, has been responsible for acute disease when the cast was opened and the spores were unintentionally made airborne.

•

Patients with a remote history of exposure, especially if immunosuppressed by medication or disease, may reactivate primary disease and suffer rapid dissemination.

•

Although cardiac disease is rare, constrictive pericarditis in the setting of disseminated coccidioidomycosis has been documented and is potentially fatal.

•

Organ transplant recipients may develop disease if the transplant donor has unrecognized active coccidioidomycosis at the time of death.

SUGGESTED READINGS Ampel NM, et al: The mannose receptor mediates the cellular immune response in human coccidioidomycosis. Infect Immun 2005; 73(b):2554-2555. Blair JE, Smilack JD, Caples SM: Coccidioidomycosis in patients with hematologic malignancies. Arch Intern Med 2005; 165(b):113-117. Parish JM, Blair JE: Coccidioidomycosis. Mayo Clin Proc 2008; 83(b):343-349. Wang CY, et al: Disseminated coccidioidomycosis. Emerg Infect Dis 2005; 11(b):177-179.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Churg-Strauss Syndrome FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Acute self-limited febrile illness caused by infection with a Coltivirus

ICD-9CM CODES

066.1 Colorado Tick Fever EPIDEMIOLOGY & DEMOGRAPHICS

•

Incidence: approximately 330 cases reported per year in the U.S.

•

Demographics: children and adults of both genders

•

Geography: Rocky Mountains at elevations of 4000 to 10,000 feet. Sporadic cases have been reported from areas of California outside the range of Dermacentor andersoni

•

Colorado has the highest incidence ( Fig. 1-58 )

FIGURE 1-58 Geographic distribution of Dermacentor andersoni (wood ticks) and reported cases of Colorado tick fever, 1990-1996, United States and Canada. (From Mandell GL: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, ed 6, New York, 2005, Churchill Livingstone.)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Incubation: 3 to 4 days is usual, but can be up to 14 days

•

First symptoms: fever, chills, severe headache, severe myalgias, and hyperesthetic skin

•

Initial signs and symptoms 1.

Tick bite

2.

Fever and chills

3.

Headache

4.

Myalgias

5.

Weakness

6.

Prostration and indifference

7.

Injected conjunctivae

8.

Erythematous pharyngitis

9.

Lymphadenopathy

10. Maculopapular or petechial rash These first symptoms last for 1 wk or less but 50% of the cases experience a febrile relapse 2 to 3 days following an initial remission. Weakness and fatigue may persist for several months after the acute phase(s). This chronic phase is more likely in older patients. In children, 5% to 10% of cases are complicated by aseptic meningitis. In adults, rare complications include pneumonia, hepatitis, myocarditis, and epididymoorchitis. Vertically transmitted fetal infection is possible. ETIOLOGY

•

Infectious agent: Coltiviruses; 7 species, including 3 in the U.S.

•

Vector: wood tick, D. andersoni.

•

Pathogenesis: human transmission occurs via tick bite. Tick season spans from March to September. The virus infects marrow erythrocytic precursors, explaining the protracted disease course as viremia lasts for the lifespan of the infected RBC.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Rocky Mountain spotted fever

•

Influenza

•

Leptospirosis

•

Infectious mononucleosis

•

CMV infection

•

Pneumonia

•

Hepatitis

•

Meningitis

•

Endocarditis

•

Scarlet fever

•

Measles

•

Rubella

•

Typhus

•

Lyme disease

•

Immune thrombocytopenic purpura (ITP)

•

Thrombotic thrombocytopenic purpura (TTP)

•

Kawasaki disease

•

Toxic shock syndrome

•

Vasculitis

WORKUP

Consider Colorado tick fever in the presence of the above symptoms associated with travel to an endemic area coupled with a history of tick exposure LABORATORY TESTS

•

CBC 1.

Leukopenia

2.

Atypical lymphocytes

3.

Moderate thrombocytopenia

•

Virus identification in RBCs by indirect immunofluorescence

•

Serology using ELISA, neutralization, or complement fixation

TREATMENT

•

No specific therapy, although Coltiviruses are sensitive to ribavirin

•

Bedrest, fluids, acetaminophen

•

Avoid aspirin because of thrombocytopenia

•

Prevention: tick avoidance measures

SUGGESTED READINGS

Jaffar FM, et al: Recombinant VP-7-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Colorado tick fever virus. J Clin Microbiology 2003; 41:2102. Tsai TF: Coltiviruses (Colorado tick fever). In: Mandell GL, Bennett JF, Dolin R, ed. Principles and practice of infectious diseases, ed 6. Philadelphia: Churchill Livingstone; 2005.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Colorectal Cancer FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Colorectal cancer (CRC) is a neoplasm arising from the luminal surface of the large bowel: descending colon (40% to 42%), rectosigmoid and rectum (30% to 33%), cecum and ascending colon (25% to 30%), transverse colon (10% to 13%).

ICD-9CM CODES

154.0 Colorectal cancer EPIDEMIOLOGY & DEMOGRAPHICS

•

CRC is the second leading cause of cancer deaths in the U.S. (>135,000 new cases and >50,000 deaths/yr).

•

Peak incidence is in the seventh decade of life. The lifetime risk of developing CRC is 1 in 17, with 90% of cases occurring after the age of 50 years.

•

50% of rectal cancers are within reach of the examiner's finger, 50% of colon cancers are within reach of the flexible sigmoidoscope.

•

CRC accounts for 14% of all cases of cancer (excluding skin malignancies) and 14% of all yearly cancer deaths.

•

Risk factors:

1.

Hereditary polyposis syndromes a.

Familial polyposis (high risk)

b.

Gardner's syndrome (high risk)

c.

Turcot's syndrome (high risk)

d.

Peutz-Jeghers syndrome (low to moderate risk)

2.

IBD, both ulcerative colitis and Crohn's disease

3.

Family history of “cancer family syndrome”

4.

Heredofamilial breast cancer and colon carcinoma

5.

History of previous colorectal carcinoma

6.

Women undergoing irradiation for gynecologic cancer

7.

First-degree relatives with colorectal carcinoma

8.

Age >40 yr

9.

Possible dietary factors (diet high in fat or meat, beer drinking, reduced vegetable consumption). Prolonged high consumption of red and processed meat may increase the risk of cancer of the large intestine.

10. Hereditary nonpolyposis colon cancer (HNPCC): autosomal-dominant disorder characterized by early age of onset (mean age of 44 yr) and right-sided or proximal colon cancers, synchronous and metachronous colon cancers, mucinous and poorly differentiated colon cancers; it accounts for 1% to 5% of all cases of CRC 11. Previous endometrial or ovarian cancer, particularly when diagnosed at an early age PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination may be completely unremarkable.

•

Digital rectal examination can detect approximately 50% of rectal cancers.

•

Palpable abdominal masses may indicate metastasis or complications of colorectal carcinoma (abscess, intussusception, volvulus).

•

Abdominal distention and tenderness are suggestive of colonic obstruction.

•

Hepatomegaly may be indicative of hepatic metastasis.

ETIOLOGY

CRC can arise through two mutational pathways: microsatellite instability or chromosomal instability. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Diverticular disease

•

Strictures

•

IBD

•

Infectious or inflammatory lesions

•

Adhesions

•

Arteriovenous malformations

•

Metastatic carcinoma (prostate, sarcoma)

•

Extrinsic masses (cysts, abscesses)

WORKUP

•

The clinical presentation of colorectal malignancies is initially vague and nonspecific (weight loss, anorexia, malaise). It is useful to divide colon cancer symptoms into those usually associated with right side of colon and those commonly associated with left side of colon, because the clinical presentation varies with the location of the carcinoma. 1.

2.

•

Right side of colon a.

Anemia (iron deficiency secondary to chronic blood loss).

b.

Dull, vague, and uncharacteristic abdominal pain may be present, or patient may be completely asymptomatic.

c.

Rectal bleeding is often missed because blood is mixed with feces.

d.

Obstruction and constipation are unusual because of large lumen and more liquid stools.

Left side of colon a.

Change in bowel habits (constipation, diarrhea, tenesmus, pencil-thin stools).

b.

Rectal bleeding (bright red blood coating the surface of the stool).

c.

Intestinal obstruction is frequent because of small lumen.

Early diagnosis of patients with surgically curable disease (Dukes' A, B) is necessary, because survival time is directly related to the stage of the carcinoma at the time of diagnosis. Appropriate screening recommendations are discussed in Section V.

CLASSIFICATION AND STAGING: Dukes' and UICC classification for CRC: A.

Confined to the mucosa-submucosa (I)

B.

Invasion of muscularis propria (II)

C.

Local node involvement (III)

D.

Distant metastasis (IV)

TNM Classification:

Stage TNM classification I

T1-2, N0, M0

IIA

T3, N0, M0

IIB

T4, N0, M0

IIIA

T1-2, N1, M0

Stage TNM classification IIIB

T3-4, N1, M0

IIIC

T(any), N2, M0

IV

T(any), N(any), M1

LABORATORY TESTS

•

Positive fecal occult blood test. Many primary care physicians use single digital fecal occult blood test (FOBT) as their primary screening test for CRC. Single FOBT has low specificity for detecting human hemoglobin, is a poor screening method for CRC (sensitivity 4.9%), and is inappropriate as the only test because negative results do not decrease the odds of advanced neoplasia. The at-home 6-sample FOBT is more sensitive (sensitivity to 23.9%) and should be offered to patients who are unwilling to undergo screening colonoscopic evaluation or barium enema. Qualitative immunochemical FOBTs are specific for the detection of human hemoglobin and have better sensitivity and specificity for detection of clinically significant neoplasia.

•

Newer modalities for early detection of colorectal neoplasms include the detection of mutations in the adenomatous polyposis coli (APC) gene from stool samples. Identification of abnormal fecal DNA has greater sensitivity for colorectal neoplasia than FOBT.

•

Microcytic anemia.

•

Elevated plasma carcinoembryonic antigen (CEA). CEA should not be used as a screening test for CRC because it can be elevated in patients with many other conditions (smoking, IBD, alcoholic liver disease). A normal CEA does not exclude the diagnosis of CRC.

•

Liver function tests.

IMAGING STUDIES

•

Colonoscopy with biopsy (primary assessment tool).

•

Virtual colonoscopy (VC) uses helical (spiral) CT scan to generate a two- or three-dimensional virtual colorectal image. VC does not require sedation, but like optical colonoscopy, it requires some bowel preparation (either bowel cathartics or ingestion of iodinated contrast medium with meals during the 48 hours before CT) and air insufflation. It also involves substantial exposure to radiation. In addition, patients with lesions detected by VC will require traditional colonoscopy.

•

CT scan of abdomen/pelvis/chest to assist in preoperative staging.

•

PET scanning can display functional information and is accurate in the detection of CRC and its distant metastases. Combined PET/CT scanners are increasingly more available and are useful to detect and characterize malignant lesions. Colonography composed of a combined modality of PET and CT is a newer diagnostic modality that can provide whole-body tumor staging in a single session.

TREATMENT GENERAL Rx

•

Surgical resection: 70% of CRC are resectable for cure at presentation; 45% of patients are cured by primary resection.

•

The backbone of treatment of CRC is fluorouracil (FL). Leucovorin (folinic acid) enhances the effect of fluorouracil and is given together with it. Adjuvant chemotherapy with combination of 5-fluorouracil (5-FU) and levamisole substantially increases cure rates for patients with stage III colon cancer and should be considered standard treatment for all such patients and selected patients with high-risk stage II colon cancer (adherence of tumor to an adjacent organ, bowel perforation, or obstruction).

•

Radiation therapy is a useful adjunct to fluorouracil and leucovorin therapy for stage II or III rectal cancers.

•

When given as adjuvant therapy after a complete resection in stage III disease, FL increases overall 5-year survival from 51% to 64%. The use of adjuvant FL in stage II disease (no involvement of regional nodes) is controversial because 5-year overall survival is 80% for treated or untreated patients and the addition of FL only increases the probability of 5-year disease-free interval from 72% to 76%. For patients with standardrisk stage III tumors (e.g., involvement of one to three regional lymph nodes), both FL alone or FL with oxaliplatin (Eloxatin, an inhibitor of DNA synthesis) are reasonable choices. Generally reversible peripheral neuropathy is the main side effect of FL plus oxaliplatin. The oral fluoropyrimidine capecitabine (Xeloda) is a prodrug that undergoes enzymatic conversion to fluorouracil. It is an effective alternative to IV fluorouracil as adjuvant treatment for stage III colon cancer because it has a lower incidence of mouth sores and bone marrow suppression. It does however have an increased incidence of palmar-plantar erythrodysesthesia (hand-foot syndrome).

•

Irinotecan (Camptosar), a potent inhibitor of topoisomerase I, a nuclear enzyme involved in the unwinding of DNA during replication, can be used to treat metastatic CRC refractory to other drugs, including 5-FU; it may offer a few months of palliation but is expensive and associated with significant toxicity.

•

Oxaliplatin (Eloxatin), a third-generation platinum derivative, can be used in combination with fluorouracil and leucovorin (FL) for patients with metastatic CRC whose disease has recurred or progressed despite treatment with fluorouracil/leucovorin plus irinotecan. FL plus oxaliplatin should be considered for high-risk patients with stage III cancers (e.g., >3 involved regional nodes [N2] or tumor invasion beyond the serosa [T4 lesion]).

•

Laboratory studies have identified molecular sites in tumor tissue that may serve as specific targets for treatment by using epidermal growth factor receptor antagonists and angiogenesis inhibitors. The monoclonal antibodies cetuximab (Erbitux), panitumumab (Vectibix), and bevacizumab (Avastatin) have been approved by the FDA for advanced CRC. Bevacizumab is an angiogenesis inhibitor that binds and inhibits the activity of human vascular endothelial growth factor (VEGF). Cetuximab and panitumumab are epidermal growth factor receptor [EGFR] blockers that inhibits the growth and survival of tumor cells that overexpress EGFR. Cetuximab has synergism with irinotecan and its addition to irinotecan in patients with advanced disease resistant to irinotecan increases response rate from 10% when cetuximab is used alone to 22% with combination of cetuximab and irinotecan. The addition of bevacizumab to FL in patients with advanced CRC has been reported to increase the response rate from 17% to 40%. Severe dermatologic toxicity can occur with both cetuximab and panitumumab.

•

The liver is generally the initial and most common site of CRC metastases. Resection of metastases limited to the liver is curative in more than 30% of selected patients. In patients who undergo resection of liver metastases, postoperative treatment with a combination of hepatic arterial infusion of floxuridine and IV fluorouracil improves the outcome at 2 yr.

CHRONIC Rx

Follow-up is indicated with:

•

Physician visits with a focus on the clinical and disease-related history, directed physical examination guided by this history, coordination of follow-up, and counseling every 3 to 6 mo for the first 3 yr then decreased frequency thereafter for 2 yr.

•

Colonoscopy yearly for the initial 2 yr, then every 3 yr.

•

CEA level should be obtained baseline; if elevated, it can be used postoperatively as a measure of completeness of tumor resection or to monitor tumor recurrence; if used to monitor tumor recurrence, CEA should be obtained every 3 to 6 mo for up to 5 yr. The role of CEA for monitoring patients with resected colon cancer has been questioned because of the small number of cures attributed to CEA monitoring despite the substantial cost in dollars and physical and emotional stress associated with monitoring.

DISPOSITION

•

The 5-yr survival varies with the stage of the carcinoma: Dukes': 1.

Dukes' A 5-yr survival, >80%

2.

Dukes' B 5-yr survival, 60%

3.

Dukes' C 5-yr survival, 20%

4.

Dukes' D 5-yr survival, 3%

TNM Classification:

Stage TNM classification 5-year survival I

T1-2, N0, M0

>90%

IIA

T3, N0, M0

60%-85%

IIB

T4, N0, M0

60%-85%

IIIA

T1-2, N1, M0

25%-65%

IIIB

T3-4, N1, M0

25%-65%

IIIC

T(any), N2, M0 to

25%-65%

IV

T(any), N(any), M1 5%-7%

•

Overall 5-yr disease-free survival has increased from 50% to 63% during the past 2 decades.

•

High-frequency microsatellite instability in CRC is independently predictive of a relatively favorable outcome and, in addition, reduces the likelihood of metastases.

•

In patients with Dukes' C (stage III) CRC there is improved 5-year survival among women treated with adjuvant chemotherapy (53% with chemotherapy vs. 33% without) and among patients with right-sided tumors treated with adjuvant chemotherapy.

•

Retention of 18q alleles in microsatellite-stable cancers and mutation of the gene for the type I receptor for TGF-B1 in cancers with high levels of microsatellite instability point to a favorable outcome after adjuvant chemotherapy with fluorouracil-based regimens for stage II colon cancer.

REFERRAL

•

Surgical referral for resection

•

Oncology referral for adjuvant chemotherapy in selected patients

•

Radiation oncology referral for patients with stage II or III rectal cancers

PEARLS & CONSIDERATIONS COMMENTS

•

Decreased fat intake to 30% of total energy intake, increased fiber, and fruit and vegetable consumption may lower CRC risk. Recent literature reports, however, do not support a protective effect from dietary fiber against CRC in women.

•

Chemoprophylaxis with aspirin (81 mg/day) reduces the incidence of colorectal adenomas in persons at risk.

•

Statins inhibit the growth of colon cancer lines. Use of statins is associated with a 47% relative reduction in the risk of CRC. Additional trials are necessary to investigate the overall benefits of statins in preventing CRC.

•

The National Cancer Institute has published consensus guidelines for universal screening for hereditary nonpolyposis colon cancer (HNPCC) in patients with newly diagnosed CRC. Tumors in mutation carriers of HNPCC typically exhibit microsatellite instability, a characteristic phenotype that is caused by expansions or contractions of short nucleotide repeat sequences. These guidelines (Bethesda Guidelines) are useful for selective patients for microsatellite instability testing. Screening patients with newly diagnosed CRC for HNPCC is cost effective, especially if the benefits to their immediate relatives are considered.

•

Expression of guanylyl cyclase C mRNA in lymph nodes is associated with recurrence of CRC in patients with stage II disease. Analysis of guanylyl cyclase mRNA expression by RT-PCR may be useful for CRC staging.

•

The use of either annual or biennial fecal occult-blood testing significantly reduces the incidence of CRC.

•

The detection of mutations in the adenomatous polyposis coli (APC) gene from stool samples is a promising new modality for early detection of colorectal neoplasms.

EVIDENCE

Adjuvant systemic chemotherapy has been shown to significantly improve overall survival compared with no adjuvant chemotherapy in patients with Dukes' C colon cancer, and Dukes' B or C rectal cancer. The results were less clear with Dukes' B tumors.[[1]] Pooled analysis of three randomized controlled trials (RCTs) of adjuvant 5-fluorouracil and folinic acid found a significant increase in survival for patients with Dukes' C colon tumors at 3 years but no survival benefit for patients with Dukes' B tumors.[[2]] A significant survival advantage was seen at 6 years in patients treated with 1 week of continuing portal vein infusion chemotherapy commenced within 5 to 7 days of surgery vs. no additional treatment after surgery, in patients with Dukes' A, B, and C colorectal tumors. The benefit was only seen for patients with colon cancer.[[3]] A systematic review found that palliative chemotherapy was effective for prolonging time to disease progression in patients with advanced CRC. An absolute improvement in survival of 16% was seen at 6 and

12 months.[[4]] In a recent multiinstitutional study, 872 patients with adenocarcinoma of the colon were randomized into two groups receiving open or laparoscopically assisted colectomy performed by credentialed surgeons. At 3 years, the rates of recurrence were similar in the two groups.[[5]] Recently the FDA approved cetuximab (a monoclonal antibody that inhibits the epidermal growth factor receptor [EGFr] pathway) for the treatment of advanced CRC. A Phase II, open-label clinical trial found that in patients who had tumors with EGFr expression and who had also demonstrated clinical failure with irinotecanon, had modest results with a once-weekly cetuximab regime.[[6]] A recent randomized controlled clinical trial compared the addition of the monoclonal antibody against vascular endothelial growth factor, bevacizumab, to a fluorouracil-based combination chemotherapy regime vs. the addition of placebo to the same regime, in patients with untreated metastatic CRC. It found that the addition of bevacizumab resulted in a statistically significant and clinically meaningful improvement in survival.[[7]] Another recent randomized controlled clinical trial compared the addition of the platinum-containing chemotherapeutic agent oxaliplatin to the standard fluorouracil plus leucovorin (FL) regime vs. no additive treatment in patients who had undergone curative resection for stage II or III colon cancer. The researchers concluded that the group that had been treated with the addition of oxaliplatin to the FL regime had improved disease-free survival.[[8]]

Evidence-Based References 1. Dube D, Heyen F, Jenicek M: Adjuvant chemotherapy in colorectal carcinoma. Results of a meta analysis. Dis Colon Rectum 1997; 40:35-41.Reviewed in: Clin Evid 11:562-570, 2003. 2. International Multicenter Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators: Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995; 348:939-944.Reviewed in: Clin Evid 11:562-570, 2003. 3. Liver Infusion Meta-analysis Group: Portal vein chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in 10 studies. J Natl Cancer Inst 1997; 89:497-505.Reviewed in: Clin Evid 11:562-570, 2003. 4. Best L et al: Palliative chemotherapy for advanced or metastatic colorectal cancer (Cochrane Review). 5. Clinical Outcomes of Surgical Therapy Study Group: A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004; 350(b):2050-2059. 6. Saltz LB, et al: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004; 22(b):1201-1208. 7. Hurwitz H, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350(b):2335-2342. 8. Andre T, et al: Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350(b):2343-2351.

SUGGESTED READINGS

Gill S, et al: Colorectal cancer. Mayo Clin Proc 2007; 82:114-129. Jonker DJ, et al: Cetuximab for the treatment of colorectal cancer. N Eng J Med 2007; 357:2040-2048. Levi Z, et al: A qualitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med 2007; 146:244-255. Meyerhardt JA, Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med 2005; 352:476-487. Poynter JN, et al: Statins and the risk of colorectal cancer. N Engl J Med 2005; 352:2184-2192. Schetter AJ, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008; 299(b):425-436. Twelves C, et al: Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005; 352:26962704. Veit-Haibach P, et al: Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography. JAMA 2006; 296:2590-2600.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Condyloma Acuminatum NIRALI BORA, M.D.

BASIC INFORMATION DEFINITION

Condyloma acuminatum is a sexually transmitted viral disease of the vulva, vagina, and cervix that is caused by the human papillomavirus (HPV). SYNONYMS

Genital warts Venereal warts Anogenital warts

ICD-9CM CODES

078.11 Condyloma acuminatum EPIDEMIOLOGY & DEMOGRAPHICS

•

Seen mostly in young adults with a mean age of onset of 16 to 25 yr

•

A sexually transmitted disease spread by skin-to-skin contact

•

Highly contagious, with 25% to 65% of sexual partners developing it

•

Virus shed from both macroscopic and microscopic lesions

•

Average incubation time 2 mo (range: 1 to 8 mo)

•

Predisposing conditions: diabetes, pregnancy, local trauma, and immunosuppression (e.g., transplant patients, those with HIV infection)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usually found in genital area, but can be present elsewhere

•

Lesions usually in similar positions on both sides of perineum

•

Initial lesions pedunculated, soft papules about 2 to 3 mm in diameter, 10 to 20 mm long; may occur as single papule or in clusters

•

Size of lesions varies from pinhead to large cauliflower-like masses

•

Usually asymptomatic, but if infected, can cause pain, odor, or bleeding

•

Vulvar condyloma more common than vaginal and cervical

•

There are four morphologic types: condylomatous, keratotic, papular, and flat warts

ETIOLOGY

•

HPV DNA types 6 and 11 usually found in exophytic warts and have no malignant potential

•

HPV types 16 and 18 usually found in flat warts and are associated with increased risk of malignancy

•

Recurrence associated with persisting viral infection of adjacent normal skin in 25% to 50% of cases

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Abnormal anatomic variants or skin tags around labia minora and introitus

•

Dysplastic warts

WORKUP

•

Colposcopic examination of lower genital tract from cervix to perianal skin with 3% to 5% acetic acid

•

Biopsy of vulvar lesions that lack the classic appearance of warts and that become ulcerated or fail to respond to treatment

•

Biopsy of flat white or ulcerated cervical lesions

LABORATORY TESTS

•

Pap smear

•

Cervical cultures for N. gonorrhoeae and Chlamydia

•

Serologic test for syphilis

•

HIV testing offered

•

Wet mount for trichomoniasis, Candida albicans, and Gardnerella vaginalis

•

Testing for diabetes (blood glucose)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Keep genital area dry and clean.

•

Keep diabetes, if present, well controlled.

•

Advise use of condoms to prevent spread of infection to sexual partner.

ACUTE GENERAL Rx

Keratolytic agents: •

•

•

Podophyllin 1.

Acts by poisoning mitotic spindle and causing intense vasospasm

2.

Applied directly to lesion weekly and washed off in 6 hr

3.

Used in minimal vulvar or anal disease

4.

Applied cautiously to nonkeratinized epithelial surfaces

5.

Contraindicated in pregnancy

6.

Discontinued if lesions do not disappear in 6 wk; switch to other treatment

Trichloroacetic acid (30% to 80% solution) 1.

Acts by precipitation of surface proteins

2.

Applied twice monthly to lesion

3.

Indicated for vulvar, anal, and vaginal lesions; can be used for cervical lesions

4.

Less painful and irritating to normal tissue than podophyllin

Fluorouracil 1.

Causes necrosis and sloughing of growing tissue

2.

Can be used intravaginally or for vulvar, anal, or urethral lesions

3.

Better tolerated; 3 g (two thirds of vaginal applicator) applied weekly for 12 wk

4.

Possible vaginal ulceration and erythema

5.

Patient's vagina examined after four to six applications

6.

80% cure rate

Physical agents: •

•

•

Cryotherapy 1.

Can be used weekly for 3 to 6 wk

2.

62% to 79% success rate

3.

Not suitable for large warts

Laser therapy 1.

Done by physician with necessary expertise and equipment

2.

Painful; requires anesthesia

Electrocautery or excision 1.

For recurrent, very large lesions

2.

Local anesthesia needed

Immunotherapy:

•

Interferon 1.

Injected intralesionally at a dose of 3 million U/m 2 three times weekly for 8 wk

2.

Side effects: fever, chills, malaise, headache

•

Imiquimod 5% cream: increases wart clearance after 3 mo

•

Interferon, topical: increases wart clearance at 4 wk

DISPOSITION

Follow-up exam every 6 to 12 months, as needed. REFERRAL

Consult gynecologist in case of extensive lesions or lesions resistant to treatment with keratolytic agents (podophyllin and trichloroacetic acid).

EVIDENCE

Podofilox and imiquimod have been shown to be more effective than placebo. [253] [254] Trichloroacetic acid and cryotherapy appear to be equally effective at producing clearance of warts. [255] [256]

Evidence-Based References 1. Wiley DJ: Genital warts. Clin Evid 2002; 8:1620. 2. Moore RA, et al: Imiquimod for the treatment of genital warts: a quantitative systematic review. BMC Infect Dis 2001; 1:3.Reviewed in: Clin Evid 10, web version only, 2003. 3. Abdullah AN, Walzman M, Wade A: Treatment of external genital warts comparing cryotherapy (liquid nitrogen) and trichloroacetic acid. Sex Transm Dis 1993; 20:344.Reviewed in: Clin Evid 10, web version only, 2003. 4. Godley MJ, et al: Cryotherapy compared with trichloroacetic acid in treating genital warts. Genitourin Med 1987; 63:390.Reviewed in: Clin Evid 10, web version only, 2003.

AUTHORS: GEORGE T. DANAKAS, M.D., and RUBEN ALVERO, M.D. Congenital Adrenal Hyperplasia

BASIC INFORMATION DEFINITION

Congenital adrenal hyperplasia (CAH) refers to several different genetic mutations in the enzymes responsible

for cortisol synthesis, which are each inherited in an autosomal recessive fashion. SYNONYMS

21-hydroxylase deficiency (equivalent to CYP21A2 deficiency) 11B-hydroxylase deficiency 3B-hydroxysteroid dehydrogenase deficiency 17-hydroxylase deficiency Lipoid adrenal hyperplasia CYP 17 deficiency

ICD-9-CM CODES

255.2 Adrenogenital disorders; hyperplasia, congenital adrenal EPIDEMIOLOGY & DEMOGRAPHICS

•

Between 90% and 95% of cases of CAH are caused by “classic” 21-hydroxylase deficiency, of which 75% of cases represent the salt-wasting form.

•

Inheritance pattern is autosomal recessive.

•

Prevalence of 21-hydroxylase deficiency is 1/16,000 infants in the U.S., but may be higher among other groups, such as Hispanics and Ashkenazi Jews (1% to 2%).

•

The frequency of heterozygous carriers is controversial; estimates range between 1:5 and 1:80 persons.

CLINICAL PRESENTATION

“Classic” salt-wasting form (impaired cortisol and aldosterone synthesis): •

Infants are acutely ill with poor weight gain, hypovolemia, hyponatremia, hyperkalemia, and elevated plasma renin.

•

If patients survive infancy, their overall life expectancy is not compromised.

•

Females are born with ambiguous genitalia and may have irregular menses and infertility as adults.

•

Males may have greater penile size and smaller testes than expected during childhood. Males may also develop adrenal rests, or ectopic islands of adrenal cortical tissue in the testes, in childhood and may experience infertility as adults.

•

Both males and females may exhibit rapid growth in childhood (due to early epiphyseal closure, which then results in short stature in adulthood).

•

Precocious puberty is common in both males and females.

“Classic” non-salt-wasting or simple virilizing form (impaired cortisol synthesis only):

•

Females present with ambiguous genitalia at birth.

•

The normal appearance of male genitalia in the simple virilizing form makes this a difficult diagnosis in male infants.

•

Characterized by precocious puberty, short stature, and testicular adrenal rests as in the salt-wasting form.

“Nonclassic” or mild, late-onset form (varying degrees of androgen excess): •

Usually presents in adolescence or adulthood and is not detected on newborn screening.

•

Often asymptomatic, but can be associated with mild virilization.

•

PCOS-like symptoms occur in women (hirsutism, oligomenorrhea, acne, infertility, insulin resistance, abnormal menses).

•

Associated with infertility in males.

ETIOLOGY

In 21-hydroxylase deficiency, the pathways for aldosterone production (from the conversion of progesterone to deoxycorticosterone) and cortisol production (from the conversion of 17-hydroxyprogesterone to 11deoxycortisol) by the cP450 enzyme 21-hydroxylase are interrupted. The production of ACTH is thus stimulated by a negative feedback mechanism, leading to adrenal hyperplasia and mineralocorticoid deficiency as the intermediaries in aldosterone and cortisol synthesis are shunted to the androgen biosynthesis pathway ( Fig. 159, A and B ). A recombination event between the active CYP21A2 gene on chromosome 6p21.3 and the CYP21A1 pseudogene is thought to create the deficient 21-hydroxylase enzyme.

FIGURE 1-59 A, Normal adrenal steroidogenesis. B, Consequences of C-21 hydroxylase deficiency. (From Cotran R, Kumar V, Collins T [eds]: Robbins pathologic basis of disease, ed 6, Philadelphia, 1999, WB Saunders, p 1158.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Precocious puberty

•

Polycystic ovarian syndrome (PCOS)

•

Androgen resistance syndromes

•

Pseudohermaphroditism

•

Mixed gonadal dysgenesis

•

Testicular carcinoma

•

Leydig cell tumors

•

Adrenocortical carcinoma

•

Addison's disease

•

Pituitary adenoma

LABORATORY TESTS

Laboratory tests (for 21-hydroxylase deficiency): •

Prenatal: chorionic villus sampling for genetic testing or measurement of 17-hydroxyprogesterone

•

Neonates, children, and adults: screening for elevated 17-hydroxyprogesterone levels (not done by all states), high-dose cosyntropin stimulation test, and genotyping

IMAGING STUDIES

•

Ultrasound to identify a uterus in cases of ambiguous genitalia.

•

Ultrasound is preferred to rule out testicular adrenal rest tumors (found in classic and nonclassic forms) and should be done beginning in adolescence. MRI and color-flow Doppler may also be used for this purpose.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Surgical correction of ambiguous genitalia is recommended by 6 months.

•

Bilateral laparoscopic adrenalectomy with lifelong glucocorticoid and mineralocorticoid replacement (controversial).

•

Gene therapy (hypothetical).

ACUTE GENERAL Rx

Overall goal is suppression of ACTH. •

Prenatal: dexamethasone 20 to 25 ug/kg/d in the first trimester in female fetuses only (controversial because long-term studies are unavailable).

•

Infants: fludrocortisone 0.1 to 0.2 mg/d, hydrocortisone 5 to 15 mg/d, NaCl 1 to 2 gm/d.

•

Stress states (e.g., major illness) require increased glucocorticoid dosing.

CHRONIC Rx

•

Chronic Rx: Children: hydrocortisone 10 to 30 mg/d (minimizes the risk of iatrogenic short stature found in other corticosteroids with longer half-lives). Adolescents/Adults: dexamethasone 0.25 to 0.75 mg po QHS (also use to treat adrenal rests) or prednisone 5 to 7.5 mg/d. Fludrocortisone: 0.1 to 0.2 mg/d (may decrease glucocorticoid requirement). Experimental four-drug regimen: flutamide and testolactone in addition to hydrocortisone and fludrocortisone. Psychologic counseling. Monitoring: serum 17-hydroxyprogesterone and androstenedione, renin, electrolytes, blood pressure, bone age and density, Tanner staging, growth velocity, weight.

•

Treatment of simple virilizing form: similar to salt-wasting form, but mineralocorticoid replacement is unnecessary.

•

Treatment of nonclassic form: In adolescent and adult women: oral contraceptives, glucocorticoids, and/or antiandrogens. In children and adult males, usually no treatment is necessary.

PEARLS & CONSIDERATIONS COMMENTS

•

Consider the diagnosis of classic salt-wasting CAH in infants with failure to thrive.

•

There is thought to be an increased prevalence of CAH in patients diagnosed with adrenal “incidentalomas”—adrenal gland lesions detected unexpectedly upon imaging, usually with MRI or CT scanning.

•

Cushing's syndrome may result from overtreatment of CAH with glucocorticoids.

•

Treatment of CAH in pregnancy with dexamethasone will confound newborn screening for 17hydroxyprogesterone such that these infants should be screened 1 to 2 weeks postpartum.

•

Patients with CAH may suffer from gender identity disorders and sexual dysfunction.

PREVENTION

•

Early CVS sampling and maternal glucocorticoid administration (see above).

•

Neonatal screening

•

Genetic counseling

SUGGESTED READINGS Levine L, DiGeorge A: Adrenal disorders and genital abnormalities: congenital adrenal hyperplasia. In: Behrman R, Kliegman R, Jenson H, ed. Nelson's Textbook of Pediatrics, Philadelphia: WB Saunders; 2000:1729-1737. Merke DP, et al: NIH conference: future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002; 136:320. Speiser PW, et al: Congenital adrenal hyperplasia. N Engl J Med 2003; 349:776.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Congestive Heart Failure FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Congestive heart failure is a pathophysiologic state characterized by congestion in the pulmonary or systemic circulation. It is caused by the heart's inability to pump sufficient oxygenated blood to meet the metabolic needs of the tissues. CLASSIFICATION: The American College of Cardiology and the American Heart Association describe the following four stages of heart failure: A.

At high risk for heart failure, but without structural heart disease or symptoms of heart failure (e.g., CAD, hypertension)

B.

Structural heart disease but without symptoms of heart failure

C.

Structural heart disease with prior or current symptoms of heart failure

D.

Refractory heart failure requiring specialized interventions

The New York Heart Association (NYHA) defines the following functional classes: I.

Asymptomatic

II.

Symptomatic with moderate exertion

III.

Symptomatic with minimal exertion

IV. Symptomatic at rest SYNONYMS

CHF Cardiac failure Heart failure

ICD-9CM CODES

428.0 Congestive heart failure EPIDEMIOLOGY & DEMOGRAPHICS

•

CHF is the most common admission diagnosis (20%) in elderly patients.

•

Heart failure occurs in 4.7 million persons in the U.S. and is the discharge diagnosis in 3.5 million hospitalizations annually.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

The findings on physical examination in patients with CHF vary depending on the severity and whether the failure is right-sided or left-sided.

•

Common clinical manifestations are: 1.

Dyspnea on exertion initially, then with progressively less strenuous activity, and eventually manifesting when patient is at rest; caused by increasing pulmonary congestion

2.

Orthopnea caused by increased venous return in the recumbent position

3.

Paroxysmal nocturnal dyspnea (PND) resulting from multiple factors (increased venous return in the recumbent position, decreased Pao 2, decreased adrenergic stimulation of myocardial function)

4.

Nocturnal angina resulting from increased cardiac work (secondary to increased venous return)

5.

Cheyne-Stokes respiration: alternating phases of apnea and hyperventilation caused by prolonged circulation time from lungs to brain

6.

Fatigue, lethargy resulting from low cardiac output

•

Patients with failure of the left side of the heart will have the following abnormalities on physical examination: pulmonary rales, tachypnea, S3 gallop, cardiac murmurs (AS, AR, MR), paradoxic splitting of S2.

•

Patients with failure of right side of the heart manifest with jugular venous distention, peripheral edema, perioral and peripheral cyanosis, congestive hepatomegaly, ascites, hepatojugular reflux.

•

In patients with heart failure, elevated jugular venous pressure and a third heart sound are each independently associated with adverse outcomes.

•

Acute precipitants of CHF exacerbations are: noncompliance with salt restriction, pulmonary infections, arrhythmias, medications (e.g., calcium channel blockers/antiarrhythmic agents), and inappropriate reductions in CHF therapy.

ETIOLOGY

LEFT VENTRICULAR FAILURE: •

Systemic hypertension

•

Valvular heart disease (AS, AR, MR)

•

Cardiomyopathy, myocarditis

•

Bacterial endocarditis

•

Myocardial infarction

•

IHSS

Left ventricular failure is further differentiated according to systolic dysfunction (low ejection fraction) and diastolic dysfunction (normal or high ejection fraction), or “stiff ventricle.” It is important to make this distinction because treatment is significantly different (see “Treatment”). Patients with heart failure and a normal ejection fraction have significant abnormalities in active relaxation and passive stiffness. In these patients, the pathophysiologic cause of elevated diastolic pressures and heart failure is abnormal diastolic function.

•

Common causes of systolic dysfunction are post-MI, cardiomyopathy, myocarditis.

•

Causes of diastolic dysfunction are hypertensive cardiovascular disease, valvular heart disease (AS, AR, MR, IHSS), restrictive cardiomyopathy.

RIGHT VENTRICULAR FAILURE: •

Valvular heart disease (mitral stenosis)

•

Pulmonary hypertension

•

Bacterial endocarditis (right-sided)

•

Right ventricular infarction

BIVENTRICULAR FAILURE: •

Left ventricular failure

•

Cardiomyopathy

•

Myocarditis

•

Arrhythmias

•

Anemia

•

Thyrotoxicosis

•

AV fistula

•

Paget's disease

•

Beriberi

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Cirrhosis

•

Nephrotic syndrome

•

Venous occlusive disease

•

COPD, asthma

•

Pulmonary embolism

•

ARDS

•

Heroin overdose

•

Pneumonia

WORKUP

•

Echocardiography plays a critical diagnostic role in patients with heart failure. Doppler echocardiography, which measures the velocity of intracardiac blood flow, is also helpful in the assessment of diastolic function.

•

Standard 12-lead ECG is useful to diagnose ischemic heart disease and obtain information about rhythm abnormalities. Over 25% of patients with CHF have some form of intraventricular conduction abnormality that is manifested as an increased QRS duration on ECG. The most common pattern is LBBB.

•

Cardiac catheterization provides direct measurement of ventricular diastolic pressure and can demonstrate impaired relaxation and filling; however, it is invasive and indicated only in selected patients.

LABORATORY TESTS

•

CBC (to rule out anemia, infections), BUN, creatinine, electrolytes, liver enzymes, TSH

•

Beta-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted from the ventricles in response to volume expansion and pressure overload. Elevated levels are indicative of left ventricular dysfunction. Bedside measurement of beta-type natriuretic peptide is useful in establishing or excluding the diagnosis of CHF in patients with acute dyspnea. Elevated BNP levels are also strong predictors of survival in patients with heart failure and possibly even in asymptomatic patients.

IMAGING STUDIES

•

Chest x-ray: 1.

Pulmonary venous congestion

2.

Cardiomegaly with dilation of the involved heart chamber

3.

Pleural effusions

•

Two-dimensional echocardiography is useful to assess global and regional left ventricular function and estimate ejection fraction.

•

Exercise stress testing may be useful for evaluating concomitant coronary disease and assess degree of disability. The decision to perform exercise stress testing should be individualized.

•

Cardiac catheterization remains an excellent method to evaluate ventricular diastolic properties, significant coronary artery disease, or valvular heart disease; however, it is invasive. The decision to perform cardiac catheterization should be individualized.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Determine if CHF is secondary to systolic or diastolic dysfunction and treat accordingly.

•

Identify and correct precipitating factors (i.e., anemia, thyrotoxicosis, infections, increased sodium load, medical noncompliance).

•

Decrease cardiac workload in patients with systolic dysfunction: restrict patients' activity only during periods of acute decompensation; the risk of thromboembolism during this period can be minimized by using heparin 5000 U SC q12h in hospitalized patients. In patients with mild to moderate symptoms aerobic training may improve symptoms and exercise capacity.

•

Restrict sodium intake to >2 g/day.

•

Restricting fluid intake to 2 L or less may be useful in patients with hyponatremia.

ACUTE GENERAL Rx

TREATMENT OF CHF SECONDARY TO SYSTOLIC DYSFUNCTION: 1.

ACE inhibitors:

2.

a.

They cause dilation of the arteriolar resistance vessels and venous capacity vessels, thereby reducing both preload and afterload.

b.

They are associated with decreased mortality and improved clinical status when used in patients with CHF caused by systolic dysfunction. They are also indicated in patients with ejection fraction 3.0 or creatinine clearance 5.5 mEQ/L), symptomatic hypotension, and history of adverse reactions (e.g., angioedema).

Diuretics: indicated in patients with systolic dysfunction and volume overload. The most useful approach to selecting the dose of, and monitoring the response to, diuretic therapy is by measuring body weight, preferably daily. a.

Furosemide: 20 to 80 mg/day produces prompt venodilation and diuresis. IV therapy may produce diuresis when oral therapy has failed; when changing from IV to oral furosemide, doubling the dose is usually necessary to achieve an equal effect.

b.

Thiazides are not as powerful as furosemide but are useful in mild to moderate CHF.

c.

The addition of metolazone to furosemide enhances diuresis.

d.

Blockade of aldosterone receptors by spironolactone (12.5 to 25 mg qd) used in conjunction with ACE inhibitors reduces both mortality and morbidity in patients with severe CHF. It is generally not associated with hyperkalemia when used in low doses, however, serum electrolytes and renal function should be closely monitored after initiation of therapy and when changing doses. Spironolactone use should be considered in patients with recent or recurrent class IV (NYHA) symptoms.

e.

Frequent monitoring of renal function and electrolytes is recommended in all patients receiving diuretics.

3.

Beta blockers: All patients with stable NYHA class II or III heart failure caused by left ventricular systolic dysfunction should receive a beta blocker unless they have a contraindication to its use or are intolerant to it. Beta blockers are especially useful in patients who remain symptomatic despite therapy with ACE inhibitors and diuretics. Carvedilol (Coreg) 3.125 mg bid initially, titrated upward as tolerated, is an effective agent.

4.

Angiotensin II receptor blockers (ARBS) block the A-II type 1 (AT) receptor, which is responsible for many of the deleterious effects of angiotensin II. These receptors are potent vasoconstrictors that may contribute to the impairment of LV function. ARBS are useful in patients unable to tolerate ACE inhibitors because of angioedema or intractable cough. They can also be used in combination with a beta blocker.

5.

Digitalis may be useful because of its positive inotropic and vagotonic effects in patients with CHF secondary to systolic dysfunction; it is of limited value in patients with mild CHF and normal sinus rhythm. It is more beneficial in patients with rapid atrial fibrillation, severe CHF, or ejection fraction of 50% in symptomatic patients with advanced disease.

•

Sudden death secondary to ventricular arrhythmias occurs in >40% of patients with heart failure.

•

Cardiac transplantation has a 5-yr survival rate of >70% in many centers and represents a viable option in selected patients.

•

The use of a left ventricular assist device in patients with advanced heart failure can result in a clinically meaningful survival benefit and improve quality of life. It is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.

•

In patients with advanced heart failure and a prolonged QRS interval, cardiac-resynchronization therapy decreases the combined risk of death from any cause or first hospitalization and, when combined with an implantable defibrillator, significantly reduces mortality.

COMMENTS

•

Diabetes and obesity are established risk factors for CHF and both are associated with insulin resistance. Insulin resistance predicts CHF incidence independently of established risk factors, including diabetes.

•

Sudden death from cardiac causes remains a leading cause of death among patients with CHF. In patients with NYHA class II or III CHF and LVEF =35% amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23%.

EVIDENCE

A large randomized controlled trial (RCT) compared patients with heart failure taking potassium-sparing diuretics and those that were not. It found that, after adjustment for covariates, the use of potassium-sparing diuretics was associated with a reduced risk of death from, or hospitalization for, progressive heart failure or all-cause or cardiovascular death, compared with patients taking only a non-potassium-sparing diuretic.[[1]]

There is good evidence that ACE inhibitors reduce mortality rates in symptomatic left ventricular dysfunction or heart failure A systematic review found that ACE inhibitors reduced mortality rates compared with placebo in patients with NYHA class III or IV heart failure.[[2]] Another systematic review found that ACE inhibitors significantly reduced rates of mortality, readmission for heart failure and reinfarction compared with placebo in patients with heart failure or left ventricular dysfunction.[[3]] There is evidence that angiotensin II receptor antagonists are effective as an alternative in patients with heart failure intolerant to ACE inhibitors A systematic review compared angiotensin II receptor antagonists vs. placebo in people with NYHA class II to IV heart failure. There were nonsignificant trends for reductions in all-cause mortality and admissions for heart failure with angiotensin II receptor antagonists.[[4]]

The review also compared angiotensin II receptor antagonists vs. ACE inhibitors in people with NYHA class II to IV heart failure. There was no significant difference between the drugs in terms of all-cause mortality or rate of admissions for heart failure. Combination therapy with angiotensin II receptor antagonists plus ACE

inhibitors was found to be significantly more effective than ACE inhibitors alone in reducing admissions for heart failure, but there was no significant difference in all-cause mortality.[[4]] An RCT of patients with heart failure (NYHA class II to IV and LV ejection fraction of 40% or less) who were intolerant to ACE Inhibitors, compared candesartan vs. placebo. It found that there was a significant reduction in cardiovascular mortality and/or hospital admissions for chronic heart failure with candesartan compared with placebo.[[5]] There is evidence that beta blockers, as an additive therapy, reduce death rates and hospital admission rates in patients with moderate and severe heart failure Systematic reviews have found that beta blockers, when added to standard therapy with ACE inhibitors, are effective in reducing the rates of death and hospital admission in patients with moderate and severe heart failure. [265] [266] There is limited evidence, from a RCT of bucindolol vs. placebo in severe heart failure, that beta blockers do not have a significantly beneficial effect in African American people.[[8]] There is evidence that the addition of spironolactone to existing medication in severe heart failure reduces mortality An RCT found that spironolactone vs. placebo significantly reduced all-cause mortality at 2 years in patients with heart failure (NYHA class III to IV). Patients were also taking ACE inhibitors and loop diuretics, and most were also taking digoxin. [[9]] Digoxin has been associated with lower rates of hospitalization in heart failure patients A systematic review compared digitalis glycosides vs. placebo in patients with heart failure who were in sinus rhythm. Some patients were also receiving diuretics, ACE inhibitors, or beta blockers. There was no improvement in the mortality rate associated with digitalis, but lower rates of hospitalization and clinical deterioration were noted.[[10]] There is limited evidence that implantation with cardiac resynchronization devices is associated with a reduction in mortality due to progressive heart failure but no long-term results are available as yet A meta-analysis of four RCTs compared cardiac resynchronization vs control in patients with heart failure (NYHA class II to IV). Only trials that used implantable cardioverter defibrillators (ICDs) were included in the analysis. The control groups in the included studies had ICDs implanted, but the cardiac resynchronization was turned off. The authors concluded that cardiac resynchronization reduces mortality from progressive heart failure in patients with symptomatic left ventricular dysfunction. They also found a reduction in heart failure hospitalization.[[11]] More evidence is required to define the benefit of anticoagulation in heart failure patients in sinus rhythm An RCT (pilot study) included in a systematic review compared warfarin (international normalized ratio 2.5), aspirin (300 mg/day), and no antithrombotic treatment in patients with heart failure. It found no significant difference in the combined outcomes of death, myocardial infarction, and stroke between the warfarin and

the no antithrombotic group after a mean of 27 months follow-up. It may be the case that this trial lacked power to detect a clinically important difference. [271] [272] The systematic review mentioned above, found evidence from a variety of study types for a reduction in mortality and cardiovascular events with anticoagulants compared with control. However, the authors conclude that although oral anticoagulation is indicated in certain groups of patients with heart failure (e.g., atrial fibrillation), the evidence available is not strong enough to advocate its routine use in heart failure patients in sinus rhythm.[[13]]

Evidence-Based References 1. Domanski M, et al: Diuretic use, progressive heart failure, and death in patients in the studies of left ventricular dysfunction (SOLVD). J Am Coll Cardiol 2003; 42:705-708. 2. Garg R, Yusuf S: Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995; 273:1450-1456.Reviewed in: Clin Evid 12:115-143, 2004. 3. Flather M, et al: Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. The ACE-inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355:1575-1581.Reviewed in: Clin Evid 12:115-143, 2004.

4. Jong P, et al: Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol 2002; 39:463-470.Reviewed in: Clin Evid 12:115-143, 2004. 5. Granger CBCHARM Investigators and Committees, et al: Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-convertingenzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362:772-776.Reviewed in: Clin Evid 12:115-143, 2004. 6. Brophy JM, Joseph L, Rouleau JL: Beta-blockers in congestive heart failure: a Bayesian metaanalysis. Ann Intern Med 2001; 134:550-560.Reviewed in: Clin Evid 12:115-143, 2004. 7. Whorlow SL, Krum H: Meta-analysis of effect of ß-blocker therapy on mortality in patients with New York Heart Association Class IV chronic congestive heart failure. Am J Cardiol 2000; 86:886889.Reviewed in: Clin Evid 12:115-143, 2004. 8. The Beta-Blocker Evaluation of Survival Trial Investigators: A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001; 344:1659-1667.Reviewed in: Clin Evid 12:115-143, 2004. 9. Pitt B, et al: Randomized Aldactone Evaluation Study Investigators. The effects of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341:709717.Reviewed in: Clin Evid 12:115-143, 2004. 10. Hood WB, et al: Digitalis for treatment of congestive heart failure in patients in sinus rhythm. Cochrane Database Syst Rev 2004; 2: 11. Bradley DJ, et al: Cardiac resynchronization and death from progressive heart failure: a metaanalysis of randomized controlled trials. JAMA 2003; 289:730-740.Reviewed in: DARE Document 20038096. York, UK, Centre for Reviews and Dissemination. 12. Jones CG, Cleland JGF: Meeting report: the LIDO, HOPE, MOXCON, and WASH studies. Eur J Heart Fail 1999; 1:425-431.Reviewed in: Clin Evid 12:115-143, 2004. 13. Lip GYH, Gibbs CR: Anticoagulation for heart failure in sinus rhythm. Cochrane Database Syst Rev 2000; 2:

SUGGESTED READINGS Aurigemma GP, Gaasch WH: Diastolic heart failure. N Engl J Med 2004; 351:1097. Bardy GH, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225-237. Bristow MR, et al: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004; 350:2140. Doust JA, et al: How well does B-Type natriuretic peptide predict death and cardiac events in patients with heart failure: symptomatic review. BMJ 2005; 330:625-633. Ezekowitz J, et al: Systematic review: Implantable cardioverter defibrillators for adults with left ventricular systolic dysfunction. Ann Intern Med 2007; 147:251-262. Gheorghiade M, et al: Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure. JAMA 2007; 297:1332-1343. Gutierrez C, Blanchard DG: Diastolic heart failure: challenges of diagnosis and treatment. Am Fam Physician 2004; 69:2609. Ingelsson E, et al: Insulin resistance and risk of congestive heart failure. JAMA 2005; 294:334-341. McAlister FA, et al: Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction. JAMA 2007; 297:2502-2514. Mueller C, et al: Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med 2004; 350:647. Pfeffer MA, et al: Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349:1893. Sackner-Bernstein DJ, et al: Short-term risk of death after treatment with nesiritide for decompensated heart failure. JAMA 2005; 293:1900-1905. Zile MR, et al: Diastolic heart failure—abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med 2004; 350:1953.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Conjunctivitis

BASIC INFORMATION DEFINITION

The term conjunctivitis refers to an inflammation of the conjunctiva resulting from a variety of causes, including allergies and bacterial, viral, and chlamydial infections. SYNONYMS

“Red eye” Pink eye Acute conjunctivitis Subacute conjunctivitis Chronic conjunctivitis Purulent conjunctivitis Pseudomembranous conjunctivitis Papillary conjunctivitis Follicular conjunctivitis Newborn conjunctivitis

ICD-9CM CODES

372.30 Conjunctivitis, unspecified EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Newborn 1.6% to 12% PREVALENCE (IN U.S.):

•

Allergic conjunctivitis, the most common form of ocular allergy, is usually associated with allergic rhinitis and may be seasonal or perennial

•

Bacterial or viral conjunctivitis is often seasonal and can be extremely contagious

PREDOMINANT AGE: Occurs at any age PEAK INCIDENCE: More common in the fall when viral infections and pollens increase PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Infection and chemosis of conjunctivae with discharge ( Fig. 1-60 )

•

Cornea clear or can be involved

•

Vision often normal, can be blurred

FIGURE 1-60 Conjunctival infection from viral conjunctivitis. (From Marx JA [ed]: Rosen's emergency medicine, ed 5, St Louis, 2002, Mosby.)

ETIOLOGY

•

Bacterial

•

Viral

•

Chlamydial

•

Allergic

•

Traumatic

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Acute glaucoma

•

Corneal lesions

•

Acute iritis

•

Episcleritis

•

Scleritis

•

Uveitis

•

Canalicular obstruction

•

The differential diagnosis of red eye is described in Section II

WORKUP

•

History and physical examination

•

Reports of itching, pain, visual changes

LABORATORY TESTS

Cultures are useful if not successfully treated with antibiotic medications; initial culture is usually not necessary.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Warm compresses if infective conjunctivitis

•

Cold compresses if irritative or allergic conjunctivitis

ACUTE GENERAL Rx

•

Antibiotic drops (e.g., levofloxacin, ofloxin, ciprofloxacin, tobramycin, gentamicin ophthalmic solution one or two drops q2 to 4h) are indicated for suspected bacterial conjunctivitis.

•

Caution: be careful with opthalmic corticosteroid treatment and avoid unless sure of diagnosis; corticosteroids can exacerbate infections and have been associated with increased intraocular pressure and cataract formation.

•

An oral antihistamine (cetirizine, loratidine, desloratidine, or fexofenadine) is effective in relieving itching.

•

Mast cell stabilizers (e.g., cromolyn [4%, 1 to 2 gtt q 4 to 6h], lodoxamine [Alomide, 0.1%, 1 to 2 gtt qid]) are effective on allergic conjunctivitis. Others include Elestat, Optivar, Patanol, etc.

•

The topical NSAID ketorolac (Voltaren, 0.5%, 1 gtt qid) is also useful in allergic conjunctivitis but expensive.

•

Antihistamine/decongestant combinations such as pheniramine/naphazoline (Visine A), available OTC, are more effective than either agent alone but have a short duration and can result in rebound vasodilatation with prolonged use. Others include Naphcon-A, Albacon-A, Opcon-A, etc.

CHRONIC Rx

•

Depends on cause

•

If allergic, nonsteroidals such as Voltaren, Acular, and Xibrom ophthalmic solution; mast cell stabilizers such as Alocril, Patanol, Zaditor are useful

•

If infections, antibiotic drops (see “Acute General Rx”)

•

Dry eyes need artificial tears, ristasis, lacrameal duct plugs when indicated

DISPOSITION

Follow carefully for the first 2 wk to make sure secondary complications do not occur. REFERRAL

To ophthalmologist if symptoms refractory to initial treatment

PEARLS & CONSIDERATIONS COMMENTS

•

Red eyes are not just conjunctivitis when there is significant pain or loss of sight. However, it is usually safe to treat pain-free eyes and the normal seeing red eye with lid hygene and topical treatment.

•

Beware of patients wearing soft contact lenses and of babies and the elderly.

•

Do not use steroids indiscriminately; use only when the diagnosis is certain.

EVIDENCE

Acute bacterial conjunctivitis is often self-limiting, but treatment with topical antibiotics improves the time to clinical recovery and rates of microbiological remission. The randomized controlled trials (RCTs) included in this systematic review were conducted in specialist centers, so the results may not be generalizable to a primary care population.[[1]] An RCT found that combination treatment with naphazoline plus pheniramine and pheniramine alone were both effective in relieving symptoms associated with allergic conjunctivitis.[[2]]

Evidence-Based References 1. Sheikh A, Hurwitz B, Cave J: Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database Syst Rev 2000; 2:CD001211, 2. Dockhorn RJ, Duckett TG: Comparison of Naphcon-A and its components (naphazoline and pheniramine) in a provocative model of allergic conjunctivitis. Curr Eye Res 1994; 13:319.

AUTHORS: MELVYN KOBY, M.D.

Contact Dermatitis

BASIC INFORMATION DEFINITION

Contact dermatitis is an acute or chronic skin inflammation, usually eczematous dermatitis resulting from exposure to substances in the environment. It can be subdivided into “irritant” contact dermatitis (nonimmunologic physical and chemical alteration of the epidermis) and “allergic” contact dermatitis (delayed hypersensitivity reaction). SYNONYMS

Irritant contact dermatitis Allergic contact dermatitis

ICD-9CM CODES

692 Contact dermatitis and other eczema EPIDEMIOLOGY & DEMOGRAPHICS

•

20% of all cases of dermatitis in children are caused by allergic contact dermatitis.

•

Rhus dermatitis (poison ivy, poison oak, and poison sumac) is responsible for most cases of contact dermatitis.

•

Frequent causes of irritant contact dermatitis are soaps, detergents, and organic solvents.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

IRRITANT CONTACT DERMATITIS: •

Mild exposure may result in dryness, erythema, and fissuring of the affected area (e.g., hand involvement in irritant dermatitis caused by exposure to soap, genital area involvement in irritant dermatitis caused by prolonged exposure to wet diapers).

•

Eczematous inflammation may result from chronic exposure.

ALLERGIC CONTACT DERMATITIS: •

Poison ivy dermatitis can present with vesicles and blisters; linear lesions (as a result of dragging of the resins over the surface of the skin by scratching) are a classic presentation.

•

The pattern of lesions is asymmetric; itching, burning, and stinging may be present.

•

The involved areas are erythematous, warm to touch, swollen, and may be confused with cellulitis.

ETIOLOGY

•

Irritant contact dermatitis: cement (construction workers), rubber, ragweed, malathion (farmers), orange and lemon peels (chefs, bartenders), hair tints, shampoos (beauticians), rubber gloves (medical, surgical personnel)

•

Allergic contact dermatitis: poison ivy, poison oak, poison sumac, rubber (shoe dermatitis), nickel (jewelry), balsam of Peru (hand and face dermatitis), neomycin, formaldehyde (cosmetics)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Impetigo

•

Lichen simplex chronicus

•

Atopic dermatitis

•

Nummular eczema

•

Seborrheic dermatitis

•

Psoriasis

•

Scabies

WORKUP

•

Medical history: gradual onset vs. rapid onset, number of exposures, clinical presentation, occupational history

•

Physical examination: contact dermatitis in the neck may be caused by necklaces, perfumes, after-shave lotion; involvement of the axillae is often secondary to deodorants, clothing; face involvement can occur with cosmetics, airborne allergens, aftershave lotion

LABORATORY TESTS

Patch testing is useful to confirm the diagnosis of contact dermatitis; it is indicated particularly when inflammation persists despite appropriate topical therapy and avoidance of suspected causative agent; patch testing should not be used for irritant contact dermatitis because this is a nonimmunologic-mediated inflammatory reaction.

TREATMENT NONPHARMACOLOGIC THERAPY

Avoidance of suspected allergens ACUTE GENERAL Rx

•

Removal of the irritant substance by washing the skin with plain water or mild soap within 15 min of exposure is helpful in patients with poison ivy, poison oak, or poison sumac dermatitis.

•

Cold or cool water compresses for 20 to 30 min five to six times a day for the initial 72 hr are effective during the acute blistering stage.

•

Oral corticosteroids (e.g., prednisone 20 mg bid for 6 to 10 days) are generally reserved for severe, widespread dermatitis.

•

IM steroids (e.g., Kenalog) are used for severe reactions and in patients requiring oral corticosteroids but unable to tolerate PO.

•

Oral antihistamines (e.g., hydroxyzine 25 mg q6h) will control pruritus, especially at night; calamine lotion is also useful for pruritus; however, it can lead to excessive drying.

•

Colloidal oatmeal (Aveeno) baths can also provide symptomatic relief.

•

Patients with mild to moderate erythema may respond to topical steroid gels or creams.

•

Patients with shoe allergy should change their socks at least once a day; use of aluminum chloride hexahydrate in a 20% solution (Drysol) qhs will also help control perspiration.

•

Use hypoallergenic surgical gloves in patients with rubber and surgical glove allergy.

DISPOSITION

Allergic contact dermatitis generally resolves within 2 to 4 wk if reexposure to allergen is prevented. REFERRAL

For patch testing in selected patients (see Laboratory Tests)

PEARLS & CONSIDERATIONS COMMENTS

Commercially available corticosteroid dose packs should be avoided, because they generally provide an inadequate amount of medication.

EVIDENCE

A double-blind, intra-individual comparative study with 18 volunteers comparing 0.05% clobetasone butyrate vs its emollient carrier base alone vs 1% hydrocortisone cream vs no treatment in nickel-induced contact dermatitis found that 0.05% clobetasone butyrate had a significantly better response in terms of a physician's global assessment than hydrocortisone 1% cream or no treatment, though it was not significantly better than its emollient base alone.[[1]] There is evidence that tacrolimus 0.1% ointment is significantly better than placebo in the treatment of nickel-induced contact dermatitis. A double-blind, randomized, controlled, bilateral paired comparison study of topical 0.1% tacrolimus ointment in the treatment of nickel-induced allergic contact dermatitis found evidence that tacrolimus was significantly more effective than placebo in ameliorating the nickel reaction in volunteers and patient groups.[[2]]

Evidence-Based References 1. Parneix-Spake A, et al: Eumovate (clobetasone butyrate) 0.05% cream with its moisturizing emollient base has better healing properties than hydrocortisone 1% cream: a study in nickel-induced contact dermatitis. J Dermatol Treat 2001; 12:191. 2. Saripalli YV, et al: Tacrolimus ointment 0.1% in the treatment of nickel-induced allergic contact dermatitis. J Am Acad Dermatol 2003; 49:477.

AUTHORS: FRED F. FERRI, M.D. Contraception

BASIC INFORMATION DEFINITION

Contraception refers to the various modalities that a sexually active couple use to prevent pregnancy. These options can be either medical or nonmedical and used by men or women or both. The options are as follows: •

No contraception: failure rate 85% both typical and perfect

•

Abstinence

•

•

1.

12.4% of unmarried men

2.

13.2% of unmarried women

3.

More frequently practiced before age 17 yr

4.

No intercourse experienced by 13% of women ages 30 to 34 yr

5.

Failure rate 0%

Withdrawal 1.

Used in only 2% of sexually active women

2.

Failure rate with perfect use, 4%; with typical use, 19%

Rhythm method (natural family planning)

•

•

•

1.

Failure rate with perfect use, 1% to 9%; with typical use, 20%

2.

Symptothermal type: mucus method and ovulation pain combined with basal body temperature

3.

Ovulation (Billings' method): takes into account mucus quality

4.

Basal body temperature method: uses biphasic temperature chart

5.

Lactation amenorrhea method: effective in fully breast-feeding women, especially 70 to 100 days after delivery; depends on number of feedings per day

Barriers 1.

Diaphragm and cervical cap: failure rate 5% to 9% in nulliparous women, 20% in multiparous women

2.

Female condom: failure rate with perfect use, 5.1%; with typical use, 12.4%; FDA labeling states 25% failure rate

3.

Male condom: failure rate with perfect use, 3%, with typical use, 12%

4.

Spermicides (aerosols, foam, jellies, creams, tabs): failure rate with perfect use, 3%; with typical use, 21%

Oral contraceptives 1.

Failure rate with perfect use, men (ratios range from 2:1 to 5:1)

•

Highest in rural areas, among undereducated, and in lower socioeconomic classes

•

Associated with axis I disorders (depression > anxiety) and axis II disorders (most commonly histrionic, passive-dependent, and passive-aggressive)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Presents with pseudoneurologic signs or symptoms.

•

Signs or symptoms do not correlate with known organic disease patterns and instead reflect the patient's concept of the disease.

•

Symptoms occur in isolation (as compared to multisystem involvement in somatization disorder).

•

Motor symptoms may include weakness, paralysis, aphonia, and involuntary movements, including pseudo-seizures.

•

Sensory deficits may include anesthesia (especially of extremities), blindness, and deafness.

•

Findings occur in the setting of marked psychological stress.

•

The symptoms or signs persist whether the patient is observed or unobserved, though are typically worse when the patient is attentive to them.

•

May last from hours to years.

•

Classic features such as la belle indifference (patients seem undisturbed by their signs or symptoms) or secondary gain need not be present for diagnosis.

ETIOLOGY

•

Complex interplay of neurologic and psychologic factors.

•

Functional brain imaging studies suggest alterations in processing of sensory and motor signals.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Broad differential diagnosis depending on presenting signs and symptoms

•

Myasthenia gravis

•

Neurologic disorders (multiple sclerosis, CNS neoplasm, Guillain-Barré syndrome, amyotrophic lateral sclerosis, Parkinson's disease, seizure disorder)

•

Systemic lupus erythematosus

•

Spinal cord compression

•

Intracerebral hemorrhage

•

Drug-induced dystonia

•

HIV (or early manifestations of AIDS)

WORKUP

Thorough history and physical examination, including careful neurologic examination LABORATORY TESTS

•

No gold standard diagnostic tests exist; no single associated finding is pathognomonic.

•

Laboratory tests or procedures may be needed to rule out other etiologies (e.g., EEG for seizures, EMG for lower motor neuron paralysis, optokinetic drum test in blindness).

IMAGING STUDIES

As indicated by presenting signs and symptoms

TREATMENT NONPHARMACOLOGIC THERAPY

•

Treatment success has been associated with a caring, long-term relationship between patient and physician and a safe, nonconfrontational approach.

•

Physical and occupational therapy can help “retrain” the patient in normal behaviors.

•

Psychotherapy (including cognitive-behavioral therapy) and addressing stress management may be effective in reducing symptoms.

ACUTE GENERAL Rx

•

Studies have shown no additional benefit to hypnosis, although significant experience exists with barbiturate-induced hypnosis as a psychotherapeutic aid.

•

Antidepressants may be helpful in treating underlying mood or anxiety disorders.

•

Patients with long-standing symptoms may require inpatient treatment.

CHRONIC Rx

See “Nonpharmacologic Therapy” and “Acute General Rx.” DISPOSITION

Long-term follow-up is essential to address recurrent conversion reactions and underlying mood disorders. REFERRAL

Refer to rule out other psychiatric disorders and for psychotherapy.

PEARLS & CONSIDERATIONS COMMENTS

•

Good prognostic factors: sudden onset, presence of psychologic stressors at onset of symptoms, short duration between diagnosis and treatment, high level of intelligence, absence of other psychiatric or medical disorders, and no ongoing compensation litigation.

•

Poor prognostic factors: severe disability, long duration of symptoms, age >40 at symptom onset, and convulsions and paralysis as presenting symptoms.

EVIDENCE

A randomized controlled trial of cognitive-behavioral therapy in the treatment of medically unexplained symptoms found that, at 6-month follow-up, 82% of patients and 64% of controls had improved (a significant difference) and that this difference was largely maintained at 12 months.[[1]]

Evidence-Based References 1. Speckens AEM, et al: Cognitive behavioural therapy for medically unexplained physical symptoms: a randomised controlled trial. BMJ 1995; 311:1328.

SUGGESTED READINGS Hinson VK, Haren WB: Psychogenic movement disorders. Lancet Neurol 2006; 5:695. Hurwitz TA: Somatization and conversion disorder. Can J Psychiatry 2004; 49(3):172. Servan-Schreiber D, et al: Somatizing patients: part II. Practical management. Am Fam Physician 2000; 61:1423.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cor Pulmonale BRIAN CASSERLY, M.D., GAURAV CHOUDHARY, M.D.

BASIC INFORMATION DEFINITION

Cor pulmonale is an alteration in the structure and function of the right ventricle due to pulmonary hypertension caused by diseases of the lungs or pulmonary vasculature. It is a state of cardiopulmonary dysfunction that may result from multiple etiologies rather than a specific disease state. Right-sided heart failure resulting from primary disease of the left heart or congenital heart disease are not considered in this disorder. SYNONYMS

Acute cor pulmonale Chronic cor pulmonale

ICD-9CM CODES

415.0 Cor pulmonale, acute 416.9 Cor pulmonale, chronic ETIOLOGY

Most conditions that cause cor pulmonale are chronic. Acute cor pulmonales are often life threatening but transient. For example, acute pulmonary embolus may present with acute cor pulmonale, cardiogenic shock, or death, but if the patient survives the initial event, then the right ventricle often recovers and cor pulmonale is no longer existent after several weeks. Mechanisms leading to pulmonary hypertension and predisposing to the development of cor pulmonale include: •

Pulmonary vasoconstriction resulting from any condition causing alveolar hypoxia and/or acidosis

•

Anatomic reduction of the pulmonary vascular bed (e.g., emphysema, interstitial lung disease, pulmonary emboli)

•

Increased blood viscosity (e.g., polycythemia vera, Waldenström's macroglobulinemia)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

No symptoms are specific for cor pulmonale. Typically, the symptoms depend on the underlying disease process. They include:

•

Dyspnea, fatigue, chest pain or syncope with exertion (secondary to pulmonary hypertension)

•

Right upper quadrant abdominal pain and anorexia (secondary to passive hepatic congestion)

•

Hoarseness (caused by compression of the left recurrent laryngeal nerve by dilation of the main pulmonary artery; known as Ortner's syndrome)

•

Signs of right ventricular failure: jugular venous distention, peripheral edema, hepatic congestion, ascites, and a right ventricular third heart sound

•

Signs of associated tricuspid regurgitation: holosystolic murmur heard best along the left parasternal border (augments during inspiration), prominent V-wave on jugular venous pulse, and pulsatile hepatomegaly (in severe tricuspid regurgitation)

•

Pulmonary hypertension will increase the intensity of the pulmonic component of S2, which may be narrowly split

•

Rarely, cough and hemoptysis

WORKUP

Search for an underlying pulmonary process resulting in pulmonary hypertension: •

Left ventricular dysfunction should be excluded in initial assessment.

•

80% to 90% of cor pulmonale cases are due to COPD.

•

Consideration of alveolar hypoventilation, chronic thromboembolic disease, and neuromuscular disease should be given in the absence of parenchymal lung disease.

LABORATORY TESTS

•

CBC may show erythrocytosis secondary to chronic hypoxia.

•

Arterial blood gas (ABG) confirms hypoxemia and acidosis or hypercapnia.

•

Pulmonary function tests.

IMAGING STUDIES

•

Chest x-ray may show underlying pulmonary disease and evidence of pulmonary hypertension (e.g., enlargement of the pulmonary arteries or right atrium, and right ventricular dilation).

•

Electrocardiogram may reveal right ventricular hypertrophy, right atrial enlargement (P-pulmonale), rightaxis deviation, or incomplete/complete right bundle branch block.

•

Echocardiogram to detect right ventricular enlargement and/or hypertrophy and estimate pulmonary artery pressure.

•

Radionuclide ventriculography to measure right ventricular ejection fraction, which may be reduced.

•

Cardiac MRI can accurately measure right ventricular dimensions and function.

•

Right-sided heart catheterization measures pulmonary artery pressures and pulmonary vascular resistance. It can also determine response to oxygen or vasodilators.

•

Chest CT can assess for pulmonary parenchymal disease and embolus in the pulmonary vasculature.

TREATMENT The treatment of cor pulmonale is directed toward the underlying etiology while at the same time reversing hypoxemia, improving right ventricular contractility, decreasing pulmonary artery vascular resistance, and improving pulmonary hypertension

NONPHARMACOLOGIC THERAPY

•

Continuous positive airway pressure (CPAP) is used in patients with obstructive sleep apnea.

•

Phlebotomy is reserved as adjunctive therapy in patients with polycythemia (hematocrit >55%) who have acute decompensation of cor pulmonale or remain polycythemic despite long-term oxygen therapy. Phlebotomy has been shown to decrease mean pulmonary artery pressure and pulmonary vascular resistance.

ACUTE GENERAL Rx

•

Pulmonary embolism is the most common cause of acute cor pulmonale (see “Pulmonary Embolism”). The treatment is anticoagulation, hemodynamic support, and consideration of thrombolytics

•

In patients with preexisting cor pulmonale, acute pulmonary illnesses or hypoxia can increase pulmonary hypertension and worsen right ventricular function. The underlying exacerbating conditions should be treated.

CHRONIC Rx

•

Long-term oxygen supplementation improves survival in hypoxemic patients with COPD.

•

Right ventricular volume overload should be treated with diuretics (e.g., furosemide). However, overdiuresis can reduce right ventricular filling and decrease cardiac output.

•

Theophylline and sympathomimetic amines may improve diaphragmatic excursion, myocardial contraction, and pulmonary artery vasodilation.

•

The long-term use of nonselective vasodilators including nitrates, calcium channel blockers, and angiotensin-converting enzyme inhibitors has not resulted in significant survival improvement. This is probably due to a lack of vasoreactivity in patients with COPD, as well as the risk of worsening of ventilation/perfusion mismatch and systemic vasodilation. Vasodilators to combat pulmonary hypertension should not be administered empirically in the absence of a right-sided heart catheterization.

DISPOSITION

The level of pulmonary artery pressure in COPD patients with cor pulmonale is a good indicator of prognosis. Right ventricular function may provide additional information. REFERRAL

Patients with pulmonary disease that have progressed to cor pulmonale should be followed by a pulmonologist.

PEARLS & CONSIDERATIONS

•

There is no differential diagnosis, but rather an evaluation of the patient to identify the underlying cause.

•

Prognosis and treatment are related to the underlying cause, whereas the presence of cor pulmonale is merely a marker of the underlying disease severity

COMMENTS

There is increasing interest in selective pulmonary vasodilators to improve right ventricular heart function in patients with cor pulmonale.

EVIDENCE

A randomized controlled trial (RCT) found that domiciliary oxygen given at a rate of 2 L/min for at least 15 hr/day to patients with COPD who were very hypoxic significantly reduced mortality vs. no oxygen therapy over 5 years.[[1]] A systematic review concluded that long-term oxygen therapy improved survival in those patients with COPD and severe hypoxemia, but not in those with moderate hypoxemia or only arterial desaturation at night. Four out of five of the RCTs included did not specifically include those diagnosed with cor pulmonale.[[2]]

Evidence-Based References 1. Medical Research Council Working Party: Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981; 1:681. 2. Cranston JM, et al: Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database Syst Rev, Issue 4, Chichester, UK: John Wiley & Sons, Ltd; 2005:27.

SUGGESTED READINGS Lehrman S, et al: Primary pulmonary hypertension and cor pulmonale. Cardiol Rev 2002; 10(b):265-278. Weitzenblum E: Chronic cor pulmonale. Heart 2003; 89(b):225-230.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Corneal Abrasion MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

A corneal abrasion is a loss of surface epithelial tissue of the cornea caused by trauma. SYNONYMS

Corneal erosion Corneal contusion

ICD-9CM CODES

918.1 Corneal abrasion EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): A universal problem PEAK INCIDENCE: Childhood through active adulthood and older and debilitated patients PREDOMINANT AGE: Any age PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Haziness of the cornea

•

Disruption of the corneal surface ( Fig. 1-61 )

•

Redness and infection of the conjunctiva

•

Pain

•

Light sensitivity

•

Tearing

•

Foreign body sensation

•

Gritty feeling

•

Pain on opening or closing eyes

•

Sensation of a foreign body

ETIOLOGY

FIGURE 1-61 Corneal epithelial abrasion. A, Epithelial defect without fluorescein highlighting the defect. An irregularity in the otherwise smooth corneal surface is the key to identifying the defect if no fluorescein is available. B, Classic fluorescein staining of an epithelial defect. (From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

•

Trauma (direct mechanical event)

•

Foreign body

•

Contact lenses

•

Unknown etiology

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Acute angle glaucoma

•

Herpes ulcers and other corneal ulcers

•

Foreign body in the cornea (be certain it is not a keratitis)

WORKUP

•

Fluorescein staining, slit lamp evaluation

•

Assessment of visual acuity

•

Intraocular pressure

•

Rule out corneal laceration

•

Rule out other eye pathology

TREATMENT NONPHARMACOLOGIC THERAPY

•

Patching is controversial (see below).

•

Bandage.

•

Contact lenses.

•

Warm compresses.

•

Pressure dressing is controversial. Although eye patching traditionally has been recommended in the treatment of corneal abrasions, several studies show that patching does not help and may hinder healing.

•

Removal of any foreign particles if present.

ACUTE GENERAL Rx

•

Topical antibiotics such as 10% sulfacetamide or ofloxacin 0.3% solution 2 drops qid.

•

Pressure patching of eye with eyelid closed is no longer recommended because it can result in decreased oxygen delivery, increased moisture, and a higher chance of infection.

•

Cycloplegics such as 5% homatropine are often prescribed to relieve ciliary muscle spasm; however, their benefit has been questioned and they are no longer routinely recommended.

•

Topical NSAIDs (e.g., diclofenac 0.1% or ketorolac 0.5%) 1 gtt qid.

•

Topical antibiotics to prevent secondary infection.

DISPOSITION

Follow-up in 24 hr and then every 3 days until abrasion has cleared and vision has returned to normal REFERRAL

To ophthalmologist if patient experiences no relief within 24 hr or for patients with deep eye injuries, foreign bodies that cannot be removed, or suspected recurrent corneal erosion (RCE)

PEARLS & CONSIDERATIONS COMMENTS

•

Never give patient topical anesthetic to use at home because these can cause decomposition of the cornea and permanent damage.

•

Most corneal abrasions heal in 24 to 48 hours and rarely progress to corneal erosion or infection.

EVIDENCE

In patients with uncomplicated corneal abrasions, the application of an eye patch does not improve the rate of corneal healing, reduce pain, or reduce complications compared with wearing no patch.[[1]]

Evidence-Based References 1. Flynn CA, D'Amico F, Smith G: Should we patch corneal abrasions? A meta-analysis. J Fam Pract 1998; 47:264-270.

SUGGESTED READINGS Wilson SA, Last A: Management of corneal abrasions. Am Fam Physician 2004; 70(1):123.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Corneal Ulceration MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

Corneal ulceration refers to the disruption of the corneal surface and/or deeper layers caused by trauma, contact lenses infection, degeneration, or other means. SYNONYMS

Infectious keratitis with ulceration Bacterial keratitis with ulceration Viral keratitis with ulceration Fungal keratitis with ulceration

ICD-9CM CODES

370.0 Corneal ulcer NOS EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 4 to 6 cases/mo seen by average general ophthalmologist PREVALENCE (IN U.S.): Common PREDOMINANT SEX: Either PREDOMINANT AGE: All ages PHYSICAL FINDINGS & clinical presentation

•

Localized, well-demarcated, infiltrative lesion with corresponding focal ulcer ( Fig. 1-62 ) or oval, yellowwhite stromal suppuration with thick mucopurulent exudate and edema. Usually red, angry-looking eye with infiltration in surrounding area of cornea

•

Eye possibly painful, with conjunctival edema and infection

•

Sterile neurotrophic ulcers with tissue breakdown and no pain

FIGURE 1-62 Peripherally located corneal ulcer. (From Marx JA [ed]: Rosen's emergency medicine, ed 5, St Louis, 2002, Mosby.)

ETIOLOGY

•

Complication of contact lens wear, trauma, or diseases such as herpes simplex keratitis, keratoconjunctivitis sicca. Often associated with collagen vascular disease and severe exophthalmus and thyroid disease

•

Viral causes often contagious

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Pseudomonas and pneumococcus and other bacterial infection—virulent

•

Moraxella, Staphylococcus, a-Streptococcus infection—less virulent

•

Herpes simplex infection or disease caused by other viruses

•

Contact lens ulcers differ

WORKUP

•

Fluorescein staining, slit lamp

•

Appearance often typical

•

Differentiate carefully with contact lens wearers

•

Note previous eye surgery or laser vision correction

LABORATORY TESTS

Microscopic examination and culture of scrapings

TREATMENT NONPHARMACOLOGIC THERAPY

•

Warm compresses

•

Bandage contact lenses

•

Patching

•

Stop contact lens wearing

•

Remove eyelid crusting

ACUTE GENERAL Rx

•

An ophthalmic emergency

•

Intense antibiotic and antiviral Rx

•

NSAIDs

•

Viroptic/Zymar

•

Bacterial infection: subconjunctival cefazolin or gentamicin (topical Zymar, Vigomax, etc.)

•

Fungal infection: hospitalization and topical application of antifungal agents

•

Herpes—Vioptic and oral Rx

DISPOSITION

Ideally treated by an ophthalmologist if the patient does not rapidly respond to antibiotics (within 24 hr)

PEARLS & CONSIDERATIONS

•

Always stop contact lens wearing

•

Always refer ulcers to ophthalmologist

•

Never treat with topical anesthetics or steroids

COMMENTS

Do not use topical steroids because herpes, fungal, or other ulcers may be aggravated, leading to perforation of the cornea. Antibiotics may delay response and result in overgrowth of nonbacterial (fungal and amoebic) pathogens. SUGGESTED READINGS Price FW: New pieces for the puzzle: nonsteroidal anti-inflammatory drugs and corneal ulcers. J Cataract Refract Surg 2000; 26(9):1263. Schaefer F, et al: Bacterial keratitis: a prospective clinical and microbiological study. Br J Ophthalmol 2001; 85(7):42. Stretton S, Gopinathan U, Willcox MD: Corneal ulceration in pediatric patients: a brief overview of progress in topical treatment. Paediatr Drugs 2002; 4(2):95. Varaprasathan G, et al: Trends in the etiology of infectious corneal ulcers at the F. I. Proctor Foundation. Cornea 2004; 23(4):360.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Costochondritis LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Costochondritis is a poorly defined chest wall pain of uncertain cause. SYNONYMS

Benign chest wall pain syndrome Costosternal syndrome Costosternal chondrodynia

ICD-9CM CODES

733.6 Costochondritis EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: Unknown PREDOMINANT SEX: Women > men PREDOMINANT AGE: Over age 40 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Tenderness of costochondral junctions (second through fifth) and/or sternum

•

Pain with coughing and deep breathing

•

Both sides of chest equal in frequency of involvement

•

Often associated with anxiety, headache, and hyperventilation

ETIOLOGY

•

Unknown

•

May be a form of regional fibrositis

•

May be referred pain from cervical or thoracic spine

•

Emotional factors often involved

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Tietze's syndrome

•

Cardiovascular disease

•

GI disease

•

Pulmonary disease

•

Osteoarthritis ( Table 1-5 )

•

Cervical disc syndrome

TABLE 1-5 -- Musculoskeletal Chest Pain Disorder Clinical Features

Comments

Tietze's Syndrome

Pain and swelling of sternoclavicular joint or second or third costochondral junctions (usually left). Worse with cough and deep breathing. Local tenderness.

Traumatic cause? Rare.

Costochondritis

Pain and tenderness but no swelling. Costochondral junctions of ribs 2-5. Increased pain with cough and sneeze.

Sometimes associated with headache and hyperventilation.

Seronegative spondyloarthropathy (ankylosing spondylitis)

Sternoclavicular or manubriosternal joint. Worse in am. Relieved by activity. May be associated with swelling.

Local chest findings usually associated with other symptoms of ankylosing spondylitis such as sacroilitis. May need HLA-B27 antigen testing.

Cervical, thoracic disc disease

Referred regional pain from affected area. No local swelling. Often aggravated by spine motion and may be accompanied by radicular pain into arm if cervical or along intercostal nerve if thoracic.

May mimic chest disease if spinal complaints are minimal and referred or radicular symptoms predominate.

Fibromyalgia

Widespread pain with other sites involved. Symptoms often change in location. Local “tender points” but no swelling or objective findings.

Female:male ratio of 9:1. Prevalent age 30-50 yr.

Osteoarthritis, sternoclavicular or manubriosternal joint

Dull, aching local pain with tenderness. Occasional bony joint enlargement with softtissue swelling.

Crepitus may rarely be present.

WORKUP

•

There are no laboratory or radiographic abnormalities.

•

Testing to rule out or rule in more serious disorders is performed on a case-by-case basis.

TREATMENT ACUTE GENERAL Rx

•

Explanation, reassurance

•

Tricyclic antidepressants for sleep disturbance (amitriptyline 10 to 25 mg)

•

Aerobic exercise program

•

NSAIDs for analgesia

DISPOSITION

•

The duration of the disorder is variable.

•

Spontaneous remission is the rule.

REFERRAL

•

Cardiology to rule out primary cardiac disease, when indicated.

•

GI to rule out gastrointestinal disorders, when indicated.

PEARLS & CONSIDERATIONS One of a large number of nonspecific musculoskeletal diagnoses based strictly on subjective symptoms and lacking any objective abnormalities. COMMENTS

In spite of the name, no inflammation is present. After other, more serious conditions are ruled out, the treatment is strictly symptomatic and supportive.

EVIDENCE

Evidence supporting these treatments is lacking. However, clinical experience indicates that one or more of these treatments may be helpful for many patients. SUGGESTED READINGS Freeston J, et al: Can early diagnosis and management of costochondritis reduce acute chest pain admissions? . J Rheumatol 2004; 31:2269. Gregory PL, Biswas AC, Batt ME: Musculoskeletal problems of the chest wall in athletes. Sports Med 2002; 32:325. Hiramuro-Shoji F, Wirth MA, Rockwood CA: Atraumatic conditions of the sternoclavicular joint. J Shoulder

Elbow Surg 2003; 12:79. Jenson S: Musculoskeletal causes of chest pain. Am Fam Physician 2001; 30:834. Rumball JS, et al: Rowing injuries. Sports Med 2005; 35:537.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Craniopharyngioma CHUN LIM, M.D., PH.D.

BASIC INFORMATION DEFINITION

Craniopharyngiomas are tumors arising from squamous cell remnants of Rathke's pouch, located in the infundibulum or upper anterior hypophysis. SYNONYMS

Subset of nonadenomatous pituitary tumors

ICD-9CM CODES

237.0 Craniopharyngioma EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: Occurs at all ages; peak during the first 2 decades of life, with a second small peak occurring in the sixth decade. PREDOMINANT SEX: Both sexes are usually equally affected. Craniopharyngiomas are the most common nonglial tumors in children and account for 3% to 5% of all pediatric brain tumors. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The typical onset is insidious and a 1- to 2-year history of slowly progressive symptoms is common.

•

Presenting symptoms are usually related to the effects of a sella turcica mass. Approximately 75% of patients complain of headache and have visual disturbances.

•

The usual visual defect is bitemporal hemianopsia. Optic nerve involvement with decreased visual acuity and scotomas and homonymous hemianopsia from optic tract involvement may also occur.

•

Other symptoms include mental changes, nausea, vomiting, somnolence, or symptoms of pituitary failure. In adults, sexual dysfunction is the most common endocrine complaint, with impotence in males and primary or secondary amenorrhea in females. Diabetes insipidus is found in 25% of cases. In children, craniopharyngiomas may present with dwarfism.

•

More than 70% of children at the time of diagnosis present with growth hormone deficiency, obstructive hydrocephalus, short-term memory deficits, and psychomotor slowing.

ETIOLOGY

Craniopharyngiomas are believed to arise from nests of squamous epithelial cells that are commonly found in the suprasellar area surrounding the pars tuberalis of the adult pituitary.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Pituitary adenoma

•

Empty sella syndrome

•

Pituitary failure of any cause

•

Primary brain tumors (e.g., meningiomas, astrocytomas)

•

Metastatic brain tumors

•

Other brain tumors

•

Cerebral aneurysm

LABORATORY TESTS

•

Hypothyroidism (low FT4, FT3 with high TSH).

•

Hypercortisolism (low cortisol) with low ACTH.

•

Low sex hormones (testosterone, estriol) with low FSH and LH.

•

Diabetes insipidus (hypernatremia, low urine osmolarity, high plasma osmolarity).

•

Prolactin may be normal or slightly elevated.

•

Pituitary stimulation tests may be required in some cases.

IMAGING STUDIES

•

Visual field testing for bitemporal hemianopsia.

•

Skull film. Enlarged or eroded sella turcica (50%) Suprasellar calcification (50%)

•

MRI ( Fig. 1-63 ) or head CT. MRI features include a multicystic and solid enhancing suprasellar mass. Hydrocephalus may also be present if the mass is large. CT usually reveals intratumoral calcifications.

FIGURE 1-63 MRI scan of a craniopharyngioma, demonstrating a cystic contrast-enhancing mass in the suprasellar area extending upward and compressing the hypothalamus. (From Goetz CG: Textbook of clinical neurology, Philadelphia, 1999, WB Saunders.)

TREATMENT GENERAL Rx

•

Surgical resection (curative or palliative). Transsphenoidal surgery for small intrasellar tumors Subfrontal craniotomy for most patients

•

Postoperative radiation.

•

Intralesional 32P irradiation or bleomycin for unresectable tumors. Long-term complications of radiation include secondary malignancies, optic neuropathy, and vascular injury.

PROGNOSIS

•

Operative mortality: 3% to 16% (higher with large tumors).

•

Postoperative recurrence rate: 30% of cases after total resection and 57% of cases after subtotal resection.

•

5-yr and 10-yr survival: 88% and 76%, respectively, with surgery and radiation.

•

The most important factors that correlate with prognosis are the extent of resection and postoperative radiation.

AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Creutzfeldt-Jakob Disease

BASIC INFORMATION DEFINITION

Creutzfeldt-Jakob disease (CJD) is a progressive, fatal, dementing illness caused by an infectious agent known as a prion. SYNONYMS

Transmissible spongiform encephalopathy Mad cow disease Prion disease

ICD-9CM CODES

046.1 Creutzfeldt-Jakob disease EPIDEMIOLOGY & DEMOGRAPHICS

•

Incidence of 1 per 1,000,000 population per yr

•

Peak age 60 yr (range 16 to 82 yr)

•

5% to 10% familial, remaining cases are sporadic; iatrogenic cases (corneal transplants, dura mater allograft, human pituitary extract) are very rare

•

Normal prion protein gene found on human chromosome 20

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

All patients present with cognitive deficits (dementing illness—memory loss, behavioral abnormalities, higher cortical function impairment).

•

More than 80% will have myoclonus.

•

Pyramidal tract signs (weakness), cerebellar signs (clumsiness), and extrapyramidal signs (parkinsonian features) are seen in more than 50% of the cases.

•

Less common features include cortical visual abnormalities, abnormal eye movements, vestibular dysfunction, sensory disturbances, autonomic dysfunction, lower motor neuron signs, and seizures.

ETIOLOGY

Small proteinaceous infections particle (prion). Noninfectious prion protein (PrP) is a cellular protein found on the surfaces of neurons. Normal function is not known. Protein is converted to protease resistant and infectious agent (PrPsc) by infectious prion protein (PrPsc).

DIAGNOSIS

•

Definite CJD: Neuropathologically confirmed spongiform encephalopathy in a case of progressive dementia.

•

Probable CJD: History of rapidly progressive dementia (less than 2 yr) with typical EEG and with at least two of the following clinical features: myoclonus, visual or cerebellar dysfunction, pyramidal or extrapyramidal features, akinetic mutism.

•

Possible CJD: Same as probable CJD without EEG findings.

DIFFERENTIAL DIAGNOSIS

•

Primary CNS lymphoma

•

Viral encephalitis

•

CNS vasculitis

•

Others (hydrocephalus, infectious, vitamin deficiency, endocrine)

•

Other dementia (Alzheimer's, frontotemporal dementia, diffuse Lewy body disease, vascular)

A clinical algorithm for the evaluation of dementia is described in Section III, “Dementia.” WORKUP

•

Evaluate for treatable causes of dementia (see “Alzheimer's Disease”).

•

Brain biopsy can be diagnostic, but it is usually not performed because there is no treatment or cure.

LABORATORY TESTS

•

Presence of periodic sharp wave complexes on EEG in cases of rapidly progressive dementia has a sensitivity of 67% and a specificity of 86%.

•

In cases of probable or possible CJD, presence of the 14,3,3 protein in CSF has a 95% positive predictive value with its absence having a 92% negative predictive value.

IMAGING STUDIES

MRI scan can show areas of restricted diffusion in the basal ganglia and cerebral cortex. MRI diffusion weighted imaging has a sensitivity of 92.3% and a specificity of 93.8% only in cases of rapidly progressive dementia.

TREATMENT NONPHARMACOLOGIC THERAPY

Full time caregiver and/or nursing home. Social work can be helpful with end of life discussions, family counseling, and optimizing appropriate home services. ACUTE GENERAL Rx

No known therapy CHRONIC Rx

No known therapy DISPOSITION

The disease is fatal. Mean duration of illness is 8 mo (range 1 to 130 mo). One in 7 survives to 1 yr and 1 in 30 survives to 2 yr. Better survival found in younger age at onset of disease and female gender. REFERRAL

•

Neurology for evaluation of any rapidly progressive dementia

•

Social work

PEARLS & CONSIDERATIONS COMMENTS

•

Related diseases in humans: Kuru, Fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, new-variant Creutzfeldt-Jacob disease.

•

Related diseases in animals: Scrapie, bovine spongiform encephalopathy (Mad cow disease).

EVIDENCE

No treatment is available to slow the inevitable decline. SUGGESTED READINGS Brown P, et al: Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 1994; 35:513. Hsich G, et al: The 14–3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform

encephalopathies. N Engl J Med 1996; 335:924. Knight RSG, Will RG: Prion disease. J Neurol Neurosurg Psychiatry 2004; 75:36. Masters CL, et al: Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1979; 5:177. Shiga Y, et al: Diffusion-weighted MRI abnormalities as an early diagnostic marker for Creutzfeldt-Jakob disease. Neurology 2004; 63:443. Steinhoff BJ, et al: Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease. Arch Neurol 1996; 53:162.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Crohn's Disease FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Crohn's disease is an inflammatory disease of the bowel of unknown etiology, most commonly involving the terminal ileum and manifesting primarily with diarrhea, abdominal pain, fatigue, and weight loss. SYNONYMS

Regional enteritis Inflammatory bowel disease (IBD)

ICD-9CM CODES

555.9 Crohn's disease, unspecified site 555.0 Crohn's disease, small intestine 555.1 Crohn's disease involving large intestine EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 1 case/1000 persons; most common in Caucasians and Jews •

Crohn's disease affects approximately 380,000 to 480,000 persons in the U.S.

•

Incidence: bimodal with a peak in the third decade of life and another one in the fifth decade

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Abdominal tenderness, mass, or distention

•

Chronic or nocturnal diarrhea

•

Weight loss, fever, night sweats

•

Hyperactive bowel sounds in patients with partial obstruction, bloody diarrhea

•

Delayed growth and failure of normal development in children

•

Perianal and rectal abscesses, mouth ulcers, and atrophic glossitis

•

Extraintestinal manifestations: joint swelling and tenderness, hepatosplenomegaly, erythema nodosum, clubbing, tenderness to palpation of the sacroiliac joints

•

Symptoms may be intermittent with varying periods of remission

ETIOLOGY

Unknown. Pathophysiologically, Crohn's disease involves an immune system dysfunction.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Ulcerative colitis

•

Infectious diseases (TB, Yersinia, Salmonella, Shigella, Campylobacter)

•

Parasitic infections (amebic infection)

•

Pseudomembranous colitis

•

Ischemic colitis in elderly patients

•

Lymphoma

•

Colon carcinoma

•

Diverticulitis

•

Radiation enteritis

•

Collagenous colitis

•

Fungal infections (Histoplasma, Actinomyces)

•

Gay bowel syndrome (in homosexual patient)

•

Carcinoid tumors

•

Celiac sprue

•

Mesenteric adenitis

LABORATORY TESTS

•

Decreased Hgb and Hct from chronic blood loss, effect of inflammation on bone marrow, and malabsorption of vitamin B12

•

Hypokalemia, hypomagnesemia, hypocalcemia, and low albumin in patients with chronic diarrhea

•

Vitamin B12 and folate deficiency

•

Elevated ESR

ENDOSCOPIC EVALUATION

Endoscopic features of Crohn's disease include asymmetric and discontinued disease, deep longitudinal fissures, cobblestone appearance, presence of strictures. Crypt distortion and inflammation are also present. Granulomas may be present. IMAGING STUDIES

•

Barium imaging studies (when performed) reveal deep ulcerations (often longitudinal and transverse) and segmental lesions (skip lesions, strictures, fistulas, cobblestone appearance of mucosa caused by submucosal inflammation); “thumbprinting” is common, “string sign” in terminal ileum may be noted. Although the diagnosis may be suggested by radiographic studies, it should be confirmed by endoscopy and biopsy when possible.

•

CT of abdomen is helpful in identifying abscesses and other complications.

•

In 5% to 10% of patients with IBD, a clear distinction between ulcerative colitis and Crohn's disease cannot be made. Generally, Crohn's disease can be distinguished from ulcerative colitis by presence of transmural involvement and the frequent presence of noncaseating granulomas and lymphoid aggregates on biopsy.

TREATMENT The medical management of Crohn's disease is based on disease activity. According to Hanauer and Sanborn, disease activity can be defined as follows: •

Mild to moderate disease: The patient is ambulatory and able to take oral alimentation. There is no dehydration, high fever, abdominal tenderness, painful mass, obstruction, or weight loss of >10%.

•

Moderate to severe disease: Either the patient has failed treatment for mild to moderate disease OR has more pronounced symptoms including fever, significant weight loss, abdominal pain or tenderness, intermittent nausea and vomiting, or significant anemia.

•

Severe fulminant disease: Either the patient has persistent symptoms despite outpatient steroid therapy OR has high fever, persistent vomiting, evidence of intestinal obstruction, rebound tenderness, cachexia, or evidence of an abscess.

•

Remission: The patient is asymptomatic OR without inflammatory sequelae, including patients responding to acute medical intervention.

NONPHARMACOLOGIC THERAPY

•

Nutritional supplementation is needed in patients with advanced disease. TPN may be necessary in selected patients.

•

Low-residue diet is necessary when obstructive symptoms are present.

•

If diarrhea is prominent, increased dietary fiber and lowering of fat in the diet are sometimes helpful.

•

Psychotherapy is useful for situational adjustment crises. A trusting and mutually understanding relationship and referral to self-help groups are very important because of the chronicity of the disease and the relatively young age of the patients.

•

Avoid oral feedings during acute exacerbation to decrease colonic activity: a low-roughage diet may be helpful in early relapse.

ACUTE GENERAL Rx

•

Sulfasalazine, 500 mg PO qid initially, increased qd or qod by 1 g until therapeutic dosages of 4 to 6 g/day are achieved. The oral salicylates, mesalamine (Asacol, Rowasa) are as effective as sulfasalazine and better tolerated but more expensive; they may be useful in patients allergic to the sulfa moiety of sulfasalazine molecule. Individuals with sulfa allergies should avoid sulfasalazine. Folate supplementation is recommended because sulfasalazine inhibits folate absorption.

•

Corticosteroids have been the mainstay for treating moderate to severe active Crohn's disease. Prednisone 40 to 60 mg/day are useful for acute exacerbation. Steroids are usually tapered over approximately 2 to 3 mo. Some patients require a low dose for prolonged period of maintenance.

•

Steroid analogues are locally active corticosteroids that target specific areas of inflammation in the GI tract. Budesonide (Entocort EC) is available as a controlled-release formulation and is approved for mild to moderate active Crohn's disease involving the ileum and/or ascending colon. The adult dose is 9 mg qd for a maximum of 8 wk.

•

Immunosuppressants such as azathioprine (Imuran) 150 mg/day, methotrexate, or cyclosporine can be used for severe, progressive disease. In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.

•

Metronidazole 500 mg qid may be useful for colonic fistulas and for treatment of mild to moderate active Crohn's disease. Ciprofloxacin 1 g qd has also been found effective in decreasing disease activity.

•

Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor-a, is effective in the treatment of enterocutaneous fistulas. This medication can induce clinical improvement in 80% of patients with Crohn's disease refractory to other agents. Its mechanism of action is incompletely understood. It is very costly. A PPD test should be done before using this medication. Adalimumab, a fully human tumor necrosis factor (TNF), is also effective in inducing remissions and may be useful in adult patients with Crohn's disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy.

•

Natalizumab, a selective adhesionmolecule inhibitor, has been reported effective in increasing the rate of remission and response in patients with active Crohn's disease. Recent trials with pegylated antibody fragments in patients with moderate-to-severe Crohn's disease involving certolizumab pegol reveal a modest improvement in response rates but no significant improvement in remission rates.

•

Hydrocortisone (Cortenema) enema bid or tid is useful for proctitis.

•

Most patients who have anemia associated with Crohn's disease respond to iron supplementation. Erythropoietin is useful in patients with anemia refractory to treatment with iron and vitamins.

CHRONIC Rx

•

Monitor disease activity with symptom review and laboratory evaluation (CBC and sedimentation rate)

•

Liver tests and vitamin B 12 levels monitored on a yearly basis

DISPOSITION

One tenth of patients have prolonged remission, three quarters have a chronic intermittent disease course, and one eighth have an unremitting course. REFERRAL

•

Surgical referral is needed for complications such as abscess formation, obstruction, fistulas, toxic megacolon, refractory disease, or severe hemorrhage. A conservative surgical approach is necessary, because surgery is not curative. Multiple surgeries may also result in short bowel syndrome.

EVIDENCE

There is evidence that corticosteroids are effective in the management of active Crohn's disease but are of limited benefit in the prevention of relapse. Prednisone is effective in the management of moderate to severe, active Crohn's disease. Budesonide is comparable to prednisone in the management of active Crohn's disease and may be associated with fewer side effects than those encountered with prednisone use.[[1]] However, systematic reviews have found little evidence for the use of either prednisone or budesonide in the maintenence of clinical remission in Crohn's disease. [316] [317] There is limited evidence that metronidazole is effective in the management of patients with Crohn's disease. Metronidazole may be effective in a proportion of patients with mild to moderate active Crohn's disease.[[1]]

There is evidence that infliximab is of benefit in the treatment of a proportion of patients with Crohn's disease. A systematic review identified one randomized controlled trial (RTC) that found that a single infusion of infliximab was effective in inducing remission in patients with active Crohn's disease.[[4]] An RCT found that maintenance treatment with infliximab produced a significant improvement in clinical response, with maintained remission, compared with placebo.[[5]] RCTs have shown that in patients with fistulizing Crohn's disease, infliximab significantly reduces the number of draining fistulas and promotes complete closure compared with placebo. Maintenance therapy with infliximab significantly improves clinical outcome in patients with fistulizing disease. [320] [321] There is some evidence that methotrexate is of benefit in some patients with refractory Crohn's disease. A recent systematic review identified one RCT that compared intramuscular methotrexate (25 mg weekly) vs. placebo in patients with active Crohn's disease, refractory to treatment with steroids. The study found that the use of methotrexate in this patient group showed a substantial benefit compared with placebo.[[8]]

Clinical consensus supports the use of surgery in the management of Crohn's disease. Guidelines from The American College of Gastroenterology state that, in patients with Crohn's disease, surgical resection, stricturoplasty, or drainage of abscesses are indicated to treat complications or medically refractory disease.[[1]]

Evidence-Based References 1. Hanauer SB, Sandborn W: Management of Crohn's disease in adults. Am J Gastroenterol 2001; 96:635. 2. Steinhart AH, et al: Corticosteroids for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2003; 3. Simms L, Steinhart AH: Budesonide for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2001; 4. Akobeng AK, Zachos M: Tumor necrosis factor-alpha antibody for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2003; 5. Hanauer SB, et al: Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002; 359:1541. 6. Present DH, et al: Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999; 340:398. 7. Sands BE, et al: Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004; 350:876. 8. Alfadhli AAF, McDonald JWD, Feagan BG: Methotrexate for induction of remission in refractory Crohn's disease. Cochrane Database Syst Rev 2004;

SUGGESTED READINGS Baumgart DC, Carding SR: Inflammatory bowel disease: cause and immunobiology. Lancet 2007; 369:1627. Baumgart DC, Carding SR: Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007; 369:1641. Sandborn WJ, et al: Adalimumab induction therapy for Crohn disease previously treated with infliximab. Ann Intern Med 2007; 146:829. Sandborn WJ, et al: Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med 2007; 357:228.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cryptococcosis STEVEN M. OPAL, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

Cryptococcosis is an infection caused by the fungal organism Cryptococcus neoformans. SYNONYMS

C. neoformans var. neoformans infection C. neoformans var. gatti infection C. neoformans var. grubii infection

ICD-9CM CODES

117.5 Cryptococcosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.) •

1 to 2 cases/1 million (non–HIV-infected) persons annually

•

6% to 7% in HIV-infected persons

PEAK INCIDENCE: 20 to 40 yr (parallel to AIDS epidemic) PREDOMINANT SEX: Equal sex distribution when corrected for HIV status PREDOMINANT AGE: Less than 2 yr of age; 20 to 40 yr of age NEONATAL INFECTION: Very uncommon PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

More than 90% present with meningitis; almost all have fever and headache.

•

Meningismus, photophobia, mental status changes are seen in approximately 25%.

•

Increased intracranial pressure.

•

Most common infections outside the CNS: 1.

In the lungs (fever, cough, dyspnea)

2.

In the skin (cellulitis, papular eruption)

3.

In the lymph nodes (lymphadenitis)

4.

Potential involvement of virtually any organ

ETIOLOGY

•

Caused by the fungal organism C. neoformans There are 3 varieties of Cryptococcus spp. and 4 capsular serotypes: Serotype A is Cryptococcus neoformans var. grubii and Serotype D is known as Cryptococcus neoformans var. neoformans. Both cause disease primarily in immunocompromised patients. Serotype B and C are known as C. neoformans var. gatti. This organism causes disease primarily in normal hosts.

•

Infection originates by inhalation into the respiratory tract followed by dissemination to the CNS in most cases, usually without recognizable lung involvement

•

Almost always in the setting of AIDS or other disorders of cellular immune function

•

Neutropenia alone poses a much lower risk of significant cryptococcal infection

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Subacute meningitis (caused by Listeria monocytogenes, Mycobacterium tuberculosis, Histoplasma capsulatum, viruses)

•

Intracranial mass lesion (neoplasms, toxoplasmosis, TB)

•

Pulmonary involvement confused with Pneumocystis jiroveci pneumonia when diffuse or confused with TB or bacterial pneumonia when focal or involving the pleura

•

Skin lesions confused with bacterial cellulitis or molluscum contagiosum

WORKUP

•

Lumbar puncture to exclude cryptococcal meningitis.

•

CT scan of the head when focal lesion or increased intracranial pressure is suspected.

•

Biopsy of enlarged lymph nodes and skin lesions if feasible.

LABORATORY TESTS

•

Culture and India ink stain (60% to 80% sensitive in culture-proven cases [ Fig. 1-64 ]) examination of the CSF in all cases when CNS involvement is suspected

•

Blood and serum cryptococcal antigen assay (>90% sensitivity and specificity)

•

Culture and histologic examination of biopsy material

FIGURE 1-64 India ink preparation of cerebrospinal fluid revealing encapsulated cryptococci. Note the large capsules surrounding the smaller organisms. (From Andreoli TE [ed]: Cecil essentials of medicine, ed 4, Philadelphia, 1997, WB Saunders.)

IMAGING STUDIES

•

CT scan or MRI of the head if focal neurologic involvement is suspected

•

Chest x-ray examination to exclude pulmonary involvement

TREATMENT ACUTE GENERAL Rx

•

Therapy is initiated with IV amphotericin B (0.5 mg/kg/day) with or without flucytosine.

•

After stabilization (usually several weeks), consider fluconazole (200 to 400 mg qd PO) for additional 6 to 8 wk. Voriconazole, a newer imidazole, also has activity against most isolates.

•

Alternative: IV fluconazole for initial therapy in patients unable to tolerate amphotericin B.

•

If symptomatic increased intracranial pressure, consider therapeutic lumbar taps or intraventricular shunt.

CHRONIC Rx

•

Fluconazole (200 mg PO qd) is highly effective in preventing a relapse in HIV-infected patients; development of resistance may occur.

•

Immune reconstitution syndrome following the institution of HARRT can cause transient worsening of meningitis and necessitate the use of a short course of corticosteroids.

DISPOSITION

Without maintenance therapy, relapse rate is >50% among AIDS patients. REFERRAL

•

For consultation with infectious diseases specialist in all cases

•

For neurologic consultation if level of consciousness is depressed or focal lesion is present

PEARLS & CONSIDERATIONS Cryptococcal meningitis can be remarkably insidious in nonimmunocomprised patients. COMMENTS

Cryptococcosis is considered an AIDS-defining infection; thus all patients should be HIV tested. SUGGESTED READINGS Lortholary O, et al: Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS 2005; 19(10):1043. Lui G, et al: Cryptococcosis in apparently immunocompetent patients. QJM 2006; 99(3):143.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cryptorchidism PAMELA ELLSWORTH, M.D., IRIS TONG, M.D.

BASIC INFORMATION DEFINITION

Cryptorchidism is the incomplete or improper descent of the testis (testes) into the scrotum during fetal development. Testes that can be manually manipulated into the scrotum are called retractile. Testes previously located but are no longer palpable in the scrotum are called ascended testes. SYNONYMS

Undescended testis

ICD-9CM CODES

752.51 Cryptorchidism EPIDEMIOLOGY & DEMOGRAPHICS

•

Cryptorchidism is the most common genitourinary disorder of male children.

•

Occurs in approximately 30% of premature and 5% of full-term males. In 10%, it can be bilateral.

•

Within the first year of life, most cryptorchid testes descend into the scrotum so that incidence becomes approximately 1% in boys.

•

Increased rates with premature birth, low birth weight, twins, and family history of cryptorchidism.

•

Associated with Kallman's and Prader-Willi syndromes, pituitary hypoplasia, testicular feminization, prune belly syndrome, cystic fibrosis, myelomeningocele, and Reifenstein syndrome.

CLINICAL PRESENTATION

•

Typically asymptomatic and is noted incidentally on screening examination. Undescended testes are at risk for testicular torsion.

•

The testis may be nonpalpable or palpable in a location along the path of normal descent ( Fig. 1-65 ); however, less commonly may be ectopic and located in the perineum, femoral canal, superficial inguinal pouch, suprapubic area, and contralateral hemiscrotum. In 80%, the undescended testis is palpable in the inguinal canal.

•

Associated with infertility and a sevenfold increased risk of testicular cancer. Risk of infertility is the greatest for a child with bilateral intra-abdominal testes and longer duration of cryptorchidism.

FIGURE 1-65 The path of testicular descent. (Reproduced with permission from Sarnat HB, Sarnat MS: Disorders of muscle in the newborn. In Moss AJ, Stern L [eds]: Pediatrics update, ed 4, New York, 1983, Elsevier-North Holland.)

ETIOLOGY

Normal testicular descent is a complex interplay among mechanical (gubernaculums, vas deferens and testicular vessel length, cremasteric muscles, and abdominal pressure), hormonal (gonadotropin, testosterone, dihydrotestosterone, and mullerian inhibiting substance), and neural (ilioinguinal and genitofemoral nerves) factors.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Retractile testis

•

Ascended testis

•

Atrophic testis

•

Vanished testis

WORKUP

•

Physical examination When done in a warm room with warm hands, can identify presence, absence, and location of palpable testes. Should be done in supine, sitting, and standing positions with adequate cremasteric relaxation to differentiate true cryptorchidism from retractile testes. Often associated with an indirect inguinal hernia as the tunica vaginalis fails to close above the testis. An enlarged contralateral testis in the presence of a nonpalpable undescended testis is suggestive of but not definitive for testicular atrophy/absence.

•

Hormonal challenge Human chorionic gonadotropin (hCG) will confirm the presence of functioning testicular tissue and is useful in the setting of bilateral nonpalpable undescended testes. If the follicular stimulating hormone level is 3× normal and there is no increase in testosterone in response to hCG, functional testes are absent.

IMAGING

•

Ultrasound: sensitivity of 76%, specificity of 100%, accuracy of 84%.

•

MRI: sensitivity of 86% and specificity of 79%. CT results are inconsistent.

TREATMENT

•

Repeat examination at 3 mo of age, because many testes will descend spontaneously. Spontaneous descent is rare after 3 mo of age.

•

Treatment can be hormonal, surgical, or both.

•

Treatment recommended as early as 6 mo and should be completed before 2 yr because histologic changes have been identified as early as 1.5 years of age.

•

Earlier orchidopexy may improve testicular function and decrease the risk of testis cancer. Orchidopexy allows testicular self-examination and detection of testicular cancer should it occur.

HORMONAL Rx

•

Results of hCG are variable for undescended testes but good for retractile testes.

•

The International Health Foundation recommends biweekly injections of 250 IU for infants, 500 IU for children up to 6 yr, and 100 IU for children 6 yr and older, for a total of 5 wk. Therapy may induce precocious puberty.

•

Administration of gonadotropin-releasing hormone before orchiopexy may improve fertility in adulthood.

SURGICAL Rx

•

For the palpable undescended testis, orchiopexy, the surgical placement of an undescended testis into the scrotum, is the standard approach.

•

In the setting of a nonpalpable undescended testis, laparoscopy is recommended to identify the presence/absence of a testis and the location of the testis if present and to determine the length of the testicular vessels.

•

A two-stage approach is recommended for an intra-abdominal testis with short vessels. The testicular vessels are clipped laparoscopically in the first stage, and the testis is brought into the scrotum in the second stage.

•

Although the risk of testicular cancer is higher, the removal of all intraabdominal testes is not warranted.

DISPOSITION

•

Earlier orchidopexy may decrease the risk of malignancy and infertility.

•

Lifelong testicular exam after puberty.

REFERRAL

Early referral to a pediatric urologist

PEARLS & CONSIDERATIONS Regular testicular exams should be performed in infants and children, particularly those with retractile testes, as ascent of scrotal testis can occur. SUGGESTED READINGS Cortes D: Scan J Nephrol 1998; 9:54. Dawson C, Whitfield H: BMJ 1996; 312(7041):1291. Docimo S, Silver R, Cromie W: Am Fam Physician 2000; 62:2037. Giannopoulos MD, et al: Horm Res 2001; 55(1):33. Lee P: Urology 2005; 66:427. Leissner J, et al: Br J Urol Int 1999; 83(8):885. Patik K, et al: BJU 2005; 95:704. Schwentner C, et al: J Urol 2005; 173:974. Thayyil S, et al: Arch Dis Child 2004; 89:890.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cryptosporidium Infection GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

The intracellular protozoan parasite Cryptosporidium parvum is associated with gastrointestinal disease and diarrhea, especially in AIDS patients or immunocompromised hosts. It is also associated with sporadic infections and waterborne outbreaks in immunocompetent hosts. Other species, including C. hominus, C. felis, C. muris, and C. meleagridis, are now described to be pathogens as well. SYNONYMS

Cryptosporidiosis

ICD-9CM CODES

007.4 Cryptosporidia infection EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Approximately 2% in industrial countries, 5% to 10% in third world countries

•

10% to 20% of HIV patients in U.S. may excrete cyst

PREVALENCE: Worldwide, especially third world countries; associated with poor hygiene as a waterborne pathogen PREDOMINANT SEX: Male = female TRANSMISSION: •

Person to person (daycare, family members)

•

Animal to person (pets, farm animals)

•

Environmental (water-associated outbreaks, including travel associated with swimming in or drinking contaminated water)

•

May be significant pathogen causing diarrhea in AIDS

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usually limited to gastrointestinal tract

•

Diarrhea, severe abdominal pain (2 to 28 days)

•

Impaired digestion, dehydration

•

Fever, malaise, fatigue, nausea, vomiting

•

Pneumonia if aspirated

ETIOLOGY

Cryptosporidium hominis, Cryptosporidium parvum, C. felis, C. muris, C. meleagridis

DIAGNOSIS Clinical presentation of acute gastrointestinal illness, especially associated with HIV or with travel and waterborne outbreaks. DIFFERENTIAL DIAGNOSIS

•

Campylobacter

•

Clostridium difficile

•

Entamoeba histolytica

•

Giardia lamblia

•

Salmonella

•

Shigella

•

Microsporidia

•

Cytomegalovirus

•

Mycobacterium avium

Disease may cause cholecystitis, reactive arthritis, hepatitis, pancreatitis, pneumonia in immunocompromised or HIV-infected patients. WORKUP

•

Stool evaluation looking for characteristic oocyst by modified acid-fast stain ( Fig. 1-66 ).

•

Direct immunofluorescence using monoclonal antibodies is the gold standard for stool exams.

FIGURE 1-66 Human stool-derived Cryptosporidium oocysts. Excysting oocyst (arrow) is releasing three of its four sporozoites. (Phasecontrol microscopy ×630.) (From Gorbach SL: Infectious diseases, ed 2, Philadelphia, 1998, WB Saunders.)

TREATMENT

•

May be self-limited in normal host—often requiring hydration. Antidiarrhea agents Pepto-Bismol, Kaopectate, or loperamide may give symptomatic relief.

•

Pharmacologic treatment with antibiotics has been largely unsatisfactory in AIDS patients. Oocyst excretion reduction has been shown with nitazoxanide 500 mg po BID for 3 days. If treatment fails, consider a trial of paromomycin, metronidazole, or Bactrim.

•

Nitazoxanide elixir has been approved for the treatment of cryptosporidiosis in children ages 1 to 11 yr.

•

Biliary cryptosporidiosis can be treated with antiretroviral therapy in the HIV setting.

DISPOSITION

•

A self-limited disease in immunocompetent patients with complete recovery over 2 to 3 weeks.

•

Chronic arthralgia, headache, malaise, and weakness may persist after cryptosporidial infection even in immunologically normal people.

•

If severe and prolonged (>30 days), testing for HIV and other immunocompromised states is appropriate along with a referral to an infectious disease specialist or gastroenterologist.

REFERRAL

•

To an infectious disease specialist if symptoms persist and if HIV infection is found

•

To a gastroenterologist if chronic malabsorption, or biliary or pancreatic complications occur

PEARLS & CONSIDERATIONS

•

Chronic cryptosporidiosis (>30 days of diarrhea from Cryptosporidium spp. infection) in a patient with HIV is an AIDS-qualifying opportunistic infection.

•

Cryptosporidium hominis has a limited host range (humans), whereas Cryptosporidium parvum has a wide host range including humans, horses, cattle, other domesticated animals, and wild animals—both species present a similar illness in humans.

SUGGESTED READINGS Hunter PR, et al: Health sequelae of human cryptosporidiosis in immunocompetent patients. Clin Infect Dis 2004; 39(b):504-510. Smith HV, Corcoran GD: New drugs and treatment for cryptosporidiosis. Curr Opin Infect Dis 2004; 17(6):557.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cubital Tunnel Syndrome LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Compression of the ulnar nerve behind the elbow (cubitus) SYNONYMS

Tardy ulnar palsy

ICD-9CM CODES

354.2 Cubital tunnel syndrome EPIDEMIOLOGY & DEMOGRAPHICS

Prevalent sex: Males = females PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Paresthesias and numbness along distribution of ulnar nerve (ulnar one and one-half fingers)

•

Positive Tinel's sign at elbow

•

Positive elbow flexion test (flexion of elbow with wrist extended for 30 sec may reproduce symptoms)

•

May be diminished sensation to tip of small finger

•

Ulnar nerve may be subluxable with elbow motion or by manipulation

•

Cubitus valgus may be present if prior bony injury

•

Interosseous weakness in longstanding cases with atrophy ( Fig. 1-67 )

FIGURE 1-67 Testing for intrinsic (ulnar) motor weakness (fanning the fingers against resistance). Always look for atrophy of the first dorsal interosseus (curved arrow) when ulnar nerve lesions are suspected. (From Mercier LR: Practical orthopedics, ed 5, St Louis, 2000, Mosby.)

ETIOLOGY

•

Direct pressure

•

Cubitus valgus deformity

•

Subluxation of ulnar nerve

•

Repeated stretching during throwing motion

•

Elbow synovitis

•

Local muscular hypertrophy

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Medial epicondylitis

•

Medial elbow instability

•

Carpal tunnel syndrome

•

Cervical disc syndrome with radicular arm symptoms

•

Ulnar nerve compression at wrist (Guyon's canal)

WORKUP

Diagnosis can usually be established clinically IMAGING STUDIES

•

Routine roentgenograms may be helpful in establishing cause or ruling out other conditions

•

Electrodiagnostic studies: nerve conduction tests and electromyography are useful in establishing diagnosis and ruling out other syndromes

TREATMENT acute GENERAL Rx

•

Protect nerve from pressure

•

Elbow pads

•

Avoid prolonged elbow flexion (talking on phone with elbow bent)

DISPOSITION

•

Prognosis is variable.

•

Mild to moderate cases recover well if offending activity can be eliminated. If muscle atrophy has developed, recovery of strength may be incomplete in spite of treatment.

•

Medical management may be continued as long as symptoms are controlled and no motor deficit has developed.

REFERRAL

Surgical referral in cases of failed medical management or if signs of motor impairment are present SUGGESTED READINGS Creighton RA, et al: Evaluation of the medial elbow in the throwing athlete. Am J Orthop 2006; 35:266. Cutts S: Cubital tunnel syndrome. Postgrad Med J 2007; 83:28. Elhassan B, Steinmann SP: Entrapment neuropathy of the ulnar nerve. J Am Acad Orthop Surg 2007; 15:672. Grana W: Medial epicondylitis and cubital tunnel syndrome in the throwing athlete. Clin Sports Med 2001; 20(3):541. Kato H, et al: Cubital tunnel syndrome associated with medial elbow ganglia and osteoarthritis of the elbow. J Bone Joint Surg 2002; 84(A):1413. Lee DH, Claussen GC, Oh S: Clinical nerve conduction and needle electroonyography studies. J Am Acad

Orthop Surg 2004; 12:276. Park GY, Kim JM, Lee SM: The ultrasonographic and electro-diagnostic findings of ulnar neuropathy at the elbow. Arch Phys Med Rehabil 2004; 85:1000. Sasaki J, et al: Ultrasonographic assessment of ulnar collateral ligament and medial elbow laxity in college baseball players. J Bone Joint Surg 2002; 84(A):525. Shin R, Ring D: The ulnar nerve in elbow trauma. J Bone Joint Surg 2007; 89:1108. Szabo RM, Kwak C: Natural history and conservative management of cubital tunnel syndrome. Hand Clin 2007; 23:311.

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Cushing's Disease and Syndrome FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

•

Cushing's syndrome is the occurrence of clinical abnormalities associated with glucocorticoid excess secondary to exaggerated adrenal cortisol production or chronic glucocorticoid therapy.

•

Cushing's disease is Cushing's syndrome caused by pituitary ACTH excess.

ICD-9CM CODES

255.0 Cushing's disease or syndrome PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Hypertension

•

Central obesity with rounding of the facies (moon facies); thin extremities

•

Hirsutism, menstrual irregularities, hypogonadism

•

Skin fragility, ecchymoses, red-purple abdominal striae, acne, poor wound healing, hair loss, facial plethora, hyperpigmentation (when there is ACTH excess)

•

Psychosis, emotional lability, paranoia

•

Muscle wasting with proximal myopathy

NOTE :

The previous characteristics are not commonly present in Cushing's syndrome secondary to ectopic ACTH production. Many of these tumors secrete a biologically inactive ACTH that does not activate adrenal steroid synthesis. These patients may have only weight loss and weakness. ETIOLOGY

•

Iatrogenic from chronic glucocorticoid therapy (common)

•

Pituitary ACTH excess (Cushing's disease; 60%)

•

Adrenal neoplasms (30%)

•

Ectopic ACTH production (neoplasms of lung, pancreas, kidney, thyroid, thymus; 10%)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Alcoholic pseudo-Cushing's syndrome (endogenous cortisol overproduction)

•

Obesity associated with diabetes mellitus

•

Adrenogenital syndrome

WORKUP

•

In patients with a clinical diagnosis of Cushing's syndrome the initial screening test is the overnight dexamethasone suppression test: 1.

Dexamethasone 1 mg PO given at 11 p.m.

2.

Plasma cortisol level measured 9 hr later (8 a.m.)

3.

Plasma cortisol level 300 µg/24 hr) indicates Cushing's syndrome.

•

The low-dose (2 mg) dexamethasone suppression test is useful to exclude pseudo-Cushing's syndrome if the previous results are equivocal. CRH stimulation after low-dose dexamethasone administration (dexamethasone-CRH test) is also used to distinguish patients with suspected Cushing's syndrome from those who have mildly elevated urinary free cortisol level and equivocal findings.

•

The high-dose (8 mg) dexamethasone test and measurement of ACTH by RIA are useful to determine the etiology of Cushing's syndrome.

•

1.

ACTH undetectable or decreased and lack of suppression indicates adrenal etiology of Cushing's syndrome.

2.

ACTH normal or increased and lack of suppression indicate ectopic ACTH production.

3.

ACTH normal or increased and partial suppression suggest pituitary excess (Cushing's disease).

A single midnight serum cortisol (normal diurnal variation leads to a nadir around midnight) >7.5 µg/dl has been reported as 96% sensitive and 100% specific for the diagnosis of Cushing's syndrome.

LABORATORY TESTS

•

Hypokalemia, hypochloremia, metabolic alkalosis, hyperglycemia, hypercholesterolemia

•

Increased 24-hr urinary free cortisol (>100 µg/24 hr)

IMAGING STUDIES

•

CT scan or MRI of adrenal glands in suspected adrenal Cushing's syndrome

•

MRI of pituitary gland with gadolinium in suspected pituitary Cushing's syndrome

•

Additional imaging studies to localize neoplasms of the lung, pancreas, kidney, thyroid, or thymus in patients with ectopic ACTH production

TREATMENT GENERAL Rx

The treatment of Cushing's syndrome varies with its cause:

•

Pituitary adenoma: transsphenoidal microadenomectomy is the therapy of choice in adults. Pituitary irradiation is reserved for patients not cured by transsphenoidal surgery. In children, pituitary irradiation may be considered as initial therapy, because 85% of children are cured by radiation. Stereotactic radiotherapy (photon knife or gamma knife) is effective and exposes the surrounding neuronal tissues to less irradiation than conventional radiotherapy. Total bilateral adrenalectomy is reserved for patients not cured by transsphenoidal surgery or pituitary irradiation.

•

Adrenal neoplasm: 1.

Surgical resection of the affected adrenal

2.

Glucocorticoid replacement for approximately 9 to 12 mo after the surgery to allow time for the contralateral adrenal to recover from its prolonged suppression

•

Bilateral micronodular or macronodular adrenal hyperplasia: bilateral total adrenalectomy

•

Ectopic ACTH: 1.

Surgical resection of the ACTH-secreting neoplasm

2.

Control of cortisol excess with metyrapone, aminoglutethimide, mifepristone, or ketoconazole

3.

Control of the mineralocorticoid effects of cortisol and 11-deoxycorticosteroid with spironolactone

4.

Bilateral adrenalectomy: a rational approach to patients with indolent, unresectable tumors

DISPOSITION

Prognosis is favorable in patients with surgically amenable disease.

PEARLS & CONSIDERATIONS COMMENTS

Screening for MEN I should be considered in patients with Cushing's disease. SUGGESTED READINGS Boscaro M, et al: The diagnosis of Cushing's syndrome. Arch Intern Med 2000; 160:3045.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Cystic Fibrosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by dysfunction of exocrine glands.

ICD-9CM CODES

277.0 Cystic fibrosis EPIDEMIOLOGY & DEMOGRAPHICS

•

It is the most common fatal hereditary disorder of caucasians in the U.S. (1 case/2500 caucasians) and second most common life-shortening childhood onset inherited disorder in the U.S., behind sickle cell disease.

•

Median age at diagnosis is 5.3 months. Median survival is 30 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Failure to thrive in children

•

Increased anterior/posterior chest diameter

•

Basilar crackles and hyperresonance to percussion

•

Digital clubbing

•

Chronic cough

•

Abdominal distention

•

Greasy, smelly feces

ETIOLOGY

Chromosome 7 gene mutation (CFTR gene) resulting in abnormalities in chloride transport and water flux across the surface of epithelial cells; the abnormal secretions cause obstruction of glands and ducts in various organs and subsequent damage to exocrine tissue (recurrent pneumonia, atelectasis, bronchiectasis, diabetes mellitus, biliary cirrhosis, cholelithiasis, intestinal obstruction, increased risk of GI malignancies)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Immunodeficiency states

•

Celiac disease

•

Asthma

•

Recurrent pneumonia

WORKUP

A diagnosis of CF requires a positive quantitative pilocarpine iontophoresis test with one or more phenotypic features consistent with CF (e.g., chronic suppurative obstructive lung disease, pancreatic insufficiency) or documented CF in a sibling or first cousin. LABORATORY TESTS

•

Pilocarpine iontophoresis (“sweat test”): diagnostic of cystic fibrosis in children if sweat chloride is >60 mmol/L (>80 mmol/L in adults) on two separate tests on consecutive days. Repeat testing may be necessary because not all infants have sufficient quantities of sweat for reliable testing

•

DNA testing may be useful for confirming the diagnosis and providing genetic information for family members

•

Sputum C&S and Gram stain (frequent bacterial infections with Staphylococcus aureus, Pseudomonas aeruginosa [most common virulent respiratory pathogen], Haemophilus influenzae)

•

Low albumin level, increased 72-hr fecal fat excretion

•

Pulse oximetry or ABGs: hypoxemia

•

Pulmonary function studies: decreased TLC, forced vital capacity, pulmonary diffusing capacity

IMAGING STUDIES

•

Chest x-ray: may reveal focal atelectasis, peribronchial cuffing, bronchiectasis, increased interstitial markings, hyperinflation

•

High-resolution chest CT scan: bronchial wall thickening, cystic lesions, ring shadows (bronchiectasis)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Postural drainage and chest percussion

•

Encouragement of regular exercise and proper nutrition

•

Psychosocial evaluation and counseling of patient and family members

ACUTE GENERAL Rx

•

Antibiotic therapy based on results of Gram stain and C&S of sputum (PO ciprofloxacin or floxacillin for Pseudomonas, cephalosporins for S. aureus, IV aminoglycosides plus ceftazidime for life-threatening Pseudomonas infections). Macrolides are also active against pseudomona aeruginosa. A recent study using azithromycin maintenance in children with CF for 6 mo found less use of additional antibiotics and improvement in some aspects of pulmonary function. Additional studies may be necessary to determine if azithromycin should be used as a primary therapy or rescue treatment

•

Bronchodilators for patients with air flow obstruction

•

Chronic pancreatic enzyme replacement

•

Alternate-day prednisone (2 mg/kg) possibly beneficial in children with cystic fibrosis (decreased hospitalization rate, improved pulmonary function); routine use of corticosteroids not recommended in adults; among children with cystic fibrosis who have received alternate-day treatment with prednisone, boys, but not girls, have persistent growth impairment after treatment is discontinued

•

Proper nutrition and vitamin supplementation

•

Recombinant human deoxyribonuclease (DNase [Dornase alpha]) 2.5 mg qd or bid given by aerosol for patients with viscid sputum. It is useful to improve mucociliary clearance by liquefying difficult-to-clear pulmonary secretions. It is, however, very expensive (annual cost to the pharmacist is >$10,000); most beneficial in patients with FVC values >40% of predicted. Its cost can be decreased by using alternate-day rhDnase therapy

•

Intermittent administration of inhaled tobramycin has been reported beneficial in CF

•

Treatment of impaired glucose tolerance and diabetes mellitus

CHRONIC Rx

Pneumococcal vaccination, yearly influenza vaccination DISPOSITION

•

More than 50% of children with cystic fibrosis live beyond age 20 yr.

•

Lung transplantation is the only definitive treatment; 3-yr survival following transplantation exceeds 50%.

•

Obstructive azoospermia is present in >98% of postpubertal males.

REFERRAL

•

To regional ambulatory care cystic fibrosis center.

•

For lung transplantation in selected patients. Indications for lung transplantation are: FEV in 1 sec >30% of predicted, rapidly progressive respiratory deterioration, increasing number of hospital admissions, massive hemoptysis, recurrent pneumothorax, arterial partial pressure of oxygen >55 mmHg, arterial partial pressure of carbon dioxide >50 mm Hg, multiresistant organisms, wasting. Young female patients should be referred earlier due to overall poor prognosis.

•

For screening of family members with DNA analysis.

PEARLS & CONSIDERATIONS COMMENTS

•

Clinicians should think of cystic fibrosis in any patient with bronchiectasis plus any of the following: male infertility, recurrent idiopathic pancreatitis, recurrent nasal polyposis.

•

Genetic testing for CF should be offered to adults with a positive family history of CF, to couples currently planning a pregnancy, and to couples seeking prenatal care.

•

Inhalation of hypertonic saline (5 ml of 7% sodium chloride qid) has been reported to produce a sustained acceleration of mucus clearance and improved lung function.

SUGGESTED READINGS Swiss Med Wkly 2003; 133:111. JAMA 2007; 298(b):1787-1793. N Engl J Med 2006; 354:241. N Engl J Med 2005; 352:1992.

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Cysticercosis ELENI PATROZOU, M.D., STACI A. FISCHER, M.D., F.A.C.P.

BASIC INFORMATION DEFINITION

Cysticercosis is an infection caused by the tissue deposition of larval forms of the pork tapeworm Taenia solium. T. solium cysts, or cysticerci, may accumulate in any tissue including the eyes, spinal cord, skin, muscle, heart, and brain. Central nervous system involvement is common and is known as neurocysticercosis. Humans acquire cysticercosis via fecal-oral transmission of T. solium eggs from human tapeworm carriers, often by ingesting tapeworm eggs or cysts in contaminated food or water. Undercooked pork is the most commonly identified food source. The eggs hatch in the gastrointestinal tract, and larvae migrate hematogenously to tissues and then encyst, forming cysticerci. SYNONYMS

Cysticerciasis Taeniasis Pork tapeworm

ICD-9CM CODES

123.1 Cysticercosis EPIDEMIOLOGY & DEMOGRAPHICS

•

T. solium infection is worldwide in distribution. Tapeworm infection and cysticercosis are endemic in rural, developing countries where pigs are raised as a food source.

•

Serologic studies from endemic areas of Latin America have demonstrated seroprevalences of 4.9% to 24%.

•

Neurocysticercosis is the most common cause of acquired epilepsy worldwide, and has become an important parasitic disease in the U.S., especially in states with large immigrant populations from countries where the disease is endemic.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Following ingestion of T. solium eggs or cysts, humans may remain asymptomatic for several years.

•

The symptoms are varied and depend on the location of cysticerci. Cysticerci in muscles and skin may form “cold” nodules, which are usually asymptomatic but may calcify.

•

Neurocysticercosis, the presence of intraparenchymal cysts, may be asymptomatic. Symptoms stem from inflammation associated with the degeneration of cysts.

•

Seizures are the most common manifestation of neurocysticercosis, occurring in 70% to 90% of symptomatic cases. Headache is also common.

•

Inflammation around degenerating cysts may result in focal encephalitis, vasculitis, chronic meningitis, and cranial nerve palsies.

•

When cysts lodge within the ventricular system (10% to 20% of neurocysticercosis cases), life-threatening acute intracranial hypertension, due to obstructive hydrocephalus, may occur. This syndrome is related to the location of the parasites in the cerebral ventricles or basal cisterns, blocking the circulation of the cerebrospinal fluid, and is caused by the presence of the parasite itself, ependymal inflammation, and/or fibrosis. Death may occur from progressive hydrocephalus, cerebral edema, or intractable seizures.

ETIOLOGY

•

T. solium has a complex two-host life cycle.

•

Humans are the only definitive host and harbor the adult worm in the intestine (taeniasis). However, both humans and pigs can serve as intermediate hosts and harbor the larvae or cysticerci ( Fig. 1-68 ).

FIGURE 1-68 Cysticercosis is most commonly acquired by ingesting undercooked pork infected with Taenia solium cysticerci. Adult worms develop in the small intestine, forming proglottids that produce many fertilized eggs. Eggs and proglottids are intermittently shed in the stools of the persons infected with an adult tapeworm, where they can be ingested by pigs (the intermediate host) or transmitted via fecal-oral contamination to other humans. In the small intestine of the host, the eggs hatch and release larvae that travel through the bloodstream to various organs, where they develop into fluid-filled cystic larvae within months. Skeletal muscle, subcutaneous tissue, the eyes, and the central nervous system are most commonly invaded.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Idiopathic epilepsy

•

Migraine

•

Central nervous system (CNS) vasculitis

•

Primary neoplasia of CNS

•

Chronic CNS infections including toxoplasmosis, coccidioidomycosis, tuberculosis, cryptococcosis

•

Brain abscess

•

CNS sarcoidosis, systemic lupus erythematosus (SLE)

WORKUP

Comprehensive clinical history: Obtain information on area and sanitary conditions of residence, previous travel, and dietary habits, most importantly consumption of undercooked pork. LABORATORY TESTS

•

Definitive diagnosis is based on the histopathologic demonstration of cysticerci in the tissue involved.

•

Peripheral eosinophilia is absent.

•

Stool examination for ova and proglottids of T. solium is insensitive and not specific for the diagnosis of cysticercosis.

•

Cerebrospinal fluid examination may demonstrate pleocytosis, with lymphocytic or eosinophilic predominance, low glucose, and elevated protein with neurocysticercosis. CSF is normal in most cases.

•

An enzyme-linked immunoelectrotransfer blot (EITB) assay is the test of choice for detecting anticysticercal antibodies. This assay uses affinity purified glycoprotein antigens and has higher sensitivity (83% to 100%) and specificity (93% to 98%) than other enzyme-linked antibody (e.g., ELISA) tests. However, the diagnostic performance of the EITB can vary in different patient populations depending on the activity of the cysts and number of lesions. Single calcified lesions are more likely to be associated with a false negative assay result. Sensitivity is greater in serum than in CSF.

•

There is no culture or nucleic acid (e.g., PCR) test available to diagnose active infection.

IMAGING STUDIES

•

Plain radiographs of the extremities may reveal calcified cysts in patients with soft tissue or muscle involvement.

•

For diagnosis of neurocysticercosis, CT and MRI are most commonly used.

•

Brain CT: Sensitivity and specificity of 95%. Can identify living cysticerci, which appear as hypodense lesions, as well as degenerating cysts, which appear as isodense or hyperdense lesions. It is considered the best method for detecting calcification associated with prior infection, which suggests inactivity. Brain MRI: Most accurate technique to assess the extent of infection, location, and evolutionary stage of the parasites. Provides detailed images of living and degenerating cysts, perilesional edema, as well as small cysts or those located in the ventricles, brain stem, and cerebellum.

TREATMENT Asymptomatic cysticercosis: There is no evidence that administering antiparasitic therapy is beneficial. Symptomatic cysticercosis: Patients with active lesions, with evidence of surrounding edema and/or

inflammation, generally warrant treatment with antiparasitics, corticosteroids, and anticonvulsants. •

Anticonvulsant therapy: Patients who present with seizures or are considered to be at risk for recurrent seizures based on imaging should be treated with anticonvulsants.

•

Antiparasitic therapy: Pharmacologic therapy is indicated in the treatment of symptomatic patients with multiple viable brain parenchymal cysticerci. Calcified cysticerci are inactive and do not warrant antiparasitic treatment. Antiparasitic therapy is often unnecessary in patients with single cysts, because treatment does not alter the natural history of single-cyst disease.

•

Cysticidal therapy: Therapy hastens the disappearance of cysts and should initially be given in conjunction with corticosteroids to control the inflammation associated with dying organisms. Patients with viable parenchymal or subarachnoid cysts should be treated with albendazole 15 mg/kg/day for 8 days or praziquantel 50 mg/kg/day for 15 days. Antiparasitics should be used cautiously in patients with massive cysticercal infection of the brain parenchyma (>50 cysts) or cysticercal encephalitis. These patients should be managed initially with corticosteroids, and perhaps mannitol, to control intracranial hypertension. Once the inflammation and the edema have resolved by MRI, antiparasitics can be administered. Praziquantel may cause drug interactions with other agents metabolized via the cytochrome p450 systems, including phenytoin and phenobarbital. Albendazole has no significant drug interactions with anticonvulsants.

•

Surgical therapy: Surgery may be indicated in patients with obstructive hydrocephalus or giant cysts with associated intracranial hypertension. Surgical interventions may include craniotomy, with cyst extraction, stereotactic cyst aspiration, or ventriculoperitoneal shunt placement to control hydrocephalus. Extraparenchymal cysticercosis, including ocular, subarachnoid, and intraventricular disease, carries poor prognosis and requires a more aggressive approach. When feasible, complete surgical excision of lesions remains the definitive therapy.

CHRONIC Rx

•

Praziquantel and albendazole may not be a definitive cure for seizures, and antiepileptic medications may need to be continued indefinitely.

•

Some patients with neurocysticercosis develop chronic or recurrent perilesional inflammation, requiring long-term, high-dose steroid therapy. Methotrexate has been reported to be of use as a steroid-sparing agent in this setting.

DISPOSITION

•

In seizure-free, stable neurocysticercosis, outpatient management can be safely done. Long-term follow-up is warranted.

•

In the U.S., law-enforced restriction of driving varies by state, and physicians have the duty to restrict or to release restriction of driving in patients with seizures.

REFERRAL

•

Infectious diseases consultation

•

Neurology consultation in patients with seizures

•

Neurosurgical consultation if extraparenchymal neurocysticercosis or obstructive hydrocephalus is present

PREVENTION

Eradication of taeniasis/cysticercosis is possible. The disease disappears with implementation of meat inspection, improvement of pig husbandry, and improvement of socioeconomic conditions. PATIENT/FAMILY EDUCATION

•

Pork must be well cooked.

•

Proper human excreta disposal and hand washing is of utmost importance to break the transmission cycle in households.

SUGGESTED READINGS Cuetter AC, et al: Neurocysticercosis: focus on intraventricular disease. Clin Infect Dis 1997; 24:157-164. Del Brutto OH, et al: Meta-analysis: cysticidal drugs for neurocysticercosis: albendazole and praziquantel. Ann Intern Med 2006; 145:43. Garcia HH, et al: New concepts in the diagnosis and management of neurocysticercosis (Taenia solium). Am J Trop Med Hyg 2005; 72:3. Garcia HH, et al: Taenia solium cysticercosis. Lancet 2003; 362:547-556. Mitre E, et al: Methotrexate as a corticosteroid-sparing agent in complicated neurocysticercosis. Clin Infect Dis 2007; 44:449-553. Nash TE, et al: Treatment of neurocysticercosis: current status and future research needs. Neurology 2006; 67:1120-1127. Sorvillo FJ, et al: Deaths from cysticercosis, United States. Emerg Infect Dis 2007; 13(b):230-235. Takayanagui OM, et al: Clinical aspects of neurocysticercosis. Parasitology International 2006; 55:S111-S115. White AC: Neurocysticercosis: a major cause of neurological disease worldwide. Clin Infect Dis 1997; 24:101115.

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Cytomegalovirus Infection STEVEN M. OPAL, M.D., MINA PANTCHEVA, M.D., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Infection with cytomegalovirus (CMV), a herpes virus, is common in the general population, with multiple mechanisms for transmission, often during childhood and adolescence. CMV is associated with pregnancy and can be a congenital disease. CMV is also associated with immunocompromised states and may be life threatening. SYNONYMS

CMV Heterophil-negative mononucleosis Cytomegalic inclusion disease virus

ICD-9CM CODES

078.5 CMV infection 771.1 Congenital or perinatal CMV infection V01.7 Exposure to CMV EPIDEMIOLOGY & DEMOGRAPHICS

•

Seroprevalence is widespread: 40% to 100% antibody positivity in adults.

•

Increased infection develops perinatally, in day care exposure, and then during reproductive age, related to sexual activity.

ROUTES OF TRANSMISSION

•

Blood transfusions

•

Sexually (STDs) via uterus, cervix, and semen

•

Perinatally via breast milk

•

Transplant of organs—bone marrow, kidneys, liver, heart, or lung

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Children: Congenital—25% of infected children with symptoms if congenital: •

Petechial rash

•

Jaundice and/or hepatosplenomegaly

•

Lethargy

•

Respiratory distress

•

CNS involvement, seizures

Postnatal acquisition: •

CMV mononucleosis

•

Pharyngitis, croup, bronchitis, pneumonia

Healthy adults: Common •

May be asymptomatic

•

CMV mononucleosis similar to EBV mononucleosis

•

Fever—lasting 9 to 30 days—mean of 19 days

Less common •

Exudative pharyngitis

•

Lymphadenopathy, hepatitis, splenomegaly

•

Interstitial pneumonia (rare)

•

Nonspecific rash

•

Thrombocytopenia/hemolytic anemia

Rare •

Guillain-Barré syndrome

•

Meningoencephalitis

•

Myocarditis

Immunosuppressed patients: •

Febrile mononucleosis

•

GI ulcerations, hepatitis, pneumonitis, retinitis, encephalopathy, meningoencephalopathy

•

HIV associated—dementia, demyelination, retinitis ( Fig. 1-69 ), acalculous cholecystitis, adrenalitis, diarrhea, enterocolitis, esophagitis

•

Diabetes associated with pancreatitis

•

Adrenalitis associated with HIV

FIGURE 1-69 Sight-threatening CMV retinitis involves the macula and optic nerve of this HIV-positive young man. White, infected retina with intraretinal hemorrhage is present in the arcuate distribution of the nerve fiber layer (1). A small amount of lipid exudation near the fovea and nasal to the optic nerve is also seen (2). (From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

Cytomegalovirus infection can remain latent, reactive with immunosuppression.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Congenital: •

Acute viral, bacterial, parasitic infections including other congenitally transmitted agents (toxoplasmosis, rubella, syphilis, pertussis, croup, bronchitis)

Acquired:

•

EBV mononucleosis

•

Viral hepatitis—A, B, C

•

Cryptosporidiosis

•

Toxoplasmosis

•

Mycobacterium avium infections

•

Human herpesvirus 6

•

Acute HIV infection

WORKUP

•

Laboratory confirmation combined with clinical findings often with leukopenia, thrombocytopenia, lymphocytosis

•

Demonstration of virus in tissue or serologic testing including CMV IgM antibodies, rising titers of complement fixation (CF) and indirect fluorescent antibody (IFA) or anticomplement IFA

•

Funduscopic—necrotic patches with white granular component of retina

•

Cultures—(viral) human fibroblast from urine, cervical swab, tissue buffy coat

•

Biopsy—“owl's eye” inclusion bodies on tissue sample

IMAGING STUDIES

•

Chest x-ray—if pneumonitis suspected, consider bronchoscopy

•

Endoscopy—if GI involvement

•

CT scan/MRI—if CNS involvement

TREATMENT NONPHARMACOLOGIC THERAPY

•

Strict handwashing and standard precautions limit CMV transmission in health care facilities

•

Highly active antiretroviral therapy (HAART) in patients with CD4 count >50/mm3for the goal of CD4 >100/mm3for a 3 to 6 mo period

ACUTE GENERAL Rx

For compromised hosts with CMV retinitis or pneumonitis: •

Ganciclovir 5 mg/kg bid IV × 21 days, then 5 mg/kg/day IV, or 1 g po tid or occular implant

•

Foscarnet 60 mg/kg tid × 3 wk, then 90 mg/kg/day

•

Cidofovir 5 mg/kg IV, repeat 1 wk later, then q2 wk IV

•

Fomivirsen-salvage therapy for CMV retinitis 300 µg injected into vitreous

DISPOSITION

•

CMV infection in patients who are immunocompromised (especially those with AIDS, bone marrow and solid organ transplant recipients, and disorders of cell-mediated immune function) will need expert, longterm follow-up by an infectious disease specialist or immunologist familiar with the care of such patients.

•

CMV mononucleosis, hepatitis, pharyngitis, etc. in immunologically normal hosts are usually self-limiting infections requiring no special follow-up plans.

REFERRAL

•

To an ophthalmologist if CMV retinitis is present

•

To an infectious disease specialist or AIDS specialist for patients who are HIV-positive with CMV disease

•

To a cellular immunologist or transplant specialist in the case of CMV infection in a transplant recipient

•

To a pediatric infectious disease specialist for congenital CMV infection

PEARLS & CONSIDERATIONS CMV is ubiquitous in the environment and is asymptomatically shed by latently infected persons with CMV infection, making it difficult to protect patients who are immunocompromised from acquiring this infection.

EVIDENCE

Ganciclovir is effective in preventing CMV disease and infections in recipients of solid organ transplants but has no effect on rate of graft loss, acute rejection, or death. It has been shown to be more effective than acyclovir in of kidney transplants. [364] [365] Uncertainty exists regarding the evidence for prophylactic oral ganciclovir in patients with advanced AIDS, and the benefits must be balanced with the serious side effects of treatment in this patient group. [366] [367] [368]

When deciding whether to institute prophylaxis in individual patients with advanced AIDS, ganciclovirinduced neutropenia, anemia, conflicting reports of efficacy, lack of proven survival benefit, risk for experiencing ganciclovirresistant CMV, and cost are among the concerns that should be addressed.[[6]] Evidence suggests that foscarnet may offer a survival advantage over ganciclovir for patients with AIDS and cytomegalovirus retinitis, but the rate of progression of retinitis is similar with both treatments.[[5]] Intravenous cidofovir is as effective as oral ganciclovir plus the ganciclovir ocular implant in treating patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis.[[7]] Intravenous cidofovir (low and high dose) delays progression of CMV retinitis in patients with AIDS, compared with deferred treatment, but is associated with some nephrotoxicity. [371] [372] A randomized controlled trial has shown a trend toward earlier mortality with valacyclovir vs. acyclovir in the treatment of CMV-seropositive patients with AIDS, and CD4 cell counts 60% of individuals having one depressive episode and >90% with three or more.

•

Without treatment, episodes last an average of 6 to 12 months.

REFERRAL

•

If treatment resistant or refractory

•

If patient suicidal or psychotic

•

For adjunctive psychotherapy in moderate to severe depression

PEARLS & CONSIDERATIONS COMMENTS

•

All threats of suicide should be taken very seriously. Clinicians can use the mnemonic SAL: Is the method Specific? Is it Available? Is it Lethal?

•

It is imperative to rule out bipolar affective disorder before initiating treatment with an antidepressant medication.

•

Many patients and families are reluctant to accept the diagnosis of depression because of associated stigma.

•

A two-question screener is as effective as longer screening instruments. A positive answer to one of the following two questions should lead to a full diagnostic assessment for depression. 1.

Over the past 2 weeks have you ever felt down, depressed, or hopeless?

2.

Over the past 2 weeks, have you felt little interest or pleasure in doing things?

EVIDENCE

SSRIs are as effective as tricyclic antidepressants (TCAs) in the treatment of depression, and are better tolerated by patients. Three systematic reviews compared SSRIs with TCAs and found no significant difference in efficacy overall. SSRIs appear to be slightly more acceptable, based on the number of patients who withdrew from clinical trials. [29] [30] [31] One of the systematic reviews above was also conducted in a primary care setting, and found average response rates of 63% for newer agents, 35% for placebo, and 60% for TCAs.[[4]] St. John's wort (Hypericum perforatum) Two systematic reviews examined the effectiveness of St. John's wort (Hypericum perforatum) in the treatment of depression and found similar results. St. John's wort was more effective than placebo for the short-term treatment of mild to moderate depression, and there was no significant difference between St. John's wort and other antidepressants. [33] [34] Cognitive-behavioral therapy (CBT) Four systematic reviews have found that cognitive therapy is effective in treating mild to moderate depression. [35] [36] [37] [38] One of these reviews also found limited evidence that cognitive therapy may result in fewer people with mild to moderate depression relapsing after treatment, compared with antidepressants or antidepressants plus cognitive therapy.[[7]] Electroconvulsive therapy (ECT) Severe and medication-resistant depression may be most effectively treated with electroconvulsive therapy (ECT). A systematic review of ECT in younger and older adults with moderate to severe depression found that real ECT was more effective than simulated ECT, and that ECT was more effective than antidepressant medication for the short-term treatment of depression.[[11]]

Evidence-Based References 1. Geddes JR, et al: Selective serotonin reuptake inhibitors (SSRIs) versus other antidepressants for depression. Cochrane Database Syst Rev 1999; 4: 2. Anderson IM: Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 2000; 58:19.Reviewed in: Clin Evid 13:1238, 2005. 3. Williams JW, et al: A systematic review of newer pharmacotherapies for depression in adults: evidence report summary: clinical guidelines, part 2. Ann Intern Med 2000; 132:743.Reviewed in: Clin Evid 13:1238, 2005. 4. Mulrow CD, et al: Efficacy of newer medications for treating depression in primary care patients. Am Med J 2000; 108:54.Reviewed in: Clin Evid 13:1238, 2005. 5. Linde K, Mulrow CD: St. John's wort for depression. Cochrane Database Syst Rev 1998; 4: 6. Whiskey A, et al: A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review. Int Clin Psychopharmacol 2001; 16:239.Reviewed in: Clin Evid 13:1238, 2005. 7. Gloaguen V, et al: A meta-analysis of the effects of cognitive therapy in depressed patients. J Affect Disord 1998; 49:59.Reviewed in: Clin Evid 13:1238, 2005. 8. Cascalenda N, et al: Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions. Am J Psychiatry 2002; 159:1354.Reviewed in: Clin Evid 13:1238, 2005. 9. Churchill R, et al: A systematic review of controlled trials of the effectiveness and cost-effectiveness of brief psychological treatments for depression. Health Technol Assess 2001; 5:1.Reviewed in: Clin Evid 13:1238, 2005. 10. van Schaik DJ, et al: Effectiveness of psychotherapy for depression in primary care: a systematic review. Tijdschrift voor Psychiatrie 2002; 44:609.Reviewed in: Clin Evid 13:1238, 2005. 11. UK ECT Review Group: Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361:799.Reviewed in: Clin Evid 13:1238, 2005.

SUGGESTED READINGS Feldman MD, et al: Let's not talk about it: suicide inquiry in primary care. Ann Fam Medicine 2007; 5(5):412. Cole S, et al: Depression. In: Feldman MD, Christensen JF, ed. Behavioral medicine: a guide for clinical practice, ed 3. New York: Lange Medical Books/McGraw-Hill; 2008. Trivedi MD, et al: Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006; 354:1243.

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De Quervain's Tenosynovitis PETER PETROPOULOS, M.D.

BASIC INFORMATION DEFINITION

De Quervain's tenosynovitis refers to a stenosing inflammatory process of the first dorsal retinacular compartment containing the tendons of the abductor pollicis longus (APL) and extensor pollicis brevis (EPB). SYNONYMS

Stenosing tenosynovitis of the radial styloid process Stenosing tenovaginitis of the first dorsal compartment

ICD-9CM CODES

727.04 Tenosynovitis radial styloid EPIDEMIOLOGY & DEMOGRAPHICS

•

More common in women than in men (10:1)

•

Usually occurs between the ages of 30 to 50

•

Associated with rheumatoid arthritis

•

Seen in occupations (e.g., clerical, assembly, and manual labor)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pain over the styloid process of the radius

•

Swelling

•

Positive Finkelstein's test ( Fig. 1-70 )

•

Crepitance

FIGURE 1-70 Finkelstein's test is positive in de Quervain's stenosing synovitis. Ulnar flexion of the wrist produces pain over the dorsal compartment containing the extensor policis brevis and abductor pollicis longus. (From Noble J [ed]: Textbook of primary care medicine, ed 2, St Louis, 1996, Mosby.)

ETIOLOGY

•

The cause is usually repetitive use or overuse of the hands (e.g., typing, writing, nailing, etc.).

•

Acute trauma can also cause tenosynovitis of the radial styloid.

DIAGNOSIS

•

•

The diagnosis of de Quervain's tenosynovitis is based on the clinical triad of: 1.

Tenderness over the radial styloid

2.

Swelling over the first dorsal retinacular compartment

3.

Positive Finkelstein's test (see Fig. 1-70 )

Sometimes 1.5 ml of 1% Xylocaine can be injected into the tenosynovial sac, and if all three physical signs resolve, the diagnosis is confirmed.

DIFFERENTIAL DIAGNOSIS

•

Carpal tunnel syndrome

•

Arithritis (e.g., degenerative osteoar-thritis or rheumatoid arthritis)

•

Gout

•

Infiltrative tenosynovitis

•

Radiculopathy

•

Compression neuropathy (e.g., superficial branch of the radial nerve “bracelet syndrome”)

•

Infection (e.g., tuberculosis, bacterial)

LABORATORY TESTS

•

Erythrocyte sedimentation rate (ESR) is usually normal in patients with de Quervain's tenosynovitis

•

Aspiration to rule out gout

•

Gram stain and culture of aspirate

IMAGING STUDIES

•

X-ray studies of the hand

TREATMENT NONPHARMACOLOGIC THERAPY

•

Rest

•

Splinting

•

Physiotherapy

ACUTE GENERAL Rx

•

Corticosteroid injection using 20 to 40 mg triamcinolone acetonide and 1% Xylocaine is effective in relieving pain.

•

NSAIDs ibuprofen 800 mg tid or naproxen 500 mg bid.

CHRONIC Rx

Surgical release is generally reserved for patients not responding to NSAIDs and corticosteroid injection therapy.

DISPOSITION

•

Approximately 90% of patients have relief of symptoms with either single or multiple steroid injections.

•

Surgical control of symptoms occurs in 90% of cases.

•

Complications of surgery include: 1.

Radial nerve damage

2.

Paresthesia (~10%)

3.

Neuroma

REFERRAL

Rheumatologist or orthopedist

PEARLS & CONSIDERATIONS

•

Pain relief is usually noted within 48 hr with patient becoming asymptomatic by the first or second wk after corticosteroid injection.

•

If there is no improvement by 6 wk post second corticosteroid injection, referral to an orthopedic hand surgeon is recommended.

•

Avoid repetitive activities.

SUGGESTED READINGS Chin DH, Jones NF: Repetitive motion hand disorder. J Calif Dent Assoc 2002; 30(2):149. Jirarttanphochai K, et al: Treatment of de Quervain disease with triamcinolone injection with or without nimesulide. A randomized, double-blind, placebo-controlled trial. J. Bone Joint Surg Am 2004; 86-A:2700. Richie CA, Briner Jr WW: Corticosteroid injection for treatment of de Quervain's tenosynovitis: a pooled quantitative literature evaluation. J Am Board Fam Pract 2003; 16:102.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Dermatitis Herpetiformis IRIS L. TONG, M.D.

BASIC INFORMATION DEFINITION

Dermatitis herpetiformis (DH) is a rare, chronic skin disorder characterized by an intensely burning, pruritic, vesicular rash. It is strongly associated with gluten-sensitive enteropathy. Twenty to seventy percent of patients with DH will have gastrointestinal symptoms, whereas approximately 10% of patients with celiac sprue will have DH. SYNONYMS

None

ICD-9CM CODES

694.0 Dermatitis herpetiformis EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 11.2 cases/100,000 persons in the U.S. The prevalence for celiac disease is 1 in 133 adults in the U.S. PREDOMINANT SEX: Slight male predominance PREDOMINANT AGE: Third and fourth decades PREDOMINANT RACE: Rarely seen in blacks/African Americans or Asians GENETICS: A specific HLA type, DQ2, is present in 90% of patients with celiac disease with or without DH. DQ8 is present in the remaining 10%. DQ2 is present in 16%-18% of the normal population. 11% of patients with DH have a first-degree relative with either DH or celiac disease. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pruritic, burning vesicles initially, frequently grouped (hence the name “herpetiform”) ( Fig. 1-71 )

•

Symmetrically distributed on extensor surfaces: elbows, knees, scalp, nuchal area, shoulder, and buttocks; rarely found in mouth

•

May evolve in time to intensely burning urticarial papules, vesicles, and rarely bullae

•

Celiac-type permanent-tooth enamel defects found in 53% of patients

FIGURE 1-71 Dermatitis herpetiformis is an immunologically mediated blistering disease. There is a strong association of dermatitis herpetiformis with HLA-B8, DR3. Gluten-sensitive enteropathy is a common associated finding. The lesions are grouped (herpetiform) and extremely pruritic. (From Callen JP [ed]: Color atlas of dermatology, ed 2, Philadelphia, 2000, WB Saunders.)

DIAGNOSIS Diagnosis is confirmed histologically by the demonstration of IgA deposits found along the subepidermal basement membrane, in the dermal papillary tips, which is specific to the diagnosis of DH. DIFFERENTIAL DIAGNOSIS

•

Linear IgA bullous dermatosis (not associated with gluten-sensitive enteropathy)

•

Herpes simplex infection

•

Herpes zoster infection

•

Bullous erythema multiforme

•

Bullous pemphigoid

WORKUP

History of chronic diarrhea and pruritic, vesicular rash highly suggestive of diagnosis LABORATORY TESTS

•

Skin biopsy for immunofluorescence studies. Diagnosis is confirmed by IgA deposits along the subepidermal basement membrane. >90% will have granular or fibrillar IgA deposits in the dermal papillae. Multiple specimens may be needed to obtain positive findings because of the focal nature of deposits. Biopsies are taken from adjacent normal skin because the diagnostic Ig deposits are usually destroyed by the blistering process.

•

Circulating antibody levels 1.

IgA antiendomysial antibody is found a.

In 70% of patients with rash and who are not on gluten-free diet and

b.

In 100% of patients with rash and grade 3 to 4 flattening of intestinal mucosa or with untreated celiac disease. Levels decrease to 0% when gluten is avoided for 3 mo.

2.

IgA antigliadin antibodies: found in 66% of patients with DH; also present in patients with pemphigus and pemphigoid

3.

IgA reticulin antibody: found in 36% of patients with DH

4.

IgA antitissue transglutaminase: elevated levels in 75% patients with DH and in 90% to 100% of patients with celiac disease

TREATMENT

•

Spontaneous remission of DH in patients on a normal diet has been described in 10% to 15% of cases.

•

Adherence to a gluten-free diet has been associated with sustained remission of DH.

•

Patients may be given a trial of pharmacologic therapy if they are extremely uncomfortable. Symptoms are often dramatically relieved within hours or days of initiation of medical therapy.

NONPHARMACOLOGIC THERAPY

•

Gluten-free diet: for at least 6 mo, which will allow most patients to begin to decrease or discontinue sulfone therapy (see “Acute General Rx”). The diet usually needs to be followed for 2 yr before medications can be discontinued. Although intestinal villous architecture improves, symptoms and lesions recur in 1 to 3 wk if a normal diet is resumed. Most patients need to follow diet indefinitely. Gluten is found in all grains, such as wheat, barley, rye, and oats, except rice and corn.

•

A recent small study demonstrated that a gluten-free diet alone was comparable to a gluten-free diet plus dapsone in the treatment of DH.

•

Elemental diet: Other dietary factors may also be important in dermatitis herpetiformis. Antigens stimulate the production of antibodies, leading to the formation of immune complexes. Most antigens that elicit a humoral immune response are proteins. Thus, a diet without full proteins, an elemental diet, is not likely to contain major antigens. A diet of amino acids, fat, and carbohydrates can produce a rapid benefit and allow a decrease in the dosage of dapsone within 2 wk.

ACUTE GENERAL Rx

•

•

•

•

Dapsone: •

Initial dose of 100 to 150 mg po qd. Itching and burning are controlled in 12 to 48 hr and new lesions stop appearing.

•

Adjust dose to the lowest level that provides adequate relief, which can range from 25 to 400 mg/day.

•

Peripheral motor neuropathy, such as paresthesias and weakness of the distal upper and lower extremities and footdrop, can occur in the first few months of therapy. Symptoms slowly improve over months to years after dapsone is discontinued.

•

Hemolysis, anemia, and methemoglobinemia occur to some degree in all patients receiving dapsone therapy. Patients at risk for having G6PD should have levels drawn before initiation as dapsone may cause severe hemolytic anemia in these patients.

•

Probenecid blocks the renal excretion of dapsone, and rifampin increases the rate of its clearance.

Sulfapyridine: •

Initial dosage 500 to 1500 mg/day.

•

Sulfapyridine is associated with agranulocytosis and aplastic anemia. It also may cause severe hemolysis in patients with G6PD.

Sulfasalazine: •

500 to 1000 mg bid.

•

Sulfasalazine is metabolized to sulfapyridine and has been demonstrated to be effective in patients who are unable to tolerate dapsone in case reports.

Tetracycline: •

•

Successful treatment has been reported with tetracycline 500 mg po qd-tid and minocycline 100 mg po bid. Cessation resulted in a flare of the rash.

Nicotinamide: •

Successful treatment has been reported with nicotinamide 500 mg po bid-tid. Cessation resulted in a flare of the rash.

•

Topical steroids: may help but can cause skin irritation and atrophy with prolonged use.

•

Nonsteroidal anti-inflammatory drugs and iodide can worsen skin inflammation.

CHRONIC Rx

Gluten-free diet

DISPOSITION

•

DH is considered to represent an intolerance to gluten, which requires lifelong avoidance of gluten.

•

Some patients may be able to reintroduce gluten into their diet without experiencing a recurrence of DH. •

A study of 38 patients demonstrated that 7 (18%) could resume a normal diet without relapse of cutaneous or gastrointestinal symptoms.

•

Patients who did not relapse after resumption of a normal diet were all diagnosed in childhood, had poor adherence to a gluten-free diet, and were more likely to have been treated with dapsone.

•

There is an increased incidence of other autoimmune disorders, including thyroid disease, type 1 diabetes mellitus, systemic lupus erythematosus, vitiligo, and Sjögren's syndrome in patients with DH.

•

Small bowel lymphoma and nonintestinal lymphoma have been reported in patients with DH and celiac disease. Patients adhering strictly to a gluten-free diet can reduce their risk of gut-related lymphomas within 5 years to that of the baseline population.

REFERRAL

To dermatologist for skin biopsy and to nutritionist to educate patients about gluten-free diet

PEARLS & CONSIDERATIONS

•

Treatment with a gluten-free diet alone was found comparable to dapsone plus a gluten-free diet in a recent small study.

•

Maintaining a gluten-free diet has been demonstrated to have a protective effect against the development of lymphoma in patients with celiac disease.

SUGGESTED READINGS Bardella MT, et al: Long-term remission in patients with dermatitis herpetiformis on a normal diet. Br J Dermatol 2003; 149:968-971. Dieterich W, et al: Antibodies to tissue transglutaminase as serologic markers in patients with dermatitis herpetiformis. J Invest Dermatol 1999; 113(1):133. Eedy DJ, et al: Updates from the British Association of Dermatologists 84th Annual Meeting. Br J Dermatol 2005; 152:13-28. Nino M, et al: A long-term gluten-free diet as an alternative treatment in severe forms of dermatitis herpetiformis. J Dermatolog Treat 2007; 13:10-12. Turchin I, Barankin B: Dermatitis herpetiformi and gluten-free diet. Dermotol Online J 2005; 11(1):6. Willsteed E, et al: Sulfasalazine and dermatitis herpetiformis. Australas J Dermatol 2005; 26(2):101. Zone JJ, et al: Warning: bread may be harmful to your health. J Am Acad Dermatol 2004; 51(suppl 1):S27.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Diabetes Insipidus FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Diabetes insipidus is a polyuric disorder resulting from insufficient production of antidiuretic hormone (ADH) (pituitary [neurogenic] diabetes insipidus) or unresponsiveness of the renal tubules to ADH (nephrogenic diabetes insipidus).

ICD-9CM CODES

253.5 Diabetes insipidus EPIDEMIOLOGY & DEMOGRAPHICS

GENETICS: •

Nephrogenic diabetes insipidus can be inherited as sex-linked recessive.

•

There is also a rare autosomal dominant form of neurogenic diabetes insipidus.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Polyuria: urinary volumes ranging from 2.5 to 6 L/day

•

Polydipsia (predilection for cold or iced drinks)

•

Neurologic manifestations (seizures, headaches, visual field defects)

•

Evidence of volume contractions

NOTE: The previous physical findings and clinical manifestations are generally not evident until vasopressin secretory capacity is reduced 295 or the patient loses =3.5% of initial body weight.

4.

Diabetes insipidus is confirmed if the plasma osmolarity is >295 and the urine osmolarity is 50%) in urine osmolarity following administration of ADH is indicative of neurogenic diabetes insipidus.

A diagnostic algorithm for diabetes insipidus is described in Section III.

LABORATORY TESTS

•

Decreased urinary specific gravity (=1.005)

•

Decreased urinary osmolarity (usually 200 mg/dl and the hemoglobin Alc level is=2 standard deviations above the laboratory mean.

•

Screening for diabetic nephropathy by measuring microalbuminuria is recommended in all patients with diabetes. It can be accomplished by any of the following three methods: 1.

Measurement of the albumin-to-creatinine ratio in random spot urine collection. This is the easiest method to administer in the office setting because it is an easy assay to perform in most laboratories. To perform this test, the physician simply orders “Urine for microalbumin level.”

2.

Measurement of a 24-hr urine collection for albumin, creatinine clearance.

3.

Timed (4-hr or overnight) urine collection.

•

The diagnosis of microalbuminuria should be based on 2 to 3 elevated levels within a 3- to 6-month period because there is a marked variability in day-to-day albumin excretion and possible transient elevations in urine albumin from short-term hyperglycemia, exercise, severe hypertension, and other illnesses such as sepsis and CHF. Patients with overt nephropathy do not need screening for microalbuminuria because the level of protein in the urine is high enough to be detected on routine urinalysis.

•

A fasting serum lipid panel, serum creatinine, and electrolytes should be obtained yearly on all adult diabetic patients.

TREATMENT NONPHARMACOLOGIC THERAPY

1.

Diet a.

Calories (1) The diabetic patient can be started on 15 calories/lb of ideal body weight; this number can be increased to 20 calories/lb for an active person and 25 calories/lb if the patient does heavy physical labor. (2) The calories should be distributed as 50% to 60% carbohydrates, 1%)

Hemodialysis and hemoperfusion: not useful because of extensive tissue binding and large volume of distribution.

COMPLICATIONS: Hyperkalemia: •

Sodium bicarbonate.

•

Glucose and insulin.

•

Sodium polystyrene sulfonate (Kayexalate).

•

Do not use calcium because it may worsen ventricular arrhythmias.

Bradycardia and heart block: •

Atropine.

•

Temporary pacemaker if symptomatic.

Supraventricular and ventricular tachycardia: •

Lidocaine or phenytoin: decrease ventricular automaticity without slowing AV node conduction.

•

Avoid quinidine, bretylium, procainamide, and verapamil; may increase ventricular arrhythmias/AV node block.

•

Elective cardioversion is relatively contraindicated, because it may precipitate ventricular fibrillation.

DISPOSITION

•

Good with prompt treatment.

•

Chronic poisoning is associated with higher mortality than acute poisoning.

REFERRAL

Poison control

PEARLS & CONSIDERATIONS

•

High index of suspicion helpful, often the signs and symptoms of toxicity are similar to those of the underlying disease.

•

To minimize toxicity, digoxin levels should be checked if there is a change in patient's condition (e.g., weight loss, worsening renal function) or an interacting drug is started or stopped.

•

Hyperkalemia in acute toxicity is suggestive of significant poisoning (reflects the amount of poisoning of the Na+-K+ ATPase) and is associated with increased mortality.

•

Falsely elevated digoxin levels may be seen in pregnant women, renal failure, hepatobiliary disease, and CHF due to the presence of an endogenous digoxin-like substance.

•

Severe toxicity from ingestion of nondigoxin cardiac glycosides (plants, etc.) may present with only mildly elevated digoxin levels due to low cross-reactivity between these substances and the digoxin assay.

SUGGESTED READINGS Antman EM, et al: Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study. Circulation 1990; 81:1744. Bauman JL, et al: Mechanisms, manifestations, and management of digoxin toxicity in the modern era. Am J Cardiovasc Drugs 2006; 6(2):77.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Diphtheria STEVEN M. OPAL, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Diphtheria is an infection of the mucous membranes or skin caused by Corynebacterium diphtheriae. SYNONYMS

Pharyngeal diphtheria Wound diphtheria Diphtheric cardiomyopathy Diphtheric polyneuropathy

ICD-9CM CODES

032.9 Diphtheria EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Fewer than 5 cases/yr since 1980 (20 yr of age are susceptible to diphtheria.

EVIDENCE

Antiserum has been used for the treatment of diphtheria for over 100 years and has stood the test of time as an effective treatment strategy. It was tested in one of the first controlled trials in clinical medicine.[[1]]

Evidence-Based References 1. Fibiger JA: Om Serumbehandling af Difteri. Hospitalstidende 1898; 6:309.Reviewed in: The controlled clinical trial turns 100 years: Fibiger's trial of serum treatment of diphtheria, BMJ 317:1243, 1998.

SUGGESTED READINGS Berrington J, Fenton A: Immunization responses in preterm infants who receive postnatal steroid treatment. Pediatrics 2004; 114(4):1127. Bissumbhar B, et al: Evaluation of diphtheria convalescent patients to serve as donors for the production of anti-diphtheria immunoglobulin preparations. Vaccine 2004; 22(15–16):1886. Broder KR, et al: Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006; 55(RR-3):1.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Discoid Lupus MOHAMMAD HAJJIRI, M.D.

BASIC INFORMATION DEFINITION

Discoid lupus erythematosus (DLE) refers to a chronic inflammatory autoimmune skin disorder. It is sometimes associated with systemic lupus erythematosus (SLE). SYNONYMS

Chronic cutaneous lupus erythematosus

ICD-9CM CODES

695.4 Lupus erythematosus (local discoid) EPIDEMIOLOGY & DEMOGRAPHICS

•

More common in African Americans.

•

More common in females, with peak incidence in the fourth decade of life.

•

Approximately 10% to 20% of patients with SLE will also have discoid lupus skin lesions.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Appearance of single or multiple asymptomatic plaque lesions ( Fig. 1-76 ).

•

Anatomic distribution: commonly involves the scalp, face, and ears, but is not limited to these areas.

•

Lesion configuration: irregularly grouped.

•

Lesion morphology:

•

•

Plaque lesions with scales

•

Follicular plugging

•

Atrophy

•

Scarring

•

Telangiectasia

Color: •

Erythematous

•

Red to violaceous

•

Hyperpigmentation or hypopigmentation

•

Alopecia can occur and is permanent.

•

Urticaria (5%).

•

May be associated with other criteria for SLE (e.g., oral ulcers, arthritis, pleuritis, pericarditis).

FIGURE 1-76 Scaling plaques with thick scales on the ear and face of a patient who has discoid lupus. (Courtesy Department of Dermatology, University of North Carolina at Chapel Hill. In Goldstein BG, Goldstein AO [eds]: Practical dermatology, ed 2, St Louis, 1977, Mosby.)

ETIOLOGY

Immune complex mediated

DIAGNOSIS Clinical inspection and skin biopsy establish the diagnosis of DLE. DIFFERENTIAL DIAGNOSIS

Psoriasis, lichen planus, secondary syphilis, superficial fungal infections, photosensitivity eruption, sarcoidosis, subacute cutaneous lupus erythematosus, rosacea, keratoacanthoma, actinic keratosis, dermatomyositis LABORATORY TESTS

•

CBC is usually normal in isolated DLE.

•

BUN/creatinine is normal.

•

Erythrocyte sedimentation rate (ESR) is elevated in active disease.

•

Urinalysis.

•

Antinuclear antibody (ANA) positive in 20% of patients with isolated DLE.

•

Anti-Ro (SS-A) autoantibodies are present in 1% to 3% of patients.

•

dsDNA and antiSm antibodies are rarely present.

•

Complement levels may be low in patients with SLE but not in DLE.

•

Skin biopsy.

IMAGING STUDIES

Chest x-ray examination is not specific.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoid sun exposure.

•

Use sun protective factor (SPF) of at least 15.

ACUTE GENERAL Rx

1.

Topical steroids: intermediate rather than high potency, steroids should be used on areas such as the face.

2.

Intradermal steroids: Triamcinolone acetonide, 3 mg/ml with 1% Xylocaine.

3.

Hydroxychloroquine 400 mg PO qd for 1 mo, then decrease the dose to 200 mg qd.

Treatment is continued for 3 to 6 mo. CHRONIC Rx

•

Dapsone: 100 mg/day can be used in patients who fail to respond to topical steroid or hydroxychloroquine.

•

Other alternatives include: 1.

Chloroquine 250 to 500 mg PO qd

2.

Auranofin 6 mg/day PO qd or divided bid; after 3 mo, may increase to 9 mg/day divided tid

3.

Thalidomide 100 to 300 mg PO before sleep, with water, and 30% of people >40 yr and >50% of people >70 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination in patients with diverticulosis is generally normal.

•

Painful diverticular disease can present with LLQ pain, often relieved by defecation; location of pain may be anywhere in the lower abdomen because of the redundancy of the sigmoid colon.

•

Diverticulitis can cause muscle spasm, guarding, and rebound tenderness predominantly affecting the LLQ.

ETIOLOGY

Diverticular disease is believed to be secondary to low intake of dietary fiber.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Irritable bowel syndrome

•

IBD

•

Carcinoma of colon

•

Endometriosis

•

Ischemic colitis

•

Infections (pseudomembranous colitis, appendicitis, pyelonephritis, PID)

•

Lactose intolerance

LABORATORY TESTS

•

WBC count in diverticulitis reveals leukocytosis with left shift.

•

Microcytic anemia can be present in patients with chronic bleeding from diverticular disease. MCV may be elevated in acute bleeding secondary to reticulocytosis.

IMAGING STUDIES

•

Barium enema should only be considered in patients unwilling to undergo colonoscopy or with contraindications to the procedure. When perforated, barium enema will demonstrate multiple diverticula and muscle spasm (“sawtooth” appearance of the lumen) in patients with painful diverticular disease. Barium enema can be hazardous and should not be performed in the acute stage of diverticulitis because it may produce free perforation.

•

A CT scan of the abdomen can be used to diagnose acute diverticulitis; typical findings are thickening of the bowel wall, fistulas, or abscess formation.

•

Evaluation of suspected diverticular bleeding: 1.

Arteriography if the bleeding is faster than 1 ml/min (advantage: the possible infusion of vasopressin directly into the arteries supplying the bleeding, as well as selective arterial embolization; disadvantages: its cost and invasive nature)

2.

Technetium-99m sulfa colloid

3.

Technetium-99m labeled RBC (can detect bleeding rates as low as 0.12 to 5 ml/min)

TREATMENT

NONPHARMACOLOGIC THERAPY

•

Increase in dietary fiber intake and regular exercise to improve bowel function

•

NPO and IV hydration in severe diverticulitis; NG suction if ileus or small bowel obstruction is present

ACUTE GENERAL Rx

TREATMENT OF DIVERTICULITIS: •

Mild case: broad-spectrum PO antibiotics (e.g., Ciprofloxacin 500 mg bid to cover aerobic component of colonic flora and metronidazole 500 mg q6h for anaerobes) and liquid diet for 7 to 10 days

•

Severe case: NPO and aggressive IV antibiotic therapy a.

Ampicillin-sulbactam (Unasyn) 3 g IV q6h or

b.

Piperacillin-tazobactam (Zosyn) 4.5 g IV q8h or

c.

Ciprofloxacin 400 mg IV q12h plus metronidazole 500 mg IV q6h or

d.

Cefoxitin 2 g IV q8h plus metronidazole 500 mg IV q6h

•

Life-threatening case: Imipenem 500 mg IV q6h or meropenem 1 g IV q8h

•

Surgical treatment consisting of resection of involved areas and reanastomosis (if feasible); otherwise a diverting colostomy with reanastomosis performed when infection has been controlled; surgery should be considered in patients with: 1.

Repeated episodes of diverticulitis (two or more)

2.

Poor response to appropriate medical therapy (failure of conservative management)

3.

Abscess or fistula formation

4.

Obstruction

5.

Peritonitis

6.

Immunocompromised patients, first episode in young patient (12 beats/min and a rise in hydrogen breath excretion had a sensitivity of 94% and specificity >92%. A nadir blood glucose 2 yr after menarche, physical examination may reveal uterine irregularity, cul-de-sac tenderness, or nodularity or pelvic masses

LABORATORY TESTS

•

No specific tests diagnostic for dysmenorrhea

•

Elevated WBC count in the presence of infection

•

hCG to rule out ectopic pregnancy

IMAGING STUDIES

•

Ultrasound scan of the pelvis to evaluate the presence of leiomyomas, ovarian cysts, or ectopic pregnancy

•

Hysterosalpingogram or saline ultrasonography to assess the uterine cavity to rule out endometrial polyps, submucosal or intraluminal leiomyomas

TREATMENT NONPHARMACOLOGIC THERAPY

•

Applying heat to the lower abdomen with hot compresses, heating pads, or hot water bottles seems to offer some relief.

•

Other reassurance that this is a treatable condition.

ACUTE GENERAL Rx

•

Nonsteroidal anti-inflammatory drugs such as ibuprofen 400 to 600 mg q4 to 6h or naproxen sodium 550 mg q12h, mefenamic acid 500 mg initial dose followed by 250 mg q6h prn, aspirin 650 mg q4 to 6h, or oral contraceptives

•

Nifedipine 30 mg qd in difficult cases of dysmenorrhea

•

Magnesium supplements have been found likely to be beneficial

•

Thiamine supplements may reduce pain

•

Secondary dysmenorrhea: treatment directed to the specific underlying condition; surgery plays a greater role

CHRONIC Rx

Acupuncture and transcutaneous electrical nerve stimulation (TENS) may be tried. In cases in which medical therapy has not worked, laparoscopy should be considered, as well as other surgical treatments depending on the secondary cause of the dysmenorrhea. DISPOSITION

The majority of patients are satisfactorily treated with good outcomes. Possible chronic complications with primary dysmenorrhea that has not been adequately treated can lead to anxiety and depression. With certain causes of secondary dysmenorrhea infertility can become a problem. REFERRAL

If a secondary cause of dysmenorrhea is revealed, refer to the appropriate specialist for further medical or surgical treatment (e.g., gynecologist, pain management center).

EVIDENCE

Nonsteroidal anti-inflammatory drugs are significantly more effective than placebo in providing pain relief in patients with primary dysmenorrhea.[[1]] A systematic review found that high-frequency transcutaneous electrical nerve stimulation (TENS) was more effective than placebo for the treatment of dysmenorrhea.[[2]] Limited evidence has shown that acupuncture is significantly more effective than placebo in the management of women with primary dysmenorrhea.[[3]]

Evidence-Based References 1. Marjoribanks J, Proctor ML, Farquhar C: Nonsteroidal anti-inflammatory drugs for primary dysmenorrhea. Cochrane Database Syst Rev 2003; 4: 2. Proctor ML, et al: Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhea. Cochrane Database Syst Rev 2002; 1: 3. Helms JM: Acupuncture for the management of primary dysmenorrhea. Obstet Gynecol 1987; 69:51.Reviewed in: Clin Evid 12, 2004.

AUTHORS: GEORGE T. DANAKAS, M.D., and RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Persistent and/or recurrent sexual intercourse associated pain SYNONYMS

Painful intercourse

ICD-9CM CODES

625.0

Pain associated with female genital organs

302.76 Sexual deviations and disorders with functional dyspareunia, psychogenic dyspareunia EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 7% to 60% depending on definition PREDOMINANT SEX: Female

AT-RISK POPULATION: No consistent findings regarding: •

Age

•

Parity

•

Educational status

•

Race

•

Income

•

Marital status

RISK FACTORS: Lower: •

Frequency of intercourse

•

Levels of desire and arousal

•

Orgasmic response

•

Physical and emotional satisfaction

•

General happiness

HISTORICAL FACTORS: •

•

Pain parameters 1.

Character

2.

Location (Introital/middle/deep)

3.

Onset

4.

Duration

5.

Timing

6.

Chronicity

7.

Cyclicity

8.

Recurrence

Gynecologic history

1.

History of STD

2.

History of HSV or HPV

3.

Other sexual dysfunctions

4.

Prior abdominal or gynecologic surgery

5.

Prior pelvic or abdominal radiation

6.

History of endometriosis, fibroids

7.

History of genital/uterine prolapse

8.

History of gynecologic infection

9.

History of pelvic pain

10. History of menopausal symptoms 11. Sexual misinformation •

•

OB history 1.

Lacerations

2.

Episiotomy

General medical causes 1.

History of chronic diseases

2.

GI or GU symptoms

3.

Medications

4.

History of psychological disorders

5.

History of dermatologic condition

6.

Religious beliefs

7.

Generalized anxiety

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Primary vs. secondary dyspareunia 1.

•

•

Latter with history of pain-free coitus

Visual inspection 1.

Discoloration

2.

Ulcerations

3.

Discharge

4.

Prolapse

5.

Dysplastic changes

6.

Infestations

Physical examination

1.

Sensitivity to light touch

2.

Tenderness to palpation

3.

Genital prolapse a.

Uterus

b.

Bladder

c.

Cervix

d.

Vagina

e.

Adnexa

f.

Rectum

g.

Bowel

4.

Ridges/septum

5.

Levator muscle tone

6.

Evidence of previous surgery

7.

Vaginal length/depth/caliber constrictions

ETIOLOGY

•

Pathology or alteration/reduction of genital-associated tissue

•

Psychosocial factors

•

Marital/relationship discord

•

History of sexual abuse

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

(Not an exhaustive list)

•

Congenital deformities (septa/agenesis)

•

Imperforate hymen

•

Menopausal changes

•

Atrophic tissue

•

Impaired lubrication

•

Psychogenic

•

Vaginismus

•

Inadequate foreplay

•

Endometriosis

•

Levator ani myalgia

•

Chronic pelvic pain

•

•

Previous surgery (posterior colporrhaphy/perineorrhaphy) 1.

Alteration in vaginal length/depth/caliber

2.

Adhesions

Infectious 1.

Human papilloma

2.

Herpes simplex

3.

Candidiasis

4.

Tinea cruris

5.

Acute/chronic salpingitis/endometritis

•

Pelvic carcinoma

•

Previous radiation

•

Adnexal attachment or tubal prolapse

•

Pelvic tumor

•

Uterine prolapse/malpositions/enlargement/retroversion

•

Genital prolapse

•

Cystocele/rectocele/enterocele

•

Urethral/bladder pathology

•

Pelvic congestion

•

Vulvar vestibulitis

•

Postcoital cystitis

•

Broad ligament pathology

•

Neuroma at the site of previous episiotomy

•

Previous sexual abuse

•

Vulvodynia

•

Contact or allergic dermatitis

•

Vitamin A, B, or C deficiency

•

Equestrian dyspareunia

•

Interstitial cystitis

•

Pudendal neuralgia

•

Myofascial pain syndrome

•

Rectal pathology

•

Structural abnormalities/alterations

WORKUP

1.

Muscle

2.

Bone

3.

Ligament

•

History and physical examination are key

•

If needed 1.

Colposcopy

2.

Cystoscopy

3.

Consider laparoscopy for unexplained deep dyspareunia

LABORATORY TESTS

•

ESR

•

WBC

•

Wet mount

•

Cultures 1.

Cervical a.

Gonorrhea

b.

Chlamydia

2.

Vaginal

3.

Lesions

4.

Urine

•

Vulva/vaginal/cervical biopsy

•

Pap smear

•

Herpes simplex virus antibodies

•

Gonadotropin levels

IMAGING STUDIES

Pelvic/abdominal ultrasonography

TREATMENT NONPHARMACOLOGIC THERAPY

•

Patient education

•

Discontinue exacerbating activity and irritants

•

Lubrication with coitus

•

Coital position changes: female superior position

•

Warm or cool soaks

•

Reassurance to patient of nonmalignant condition

•

Psychosocial interventions 1.

Systemic desensitization techniques

2.

Behavior modification

•

Vaginal dilators

•

Vaginal muscle exercises and relaxation techniques

•

Excision of pathologic tissue

•

Surgical correction of altered/reduced/deformed tissues

ACUTE GENERAL Rx

•

Topical lidocaine

•

Corticosteroids

•

Antiinfective agents

•

Trigger point injections

•

Massage

•

Acupuncture

•

TENS

•

Stress reduction techniques

•

Safe sexual practices

•

Hormonal replacement therapy

•

Antiviral agents

•

Intralesional interferon

•

Mild analgesics

•

Antidepressants

CHRONIC Rx

All the previous plus: •

Set supportive visits, as needed

•

Oral contraceptives

•

Regular sexual activity

•

Balanced diet

•

Vitamin supplementation

•

Proper hygiene

DISPOSITION

Most patients will have a reduction and/or resolution of their symptoms by using the appropriate therapeutic approaches. REFERRAL

A multidisciplinary approach using the expertise of psychologists, dermatologists, gynecologic surgeons, infectious disease specialists, or urologists is helpful.

PEARLS & CONSIDERATIONS

•

Dyspareunia is a symptom complex resulting from a multitude of etiologies, some of which are acting simultaneously.

•

Uncovering the etiology of dyspareunia is predominately based on a comprehensive history and physical examination.

•

The differential diagnoses can be sorted into superficial, intermediate, and deep dyspareunia categories.

•

As with the physical evaluation of any painful condition, attempt, by precise touching (moistened cotton swab), palpation, or applied pressure, to reproduce the patient's chief complaint.

•

Performing a one-finger pelvic exam, without concurrent abdominal palpation, allows for a more precise assessment of the source of genital pain.

•

Individualize therapy.

•

Initiate and maintain an honest diagnosis and compassionate demeanor with the patient and her mate.

•

Be open-minded, approachable, nonjudgmental, and diligent in your search for a solution to help these often silently suffering patients.

EVIDENCE

We are unable to cite evidence that meets our criteria for most of the recommended therapies. Although the management recommendations are not evidence-based, they have been found to be successful clinically. A Cochrane systematic review found that perineal repair with synthetic absorbable suture material vs catgut following childbirth was associated with less pain in the subsequent 3 days. However, there was no significant difference in long-term rates of dyspareunia experienced.[[1]] Another Cochrane systematic review concluded that there is not enough evidence to evaluate the use of ultrasound in treating perineal pain and/or dyspareunia following childbirth.[[2]]

Evidence-Based References 1. Kettle C, Johanson RB: Absorbable synthetic versus catgut suture material for perineal repair. Cochrane Database Syst Rev 2000; 2:CD000006, 2. Hay-Smith EJC: Therapeutic ultrasound for postpartum perineal pain and dyspareunia. Cochrane Database Syst Rev 2000; 2:CD000495,

SUGGESTED READINGS Hawton RL: Female dyspareunia. BMJ 2004; 328(7452):1357. Helm LJ: Evaluation and differential diagnosis of dyspareunia. Am Fam Physician 2001; 63:1535. Nichols D: Reoperative gynecologic and obstetric surgery, ed 2. St Louis, Mosby, 1997.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Dyspepsia, Nonulcerative HANNAH VU, D.O.

BASIC INFORMATION DEFINITION

Nonulcerative dyspepsia is persistent or recurrent dyspepsia centered in the upper abdomen without evidence of organic disease. SYNONYMS

Functional dyspepsia Idiopathic dyspepsia

ICD-9CM CODES

536.8 onulcerative dyspepsia EPIDEMIOLOGY & DEMOGRAPHICS

•

Annual prevalence of dyspepsia approximately 25% of population.

•

Dyspepsia, GERD, PUD account for 2% to 5% of all primary care visits.

CLINICAL PRESENTATION

An international committee of clinical investigators developed the Rome II criteria to define nonulcerative dyspepsia for both research purposes and clinical practice:

•

•

Having at least 12 weeks (may be nonconsecutive) within preceding 12 months of: 1.

Persistent or recurrent dyspepsia

2.

No evidence of organic disease that is likely to explain symptoms

3.

No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool frequency or form

Additional symptoms include: •

Bloating

•

Early satiety

•

Indigestion

•

Nausea, vomiting

•

Weight loss/anorexia

ETIOLOGY

Pathophysiology is still unclear but research is focused on the following factors: •

Abnormalities of gastric motor function—especially in delayed gastric emptying, antral hypomotility, the relationship between low fasting gastric volumes and faster gastric emptying, and lower gastric compliance

•

Visceral hypersensitivity

•

Helicobacter pylori infection

•

Psychosocial factors—associated with anxiety and depression

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

Made from the exclusion of other causes of dyspepsia Other possible etiologies for dyspepsia: •

Peptic ulcer disease

•

Gastroesophageal reflux

•

Gastric/esophageal/all abdominal cancers

•

Biliary tract disease

•

Gastroparesis

•

Pancreatitis

•

Medications (i.e., NSAIDs, erythromycin, steroids)

•

Infiltrative diseases of the stomach (i.e., Crohn's or sarcoidosis)

•

Metabolic disturbances (i.e., hypercalcemia or hyperkalemia)

•

Ischemic bowel disease

•

System disorders (i.e., diabetes, thyroid disorders, or connective tissue diseases)

LABORATORY TESTS

WORKUP: •

The pattern of symptoms overlap considerably for all types of dyspepsia; therefore, the history should focus on finding specific symptoms that help exclude other causes of dyspepsia.

•

However, the specific etiology of dyspepsia often cannot be identified by history and physical exam alone and much controversy surrounds the optimal approach for further testing and treatment.

IMAGING STUDIES

ENDOSCOPY: The American Gastroenterological Association as well as the Maastricht European consensus report both recommend: •

Patients older than age 45 or those with alarming symptoms (weight loss, bleeding, anemia, or dysphagia) should have early upper endoscopy for tissue sampling to evaluate for gastric malignancy, as well as H. pylori testing. Patients whose symptoms have failed to respond to empiric therapeutic approaches should also undergo endoscopy.

•

AGA also recommends empiric trial of antisecretory therapy or prokinetic agent for 1 month in patients younger than 45 years without alarming symptoms who are H. pylori negative. H. pylori testing includes serology, stool antigen, or urea breath test.

TREATMENT NONPHARMACOLOGIC THERAPY

Controversial and often disappointing. Goal should be to help patients accept, diminish, and cope with symptoms rather than eliminate them. ACUTE GENERAL Rx

PHARMACOLOGIC THERAPY: Treatment sometimes depends on the predominant symptoms.

Predominant Symptom

Possible Etiology

Medication Recom-mended

Nausea

Motility Dysfunction

Prokinetic Agent

Bloating

Motility Dysfunction

Prokinetic Agent

Pain

Mucosal Disease or H. pylori Infection

Trial of medications listed below or H. pylori regimen

Somatic Complaints

Medication Categories Antacids (i.e., aluminum hydroxide, calcium carbonate)

Psychotropic Medication

Proton pump inhibitors (PPIs) (i.e., omeprazole) H2-receptor antagonists (i.e., cimetidine) Prokinetic agents (i.e., metoclopramide) Antidepressants (i.e., selective serotonin receptor inhibitors) H. pylori therapy/antibiotic therapy (clarithromycin + amoxicillin or metronidazole + PPI) REFERRAL

Gastroenterology if patient with alarming symptoms or when endoscopy is indicated SUGGESTED READING Dickerson LM, et al: Evaluation and management of nonulcer dyspepsia. Am Fam Physician 2004; 70:1.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Dystonia LYNN MCNICOLL, M.D., F.R.C.P.C., MARK FAGAN, M.D.

BASIC INFORMATION DEFINITION

Dystonia is characterized by involuntary muscle contractions (sustained or spasmodic) that lead to abnormal body movements or postures. Dystonia can be generalized or focal; of early onset (90% sensitive and specific for liver cysts, but less accurate for cysts in other sites. A PCR assay is now available for problematic cases. IMAGING STUDIES

Ultrasonography and/or CT scan: •

Both are extremely sensitive for the detection of cysts, especially in the liver ( Fig. 1-80 ).

•

Both lack specificity and are inadequate to establish the diagnosis of echinococcosis with certainty.

FIGURE 1-80 Computed tomography scan of an echinococcal cyst in a 25-year-old man, demonstrating the complex structure of the wall and the interior. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Treatment of choice for echinococcal cysts is surgical resection, when feasible.

•

If resection is not feasible, perform percutaneous drainage with instillation of 95% ethanol to prevent dissemination of viable larvae.

•

Surgical therapy is followed by medical therapy with albendazole (see “Acute General Rx”).

ACUTE GENERAL Rx

For echinococcosis confined to the liver: •

Albendazole (400 mg bid for 28 days followed by 14 days of rest for at least three cycles)

•

Mebendazole (50 to 70 mg/kg qd) if albendazole not available

CHRONIC Rx

See “Acute General Rx.”

DISPOSITION

•

Long-term follow-up is necessary following surgical or medical therapy because of the high incidence of late relapse.

•

Antibody assays and imaging studies are repeated every 6 to 12 mo for several years following successful surgical or medical therapy.

REFERRAL

All patients for evaluation for possible surgical resection of cysts

PEARLS & CONSIDERATIONS COMMENTS

Cyst resection, if indicated, should be performed by surgeons experienced with this procedure. SUGGESTED READINGS Eckert J, Deplazes P: Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev 2004; 17(1):107. Yang YR, et al: A hospital-based retrospective survey of human cystic and alveolar echinococcosis in Ningxia Hui Autonomous Region, PR China. Acta Trop 2006; 97(3):284. Zhang W, McManus DP: Recent advances in the immunology and diagnosis of echinococcosis. FEMS Immunol Med Microbiol 2006; 47(1):24.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Eclampsia SCOTT J. ZUCCALA, D.O., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Eclampsia is the occurrence of seizures or coma in a woman with preeclampsia, occurring at >20 wk gestation or 6.9 mg/dl found in 70% of eclamptics

•

ABG: maternal acidemia and hypoxia

IMAGING STUDIES

•

CT scan or MRI indicated in atypical presentation, suspected intracerebral bleeding, focal neurologic deficit.

•

There are abnormal findings, including cerebral edema, hemorrhage, and infarction, in 50% of patients.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Airway protection (risk of aspiration)

•

Supportive care during acute event

ACUTE GENERAL Rx

•

Maintain airway, adequate oxygenation, and IV access.

•

Fetal resuscitation, involving maternal oxygenation, left lateral positioning, and continuous fetal heart rate monitoring, is needed.

•

Magnesium sulfate is drug of choice. Give magnesium sulfate 6 g IV load over 20 min, then 3 g/hr maintenance, for recurrent seizure prophylaxis. If repeated convulsion, may give an additional 2 g IV over 3 to 5 min. About 10% to 15% of patients will have a second seizure after initial loading dose. Check magnesium level 1 hr after loading dose, then q6h (therapeutic range 4 to 6 mg/dl). Antidote for toxicity is calcium gluconate 10 ml of 10% solution. Phenytoin has been used as an alternative in patients in whom magnesium sulfate is contraindicated (renal insufficiency, heart block, myasthenia gravis, hypoparathyroidism).

•

Give sodium amobarbital 250 mg IV over 3 min for persistent seizures.

•

Treat blood pressure if >160 mm Hg/110 mm Hg, with labetalol 20- to 40-mg IV bolus, hydralazine 10 mg IV, or nifedipine 10 to 20 mg sublingual q20 min.

•

Evaluate patient for delivery.

CHRONIC Rx

•

The first priority is stabilization of the mother in terms of adequate oxygenation, hemodynamics, and laboratory abnormalities, such as associated coagulopathies.

•

Cervical status and gestational age should be assessed. If unfavorable cervix and 80% will have a complication by age 40.

•

Most vascular complications consist of arterial dissections.

•

Median age of survival is 48 years. Most deaths are related to arterial rupture.

REFERRAL

Referral to dermatology for skin biopsy to confirm diagnosis of vascular EDS and to cardiology, orthopedic surgery, general surgery, and physical therapy as needed.

PEARLS & CONSIDERATIONS

•

Women with vascular EDS should be counseled about the risk of uterine, intestinal, and arterial rupture. Pregnancy is associated with an 11% mortality rate, and there is a 50% chance that the child will be affected.

•

Family members of patients with EDS should be recommended for evaluation for EDS and genetic testing/counseling.

SUGGESTED READINGS Oderich GS: Current concepts in the diagnosis and management of vascular Ehlers-Danlos syndrome. Perspect Vasc Surg Endovasc Ther 2006; 18(3):206. Pepin M, et al: Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med 2000; 342:673. Prahlow JA: Death due to Ehlers-Danlos syndrome type IV. Am J Forensic Med Pathol 2005; 26(1):78. Pyeritz R: Ehlers-Danlos syndrome. N Engl J Med 2000; 342(10):730. Pyeritz RE: Ehlers-Danlos syndromes. In: Goldman L, Bennett JC, ed. Cecil textbook of medicine, 1. ed 21. Philadelphia: WB Saunders; 2000. Shapiro JR: Heritable disorders of structural proteins. Kelley's textbook of rheumatology, ed 6. Philadelphia, WB Saunders, 2001.

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Ejaculation Disorders DANIEL KAPLON, M.D., MARK SIGMAN, M.D.

BASIC INFORMATION DEFINITION

The clinically significant disorders of ejaculation are failure of emission, retrograde ejaculation, premature ejaculation, and anorgasmia. Failure of emission occurs when semen is not propulsed into the urethra during orgasm. This results in a dry ejaculate. Retrograde ejaculation is a backward flow of semen into the bladder. Premature ejaculation is the inability to control ejaculation for sufficient time to allow adequate penetration and intercourse. Anorgasmia is the inability to achieve orgasm in a timely manner. SYNONYMS

Ejaculatory dysfunction Retarded ejaculation Early or rapid ejaculation Inhibited ejaculation

ICD-9CM CODES

608.87 Ejaculation, retrograde 306.59 Ejaculation, psychogenic 302.75 Ejaculation, premature 302.74 Orgasm inhibited male (psychosexual) EPIDEMIOLOGY & DEMOGRAPHICS

The prevalence of premature ejaculation is estimated to be approximately 20% in adult men. CLINICAL PRESENTATION

•

Failure of emission: no ejaculate is expelled either antegrade or retrograde during orgasm; physical findings may be normal or may reveal nervous system dysfunction (e.g., spinal cord injury); may present with infertility.

•

Retrograde ejaculation: little or no ejaculate is expelled at orgasm (0.5 or pleural fluid to serum LDH >0.6. Characteristically, empyema fluid is grossly purulent with visible organisms on Gram stain with glucose 65 years of age.

•

Rabies may occur months after contact with the rabid animal, and the exposure (especially bat rabies) may have been seemingly insignificant and even inapparent.

•

Experimental therapies are worthy of consideration for some forms of viral encephalitis (e.g., immune plasma, ribavirin, interferons), and expert consultation should be obtained early on for possible treatment interventions with promising experimental therapies.

SUGGESTED READINGS Beckwith WH, et al: Isolation of eastern equine encephalitis virus and West Nile virus from crows during increased arbovirus surveillance in Connecticut, 2000. Am J Trop Med Hyg 2002; 66(4):422. De Tiege X, et al: Postinfectious immune-mediated encephalitis after pediatric herpes simplex encephalitis. Brain Dev 2005; 27(b):304-307. Frenkel LM: Challenges in the diagnosis and management of neonatal herpes simplex virus encephalitis. Pediatrics 2005; 115(b):795-797. Kennedy PG: Viral encephalitis. J Neurol 2005; 252(3):268. Roos KL: Fatal encephalitis due to rabies virus transmitted by organ transplantation. Arch Neurol 2005; 62(b):855-856. Sellal F, Stoll-Keller F: Rabies: ancient yet contemporary cause of encephalitis. Lancet 2005; 365(b):921-923. Steiner I, et al: Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 2005; 12(b):331-343.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Encephalopathy MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Encephalopathy is a clinical syndrome of global cognitive impairment that is characterized by impaired arousal, inattention, and disorientation. SYNONYMS

Delirium, acute confusional state

ICD-9CM CODES

348.3

Encephalopathy, NOS

348.30 Encephalopathy, unspecified 348.31 Encephalopathy, metabolic 348.39 Encephalopathy, other 349.82 Encephalopathy, toxic EPIDEMIOLOGY & DEMOGRAPHICS

POINT PREVALENCE: 1.1% of adults in the general population >55 years of age, 10% to 40% of hospitalized elderly, and 60% of nursing home patients >75 years of age; 100,000 to 200,000 cases annually with anoxic encephalopathy RISK FACTORS: Age, cancer, AIDS, terminal illness, bone marrow transplant, surgery PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The essential feature of encephalopathy is the patient's inability to maintain a coherent stream of thought or action.

•

The history may often suggest a waxing and waning of the level of arousal and general cognitive ability.

•

Because toxins and metabolic disturbances are common causes of encephalopathy, the history should focus on exposure to toxins (including medications) and symptoms suggesting a concurrent illness such as a urinary tract infection or pneumonia.

•

Common to all encephalopathies is a fluctuating level of arousal, poor attention, and disorientation.

•

Some patients may appear agitated and others lethargic.

•

Delusions (fixed false beliefs) and hallucinations are common.

•

Asterixis (negative myoclonus) is extremely common.

•

Other physical findings may vary depending on the underlying cause of encephalopathy: fever, ascites, jaundice, and tachycardia.

ETIOLOGY

•

The final common pathway of all causes of encephalopathy is widespread cortical and subcortical neuronal dysfunction. The causes may be structural or functional.

•

Many conditions are reversible and carry a good prognosis if treated in a timely manner.

•

Organ failure (e.g., hepatic encephalopathy, hypoxia, hypercapnia, uremia).

•

Infection—systemic (e.g., urinary tract, pneumonia) or involving the central nervous system (e.g., meningitis, encephalitis).

•

Toxin ingestion or withdrawal (e.g., alcohol, medications, recreational drugs).

•

Metabolic disturbances—hyperosmolar states, hypernatremia, hyponatremia, hyperglycemia, hypoglycemia, hypercalcemia, hypophosphatemia, acidosis, alkalosis, inborn errors of metabolism.

•

Endocrinopathy—hyperthyroidism, hypothyroidism, Cushing's syndrome, adrenal insufficiency, pituitary failure.

•

Neoplasm—tumors of the central nervous system, primary or metastatic. Also effect of distant tumors (e.g., paraneoplastic limbic encephalitis).

•

Nutritional deficiency, mostly in alcoholics and chronically ill patients, such as vitamin B12 deficiency or folate deficiency (Wernicke's encephalopathy).

•

Seizures—postictal state, nonconvulsive status epilepticus, complex partial seizures, absence seizures.

•

Trauma—concussion, contusion, subdural hematoma, epidural hematoma, diffuse axonal injury.

•

Vascular—both ischemic and hemorrhagic strokes, vasculitis, venous thrombosis.

•

Postanoxic encephalopathy.

•

Others—hypertensive encephalopathy, postoperative, sleep deprivation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Dementia—distinguished from encephalopathy by a history of slowly progressive cognitive decline over time (fluctuating cognitive function is rare except in diffuse Lewy body disease).

•

Hypersomnia.

•

Aphasia—distinguished from encephalopathy by virtue of it representing a specific disorder of language rather than a global disturbance of cognitive function.

•

Depression.

•

Psychosis—some overlap with encephalopathy as delusions and hallucinations may be common to both.

•

Mania.

•

Coma—a severe form of encephalopathy.

•

Vegetative state—one potential outcome of coma; these patients appear awake (eyes are open) but there is no content to their consciousness.

•

Akinetic mutism—these patients do not talk and do not move; there is little fluctuation in their state and there is no asterixis.

•

Locked-in syndrome—may be distinguished from encephalopathy by the presence of fixed neurologic deficits (i.e., paralysis of all four limbs).

WORKUP

•

EEG is helpful to confirm the presence of encephalopathy (diffuse slowing) and also to exclude nonconvulsive seizures.

•

Chest x-ray to rule out pneumonia secondary to silent aspiration (common in elderly hospitalized patients).

LABORATORY TESTS

•

General chemistry—electrolytes, glucose, creatinine, ammonia, blood urea nitrogen, transaminases, amylase, lipase

•

Arterial blood gases

•

Complete blood count

•

Drug screen and alcohol level

•

Lumbar puncture if meningitis, encephalitis, or subarachnoid hemorrhage with negative imaging are suspected

•

HIV testing

•

Endocrine testing—cortisol level, thyroid function test

•

Urine analysis and microscopy

IMAGING STUDIES

•

Computed tomography to rule out bleeding, hydrocephalus, tumors

•

Magnetic resonance imaging with diffusion-weighted images for suspected encephalitis, tumors, and acute strokes

•

Magnetic resonance angiography/venography for strokes, arterial dissection, venous thrombosis

•

Conventional angiography for CNS vasculitis and aneurysms

TREATMENT NONPHARMACOLOGIC THERAPY

The best approach is to treat the underlying toxic or metabolic disturbance. The encephalopathy itself is a symptom of these underlying problems. In general, it is best to avoid treating the symptom of encephalopathy with antipsychotics or sedatives. GENERAL Rx

•

Glucose if hypoglycemia

•

Antibiotics in cases of infections (choice of an agent with good CNS penetration in cases of primary CNS infections)

•

Insulin in hyperglycemic conditions (e.g., diabetic ketoacidosis, hyperosmolar nonketosis, and in sepsis)

•

Lactulose in hepatic encephalopathy

•

Folate replacement when deficiency suspected

•

Anticonvulsants if seizures likely

•

Librium or diazepam for delirium tremens (alcohol withdrawal)

•

Assure hemodynamic stability (blood pressure and heart rate)

AUTHOR: ACHRAF A. MAKKI, M.D., M.S. Encopresis

BASIC INFORMATION DEFINITION

Encopresis is the voluntary or involuntary passage of stool into inappropriate places in children over the developmental age of 4 yr, with the absence of direct physiologic causes. Occurs at least once per month for at least 3 months. SYNONYMS

Functional incontinence of stool

ICD-9CM CODES

787.6 Incontinence of feces 307.7 Encopresis EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: 4 to 5 yr of age PREVALANCE (IN U.S.): 1% to 1.5% of children ages 5 to 8.

PREDOMINANT SEX: Male > female (ratio of 4:1) PREDOMINANT AGE: 4 to 9 yr of age GENETICS: Factors that contribute to slow gut motility may predispose to encopresis PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most children attain fecal continence by the age of 4. In “primary encopresis,” continence is never fully established, whereas in “secondary encopresis” incontinence is preceded by a year or more of continence.

•

In secondary encopresis, constipation is generally severe, causing an overflow incontinence in which soft or liquid stool flows around the retained feces, often several times per day.

•

When constipation and overflow incontinence are causative, defecation is usually uncomfortable or painful, so patient avoids defecation with consequent stool retention.

•

Stool is usually poorly formed and leakage is continuous (occurring during sleep and wakefulness).

•

Encopresis resolves when the constipation is resolved.

•

In primary encopresis, stool is more likely to be normal in character.

•

Soiling is intermittent and usually in a prominent location.

•

Coexisting oppositional-defiant or conduct disorders are frequent.

ETIOLOGY

•

Children with encopresis exhibit abnormal anorectal dynamics.

•

Primary encopresis may be related to developmental delay of sphincter control whereas secondary encopresis develops in the setting of constipation.

•

Approximately 96% of children will have bowel movements between three times daily to once every other day. When bowel movements are less frequent, stool becomes drier and harder and much more uncomfortable to pass. Children may avoid the discomfort by avoiding elimination, but this only results in worsening constipation. Soiling results from liquid stool that leaks around the main stool mass.

•

Constipation may begin gradually as a result of a slow decrease in elimination frequency or more acutely after an illness, dehydration, or prolonged bed rest.

•

In encopresis without constipation and overflow incontinence, soiling is often intentional. This may occur in the setting of oppositional-defiant disorder or conduct disorder.

•

Harsh or inconsistent toilet training and resultant anxiety may lead to retention of stool, constipation, and eventually encopresis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hirschsprung's disease

•

Endocrine disease (hypothyroidism)

•

Cerebral palsy

•

Myelomeningocele

•

Pseudoobstruction

•

Anorectal lesions (rectal stenosis)

•

Malformations

•

Trauma

•

Rectal prolapse

•

Hypothyroidism

•

Medications

WORKUP

•

History: pay particular attention to frequency of elimination, character of the stool, associated pain, and presence of enuresis (with which it is frequently associated).

•

Evaluate child for other developmental or psychiatric problems.

•

Physical examination: pay particular attention to the abdomen, anus, rectum, and saddle sensation.

LABORATORY TESTS

Consider thyroid function tests, electrolytes, calcium, urinalysis, and culture. IMAGING STUDIES

•

Abdominal imaging to determine extent of obstruction or megacolon

•

Anorectal manometric studies to determine sphincter function if Hirschsprung's disease is suspected; if abnormal, follow up with a barium enema and rectal biopsy

TREATMENT NONPHARMACOLOGIC THERAPY

•

Behavioral and/or individual psychotherapy and family therapy.

•

Biofeedback advocated by some to improve sphincter function.

ACUTE GENERAL Rx

•

In secondary encopresis, disimpaction with hypertonic phosphate (30 ml/5 kg body weight) or isotonic saline enemas

•

Resistant cases: repeated instillation of 200 to 600 ml of milk of magnesia enemas

•

If child does not permit enemas: oral disimpaction with large doses of mineral oil or lactulose until stool mass is cleared

CHRONIC Rx

•

Prevention of recurrence of constipation by increased dietary fiber and bulk agents and the use of laxatives (Senokot) and stool softeners (docusate sodium)

•

In immediate postdisimpaction period (3 mo following acute treatment) laxatives needed because bowel tone remains low

•

In primary encopresis, continue with nonpunitive toilet training and encourage regular toilet times (the latter is also helpful in secondary encopresis)

DISPOSITION

In most cases encopresis is self-limited and of relatively brief duration REFERRAL

If patient is resistant to treatment, explore for complicating family factors, and/or encopresis.

PEARLS & CONSIDERATIONS It is important to educate parents and children as to the nature of the problem and to defuse hostile or negative interactions between them.

EVIDENCE

Behavioral therapy A systematic review found some evidence that behavioral intervention plus laxative therapy, rather than behavioral therapy or laxative therapy alone, improves continence in children with primary and secondary encopresis. There was no evidence that biofeedback adds any benefit to conventional management of encopresis and constipation in children.[[1]]

Evidence-Based Reference 1. Brazelli M, Griffiths P: Behavioural and cognitive interventions with or without other treatments for defaecation disorders in children. Cochrane Database Syst Rev 2001; 4:CD002240,

SUGGESTED READINGS Klages T, et al: Controlled study of encopresis and enuresis in children with a prepubertal and early adolescent bipolar-I disorder phenotype. J Am Acad Child Adolesc Psychiatry 2005; 44(10):1050. Reid H, Bahar RJ: Treatment of encopresis and chronic constipation in young children: clinical results from interactive parent-child guidance. Clin Pediatr 2006; 45(2):157.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Endocarditis, Infective GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Infective endocarditis is an infection of the endocardial surface of the heart or mural endocardium. ACUTE ENDOCARDITIS: Usually caused by Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Neisseria organisms; classic clinical presentation of high fever, positive blood cultures, vascular and immunologic phenomenon SUBACUTE ENDOCARDITIS: Usually caused by viridans streptococci in the presence of valvular pathology; less toxic, often indolent presentation with lower fevers, night sweats, fatigue ENDOCARDITIS IN INJECTION DRUG USERS: Often involving S. aureus or Pseudomonas aeruginosa with variation that may be geographically influenced; tricuspid or multiple valvular involvement; high mortality rate of 50% to 60% PROSTHETIC VALVE ENDOCARDITIS (EARLY): Usually caused by S. epidermidis within 2 mo of valve replacement; other organisms include S. aureus, gram-negative bacilli, diphtheroids, Candida organisms PROSTHETIC VALVE ENDOCARDITIS (LATE): Typically develops >60 days after valvular replacement; involved organisms similar to early prosthetic valve endocarditis, including viridans streptococci, enterococci, and group D streptococci NOSOCOMIAL ENDOCARDITIS: Secondary to intravenous catheters, TPN lines, pacemakers; coagulasenegative staphylococci, S. aureus, and streptococci most common SYNONYMS

Bacterial endocarditis Subacute bacterial endocarditis (SBE) Endocarditis

ICD-9CM CODES

421.0

Infective endocarditis

996.61 Prosthetic valve endocarditis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 1.7 to 3.8 cases/100,000 persons/yr PEAK INCIDENCE: Females: often female PREDOMINANT AGE: 45 to 65 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Fever may be variable in presentation; may be high, hectic, or absent.

•

Fever, chills, fatigue, and rigors occur in 25% to 80% of patients.

•

Heart murmur may be absent in right-sided endocarditis.

•

Embolic phenomenon with peripheral manifestations is found in 50% of patients.

•

Skin manifestations include petechiae, Osler nodes, splinter hemorrhages, Janeway lesions.

•

Splenomegaly is more common with subacute course.

ETIOLOGY

Streptococcal and staphylococcal infections are the most common causes of infective endocarditis. Variation in incidence may occur that is influenced by the patient's risk for developing infection. ACUTE ENDOCARDITIS: •

S. aureus

•

Streptococcus pneumoniae

•

Streptococcal species and groups A through G

•

Haemophilus influenzae

SUBACUTE ENDOCARDITIS:

•

Viridans streptococci (alpha-hemolytic)

•

S. bovis

•

Enterococci

•

S. aureus

ENDOCARDITIS IN INJECTION DRUG USERS: •

S. aureus

•

P. aeruginosa

•

Candida species

•

Enterococci

PROSTHETIC VALVE ENDOCARDITIS (EARLY):

•

S. epidermidis

•

S. aureus

•

Gram-negative bacilli

•

Group D streptococci

PROSTHETIC VALVE ENDOCARDITIS (LATE):

•

S. epidermidis

•

Viridans streptococci

•

S. aureus

•

Enterococci and group D streptococci

NOSOCOMIAL ENDOCARDITIS:

•

Coagulase-negative staphylococci

•

S. aureus

•

Streptococci: viridans, group B, enterococcus

HACEK ORGANISMS: •

Fastidious gram-negative bacilli

•

Haemophilus parainfluenzae

•

Haemophilus aphrophilus

•

Actinobacillus actinomycetemcomitans

•

Cardiobacterium hominis

•

Eikenella corrodens

•

Kingella kingae

RISK FACTORS

•

Poor dental hygiene

•

Long-term hemodialysis

•

Diabetes mellitus

•

HIV infection

•

Mitral valve prolapse

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Brain abscess

•

FUO

•

Pericarditis

•

Meningitis

•

Rheumatic fever

•

Osteomyelitis

•

Salmonella

•

TB

•

Bacteremia

•

Pericarditis

•

Glomerulonephritis

WORKUP

Physical examination to evaluate for the previous physical findings followed by laboratory testing (see “Laboratory Tests”) LABORATORY TESTS

•

Blood cultures: three sets in first 24 hr

•

More culturing if patient has received prior antibiotic

•

CBC (anemia possibly present, subacute)

•

WBC (leukocytosis is higher in acute endocarditis)

•

ESR and C-reactive protein (elevated)

•

Positive rheumatoid factor (subacute endocarditis)

•

False-positive VDRL

•

Proteinuria, hematuria, RBC casts

•

Electrocardiogram: look for cardiac conduction abnormalities, injury pattern, or evidence of pericarditis—any such new findings are suggestive of myocardial abscess.

IMAGING STUDIES

•

Echocardiogram: two-dimensional

•

Transesophageal echocardiography (TEE): more sensitive in detecting vegetations if two dimensional is negative, especially helpful with prosthetic valves or in detecting perivalvular disease

TREATMENT Initial IV antibiotic therapy (before culture results) is aimed at the most likely organism: •

In patients with prosthetic valves or patients with native valves who are allergic to penicillin: vancomycin (1 g IV every 12 hr for 4 wk) plus rifampin 600 mg by mouth daily and gentamicin (1 mg/kg IV every 8 hr for 2 wk)—assuming normal renal function in adult patients.

•

In IV drug users: nafcillin or oxacillin (2 g IV every 4 hr) plus gentamicin (1 mg/kg every 8 hr for 3 to 5 days until blood cultures are negative); if MRSA, vancomycin (1 g IV every 12 hr for 4 wk) plus gentamicin (1 mg/kg every 8 hr for 3 to 5 days until blood cultures are negative).

•

In native valve endocarditis with a penicillin-susceptible streptococcal isolate: combination of penicillin (18 to 24 million units/day IV for 4 wk) and gentamicin (1 mg/kg every 8 hr for 2 wk) assuming normal renal function. Extend the gentamicin therapy for 4 wk if a relatively penicillin-resistant strain of streptococcus is isolated (penicillin MIC >0.5 microgram/ml); a penicillase-resistant penicillin (oxacillin or nafcillin—2 g IV every 4 hr for 4 to 6 wk plus gentamicin 1 mg/kg IV every 8 hr for 3 to 5 days) can be used if acute bacterial endocarditis is present or if S. aureus is suspected as one of the possible causative organisms; for Hacek organisms, treat with third-generation cephalosporin (ceftriaxone—2 g IV every 24 hr for 4 to 6 wk).

•

Ceftriaxone: 2 g IV every 24 hr and an aminoglycoside (e.g., gentamicin 1 mg/kg IV every 8 hr for 2 wk) effective for Streptococcus viridans endocarditis.

•

Daptomycin (6 mg/kg/day for 4 to 6 wk) has recently been approved for use in S. aureus bacteremia and right-sided endocarditis; may prove useful in MRSA infections.

Antibiotic therapy after identification of the organism should be guided by susceptibility testing—preferably by formal testing by MIC (minimum inhibitory testing). DISPOSITION

•

The patient may need outpatient IV antibiotic therapy, and arrangements need to be made to assure safe vascular access and continuity of care with outpatient IV therapy team.

•

Long-term follow-up is essential after therapy has ended; relapse of endocarditis may occur.

•

Prophylaxis with antibiotics will be needed before dental procedures as a previous episode of endocarditis increases the risk of recurrent endocarditis associated with transient bacteremia from dental procedures.

REFERRAL

•

To an infectious disease specialist for an optimal antibiotic regimen

•

To a cardiologist or a cardiac surgeon if evidence of heart failure, refractory infection, myocardial abscess, valve disruption, or major embolic events occur

•

To a dentist or oral surgeon if dental work needs to be conducted with appropriate use of prophylactic antibiotics to prevent recurrent endocarditis

PEARLS & CONSIDERATIONS COMMENTS

For endocarditis prophylaxis refer to Section V.

EVIDENCE

We are unable to cite evidence that meets our criteria for most therapies used in infective endocarditis. A randomized controlled trial in patients with endocarditis due to penicillin-susceptible streptococci found monotherapy with ceftriaxone administered once daily for 4 weeks to be effective and safe.[[1]]

Evidence-Based References 1. Sexton DJ, et al: Endocarditis Treatment Consortium Group. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Clin Infect Dis 1998; 27:1470-1474.

SUGGESTED READINGS Cecchi E, et al: Are the Duke criteria really useful for the early bedside diagnosis of infective endocarditis? Results of a prospective multicenter trial. Ital Heart J 2005; 6(b):41-48. Cha R, Brown WJ, Rybak MJ: Bactericidal activities of daptomycin, quinupristin-dalfopristin, and linezolid against vancomycin-resistant Staphylococcus aureus in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 2003; 47(b):3960-3963. Fowler VG, et al: Daptomycin versus standard therapy for bacteremia and endocarditis caused by. Staphylococcus aureus, N Engl J Med 2006; 355(7):653. McDonald JR, et al: Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database. Am J Med 2005; 118(7):759. Morris AJ, et al: Gram stain, culture, and histopathological examination findings for heart valves removed because of infective endocarditis. Clin Infect Dis 2003; 36(b):697-704.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Endometrial Cancer GIL FARKASH, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Endometrial cancer is a malignant transformation of endometrial stroma and/or glands typified by irregular nuclear membranes, nuclear atypia, mitotic activity, loss of glandular pattern, irregular cell size ( Fig. 1-82 ).

FIGURE 1-82 Carcinoma of the endometrium. A, Stage I. B, Stage III, myometrial invasion. (From Sabiston D: Textbook of surgery, ed 15, Philadelphia, 1997, WB Saunders.)

SYNONYMS

Uterine cancer (some forms)

ICD-9CM CODES

182 Malignant neoplasm of body of uterus EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 21.2 cases/100,000 persons; approximately 30,000 new cases annually PREDOMINANCE: Median age at onset: 60 yr; only 5% occur in women 37.8° C

•

Localized uterine tenderness, purulent or foul lochia; physical examination revealing uterine or parametrial tenderness

•

Nonspecific signs and symptoms such as malaise, abdominal pain, chills, and tachycardia

ETIOLOGY

Endometritis is usually associated with multiple organisms: group A or B streptococci, Staphylococcus aureus and Bacteroides species, Neisseria gonorrhoeae, Chlamydia trachomatis, enterococci, Gardnerella vaginalis, E. coli, and Mycoplasma.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Causes of postoperative or postprocedural infections WORKUP

Diagnosis based on symptoms of fever, malaise, abdominal pain, uterine tenderness, and purulent, foul vaginal discharge LABORATORY TESTS

CBC, blood cultures, and uterine culture IMAGING STUDIES

Ultrasound may be useful if retained products are considered a possible source of infection.

TREATMENT ACUTE GENERAL Rx

•

In treating endometritis after a vaginal delivery, ampicillin 2 g IV q6h plus gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg of body weight) q8h are used.

•

Regimen should be continued for at least 48 hr after substantial clinical improvement. If response is not adequate, check cultures and treat with appropriate antibiotics ( Table 1-11 ).

•

Endometritis following C-section should be treated with ampicillin 2 g IV q6h plus gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg of body weight) q8h and clindamycin 900 mg IV q8h. If Chlamydia is one of the etiologic agents, add doxycycline 100 mg PO bid for completion of a 14-day course of therapy (if breast-feeding, use erythromycin).

TABLE 1-11 -- Identified Causes of Poor Response to Antibiotic Therapy in Patients with Endometritis Approximate Cause Prevalence (%) Infected mass, including abscess, hematoma, septic pelvic thrombophlebitis, pelvic cellulitis, retained placenta

40-50

Resistant organisms, commonly enterococci, in a patient receiving clindamycinaminoglycoside or a cephalosporin

20

Additional cause, including catheter phlebitis, inadequate dose of antibiotics

10

No cause evident but response to empirical change in antibiotic therapy From Gorbach SL: Infectious diseases, ed 2, Philadelphia, 1998, WB Saunders. CHRONIC Rx

Watch for recurrent infection.

20-30

DISPOSITION

With appropriate antibiotic therapy, 95% to 98% cure rate REFERRAL

For patients who do not respond within 48 to 72 hr of appropriate antibiotic therapy, obtain an infectious disease consult or gynecologic consultation.

EVIDENCE

Combined gentamicin and clindamycin is an appropriate treatment, and regimens with activity against penicillin-resistant anaerobic bacteria are better than those without. [[1]] After clinical improvement of uncomplicated endometritis with intravenous therapy, oral therapy is unnecessary.[[1]] Prophylactic antibiotics are effective in reducing endometritis in women undergoing cesarean section. Prophylactic ampicillin and first-generation cephalosporins are equally effective in reducing postoperative endometritis following cesarean section and should be used as first line agents. The use of a more broadspectrum agent or a multiple-dose regimen provides no additional clinical benefit.[[2]] Antibiotics significantly reduce the risk of endometritis in women in preterm labor with intact membranes and in those with prelabor rupture of the membranes. In the treatment of women in preterm labor with intact membranes, antibiotics, namely beta-lactams (alone or in combination with a macrolide), significantly reduce maternal chorioamnionitis and endometritis.[[3]] The use of prophylactic antibiotics significantly reduces the risk of endometritis and chorioamnionitis in women with prelabor rupture of the membranes, at 36 weeks or beyond.[[4]]

Evidence-Based References 1. French LM, Smaill FM: Antibiotic regimens for endometritis after delivery. Reviewed. Cochrane Library 4, Chichester, UK, John Wiley, 2004. 2. Hopkins L, Smaill F: Antibiotic prophylaxis regimens and drugs for cesarean section (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. Cochrane Library 1 3. King J, Flenady V: Prophylactic antibiotic for inhibiting preterm labour with intact membranes. Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 4. Flenady V, King J: Antibiotics for prelabour rupture of membranes at or near term (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004.

AUTHORS: GEORGE T. DANAKAS, M.D., and RUBEN ALVERO, M.D. Enuresis

BASIC INFORMATION DEFINITION

Enuresis refers to the voiding of urine into clothes or in bed that is usually involuntary in individuals who are expected to be continent (i.e., 50% of patients, no specific cause is identified.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Chronic urticaria

•

Secondary syphilis

•

Pityriasis rosea

•

Contact dermatitis

•

Pemphigus vulgaris

•

Lichen planus

•

Serum sickness

•

Drug eruption

•

Granuloma annulare

•

Polymorphic light eruption

•

Viral exanthem

WORKUP

•

Medical history with emphasis on drug ingestion

•

Laboratory evaluation in patients with suspected collagen-vascular diseases

•

Skin biopsy when diagnosis is unclear

LABORATORY TESTS

•

CBC with differential

•

ANA

•

Serology for Mycoplasma pneumoniae, HSV-1, HSV-2

•

Urinalysis

TREATMENT NONPHARMACOLOGIC THERAPY

•

Mild cases generally do not require treatment; lesions resolve spontaneously within 1 mo.

•

Potential drug precipitants should be removed.

ACUTE GENERAL Rx

•

Treatment of associated diseases (e.g., acyclovir for herpes simplex, erythromycin for Mycoplasma infection).

•

Prednisone 40 to 80 mg/day for 1 to 3 wk may be tried in patients with many target lesions; however, the role of systemic steroids remains controversial.

•

Levamisole, an immunomodulator, may be effective in treatment of patients with chronic or recurrent oral lesions (dose is 150 mg/day for 3 consecutive days used alone or in combination with prednisone).

DISPOSITION

The rash of EM generally evolves over a 2-wk period and resolves within 3 to 4 wk without scarring. A severe bullous form can occur (see “Stevens-Johnson Syndrome”).

REFERRAL

Hospital admission in patients with Stevens-Johnson syndrome

PEARLS & CONSIDERATIONS COMMENTS

The risk of recurrence of erythema multiforme exceeds 30%. Recurrent EM may be treated with valacyclovir 500 to 1000 mg/day, famcyclovir 125 to 250 mg/day, or acyclovir 400 mg bid. Dapsone, antimalarials, azathioprine, or cyclosporine use is reserved for cases resistant to antivirals. SUGGESTED READINGS Lamoreux M, et al: Erythema multiforme. Am Fam Phys 2006; 74:1883.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Erythema nodosum FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Erythema nodosum is an acute, tender, erythematous, nodular skin eruption resulting from inflammation of subcutaneous fat, often associated with bruising. It is the most common form of panniculitis.

ICD-9CM CODES

695.2

Erythema nodosum

017.10 Erythema nodosum, tuberculous, NOS EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 2 to 3 cases/100,000 persons per yr PREDOMINANT SEX: Female:male ratio of 3 to 4:1 PREDOMINANT AGE: 25 to 40 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Acute onset of tender nodules typically located on shins ( Fig. 1-93 ), occasionally seen on thighs and forearms.

•

The nodules are usually to 1 inch in diameter but can be as large as 4 inches; they begin as light red lesions, then become darker and often ecchymotic. The nodules heal within 8 wk without ulceration

•

Associated findings: Fever Lymphadenopathy Arthralgia Signs of the underlying illness

FIGURE 1-93 Erythema nodosum. (From Arndt KA et al: Cutaneous medicine and surgery, vol 1, Philadelphia, 1997, WB Saunders.)

ETIOLOGY

Cell-mediated hypersensitivity reaction seen more frequently in persons with human leukocyte antigen (HLA) B8. The lesion results from an exaggerated interaction between an antigen and cell-mediated immune mechanisms leading to granuloma formation. Up to 55% of cases of erythema nodosum are idiopathic. Infections:

•

Bacteria Streptococcal pharyngitis (28% to 48%) Salmonella enteritis Yersinia enteritis Psittacosis Chlamydia pneumoniae infection Mycoplasma pneumonia Meningococcal infection Gonorrhea Syphilis Lymphogranuloma venereum Tularemia Cat-scratch disease Leprosy Tuberculosis

•

Fungi Histoplasmosis Coccidioidomycosis Blastomycosis Trichophyton verrucosum

•

Viruses Cytomegalovirus

•

•

Hepatitis B

•

Epstein-Barr virus

Drugs (3% to 10%) Sulfonamides Penicillins Oral contraceptives Gold salts Prazosin Aspirin Bromides

•

Sarcoidosis (11% to 25%)

•

Cancer, usually lymphoma

•

Ankylosing spondylosis and reactive arthropathies (e.g., associated with inflammatory bowel disease)

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Insect bites

•

Posttraumatic ecchymoses

•

Vasculitis

•

Weber-Christian disease

•

Fat necrosis associated with pancreatitis

•

Necrobiosis lipoidica

•

Scleroderma

•

Lupus panniculitis

•

Subcutaneous granuloma

•

Alpha-1 antitrypsin deficiency

WORKUP

•

Physical examination

•

Diagnosis of underlying illness by history, physical examination, and laboratory tests as indicated

LABORATORY TESTS

•

Erythrocyte sedimentation rate (ESR)

•

Throat culture and antistreptolysin O titer

•

PPD

•

Others depending on index of suspicion (e.g., stool culture and evaluation for ova and parasites in patients with diarrhea and GI symptoms)

•

Skin biopsy in doubtful cases: Early lesion: inflammation and hemorrhage in subcutaneous tissue Late lesion: giant cells and granulomata

IMAGING STUDIES

Chest x-ray to rule out sarcoidosis and TB

TREATMENT

•

The disease is self-limited and treatment is symptomatic. Erythema nodosum nodules develop in pretibial locations and resolve spontaneously over several weeks without scarring or ulceration.

•

Treatment of underlying disorders.

•

Avoidance of contact irritation of affected areas.

•

NSAIDs for pain.

•

Systemic steroids (prednisone 1 mg/kg of body weight/day, tapered over several days) may be useful in severe cases if underlying risk of sepsis and malignancy have been excluded.

PROGNOSIS

Typical case: •

Pain for 2 wk

•

Resolution within 8 wk

SUGGESTED READINGS Schwartz RA, Nervi S: Erythema nodosum: a sign of systemic disease. Am Fam Physician 2007; 75:695-700.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Esophageal Tumors LYNN MCNICOLL, M.D., F.R.C.P.C.

BASIC INFORMATION DEFINITION

Esophageal tumors are defined as benign and malignant tumors arising from the esophagus. Approximately 15% of esophageal cancers arise in the cervical esophagus, 50% in the middle third of the esophagus, and 35% in the lower third. Eighty-five percent of esophageal tumors are squamous cell carcinoma (arising from squamous epithelium). Adenocarcinomas arise from columnar epithelium in the distal esophagus, which have become dysplastic secondary to chronic gastric reflux, Barrett's esophagus. SYNONYMS

Neoplasm of the esophagus Malignancy of the esophagus

ICD-9CM CODES

150.8 Esophageal cancer, NEC 150.9 Esophageal cancer, NOS 230.1 Carcinoma of esophagus, in situ EPIDEMIOLOGY & DEMOGRAPHICS

Carcinomas of the esophageal epithelium, both squamous cell and adenocarcinoma, are by far the most common tumors of the esophagus. Benign neoplasms are much less common (leiomyoma, papilloma, and fibrovascular polyps). PREVALENCE: Varies widely worldwide. It is the sixth leading cause of cancer death. Rates are highest in the Asian esophageal cancer belt, extending from the Caspian Sea to northern China, with certain high-incidence pockets in Finland, Ireland, SE Africa, and NW France. In the U.S., 14,550 new cases in 2006 and 13,000 deaths occur per year, making it the seventh leading cause of death by cancer among men. AGE & SEX PREDOMINANCE: Esophageal cancer is more common among blacks than whites and has a high male:female ratio of 3:1. It usually develops in the seventh and eighth decades and is associated with lower socioeconomic status. The majority are diagnosed at an advanced stage (unresectable or metastatic disease). GENETICS: Increasing evidence that genetics may play a role by incresing susceptibility to esophageal cancer.

CLINICAL PRESENTATION

Symptoms and signs: •

Dysphagia: initially occurs with solid foods and gradually progresses to include semisolids and liquids; latter signs usually indicate incurable disease with tumor involving more than 60% of the esophageal circumference. Occurs in 74%.

•

Weight loss: usually of short duration. Weight loss >10% of body mass is an independent predictor of poor prognosis.

•

Hoarseness: suggests recurrent laryngeal nerve involvement.

•

Odynophagia: an unusual symptom.

•

Cervical adenopathy: usually involving supraclavicular lymph nodes.

•

Dry cough: suggests tracheal involvement.

•

Aspiration pneumonia: caused by development of a fistula between the esophagus and trachea.

•

Massive hemoptysis or hematemesis: results from the invasion of vascular structures.

•

Advanced disease spreads to liver, lungs, and pleura.

•

Hypercalcemia: associated with squamous cell carcinoma because of the secretion of a tumor peptide similar to the parathyroid hormone.

ETIOLOGY

Pathogenesis of esophageal cancers is due to chronic recurrent oxidative damage from any of the following etiologic agents, which cause inflammation, esophagitis, increased cell turnover, and ultimately, initiation of the carcinogenic process. ETIOLOGIC AGENTS: •

Excess alcohol consumption: accounts for 80% to 90% of esophageal cancer in the U.S.; whiskey is associated with a higher incidence than wine or beer.

•

Tobacco and alcohol use combined increases risk substantially.

•

Obesity.

•

Other ingested carcinogens: Nitrates (converted to nitrites): South Asia, China Smoked opiates: Northern Iran Fungal toxins in pickled vegetables Mucosal damage: Long-term exposure to extremely hot tea Lye ingestion

•

Radiation-induced strictures

•

Chronic achalasia: incidence is 7 × 3.

•

Host susceptibility secondary to precancerous lesions: Plummer-Vinson syndrome (Paterson-Kelly): glossitis with iron deficiency Congenital hyperkeratosis and pitting of palms and soles

•

Chronic GERD leading to Barrett's esophagus and adenocarcinoma (whites are affected more than blacks).

DIAGNOSIS

•

Possible association with celiac sprue or dietary deficiencies of molybdenum, zinc, vitamin A.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Achalasia

•

Scleroderma of the esophagus

•

Diffuse esophageal spasm

•

Esophageal rings and webs

LABORATORY TESTS

Complete blood cell count, chemistries, liver enzymes IMAGING STUDIES

•

Double contrast esophagogram effectively identifies large esophageal lesions ( Fig. 1-94 ). In contrast to benign esophageal leiomyomata, which cause narrowing with preservation of normal mucosal pattern, esophageal carcinomas cause ragged ulcerating mucosal changes in association with deeper infiltration.

•

Esophagoscopy is performed to visualize smaller tumors missed by esophagogram and obtain histopathologic confirmation. In conjunction, an endoscopic sonogram is often performed to determine the depth of tumor invasion. Endoscopic inspection of the larynx, trachea, and bronchi may identify concomitant cancers of head, neck, and lung. Endoscopic biopsies fail to recover malignant tissue one third of the time, thus cytologic examination of tumor brushings should be routinely performed. Examination of the fundus of the stomach via retroflexion of the endoscope is also imperative.

•

Chest and abdominal CT or integrated CT-PET scan should be performed to determine the extent of tumor spread to mediastinum, paraaortic lymph nodes, and liver.

FIGURE 1-94 Barium swallow demonstrating the classic findings in cancer of the distal third of the espophagus. (From Nobel J [ed]: Primary care medicine, ed 2, St Louis, 1996, Mosby.)

TREATMENT

ACUTE GENERAL Rx SURGICAL RESECTION: •

Surgical resection of squamous cell and adenocarcinoma of the lower third of the esophagus is indicated if there is no widespread metastasis. Usually stomach or colon is used for esophageal replacement.

•

Endoscopic resections may replace radical surgical resections in early tumors with no lymph node involvement.

Complications of surgery: •

Anatomic fistula (usually with colon interposition, subphrenic abscesses).

•

Respiratory complications.

•

Cardiovascular complications are most common, including MI, CVA, and PE.

RADIATION THERAPY: •

Squamous cell carcinomas are more radiosensitive than adenocarcinoma, and radiation achieves good local control and is an excellent palliative modality for obstructive symptoms. Best used for upper esophageal tumors.

•

About 40% of tumors cannot be destroyed even after 6000 rads.

•

Palliative radiation therapy for bone metastasis is also effective.

•

Preoperative radiotherapy: No consistent evidence of effectiveness or that it improves survival in patients with potentially resectable esophageal tumors.

Complications of radiation therapy: •

Esophageal stricture, radiation-induced pulmonary fibrosis, transverse myelitis are the most feared complications.

•

Radiation-induced cardiomyopathy and skin changes are rare.

COMBINATION CHEMOTHERAPY, RADIATION Rx, & SURGICAL Rx: •

Single-agent chemotherapy resulted in significant tumor regression in 15% to 25% of patients.

•

Combination chemotherapy including cisplatin achieved significant tumor reduction in 30% to 60% of patients.

•

Complications of chemotherapy include mucositis, GI toxicity, myelosuppression, nephrotoxicity; ototoxicity and neurotoxicity with cisplatin.

•

Many centers are using preoperative chemoradiotherapy for patients with esophageal cancer.

•

Chemoradiotherapy plus surgery significantly reduced the 3-year mortality rate compared with surgery alone in patients with resectable esophageal cancer.

•

Most beneficial chemotherapy appeared to be a cisplatin, 5-fluorouracil-based combination.

•

Conflicting evidence on the effects of cisplatin and 5-fluorouracil on survival time over surgery alone.

•

Chemoradiotherapy is superior to radiotherapy alone for the primary treatment of esophageal carcinoma when a nonoperative approach is selected, but is associated with significant toxicity and perioperative mortality.

CHRONIC Rx

•

Palliative procedures such as repeated endoscopic dilation, surgical placement of feeding tube, or polyvinyl prosthesis to bypass tumors have been used for unresectable patients.

DISPOSITION

•

Overall 5-yr survival is 13%.

•

Surgery: 5-yr survival rate is 48% in stages I and II, 20% in advanced stages.

•

Radiation therapy: 5-yr survival rate is between 6% and 20%.

•

Chemotherapy: Single-agent response rate 15% to 38%; combination response rate 80%.

•

Combined modality: 18% response rate.

•

Patients with stage IV disease receive palliative chemotherapy with a median survival of less than 1 year.

REFERRAL

•

Gastroenterologist or general surgeon for endoscopy for patients with chronic dysphagia, odynophagia, or unexplained weight loss

•

Medical oncologist for evaluation of preoperative chemotherapy

•

Radiation oncologist for palliative therapy if unresectable or obstruction

•

Hospice referral if appropriate

PEARLS & CONSIDERATIONS COMMENTS

>50% of patients with esophageal cancer are diagnosed when the disease is metastatic or unresectable. PREVENTION

•

A diet high in fruits and vegetables is associated with lower risk of esophageal cancer.

•

Avoid excessive alcohol and tobacco use.

•

Avoid ingested toxins known to cause esophageal cancers.

•

Endoscopic evaluation of persons with chronic dysphagia, or GERD symptoms with regularly scheduled surveillance endoscopies if Barrett's esophagus is detected.

PATIENT/FAMILY EDUCATION

Provide education and support about the likely prognosis because most esophageal cancers are diagnosed at an advanced stage. SUGGESTED READINGS Arnott SJ, et al: Preoperative radiotherapy for esophageal carcinoma. Cochrane Database Syst Rev 2005; 4:CD001799 Chang JT, Katzka DA: Gastroesophageal reflux disease, Barrett esophagus, and esophageal adenocarcinoma. Arch Intern Med 2004; 164:1482. Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med 2003; 349:2241. Walsh TN, et al: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996; 335:462-467. Wong R, Malthaner R: Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus. Cochrane Database Syst Rev 2006; 1:CD002092

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Essential Tremor CINDY ZADIKOFF, M.D.

BASIC INFORMATION DEFINITION

A predominantly postural and action tremor that is bilateral and tends to progress slowly over the years in the absence of other neurological abnormalities. SYNONYMS

Benign essential tremor Familial tremor

ICD-9CM CODES

333.1 Essential tremor EPIDEMIOLOGY & DEMOGRAPHICS

PREDOMINANT AGE: About 415/100,000 in persons over 40 GENETICS: No gender or racial predominance PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Patients complain of tremor that is most bothersome when writing or holding something, such as a newspaper, or trying to drink from a cup. Worsens under emotional duress and drinking liquids.

•

Tremor, 4 to 12 Hz, bilateral postural and action tremor of the upper extremities. May also affect the head, voice, trunk, and legs. Typically is the same amplitude throughout the action, such as bringing a cup to the mouth. No other neurologic abnormalities on examination, except for possibly some difficulty with tandem gait. Patients often note improvement with small amount of alcohol.

ETIOLOGY

Often an inherited disease, autosomal dominant; sporadic cases without a family history are frequently encountered

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Parkinson's disease—tremor is usually asymmetric, especially early on in the disease, and is predominantly a resting tremor. Patients with Parkinson's disease will also have increased tone, decreased facial expression, slowness of movement, and shuffling gait.

•

Cerebellar tremor—an intention tremor that increases at the end of a goal-directed movement (such as finger to nose testing). Other associated neurologic abnormalities include ataxia, dysarthria, and difficulty with tandem gait.

•

Drug-induced—there are many drugs that enhance normal, physiologic tremor. These include caffeine, nicotine, lithium, levothyroxine, × b-adrenergic bronchodilators, valproate, and SSRIs.

•

Wilson's Disease—wing-beating tremor that is most pronounced with shoulders abducted, elbows flexed, and fingers pointing towards each other. Usually there are other neurologic abnormalities including dysarthria, dystonia, and Keyser Fleischer rings on ophthalmologic examination.

WORKUP

•

All imaging studies normal (MRI, CT) and are usually unnecessary unless there are other associated neurologic abnormalities

•

Check TSH

•

In patients younger than 40 yr with other neurologic abnormalities, send ceruloplasmin, serum Cu, 24-hr urine Cu to rule out Wilson's disease

TREATMENT Do not need to treat essential tremor unless it is functionally impairing. Patients need to understand that treatments are only 40% to 70% effective. NONPHARMACOLOGIC THERAPY

Reduction of stress. Minimize use of caffeine. Small quantities of alcohol at social functions tend to be beneficial. ACUTE GENERAL Rx

Can take a dose of propranolol (20 to 40 mg) in preparation for specific event. CHRONIC Rx

First-line agents •

Propranolol/Propranolol LA: Usual starting dose is 30 mg. The usual therapeutic dose is 160 to 320 mg. Although not contraindicated, they must be used with caution in those with asthma, depression, cardiac disease, and diabetes.

•

Primidone: Usual starting dose is 12.5 to 25 mg qhs. Usual therapeutic dose is between 62.5 and 750 mg daily. Sedation and nausea when first begin medication are biggest side effects.

Other agents

•

Gabapentin: 400 mg qhs, usual therapeutic dose is 1200 to 3600 mg

•

Topiramate: 25 mg qhs, may titrate up to about 400 mg

•

Alprazolam: 0.75 to 2.75 mg

For head tremor, propanolol may be more effective than others. Consideration should be given to referral for Botulinum toxin injections to treat head tremor. Not very useful for limb tremor. The previously mentioned drugs can be tried in combination if monotherapy is ineffective. SURGICAL Rx

Thalamic deep brain stimulation contralateral to side of tremor DISPOSITION

Patients should be reassured that the condition is not associated with other neurologic disabilities; however, it can become quite functionally disabling over time. REFERRAL

This is a condition that usually can be treated by the primary care physician; however, if patient fails first-line therapies then patient should be referred to specialists for other drug trials and possible surgical options.

PEARLS & CONSIDERATIONS Essential tremor is the most common of all movement disorders.

EVIDENCE

A recent American Academy of Neurology Practice Parameter was released in June 2005.[[1]] They found that propranolol, propranolol LA, and primidone are effective in reducing limb tremor in essential tremor. The magnitude of effect of propranolol and primidone is roughly equivalent, and either can be tried as initial therapy. There is conflicting evidence for the use of gabapentin and limited evidence for the other drugs listed. Based on available studies, these agents are either “probably” or “possibly” effective in the treatment of limb tremor in essential tremor.

Evidence-Based References 1. Zesiewicz TA, et al: Practice parameter: therapies for essential tremor. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2005; 64:2008.

SUGGESTED READINGS Deuschel G, Volkmann J: Tremors: differential diagnosis, pathophysiology, and therapy. In Jankovic J, Tolosa E (eds): Parkinson's disease and movement disorders, ed 4, 2002, pp. 270-291.

Louis ED: Essential tremor. N Engl J Med 2001; 345(12):887. Zesiewicz TA, et al: Phenomenology and treatment of tremor disorders. Neurologic clinics: movement disorders 2001; 19:3-680.Hurtig H, Stern M (eds)::651

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

F Factitious Disorder (Including Munchausen's Syndrome) STUART J. EISENDRATH, M.D.

BASIC INFORMATION DEFINITION

Factitious physical disorder is one in which an individual intentionally strives to create signs or symptoms of disease. The individual may create signs or symptoms by (1) lying, (2) simulating (e.g., putting drops of blood into a urine sample), or (3) actually creating disease (e.g., injecting bacteria or medications). The primary aim is to achieve the patient role, and the individual may seek invasive diagnostic testing, surgery, and treatment. Munchausen's syndrome is the most severe variant of factitious physical disorder and is exaggerated lying (pseudologia fantastica), sociopathy, geographic wandering from hospital to hospital, and a continuous life of patienthood. SYNONYMS

Factitious disorder Munchausen's syndrome (the most severe variant of factitious disorder) Munchausen by proxy (factitious disorder created in another person, usually a child) Deliberate disability Hospital addiction syndrome Artifactual illness Peregrinating problem patients Dermatitis artefacta Surreptitious illness

ICD-9CM CODES

300.19 Factitious disorder

EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Unknown PEAK INCIDENCE: 30s PREVALENCE (IN U.S.): Unknown but considerable in specific illnesses. For example, 3.3% of patients with fever of unknown origin have a factitious disorder. PREDOMINANT SEX: Male:female ratio of 2:1 for Munchausen's syndrome but 1:2 for individuals with nonMunchausen type of factitious physical disorder. PREDOMINANT AGE: 30 to 40 yr GENETICS: No genetic predisposition known. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

False complaints or self-inflicted injury or symptoms without clear secondary gain. The intentional aspect of the disorder is often evident, such as injecting bacteria to produce infection or taking medication to produce an abnormality.

•

Presentation may be acute and dramatic but can be a chronic, recurring problem.

•

Workup is usually negative for naturally occurring organic etiology.

•

Clinical picture is atypical for the natural history of disease (e.g., an infection that fails to respond to multiple courses of appropriate antibiotics).

ETIOLOGY

•

A history of significant childhood illness; physical or sexual abuse are thought to predispose.

•

Personality disorders and psychodynamic factors often play a significant role.

DIAGNOSIS The diagnosis can be made by (1) direct observation of fabrication, (2) the presence of signs or symptoms that contradict laboratory testing, (3) nonphysiologic response to treatment, (4) finding physical evidence of fabrication (e.g., syringes), and (5) recurrent patterns of illness exacerbation (e.g., just before discharge). DIFFERENTIAL DIAGNOSIS

•

Malingering: a clear secondary gain (e.g., financial gain or avoidance of unwanted duties) is present.

•

Somatoform disorders or hypochondriasis: these disorders are produced unconsciously and are not intentionally produced.

•

Self-injurious behavior is common in many other psychiatric conditions; in those conditions the patients confess the intentional self-harm and describe motivating factors; the main intent is the self-harm and not to attain the patient role as occurs in factitious disorder.

•

May also present as Munchausen by proxy in which a mother (86% of time) or other caregiver induces illness in a child (52% between ages of 3 and 13 yr) for the purpose of obtaining medical attention or some other psychological need. Mothers often have a history of somatoform, factitious, or personality disorder themselves.

WORKUP

•

Dictated by the presenting complaints.

•

No specific tests for Munchausen's syndrome.

•

Diagnosis may be made when the patient is caught in the act of lying or inducing an injury. The diagnosis often rests on organic workup failing to reveal a plausible natural organic disease. The failure of usual, or even extensive, treatment to ameliorate a condition is an important clue.

LABORATORY TESTS

•

Laboratory testing often reveals inconsistencies.

•

Other laboratory abnormalities may reflect the underlying factitious behavior (e.g., hypokalemia in an individual surreptitiously taking furosemide).

TREATMENT NONPHARMACOLOGIC THERAPY

Two major approaches: •

Nonpunitive confrontation. Primary physician and psychiatrist conjointly meet with patient and say, “You must be in a lot of distress to be harming yourself as we believe you have been. We would like to help you deal with your distress more adaptively and get you into psychiatric treatment.”

•

Avoid overt confrontation with patient but provide him or her with a face-saving way to recover. For example, a therapeutic double bind would involve saying, “There are two possibilities here, one is that you have a medical problem that should respond to the next intervention we do, or two, you have a factitious disorder. The outcome will give us the answer.”

•

Munchausen's syndrome is the most severe variant and may be virtually impossible to treat except to avoid further invasive and iatrogenic disease.

ACUTE GENERAL Rx

Treatment of comorbid psychiatric disorders may be helpful. Treatment with antidepressants or psychotherapy may ameliorate the factitious behavior. Multidisciplinary staff meetings are useful to ventilate feelings and develop cohesive treatment plans. DISPOSITION

•

After being confronted with their behavior, patients may cease factitious behavior but more commonly seek other physicians or hospitals in the Munchausen variant. Other factitious disorder patients may enter psychotherapy, particularly when they have been given a face-saving approach with an avoidance of a humiliating confrontation.

•

Extensive medical workups and exploratory surgery are frequent.

REFERRAL

Always obtain psychiatric referral. Risk management attorneys and hospital ethicists may contribute to challenging decision making in these patients.

PEARLS & CONSIDERATIONS Think of factitious disorders whenever there is an unexplained medical course that continues to repeat despite appropriate treatment, particularly in patients associated with the health care field. SUGGESTED READINGS Eisendrath S, Young J: Factitious physical disorders. In: Maj M, et al ed. Somatoform disorders, West Sussex, England: John Wiley and Sons; 2005:325-338. Stone J, Carson A, Sharpe M: Functional symptoms in neurology: management. J Neurol Neurosurg Psychiatry 2005; 76(suppl 1):i13-i21.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Falls in the Elderly SEAN H. UITERWYK, M.D., ALICIA J. CURTIN, PH.D., G.N.P.

BASIC INFORMATION DEFINITION

A fall is an “event which results in a person coming to rest inadvertently on the ground and other than a consequence of the following: loss of consciousness, sudden onset of paralysis, or epileptic seizure” (Kellogg International Work Group, Danish Medical Bulletin, 34, 1-24). SYNONYMS

Syncope Collapse

ICD-9CM CODES

Accidental fall (E880-E888.9) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: •

Falls are the leading cause of accidental death among older adults.

•

The incidence of falls among community-dwelling older adults is 35% to 40%.

•

The incidence of falls for nursing home and hospitalized older adults is three times the rate of communitydwelling older adults.

•

Twenty to thirty percent of older adults, who fall, suffer significant injury leading to immobility and dependence.

PREDOMINANT SEX & AGE: •

Fall-related mortality is highest among older white men followed by white women, black men, and black women.

•

The incidence rates of falls increase with advancing age.

•

Older adults aged 85 years and over are 10 to 15 times more likely to have a fracture compared with those aged 60 to 65 years.

RISK FACTORS:

Three groups of risk factors for falls have been identified ( Table 1-13 ): 1.

Intrinsic factors inherent in the older adult who falls

2.

Extrinsic factors circumstantial to the older adult who falls

3.

Situational or the activity in which the older adult is engaged in when a fall occurs

TABLE 1-13 -- Risk Factors for Falls in the Elderly Intrinsic Aging Age-related decline in vestibular function might lead to increased sway, dizziness, and falls. Aging of the vision system may result in decreased visual acuity, inability to discriminate dark/light, and decreased spatial perception. Cardiac Cardiac arrhythmias, carotid sinus hypersensitivity Neurologic Parkinson's disease, normal pressure hydrocephalus (NPH), sensory neuropathy, dementia/impaired cognition, cervical myelopathy, senile gait disorder, prior stroke Musculoskeletal Lower extremity weakness, deconditioning, arthritis, foot abnormalities (such as bunions, calluses, or nail abnormalities) Vascular Vertebrobasilar insufficiency, postural hypotension, postprandial hypotension Metabolic Hypoglycemia, hypothyroidism, hyponatremia Psychiatric Depression Extrinsic Medications Use of more than four medications may be associated with an increased risk of falls. Medications that may increase fall risk include benzodiazepines, sleeping medications, neuroleptics, antidepressants, anticonvulsants, class I antiarrythmics, and antihypertensives (Rao, 2005). Environmental Inadequate lighting, ill-fitting shoes, slippery floor surfaces, loose rugs, uneven steps Situational Tripping over obstacles, carrying heavy items, descending/ascending stairs, rapid turning, reaching overhead, climbing ladders CLINICAL PRESENTATION

•

Older adults who fall may present with minor soft tissue injuries, such as lacerations or bruising, hip fracture or head trauma; however, most falls are not reported unless an injury has occurred.

•

A detailed history of events and circumstances surrounding fall, risk factors, medications, chronic illnesses, and a review of systems for acute medical illnesses, cognitive status, and functional status should be obtained.

•

Physical examination should focus on the identified risk factors and include: Cardiovascular examination: heart rate and rhythm, orthostatics, carotid pulses Neurologic examination: mental status, visual screen, lower extremity assessment of strength, tone, proprioception, sensation, reflexes and testing of cortical and cerebellar function Gait and balance assessment: “Get up and go test”

ETIOLOGY

•

Falls are a multifactorial syndrome resulting from the cumulative effects of impaired gait and balance, aging, polypharmacy, depression, cognitive impairment, acute medical illness, or environmental factors ( Fig. 1-95 ).

•

Most falls among community-dwelling older adults are due to environmental factors whereas falls among nursing home residents are a result of confusion, gait impairment, or postural hypotension.

FIGURE 1-95 Guideline for the prevention of falls in older persons. Algorithm summarizing the assessment and management of falls. (From American Geriatrics Society, British Society, and American Academy of Orthopaedic Surgeons Panel on Falls Prevention.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Falls are often a nonspecific symptom of an acute illness (such as a UTI, acute anemia, or pneumonia) or an exacerbation of a chronic disease (CHF or COPD). WORKUP

•

Older adults presenting with a noninjurious fall need a detailed history and physical exam to identify acute medical illnesses and potential modifiable risk factors. Laboratory and neuroimaging studies may be necessary if the history and physical exam indicate a specific problem. ECG and Holter monitoring may be considered if cardiac arrhythmia is suspected.

•

See Fig. 1-95

LABORATORY TESTS

CBC, chemistries, thyroid function, drug levels, and urinalysis depending on physical/historical findings IMAGING STUDIES

•

CT or MRI of the brain or cervical spine films in the presence of neurologic or gait impairment.

•

Consider ECG, echocardiography, or Holter monitor if suspicious for structural cardiac abnormality or syncope.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Assisted devices such as a cane, walker to improve mobility

•

Fall prevention equipment including bed alarms, low beds, and hip protectors

•

Physical therapy evaluation for gait and balance training and home safety assessment

•

Discontinuation of certain medications associated with falls

•

Exercise program to improve strength and balance

•

Evaluation of proper footwear, hard sole, and low heel height

ACUTE GENERAL Rx

Hospitalization may be necessary for treatment of hip fracture, subdural hematoma, lacerations, or trauma as well as the treatment of underlying cause of the fall such as infection, metabolic disturbances, cardiovascular or neurologic abnormality. CHRONIC Rx

•

Screen and treat for osteoporosis as low bone density increases the risk of hip or other fractures.

•

Optimize treatment of chronic illnesses such as CHF, COPD, OA, Parkinson's disease, dementia and visual problems.

COMPLEMENTARY & ALTERNATIVE MEDICINE

Tai Chi has been shown to reduce the risk of falls in community-dwelling study participants. DISPOSITION

Falls increase the older adult's risk of hospitalization, institutionalization, and mortality. REFERRAL

•

Referral may be appropriate to cardiologist, ophthalmologist, neurologist, or podiatrist depending on the presence of a specific condition.

•

Consider referral to physical therapist for gait and balance training, evaluation for assisted device, or strengthening program.

PEARLS & CONSIDERATIONS COMMENTS

•

Fear of falling may lead to restriction of activities, social isolation, and dependence.

•

Older adults with four or more risk factors have a 78% chance of falling.

PREVENTION

The USPSTF does recommend counseling elderly patients about fall prevention during routine visits as well as arranging individualized multifactorial home interventions for high-risk elders (USPSTF Guidelines, 1996). PATIENT/FAMILY EDUCATION

Counseling patient and family about reducing the risks of falling SUGGESTED READINGS American Geriatrics Society, British Geriatrics Society, and American Academy of Orthopedic Surgeons Panel on Falls Prevention: Guideline for the prevention of falls. J Am Geriatr Soc 2001; 49:664-672. Centers for Disease Control and Prevention: http://www.cdc.gov/ncipc/factsheets/falls.htm Rao S: Prevention of falls in older patients. Am Fam Physician 2005; 72:81-88. Tinetti M, Falls : In: Cassel C, et al ed. Geriatric medicine, ed 3. New York: Springer-Verlag; 1996:528-534. Tinetti ME: Preventing falls in the elderly. N Engl J Med 2003; 348:42-49. U.S. Preventive Services Task Force: Guide to Clinical Preventive Services, Baltimore, Williams and Wilkins, 1996. Wolf SL, et al: Intense tai chi exercise training and fall occurrences in older, transitionally frail adults: a randomized, controlled trial. J Am Geriatr Soc 2003; 51:1693-16970.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Fatty Liver of Pregnancy, Acute ARUNDATHI G. PRASAD, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Acute fatty liver of pregnancy (AFLP) is characterized histologically by microvesicular fatty cytoplasmic infiltration of hepatocytes with minimal hepatocellular necrosis. SYNONYMS

Acute fatty metamorphosis Acute yellow atrophy

ICD-9CM CODES

646.7 Liver disorders in pregnancy EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: •

Approximately 1 in 10,000 pregnancies

•

Equal frequencies in all races and at all maternal ages

AVERAGE GESTATIONAl AGE: 37 wk (range 28 to 42 wk) RISK FACTORS: •

Primiparity

•

Multiple gestation

•

Male fetus

GENETICS: Some with a familial deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Initial manifestations 1.

Nausea and vomiting (70%)

2.

Pain in RUQ or epigastrium (50% to 80%)

3.

Malaise and anorexia

•

Jaundice often in 1 to 2 wk

•

Late manifestations

•

1.

Fulminant hepatic failure

2.

Encephalopathy

3.

Renal failure

4.

Pancreatitis

5.

GI and uterine bleeding

6.

Disseminated intravascular coagulation

7.

Seizures

8.

Coma

Liver 1.

Usually small

2.

Normal or enlarged in preeclampsia, eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and acute hepatitis

3.

Coexistent preeclampsia in up to 46% of patients

ETIOLOGY

•

Postulated that inhibition of mitochondrial oxidation of fatty acids may lead to microvesicular fatty infiltration of liver

•

Fatty metamorphosis of preeclamptic liver disease thought to be of different etiology

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Acute gastroenteritis

•

Preeclampsia or eclampsia with liver involvement

•

HELLP syndrome

•

Acute viral hepatitis

•

Fulminant hepatitis

•

Drug-induced hepatitis caused by halothane, phenytoin, methyldopa, isoniazid, hydrochlorothiazide, or tetracycline

•

Intrahepatic cholestasis of pregnancy

•

Gallbladder disease

•

Reye's syndrome

•

Hemolytic-uremic syndrome

•

Budd-Chiari syndrome

•

SLE

WORKUP

•

A clinical diagnosis is based predominantly on physical and laboratory findings.

•

Most definitive diagnosis is through liver biopsy with oil red O staining and electron microscopy.

•

Liver biopsy is reserved for atypical cases only and only after any existing coagulopathy corrected with FFP.

LABORATORY TESTS

Tests to determine the following: •

Hypoglycemia (often profound 90%). Recently a new card test for 14C urea has been developed providing a testing option in primary care settings. It uses a flat breath card that is read by a small analyzer.

2.

Stool antigen test is an enzymatic immunoassay (ELISA) that identifies H. pylori antigen in stool specimen through a polyclonal anti-H. pylori antibody. It is as accurate as the urea breath test for diagnosis of active infection and follow-up evaluation of patients treated for H. pylori. A negative result on the stool antigen test 8 wk after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.

3.

Histologic evaluation of endoscopic biopsy samples is considered by many the gold standard for accurate diagnosis of H. pylori infection. However, detection of H. pylori depends on the site and number of biopsy samples, the method of staining, and experience of the pathologist.

4.

Serologic testing for antibodies to H. pylori is easy and inexpensive; however, the presence of antibodies demonstrates previous but not necessarily current infection. Antibodies to H. pylori can remain elevated for months to years after infection has cleared; therefore antibody levels must be interpreted in light of patient's symptoms and other test results (e.g., PUD seen on UGI series).

•

Vitamin B12 level in patients with atrophic gastritis.

•

Hct (low if significant bleeding has occurred).

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoidance of mucosal irritants such as alcohol and NSAIDs

•

Lifestyle modifications with avoidance of tobacco and foods that trigger symptoms

ACUTE GENERAL Rx

Eradication of H. pylori, when present, can be accomplished with various regimens: 1.

PPI bid plus amoxicillin 500 mg bid plus metronidazole 500 mg for 10 days.

2.

PPI bid plus clarithromycin 500 mg bid and metronidazole 500 mg bid for 10 days. This regimen is useful in those with penicillin allergy.

3.

A 1-day quadruple therapy may be as effective as a 7-day triple therapy regimen. The 1-day quadruple therapy regimen consists of two tablets of 262 mg bismouth subsalicylate qid, one 500 mg metronidazole tablet qid, 2 g of amoxicillin suspension qid, and two capsules of 30 mg of lansoprazole.

4.

A 5-day treatment with three antibiotics (amoxicillin 1 g bid, clarithromycin 250 mg bid, and metronidazole 400 mg bid) plus either lansoprazole 30 mg bid or ranitidine 300 mg bid is an efficacious cost-saving option for patients older than 55 yr with no prior history of PUD.

5.

A combination of levofloxacin 250 mg bid, amoxicillin 1000 mg bid, and a PPI bid for 10 to 14 days can be used as salvage therapy after unsuccessful attempts to eradicate H. pylori using other regimens.

•

Prophylaxis and treatment of stress gastritis with sucralfate suspension 1 g orally q4 to 6h, H2-receptor antagonists, or PPIs in patients on ventilator support

•

Misoprostol (Cytotec) or PPIs in patients on chronic NSAIDs therapy

CHRONIC Rx

•

Misoprostol 100 mg qid or Omeprazole 20 mg/qd in patients receiving chronic NSAIDs

•

Avoidance of alcohol, tobacco, and prolonged NSAID use

DISPOSITION

•

Undetectable stool antigen 4 wk after therapy accurately confirm cure of H. pylori infection in initially seropositive healthy subjects with reasonable sensitivity.

•

Surveillance gastroscopy in patients with atrophic gastritis (increased risk of gastric cancer).

AUTHOR: FRED F. FERRI, M.D. Gastroesophageal Reflux Disease

BASIC INFORMATION DEFINITION

Gastroesophageal reflux disease (GERD) is a motility disorder characterized primarily by heartburn and caused by the reflux of gastric contents into the esophagus. SYNONYMS

Peptic esophagitis Reflux esophagitis GERD

ICD-9CM CODES

530.81 Gastroesophageal reflux disease 530.1

Esophagitis

787.1

Heartburn

EPIDEMIOLOGY & DEMOGRAPHICS

GERD is one of the most prevalent GI disorders. Nearly 7% of persons in the United States experience heartburn daily, 20% experience it monthly, and 60% experience it intermittently. Incidence in pregnant women exceeds 80%. Nearly 20% of adults use antacids or OTC H2-blockers at least once a week for relief of heartburn. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination: generally unremarkable

•

Clinical signs and symptoms: heartburn, dysphagia, sour taste, regurgitation of gastric contents into the mouth

•

Chronic cough and bronchospasm

•

Chest pain, laryngitis, early satiety, abdominal fullness, and bloating with belching

•

Dental erosions in children

ETIOLOGY

•

Incompetent LES

•

Medications that lower LES pressure (calcium channel blockers, ß-adrenergic blockers, theophylline, anticholinergics)

•

Foods that lower LES pressure (chocolate, yellow onions, peppermint)

•

Tobacco abuse, alcohol, coffee

•

Pregnancy

•

Gastric acid hypersecretion

•

Hiatal hernia (controversial) present in >70% of patients with GERD; however, most patients with hiatal hernia are asymptomatic

•

Obesity is associated with a statistically significant increase in the risk for GERD symptoms, erosive esophagitis, and esophageal carcinoma

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Peptic ulcer disease

•

Unstable angina

•

Esophagitis (from infections such as herpes, Candida), medication induced (doxycycline, potassium chloride)

•

Esophageal spasm (nutcracker esophagus)

•

Cancer of esophagus

WORKUP

•

Aimed at eliminating the conditions noted in the differential diagnosis and documenting the type and extent of tissue damage.

•

Upper GI endoscopy is useful to document the type and extent of tissue damage in GERD and to exclude potentially malignant conditions such as Barrett's esophagus. The American College of Gastroenterology recommends endoscopy to screen for Barrett's esophagus in patients who have chronic GERD symptoms. The data demonstrating the cost-effectiveness of endoscopic screening remain controversial.

LABORATORY TESTS

•

24-hr esophageal pH monitoring and Bernstein test are sensitive diagnostic tests; however, they are not very practical and generally not done. They are useful in patients with atypical manifestations of GERD, such as chest pain or chronic cough.

•

Esophageal manometry is indicated in patients with refractory reflux in whom surgical therapy is planned.

IMAGING STUDIES

Upper GI series can identify ulcerations and strictures; however, it may miss mucosal abnormalities. It may be useful in patients unwilling to have endoscopy or with medical contraindications to the procedure. Only one third of patients with GERD have radiographic signs of esophagitis on UGI series.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Lifestyle modifications with avoidance of foods (e.g., citrus- and tomato-based products) and drugs that exacerbate reflux (e.g., caffeine, ß-blockers, calcium channel blockers, a-adrenergic agonists, theophylline)

•

Avoidance of tobacco and alcohol use

•

Elevation of head of bed (4 to 8 in) using blocks

•

Avoidance of lying down directly after late or large evening meals

•

Weight reduction, decreased fat intake

•

Avoidance of clothing that is tight around the waist

GENERAL Rx

•

Proton pump inhibitors (PPIs) (esomeprazole 40 mg qd, omeprazole 20 mg qd, lansoprazole 30 mg qd, rabeprazole 20 mg qd, or pantoprazole 40 mg qd) are safe, tolerated, and very effective in most patients.

•

H2-Blockers (nizatidine 300 mg qhs, famotidine 40 mg qhs, ranitidine 300 mg qhs, or cimetidine 800 mg qhs) can be used but are generally much less effective than PPIs.

•

Antacids (may be useful for relief of mild symptoms; however, they are generally ineffective in severe cases of reflux).

•

Prokinetic agents (metoclopramide) are indicated only when PPIs are not fully effective. They can be used in combination therapy; however, side effects limit their use.

•

For refractory cases: surgery with Nissen fundoplication. Potential surgical candidates should have reflux esophagitis documented by EGD and normal esophageal motility as evaluated by manometry. Surgery generally consists of reduction of hiatal hernia when present and placement of a gastric wrap around the GE junction (fundoplication). Although laparoscopic fundoplication is now widely used, surgery should not be advised with the expectation that patients with GERD will no longer need to take antisecretory medications or that the procedure will prevent esophageal cancer among those with GERD and Barrett's esophagus.

•

Endoscopic radiofrequency heating of the GE junction (Stretta procedure) is a newer treatment modality for GERD patients unresponsive to traditional therapy. Its mechanism of action remains unclear. Endoscopy gastroplasty (EndoCinch procedure) also aims at treating GERD. Initial results appear encouraging; however, long-term studies are needed before recommending these procedures.

•

Lifestyle modification must be followed lifelong, because this is generally an irreversible condition.

DISPOSITION

•

The majority of the patients respond well to therapy.

•

Recurrence of reflux is common if treatment is discontinued.

•

Postsurgical complications occur in nearly 20% of patients (dysphagia, gas, bloating, diarrhea, nausea). Long-term follow-up studies also reveal that within 3 to 5 yr, 52% of patients who had undergone antireflux surgery are taking antireflux medications again.

REFERRAL

•

There is a strong and probably causal relation between symptomatic prolonged and untreated GERD, Barrett's esophagus, and esophageal adenocarcinoma. GI referral for upper endoscopy is needed when there are concerns about associated PUD, Barrett's esophagus, or esophageal cancer.

•

Patients with Barrett's esophagus should undergo surveillance endoscopy with mucosal biopsy every 2 yr or less because the risk of developing adenocarcinoma of esophagus is at least 30 times greater than that of the general population.

•

Testing and treating for Helicobactor pylori in patients with GERD has not been shown to improve symptoms.

•

All children with dental erosions should be evaluated for GERD.

EVIDENCE

Adults H2R antagonists are more effective than placebo but less effective than proton pump inhibitors (PPIs). Antagonists vs. placebo are more likely to relieve heartburn in patients with endoscopy-negative reflux disease.[[1]] Antagonists are less effective than PPIs in the empirical treatment of typical GERD symptoms, although the difference is not significant for heartburn remission.[[1]] Antagonists are more effective than placebo but less effective than PPIs at reducing the risk of persistent esophagitis.[[2]] Ranitidine is less effective at 6 months than PPIs at reducing relapse rate in people with healed esophagitis.[[3]] Ranitidine is less effective than omeprazole at maintaining remission at 12 months in patients with healed esophagitis and no reflux symptoms.[[4]] There is some evidence that esomeprazole may be more effective than other PPIs at promoting healing from esophagitis at 4 weeks. Otherwise there is little or no evidence to suggest that some PPIs are more effective than others. A systematic review that compared various PPIs in people with reflux esophagitis found that esomeprazole was more effective than omeprazole at promoting healing at 4 weeks. There were no significant differences between lansoprazole and omeprazole, pantoprazole and omeprazole, or rabeprazole and omeprazole.[[5]]

Another systematic review and three RCTs also compared various PPIs with each other in people with reflux esophagitis. There were no significant differences in clinical benefit between other PPIs.[[6]] Open surgery appears to be more effective than medical therapy in severe or complicated GERD in the short term; there may be no difference in the long term. There is no evidence to suggest a difference between open and laparoscopic fundoplication. A systematic review of randomized controlled trials (RCTs) showed that open surgery vs. medical therapy in patients with severe or complicated GERD significantly reduced symptoms and produced endoscopic improvements in esophagitis.[[7]] However, a 10-year follow-up of one of the RCTs in this review found no significant difference in endoscopic appearance between those who had been treated with open surgery and those who had received medical therapy. [[8]] There appears to be no clear difference in efficacy between open and laparoscopic fundoplication. [20] [21]

Evidence-Based References 1. van Pinxteren B, et al: Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Reviewed. Cochrane Library, 3, Chichester, UK, John Wiley, 2004. 2. Delaney B, Moayyedi P: Dyspepsia. In: Stevens A, Raftery J, ed. Health care needs assessment, ed 4. NHS Executive; 2002.Reviewed in: Clin Evid 10:518, 2003. 3. Caro JJ, Salas M, Ward A: Healing and relapse rates in gastro-oesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole and pantoprazole compared with omeprazole, ranitidine and placebo: evidence from randomized controlled trials. Clin Ther 2001; 23:998.Reviewed in: Clin Evid 10:518, 2003. 4. Festen HPM, et al: Omeprazole versus high-dose ranitidine in mild gastro-oesophageal reflux disease: short- and long-term treatment. Am J Gastroenterol 1999; 94:931.Reviewed in: Clin Evid 10:518, 2003. 5. Edwards SJ, Lind T, Lundell L: Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis. Aliment Pharmacol Ther 2001; 15:1729.Reviewed in: Clin Evid 10:518, 2003. 6. Moayyedi P, Delaney B, Forman D: Gastro-oesophageal reflux disease. Reviewed. Clin Evid, 10. London: BMJ Publishing Group; 2003:518. 7. Allgood PC, Bachmann M: Medical or surgical treatment for chronic gastro-oesophageal reflux? A systematic review of published evidence of effectiveness. Eur J Surg 2000; 166:713.Reviewed in: Clin Evid 10:518, 2003. 8. Spechler SJ, et al: Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease. JAMA 2001; 285:2331.Reviewed in: Clin Evid 10:518, 2003. 9. Bias JE, et al: Laparoscopic or conventional Nissen fundoplication for gastro-oeosophageal reflux disease: randomized clinical trial. Lancet 2000; 355:170.Reviewed in: Clin Evid 10:518, 2003. 10. Heikkinen T-J, et al: Comparison of laparoscopic and open Nissen fundoplication 2 years after

operation. Surg Endosc 2000; 14:1019.Reviewed in: Clin Evid 10:518, 2003.

Children Cimetidine has been found to be more effective than placebo for the treatment of children with GERD and esophagitis in a small randomized controlled trial (RCT).[[1]] Another small RCT found that significantly more children achieved healing of esophagitis and symptomatic improvement when treated with nizatidine, compared with placebo.[[2]] There is insufficient evidence for the use of metoclopramide in the treatment of GERD in children.[[3]] A systematic review found that adults and children with asthma and GERD did not achieve an overall improvement in asthma following antireflux treatment. The patients were not specifically recruited on the basis of reflux-associated respiratory symptoms. Subgroups of patients may benefit, but it appears difficult to predict responders.[[4]]

Evidence-Based References 1. Cucchiara S, et al: Cimetidine treatment of reflux esophagitis in children: an Italian multicenter study. J Pediatr Gastroenterol Nutr 1989; 8:150.Reviewed in: Clin Evid 11:414, 2004. 2. Simeone D, et al: Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of nizatidine. J Pediatr Gastroenterol Nutr 1997; 25:51. 3. Kumar Y, Sarvananthan R: Gastro-oesophageal reflux in children. Reviewed. Clin Evid, 11. London: BMJ Publishing Group; 2004:414. 4. Gibson PG, Henry RL, Coughlan JL: Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev 2003; 1:

SUGGESTED READINGS Hampel H, et al: Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med 2005; 143(3):199. Heidelbaugh JL, et al: Management of gastroesophageal reflux disease. Am Fam Physician 2003; 68:1311. Kabrilas PJ: Radiofrequency energy treatment of GERD. Gastroenterology 2003; 125:970. Shaheen N, Ransohoff DF: Gastroesophageal reflux, Barret esophagus, and esophageal cancer. JAMA 2002; 287:1972.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Giant Cell Arteritis U. SHIVRAJ SOHUR, M.D., PH.D.

BASIC INFORMATION DEFINITION

Giant cell arteritis (GCA) is a segmental systemic granulomatous arteritis affecting medium- and large-sized arteries in individuals >50 years. Inflammation primarily targets extracranial blood vessels, and although the carotid system is usually affected, pathology in posterior cerebral artery has been reported. SYNONYMS

Temporal arteritis Cranial arteritis

ICD-9CM CODES

446.5 Temporal arteritis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 17 to 23.3 new cases/100,000 persons >50 yr PREVALENCE: 200 cases/100,000 persons; female-to-male predominance of two- to fourfold PHYSICAL FINDINGS & CLINICAL PRESENTATION:

GCA can present with the following clinical manifestations: •

Headache, often associated with marked scalp tenderness

•

Constitutional symptoms (fever, weight loss, anorexia, fatigue)

•

Polymyalgia syndrome (aching and stiffness of the trunk and proximal muscle groups)

•

Visual disturbances (transient or permanent monocular visual loss)

•

Intermittent claudication of jaw and tongue on mastication

Important physical findings in GCA: •

Vascular examination: tenderness, decreased pulsation, and nodulation of temporal arteries; diminished or absent pulses in upper extremities

ETIOLOGY

Vasculitis of unknown etiology

DIAGNOSIS Clinical history and vascular examination are cornerstones of diagnosis. The presence of any three of the following five items allows the diagnosis of GCA with a sensitivity of 94% and a specificity of 91%: •

Age of onset >50 yr

•

New-onset or new type of headache

•

Temporal artery tenderness or decreased pulsation

•

Westergren ESR >50 mm/hr

•

Temporal artery biopsy with vasculitis and mononuclear cell infiltrate or granulomatous changes

DIFFERENTIAL DIAGNOSIS

•

Other vasculitic syndromes

•

Nonarteritic anterior ischemic optic neuropathy (AION)

•

Primary amyloidosis

•

TIA, stroke

•

Infections

•

Occult neoplasm, multiple myeloma

LABORATORY TESTS

•

ESR >50 mm/hr; however, up to 22.5% patients with GCA have normal ESR before treatment.

•

C-reactive protein is typically included in lab investigation; it has greater sensitivity than ESR.

•

Mild to moderate normochromic normocytic anemia, elevated platelet count.

IMAGING STUDIES

•

Reliability of color duplex ultrasonography of temporal artery is controversial as it is thought that it does not improve diagnostic accuracy over careful physical examination.

•

Fluorescein angiogram of ophthalmic vessels may be warranted to differentiate between arteritic AION (i.e., GCA) and nonarteritic AION.

TREATMENT ACUTE GENERAL Rx

•

Intravenous methylprednisolone (500-1000 mg qd for 3 to 5 days) is indicated in those with significant clinical manifestations (e.g., visual loss).

•

Oral prednisone (1 mg/kg/day) may be used under less urgent circumstances or following the initial period of treatment with intravenous methylprednisolone. High-dose oral regimen should be continued at least until symptoms resolve and ESR returns to normal. Prednisone treatment may last up to 2 yr and is tapered over several wk to mo.

DISPOSITION

If steroid therapy is initiated early, GCA has excellent prognosis; however, 20% of patients have permanent partial or complete loss of vision. Once there is visual loss, improvement is dismal: in one study, only 4% of eyes improved in both visual acuity and central visual field. REFERRAL

•

Surgical referral for biopsy of temporal artery

•

Ophthalmology referral in patients with visual disturbances and following initiation of corticosteroid therapy

•

Rheumatology referral for difficult cases

PEARLS & CONSIDERATIONS The diagnostic utility of temporal artery biopsy is not compromised if performed within days of starting steroid therapy. COMMENTS

•

The relationship between polymyalgia rheumatica and GCA is unclear, but the two may frequently coexist.

•

Clinical picture rather than ESR should be the prime yardstick for continuing prednisone therapy. A rising ESR in a clinically asymptomatic patient with normal hematocrit should raise suspicion for alternate explanations (e.g., infections, neoplasms).

•

GCA is associated with a markedly increased risk for the development of aortic aneurysm, which is often a late complication and may cause death. Annual chest radiograph in chronic GCA patients has been suggested, as well as emergent chest CT or MRI for clinical suspicion.

EVIDENCE

The recommendation to perform temporal artery biopsy before beginning long-term corticosteroid therapy is based on consensus rather than evidence. The recommendation that daily high-dose corticosteroid therapy should not be delayed pending confirmation of the diagnosis from temporal artery biopsy is similarly based on consensus rather than evidence. Low-dose aspirin prophylaxis is proven to decrease visual loss and stroke in patients with GCA. The efficacy of adding methotrexate or azathioprine to the steroid regimen for their steroid-sparing effect is unproven. SUGGESTED READINGS Gold R, et al: Therapy of neurological disorders in systemic vasculitis. Sem Neurol 2003; 23(2):207. Gonzalez-Gay MA: The diagnosis and management of patients with giant cell arteritis. J Rheumatol 2005; 32:1186. Hoffman GS, et al: A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate for giant-cell arteritis. Arthritis Rheum 2002; 46(5):1309. Karassa FB, et al: Meta-analysis: test performance of ultrasonography for giant cell arteritis. Ann Intern Med 2005; 142:359-369. Nesher G, et al: Low-dose aspirin and prevention of cranial ischemic complications in giant cell arteritis. Arth & Rheum 2004; 50(4):1332. Norborg E, Norborg C: Giant cell arteritis: epidemiological clues to its pathogenesis and an update on its treatment. Rheumatol 2003; 42:413. Salvarani C, et al: Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med 2002; 347(4):261. Smetana GW, Shmerling RH: Does this patient have temporal arteritis?. JAMA 2002; 287:92.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Giardiasis GLENN G. FORT, M.D., M.P.H., JOSEPH R. MASCI, M.D., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Giardiasis is an intestinal and/or biliary tract infection caused by the protozoal parasite Giardia lamblia. The organism is a widespread zoonotic parasite and frequently contaminates fresh water sources worldwide. SYNONYMS

Giardiasis Giardia duodenalis Giardia intestinalis

ICD-9CM CODES

007.1 Giardiasis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Exact incidence unknown

•

Frequently occurs in outbreaks

PEAK INCIDENCE: •

Varies with risk factors, outbreaks

•

All age groups affected

PREVALENCE (IN U.S.): 4% PREDOMINANT SEX: Male = female PREDOMINANT AGE: •

Preschool children, especially if in day care

•

20 to 40 yr of age, especially among sexually active homosexual men

GENETICS:

Familial Disposition: Patients with common variable immunodeficiency or X-linked agammaglobulinemia are at increased risk of infection. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

More than 70% with one or more intestinal symptoms (diarrhea, flatulence, cramps, bloating, nausea)

•

Fever in 5% of the U.S. population PREDOMINANT SEX: Male:female ratio of 3:1 GENETICS: Most common hereditary hyperbirubinemia (genotypic prevalence 12%) PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

No abnormalities on physical examination other than mild jaundice when bilirubin exceeds 3 mg/dl.

•

A family history of unconjugated hyperbilirubinemia may be present.

ETIOLOGY

•

Decreased elimination of bilirubin in bile is caused by inadequate conjugation of bilirubin.

•

Alcohol consumption and starvation diet can increase the bilirubin level.

•

The pathogenesis of Gilbert's syndrome has been linked to a reduction in bilirubin UGT-1 gene (HUG-Brl) transcription resulting from a mutation in the promoter region.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hemolytic anemia

•

Liver disease (chronic hepatitis, cirrhosis)

•

Crigler-Najjar syndrome

WORKUP

•

Most patients are diagnosed during or after adolescence, when isolated hyperbilirubinemia is detected as an incidental finding on routine biochemical testing

•

Laboratory evaluation to exclude hemolysis and liver diseases as a cause of the elevated bilirubin level ( Table 1-14 )

TABLE 1-14 -- Characteristic Patterns of Liver Function Tests Disorder

Bilirubin

Alkaline Phosphatase

Gilbert's syndrome (abnormal bilirubin metabolism)

NL

AST ALT NL

Prothrombin Time

Albumin

NL

NL

-

NL

NL

Bile duct obstruction (pancreatic cancer) Acute hepatocellular damage (toxic, viral hepatitis) Cirrhosis

-

-

NL-

NL-

NL-

NL-

NL-

NL-

NL-

NL-

From Andreoli TE (ed): Cecil essentials of medicine, ed 6, Philadelphia, 2005, WB Saunders. ALT, Alanine aminotransferase; AST, aspartate aminotransferase; NL, normal; T, increase; - , decrease (arrows indicate extent of change: - , slight to large).

LABORATORY TESTS

Elevated indirect (unconjugated) bilirubin (rarely exceeds 5 mg/dl)

TREATMENT ACUTE GENERAL Rx

Treatment is generally unnecessary. Phenobarbital (if clinical jaundice is present) can rapidly decrease serum indirect bilirubin level. DISPOSITION

Prognosis is excellent. Treatment is generally unnecessary.

REFERRAL

Referral is generally not necessary.

PEARLS & CONSIDERATIONS COMMENTS

•

Patients should be reassured about the benign nature of their condition.

•

Fasting for 2 days or significant dehydration may raise the bilirubin level and result in the clinical recognition of jaundice.

AUTHOR: FRED F. FERRI, M.D. Gingivitis

BASIC INFORMATION DEFINITION

Inflammation of the gums covering the maxilla and mandible SYNONYMS

None

ICD-9CM CODE 523.1 EPIDEMIOLOGY & DEMOGRAPHICS

Gingivitis generally occurs in adults. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Inflammation is usually painless.

•

Bleeding may occur with minor trauma such as brushing teeth.

•

A bluish discoloration of the gums and halitosis are sometimes present.

•

Subgingival plaque may be seen on close examination, and in time, there is detachment of soft tissue from the tooth surface.

•

Long-standing infection may lead to destructive periodontal disease, which may involve teeth and bones.

•

A dramatic form of gingivitis called acute ulcerative necrotizing gingivitis (ANUG or “trench mouth”) can occur. This is manifested by acute, painful, inflammation of the gingivae, with bleeding, ulceration, and halitosis. At times this is accompanied by fever and lymphadenopathy.

•

Linear gingival erythema (“HIV Gingivitis”) presents as a brightly inflamed band of marginal gingiva. It may be painful, with easy bleeding and rapid destruction.

•

Severe periodontitis can occur in patients with diabetes mellitus or HIV infection and in primary HIV infection (acute retroviral syndrome).

•

Pregnancy may be associated with an acute form of gingivitis. Gingivae become inflamed and hypertrophic; this is likely due to hormonal shifts.

ETIOLOGY

•

A variety of organisms may be found in the environment of plaque. Anaerobes play a predominant role in periodontal disease.

•

Improper hygiene and poorly fitting dentures may contribute to development of gingivitis.

•

Excessive use of tobacco and alcohol may predispose individuals to gingival disease.

•

In patients with HIV infection, gram-negative anaerobes, enteric organisms, and yeast predominate.

•

Appropriate oral hygiene, such as flossing and tooth brushing, can prevent the accumulation of bacterial plaque; once dense plaque is present, adequate hygiene becomes more difficult.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Gingival hyperplasia, which may be caused by long term use of phenytoin or nifedipine WORKUP

Oral examination LABORATORY TESTS

Elevated serum glucose in diabetics IMAGING STUDIES

Radiographs of the teeth and facial bones may reveal extension of infection to these structures.

TREATMENT NONPHARMACOLOGIC THERAPY

Removal of plaque, and at times, debridement of soft tissue ACUTE GENERAL Rx

•

Penicillin VK, 500 mg po qid for 1 to 2 wk or

•

Clindamycin, 300 mg po qid for 1 to 2 wk

•

For linear gingival erythema, chlorhexidene gluconate rinses and nystatin rinses or troches may be used

CHRONIC Rx

Extensive or recurrent infection may require periodic evaluation and debridement. DISPOSITION

Continued inflammation can eventually lead to destruction of teeth and bone. REFERRAL

Patients should be referred to a dentist or periodontist.

PEARLS & CONSIDERATIONS COMMENTS

•

Presence of periodontal disease is associated with an increased incidence of anaerobic pleuropulmonary infections.

•

Existing data support the recommendation to change a toothbrush every 3 mo. Worn brushes seem to be less effective in plaque reduction.

EVIDENCE

Professional cleaning and scaling reaches subgingival areas not usually accessible to the patient through toothbrushing and flossing.[[1]] Failure of the patient to remove plaque deposits regularly between visits will result in extension of plaque to subgingival crevices and accumulation of calculus. Parameter on plaque-associated gingivitis. Chicago: American Academy of Periodontology, National Guideline Clearinghouse: patient education, including oral hygiene instruction; debridement of tooth surfaces to remove plaque and calculus; correction of restorations hindering oral hygiene; surgical correction of the gums where indicated; and outcomes assessment.[[2]]

Evidence-Based References 1. Axelsson P, Lindhe J: Effect of controlled oral hygiene procedures on caries and periodontal disease in adults: results after 6 years. J Clin Periodontol 1981; 8:239. 2. American Academy of Periodontology: Guidelines for periodontal therapy. J Periodontol 1998; 69:405.

SUGGESTED READINGS Sharma NC, et al: Antiplaque and antigingivitis effectiveness of a hexetidine mouthwash. J Clin Periodontol 2003; 30(7):590. Rudiger SG, et al: Dental biofilms at healthy and inflamed gingival margins. J Clin Periodontol 2002; 29(6):524.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Glaucoma, Chronic Open-Angle MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

Chronic open-angle glaucoma refers to optic nerve damage often associated with elevated intraocular pressure; it is a chronic, slowly progressive, usually bilateral disorder associated with visual loss, eye pain, and optic nerve damage. Now felt to be a primary disease of the optic nerve with high pressure a high risk factor for glaucoma. SYNONYMS

Chronic simple glaucoma Primary open-angle glaucoma (POAG)

ICD-9CM CODES

365.1 Open-angle glaucoma EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Third most common cause of visual loss (75% to 95% of all glaucomas are open angle.) PEAK INCIDENCE: •

Increases after 40 yr

•

Because of rapid aging of the U.S. population, expect 3 million cases by year 2020.

PREVALENCE (IN U.S.): •

Overall prevalence in U.S. population >40 yr of age is estimated to be 1.86%, with 1.57 million white and 398,000 black patients affected.

•

150,000 patients suffer bilateral blindness.

•

Disease occurs in 2% of people >40 yr old.

•

Prevalence is higher in diabetics, with high myopia, and among older persons.

•

More common in blacks (3× the age-adjusted prevalence than whites).

PREDOMINANT AGE:

•

Persons >50 yr

•

Can occur in 30s and 40s

GENETICS: •

Four to six times higher incidence in blacks than whites

•

No clear-cut hereditary patterns but a strong hereditary tendency

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

High intraocular pressures and large optic nerve cup (OHTS study—very important)

•

Corneal edema causes vision loss and blurring

•

Abnormal visual fields

•

Open-angle gonioscopy

•

'Red eye

•

Restricted vision and field

ETIOLOGY

•

Uncertain hereditary tendency

•

Topical steroids

•

Trauma

•

Inflammatory

•

High-dose oral corticosteroids taken for prolonged periods

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other optic neuropathies

•

Secondary glaucoma from inflammation and steroid therapy

•

Red eye differential

•

Trauma

•

Contact lens injury

WORKUP

•

Intraocular pressure

•

Slit lamp examination

•

Visual fields

•

Gonioscopy

•

Nerve fiber analysis—GDx, etc.

•

Corneal thickness—very important in prognosis

LABORATORY TESTS

Blood sugar IMAGING STUDIES

•

Optic nerve photography—stereo photographs

•

Visual field testing

•

GDx (laser scan of nerve fiber layer), OCT, HRT

TREATMENT ACUTE GENERAL Rx

•

ß-Blockers (Timolol) qd to bid depending on individual response to drug

•

Diamox 250 mg qid or 500 mg bid

•

Hyperosmotic agents (mannitol) in acute treatment (IV)

•

Prostaglandins very commonly used as first-line treatment

•

Laser trabeculoplasty (SLT) as needed

•

Pilocarpine qid

CHRONIC Rx

•

At least biannual checks of intraocular pressure and adjustment of medication

•

Poor control = frequent examinations; good control = drugs

•

Trabeculectomy

•

Filter valves

DISPOSITION

Must be followed by ophthalmologist REFERRAL

Immediately to ophthalmologist

PEARLS & CONSIDERATIONS COMMENTS

•

Glaucoma is a serious blinding disease. Must be followed professionally by an ophthalmologist.

•

Early diagnosis and treatment may minimize visual loss.

•

Glaucoma is not solely caused by increased intraocular pressure, because approximately 20% of patients with glaucoma have normal intraocular pressure, but high pressure is definitely a risk factor to be considered. Potential sites of increased resistance to aqueous flow are described in Fig. 1-106 .

FIGURE 1-106 Potential sites of increased resistance to aqueous flow. (From Yanoff M, Duker JS: Ophthalmology, ed 2, St Louis, 2004, Mosby.)

EVIDENCE

One systematic review found that topical medical treatments significantly reduced intraocular pressure in patients with primary open-angle glaucoma after a minimum of 3 months of treatment. It is, however, not clear which types of medical treatments were used.[[1]] One large randomized controlled trial (RCT) recruited 1636 participants with increased intraocular pressures but no other ophthalmologic changes aged between 40 and 80 years. Patients were randomized to observation or treatment groups. Treatment groups received commercially available topical ocular hypotensives. The study found that this treatment was effective in delaying or preventing the onset of primary open-angle glaucoma in patients after 5-year's follow-up compared with the observation group.[[2]]

RCTs have found that laser trabeculoplasty combined with medical treatment is more effective at decreasing intraocular pressures in patients with open-angle glaucoma than no initial treatment or medical treatment alone. [50] [51] There is some evidence to suggest that both surgical trabeculectomy and laser trabeculoplasty produce

decreases in intraocular pressure, but the long-term differences between the efficacies of each treatment are less clear. [52] [53] There is evidence that there is no significant difference in visual acuity or intraocular pressure in the long term between Nd:YAG laser iridotomy and peripheral iridectomy for the treatment of acute angle-closure glaucoma.[[7]] There is strong consensus for the efficacy of medical treatments that lower intraocular pressure in the treatment of acute angle-closure glaucoma. There is no apparent evidence available from any RCTs.[[8]] An RCT of patients with normal-tension glaucoma showed that treatment to reduce the pressures by 30% significantly reduced the progression to visual field loss over 8 years compared with no treatment. The treatment consisted of drugs with or without surgical trabeculectomy.[[9]] A Cochrane systematic review of the interventions for normal tension glaucoma was only able to find three studies that focused on patient relevant outcomes. In one study, the effect of intraocular pressure lowering on visual field outcome was only significant when data were corrected for cataract development. In two small studies, a calcium antagonist, brovincamine, produced a beneficial effect concerning visual field loss.[[10]]

Evidence-Based References 1. Rossetti L, et al: Randomised clinical trials on medical treatment of glaucoma: are they appropriate to clinical practice?. Arch Ophthalmol 1993; 111:96.Reviewed in: Clin Evid 9:729, 2003. 2. Kass M, et al: The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120:701. 3. Glaucoma Laser Research Group: The Glaucoma Laser Trial and Glaucoma Laser Trial follow-up study. 7. Results. Am J Ophthalmol 1995; 120:718.Reviewed in: Clin Evid 9:729, 2003. 4. Heijl A, et al: Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002; 120:1268. 5. Migdal C, et al: Long-term functional outcome after early surgery compared with laser and medicine in open angle glaucoma. Ophthalmology 1994; 101:1651.Reviewed in: Clin Evid 9:729, 2003. 6. The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes with race. Seven year results. Ophthalmology 1998; 105:1146.Reviewed in: Clin Evid 9:729, 2003. 7. Fleck BW, Wright E, Fairley EA: A randomised prospective comparison of operative peripheral iridectomy and Nd:YAG laser iridotomy treatment of acute angle closure glaucoma: 3 year visual acuity and intraocular pressure control outcome. Br J Ophthalmol 1997; 81:884.Reviewed in: Clin Evid 9:729, 2003. 8. Shah R, Wormald R: Glaucoma. Reviewed. Clin Evid, 9. London: BMJ Publishing Group; 2003:729. 9. Collaborative Normal-Tension Glaucoma Study Group: Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressure. Am J Ophthalmol 1998; 126:487.Reviewed in: Clin Evid 9:729, 2003. 10. Sycha T, Vass C, Findl O: Interventions for normal tension glaucoma. Cochrane Database Syst Rev 2004; 2:

SUGGESTED READINGS Gordon MO, et al: Baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120:714. Heijl A, et al: Reduction of intraocular pressure and glaucoma progression: Results from the early manifest glaucoma trial. Arch Ophthalmol 2002; 120:1268. Higginbotham EJ, et al: The Ocular Hypertension Treatment Study: topical medication delays or prevents primary open-angle glaucoma in African American individuals. Arch Ophthalmol 2004; 122(6):813. Rezaie T, et al: Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 2002; 295:1077.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Glaucoma, Primary Angle-Closure MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

Primary angle-closure glaucoma (PACG) occurs when elevated intraocular pressure is associated with closure of the filtration angle or obstruction in the circulating pathway of the aqueous humor. SYNONYMS

Acute glaucoma, angle-closure Pupillary block glaucoma Narrow-angle glaucoma

ICD-9CM CODES

365.2 Primary angle-closure glaucoma (PACG) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

In 2% to 8% of all patients with glaucoma

•

Higher incidence among those with hyperopia, small eyes, dense cataracts, shallow anterior chambers

PEAK INCIDENCE: Greater after 50 yr of age; high association with hypopia, cataracts, and eye trauma PREDOMINANT SEX: Females > males PREDOMINANT AGE: 50 to 60 yr GENETICS: High family history PHYSICAL FINDINGS & CLINICAL presentation

•

Hazy cornea ( Fig. 1-107 )

•

Narrow angle

•

Red eyes

•

Pain

•

Injection of conjunctiva

•

Shallow anterior chamber

•

Thick cataract

•

Old trauma

•

Chronic eye infections

FIGURE 1-107 Acute angle-closure glaucoma. A, Acutely elevated pressure produces an inflamed eye with corneal edema (note fragmented light reflex) and a middilated pupil. B, Slit lamp examination shows a very shallow central anterior chamber (space between cornea and iris) and no peripheral chamber. (From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

•

Narrow angles with acute closure—blockage of circulatory path of the aqueous humor causing increase in interior ocular pressure

•

Secondary angle-closure glaucoma (SACG) resulting from neovascularization of iris, iris tumors, pharmacology, lens induced, iris scarring, trauma, chronic inflammation with scarring, malignant glaucoma with aqueous misdirection

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

High pressure

•

Optic nerve cupping

•

Field loss

•

Shallow chamber

•

Open-angle glaucoma

•

Conjunctivitis

•

Corneal disease-keratitis

•

Uveitis

•

Scleritis

•

Allergies

•

Contact lens wearing with irritation

WORKUP

•

Intraocular pressure

•

Gonioscopy

•

Slit lamp examination

•

Visual field examination

•

GDx examination (laser scan of nerve fiber layer), OCT

•

Optic nerve evaluation

•

Anterior chamber depth

•

Cataract evaluation

•

High hyperopia

•

Dilatin provocative testing

LABORATORY TESTS

•

Blood sugar and CBC (if diabetes or inflammatory disease is suspected)

•

Visual field

•

GDx nerve fiber analysis, OCT, HRT

IMAGING STUDIES

•

Fundus photography

•

Fluorescein angiography for neurovascular disease

TREATMENT

The goal of treatment is to acutely lower pressure on eye and keep it down. NONPHARMACOLOGIC THERAPY

Laser iridotomy early in disease process ACUTE GENERAL Rx

•

IV mannitol

•

Pilocarpine

•

ß-Blockers

•

Diamox

•

Laser iridotomy

•

Anterior chamber paracentesis (as emergency treatment)

CHRONIC Rx

•

Iridotomy

•

Trabeculectomy

•

Filter valves

•

Other laser procedures

DISPOSITION

Refer to ophthalmologist immediately. REFERRAL

This is an emergency—refer immediately to an ophthalmologist.

PEARLS & CONSIDERATIONS COMMENTS

•

Do not use antihistamines or vasodilators with narrow angle glaucoma.

•

After iridotomy, the majority of patients will be totally cured and will need no further medication and have no visual loss.

•

Lower socioeconomic status and higher levels of social deprivation are risk factors for delayed detection and probable worse outcomes in glaucoma.

EVIDENCE

One systematic review found that topical medical treatments significantly reduced intraocular pressure in patients with primary open-angle glaucoma after a minimum of 3 months of treatment. It is, however, not clear which types of medical treatments were used.[[1]]

One large randomized controlled trial (RCT) recruited 1636 participants with increased intraocular pressures but no other ophthalmologic changes aged between 40 and 80 years. Patients were randomized to observation or treatment groups. Treatment groups received commercially available topical ocular hypotensives. The study found that this treatment was effective in delaying or preventing the onset of primary open-angle glaucoma in patients after 5-year's follow-up compared with the observation group.[[2]]

RCTs have found that laser trabeculoplasty combined with medical treatment is more effective at decreasing intraocular pressures in patients with open-angle glaucoma than no initial treatment or medical treatment alone. [64] [65] There is some evidence to suggest that both surgical trabeculectomy and laser trabeculoplasty produce decreases in intraocular pressure but the long-term differences between the efficacies of each treatment are less clear. [66] [67] There is evidence that there is no significant difference in visual acuity or intraocular pressure in the long term between Nd:YAG laser iridotomy and peripheral iridectomy for the treatment of acute angle-closure glaucoma.[[7]] There is strong consensus for the efficacy of medical treatments that lower intraocular pressure in the treatment of acute angle-closure glaucoma. There is no apparent evidence available from any RCTs.[[8]] An RCT of patients with normal-tension glaucoma showed that treatment to reduce the pressures by 30% significantly reduced the progression to visual field loss over 8 years compared with no treatment. The treatment consisted of drugs with or without surgical trabeculectomy.[[9]] A Cochrane systematic review of the interventions for normal tension glaucoma was only able to find three studies that focused on patient relevant outcomes. In one study the effect of intraocular pressure lowering on visual field outcome was only significant when data were corrected for cataract development. In two small studies, a calcium antagonist, brovincamine, produced a beneficial effect concerning visual field loss.[[10]]

Evidence-Based References 1. Rossetti L, et al: Randomised clinical trials on medical treatment of glaucoma; are they appropriate to clinical practice?. Arch Opthalmol 1993; 111:96.Reviewed in: Clin Evid 9:729, 2003. 2. Kass M, et al: The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120:701. 3. Glaucoma Laser Research Group: The Glaucoma Laser Trial and Glaucoma Laser Trial follow-up study. 7. Results. Am J Ophthalmol 1995; 120:718.Reviewed in: Clin Evid 9:729, 2003. 4. Heijl A, et al: Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002; 120:1268. 5. Migdal C, et al: Long-term functional outcome after early surgery compared with laser and medicine in open angle glaucoma. Ophthalmology 1994; 101:1651.Reviewed in: Clin Evid 9:729, 2003. 6. The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes with race. Seven year results. Ophthalmology 1998; 105:1146.Reviewed in: Clin Evid 9:729, 2003.

7. Fleck BW, Wright E, Fairley EA: A randomised prospective comparison of operative peripheral iridectomy and Nd:YAG laser iridotomy treatment of acute angle closure glaucoma: 3 year visual acuity and intraocular pressure control outcome. Br J Ophthalmol 1997; 81:884.Reviewed in: Clin Evid 9:729, 2003. 8. Shah R, Wormald R: Glaucoma. Reviewed. Clin Evid, 9. London: BMJ Publishing Group; 2003:729. 9. Collaborative Normal-Tension Glaucoma Study Group: Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressure. Am J Ophthalmol 1998; 126:487.Reviewed in: Clin Evid 9:729, 2003. 10. Sycha T, Vass C, Findl O: Interventions for normal tension glaucoma. Cochrane Database Syst Rev 2004; 2:

SUGGESTED READINGS Foster PJ, et al: Defining “occludable” angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in East Asian people. Br J Opthalmol 2004; 88(4):486. Fraser S, et al: Deprivation and late presentation of glaucoma: case control study. BMJ 2001; 322:638. Gazzard G, et al: Intraocular pressure and visual field loss in primary angle closure and primary open angle glaucomas. Br J Ophthalmol 2003; 87(6):720. Kapur SB: The lens and angle-closure glaucoma. J Cataract Refract Surg 2001; 27(2):176. Lam DS, et al: Angle-closure glaucoma. Opthalmology 2002; 109:1.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Glenohumeral Dislocation LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Complete separation or displacement of the humeral head from the glenoid surface. (Partial separation is termed subluxation.) Most often the cause is traumatic, and the humeral head dislocates anterior and inferior. This may cause a tear of the glenoid labrum (the Bankart lesion). Less commonly, the head dislocates posteriorly. Rarely, multidirectional instability may be present in which dislocation or subluxation, often bilateral, may occur in multiple directions, usually the result of excessive joint laxity and generally without trauma.

ICD-9CM CODES

831.01 Anterior 831.02 Posterior 831.03 Inferior 718.31 Recurrent 718.81 Instability PHYSICAL FINDINGS & CLINICAL PRESENTATION

Traumatic •

The arm is held in external rotation with anterior dislocation, internal rotation with posterior dislocation.

•

Little movement is possible without pain.

•

The acromion may appear more prominent and there is absence of the normal “fullness” beneath the acromion.

•

The status of the axillary nerve must always be checked (sensation to the middeltoid should be assessed).

•

The apprehension test may become positive if anterior instability persists (pain and apprehension that the shoulder will dislocate when the relaxed arm is manually placed in the “throwing position” of external rotation and abduction).

•

Recurrent episodes of anterior dislocation may occur with minor movement such as putting on a coat or turning a light off at night.

Multidirectional

•

Often difficult to diagnose, especially if only subluxation occurs

•

Recurrent episodes of giving out, weakness, often bilateral without trauma

•

Sulcus sign often positive (the arms are pulled downward with the patient standing; a sulcus [indentation] will form between the acromion and humeral head, indicating excessive inferior movement of the head)

•

Other signs of generalized joint laxity may be present, such as joint hyperextensibility and the ability of the patient to touch the thumb against the flexor aspect of the forearm

ETIOLOGY

•

Trauma

•

Generalized joint laxity (multidirectional)

•

Seizures (posterior dislocations)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Rotator cuff rupture

•

Frozen shoulder (posterior dislocation)

•

Suprascapular nerve paralysis

•

Anterior instability

IMAGING STUDIES

•

Acute shoulder injury: True AP roentgenogram plus lateral view of the glenohumeral joint, either transaxillary or transcapular

•

MRI: To determine soft tissue status, especially the presence of Bankart lesion or rotator cuff tear; may be indicated following a second episode of dislocation

TREATMENT

•

Reduction of the acute dislocation by gentle straight traction in the relaxed patient followed by light immobilization

•

Gentle limited range of motion exercises as pain subsides followed by strengthening exercises at 2 wk

DISPOSITION

•

Recurrence of anterior dislocation is common in the young; this patient may have to avoid the arm position associated with dislocation (external rotation with abduction)

•

Primary dislocations in patients over 40 yr are not generally complicated by recurrence, but may result in shoulder stiffness and may have associated rotator cuff injuries

•

There is an almost 100% recurrence after the third dislocation

REFERRAL

Surgical reconstruction may be required in the recurrent dislocator

PEARLS & CONSIDERATIONS COMMENTS

•

It is important to know if there was an injury involved in the first episode and if a radiograph was taken to determine direction of the dislocation.

•

Up to 50% of posterior dislocations are missed by the first examiner, usually the result of an inadequate lateral radiograph of the glenohumeral joint.

•

“Voluntary” posterior dislocators should always be treated nonsurgically.

•

Sports activities may be resumed when there is pain-free full flexibility and normal strength.

•

Multidirectional instabilities are usually treated nonsurgically with strengthening exercises.

SUGGESTED READINGS Caplan J, et al: Multidirectional instability of the shoulder in elite female gymnasts. Am J Orthop 2007; 36:660. Cicak N: Posterior dislocation of the shoulder. J Bone Joint Surg Br 2004; 86(3):324. Matsen III FA, et al: Principles for the evaluation and management of shoulder instability. J Bone Joint Surg 2006; 88A:648. McFarland EG, et al: The effect of variation in definition on the diagnosis of multidirectional instability of the shoulder. J Bone Joint Surg 2003; 85A:2138. O'Connor DR, et al: Painless reduction of acute anterior shoulder dislocations without anesthesia. Orthopedics 2006; 29:528. Robinson CM, Dobson RJ: Anterior instability of the shoulder after trauma. J Bone Joint Surg Br 2004; 86(4):469. Robinson CN, Kelly M, Wakefield AE: Redislocation of the shoulder during the first 6 weeks after a primary anterior dislocation: risk factor and results of treatment. J Bone Joint Surg 2002; 84:1552. Sachs RA, et al: Can the need for future surgery for acute traumatic anterior dislocation be predicted?. J Bone Joint Surg 2007; 89A:1665. Sugaya H, Moriishi J, et al: Glenoid rim morphology in recurrent anterior glenohumeral instability. J Bone Joint Surg 2003; 85:878. te Slaa RL, et al: The prognosis following acute primary glenohumeral dislocation. J Bone Joint Surg Br 2004; 1(86):58.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Glomerulonephritis, Acute FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Acute glomerulonephritis is an immunologically mediated inflammation primarily involving the glomerulus that can result in damage to the basement membrane, mesangium, or capillary endothelium. Table 1-15 summarizes primary renal diseases that present as acute glomerulonephritis.

TABLE 1-15 -- Summary of Primary Renal Diseases That Present as Acute Glomerulonephritis Idiopathic Rapidly Poststreptococcal Progressive Glomerulonephritis IgA Membranoproliferative Glomerulonephritis Diseases (PSGN) Nephropathy Glomerulonephritis (RPGN) Clinical manifestations

All ages, mean 7 yr, 2:1 male

15-35 yr, 2:1 male

15-30 yr, 6:1 male

Mean 58 yr, 2:1 male

Age and sex

90%

50%

90%

90%

Acute nephritic syndrome

Occasionally

50%

Rare

Rare

Asymptomatic hematuria

10%-20%

Rare

Rare

10%-20%

Nephrotic syndrome

70%

30%-50%

Rare

25%

Hypertension

50% (transient)

Very rare

50%

60%

Acute renal failure

Latent period of 1-3 wk

Follows viral syndromes

Pulmonary hemorrhage; iron-deficiency anemia

None

ASO titers (70%)

Serum IgA (50%)

Positive anti-GBM antibody

Positive ANCA

Positive streptozyme (95%)

IgA in dermal capillaries

HLA-B12, D “EN” (9)[*] HLA-Bw 35, DR4 (4)[*]

HLA-DR2 (16)[*]

None established

Diffuse proliferation

Focal diffuse proliferation with crescents

Crescentic GN

Other Laboratory findings

C3-C9 Normal Cl, C4 Immunogenetics Renal pathology Light microscopy

Immunofluorescence Granular IgG, C3

Focal proliferation

Diffuse Linear IgG, C3 mesangial IgA

No immune deposits

Diseases Electron microscopy

Poststreptococcal Glomerulonephritis (PSGN) Subepithelial humps

Prognosis

95% resolve spontaneously

IgA Membranoproliferative Nephropathy Glomerulonephritis Mesangial deposits

No deposits

Idiopathic Rapidly Progressive Glomerulonephritis (RPGN) No deposits

Slow 75% stabilize or improve 75% stabilize or progression in if treated early improve if treated early 25%-50%

5% RPGN or slowly progressive Treatment

Supportive

None established

Plasma exchange, steroids, cyclophosphamide

Steroid pulse therapy

Modified from Goldman L, Ausiello D (eds): Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders. ANCA, Antineutrophil cytoplasm antibody; GBM, glomerular basement membrane; GN, glomerulonephritis; Ig, immunoglobulin.

* Relative risk.

SYNONYMS

Postinfectious glomerulonephritis Acute nephritic syndrome

ICD-9CM CODES

583.9 Glomerulonephritis, acute EPIDEMIOLOGY & DEMOGRAPHICS

•

Over 50% of cases involve children 70% of patients with mesangial capillary glomerulonephritis will develop chronic renal failure.

•

Generally prognosis is worse in patients with heavy proteinuria, severe hypertension, and significant elevations of creatinine.

•

Recovery of renal function occurs within 8 to 12 wk in 95% of patients with poststreptococcal glomerulonephritis.

REFERRAL

•

Nephrology consultation. The urgency for referral depends on the GFR. Urgent consultation is recommended if GFR is significantly abnormal, rapidly deteriorating, or if there are systemic symptoms

•

Surgical referral for biopsy in selected cases

PEARLS & CONSIDERATIONS COMMENTS

•

Anticoagulation to prevent DVT should be considered in patients with a low level of physical activity.

•

Monitoring of lipids and aggressive treatment of hyperlipidemias is recommended.

•

Close monitoring of side effects of immunosuppressive drugs and complications of corticosteroids is necessary.

SUGGESTED READINGS Contreras G, et al: Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004; 350:971. Hricik D, et al: Glomerulonephritis. N Engl J Med 1998; 339:888. Madaio MP, Harrington JT: The diagnosis of glomerular diseases. Arch Intern Med 2001; 161:25.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Glossitis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Glossitis is an inflammation of the tongue that can lead to loss of filiform papillae.

ICD-9CM CODES

529.0 Glossitis EPIDEMIOLOGY & DEMOGRAPHICS

Glossitis is seen more frequently in patients of lower socioeconomic status, malnourished patients, alcoholics, smokers, elderly patients, immunocompromised patients, and patients with dentures. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The appearance of the tongue is variable depending on the etiology of the glossitis. Loss of filiform papillae results in red, smooth-surfaced tongue ( Fig. 1-109 ).

•

The tongue may appear pale in patients with significant anemia.

•

Pain and swelling of the tongue may be present when glossitis is associated with infections, trauma, or lichen planus.

•

Ulcerations may be present in patients with herpetic glossitis, pemphigus, or streptococcal infection.

•

Excessive use of mouthwash may result in a “hairy” appearance of the tongue.

FIGURE 1-109 Glossitis. (From Seidel HM [ed]: Mosby's guide to physical examination, ed 4, St Louis, 1999, Mosby.)

ETIOLOGY

•

Nutritional deficiencies (vitamin E, riboflavin, niacin, vitamin B12, iron deficiency)

•

Infections (viral, candidiasis, TB, syphilis)

•

Trauma (generally caused by poorly fitting dentures)

•

Irritation of the tongue secondary to toothpaste, medications, alcohol, tobacco, citrus

•

Lichen planus, pemphigus vulgaris, erythema multiforme

•

Neoplasms

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Infections

•

Use of chemical irritants

•

Neoplasms

•

Skin disorders (e.g., Behçet's syndrome, erythema multiforme)

WORKUP

•

Laboratory evaluation to exclude infectious processes, vitamin deficiencies, and systemic disorders

•

Biopsy of lesion only when there is no response to treatment

LABORATORY TESTS

•

CBC: Decreased Hgb and Hct, low MCV (iron deficiency anemia), elevated MCV (vitamin B12 deficiency)

•

Vitamin B12 level

•

10% KOH scrapings in patients with white patches suspect for candidiasis

TREATMENT NONPHARMACOLOGIC THERAPY

Avoidance of primary irritants such as hot foods, spices, tobacco, and alcohol ACUTE GENERAL Rx

Treatment varies with the etiology of the glossitis. •

Malnutrition with avitaminosis: multivitamins

•

Candidiasis: fluconazole 200 mg on day 1, then 100 mg/day for at least 2 wk or nystatin 400,000 U suspension qid for 10 days or 200,000 pastilles dissolved slowly in the mouth four to five times qd for 10 to 14 days

•

Painful oral lesions: rinsing of the mouth with 2% lidocaine viscous, 1 to 2 tablespoons q4h prn; triamcinolone 0.1% applied to painful ulcers prn for symptomatic relief

CHRONIC Rx

•

Lifestyle changes with elimination of tobacco, alcohol, and other primary irritants

•

Dental evaluation for correction of ill-fitting dentures

•

Correction of associated metabolic abnormalities such as hyperglycemia from diabetes mellitus

DISPOSITION

Most patients experience prompt improvement with identification and treatment of the cause of the glossitis. REFERRAL

Surgical referral for biopsy of solitary lesions unresponsive to treatment to rule out neoplasm

PEARLS & CONSIDERATIONS COMMENTS

If the primary cause of glossitis is not identified or cannot be corrected, enteric nutritional replacement therapy should be considered in malnourished patients. AUTHOR: FRED F. FERRI, M.D. Gonorrhea

BASIC INFORMATION DEFINITION

Gonorrhea is a sexually transmitted bacterial infection with a predilection for columnar and transitional epithelial cells. It commonly manifests as urethritis, cervicitis, or salpingitis. Infection may be asymptomatic. It differs in males and females in course, severity, and ease of recognition. SYNONYMS

Gonococcal urethritis Gonococcal vulvovaginitis Gonococcal cervicitis Gonococcal bartholinitis Clap; GC

ICD-9CM CODES

098 Gonococcal infections EPIDEMIOLOGY & DEMOGRAPHICS

•

The disease is common worldwide, affects both sexes, all ages, especially younger adults; highest incidence is in inner-city areas, with an estimated 3 million new cases annually.

•

Asymptomatic anterior urethral carriage may occur in 12% to 50% of cases in men.

•

Asymptomatic in 50% to 80% of cases in women. Most common dissemination by mucosal passage to fallopian tubes, resulting in PID in 10% to 15% of infected women. Hematogenous spread may result in septic arthritis and skin lesions. Conjunctivitis rarely occurs but may result in blindness if not rapidly treated. Infection can occur in both men and women in oropharynx and anorectally.

•

600,000 new infections/yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Males: purulent discharge from anterior urethra with dysuria appearing 2 to 7 days after infecting exposure. May have rectal infection causing pruritus, tenesmus, and discharge or may be asymptomatic.

•

Females: initial urethritis, cervicitis may occur a few days after exposure, frequently mild. In about 20% of cases, uterine invasion occurs after menstrual period with signs and symptoms of endometritis, salpingitis, or pelvic peritonitis. The patient may have purulent discharge, inflamed Skene's or Bartholin's glands.

•

Classic presentation of acute gonococcal PID is fever, abdominal and adnexal tenderness, often absence of purulent discharge. Physical examination may be normal if asymptomatic.

ETIOLOGY

Neisseria gonorrhoeae is the gonococcus. Plasmids coding for ß-lactamase render some strains resistant to penicillin or tetracycline (PPNG, TRNG). There is an increasing frequency of chromosomally mediated resistance to penicillin, tetracycline, and cefoxitin. In the Far East, high-level resistance to spectinomycin is endemic. There are a rising number of cases of quinolone-resistant N. gonorrhoeae (QRNG) worldwide, with the expected number to rise in the U.S. from importation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Nongonococcal urethritis (NGU)

•

Nongonococcal mucopurulent cervicitis

•

Chlamydia trachomatis

WORKUP

•

Diagnosis is dependent on bacteriologic investigation.

•

Gram-negative intracellular diplococci are diagnostic in male urethral smears. There is a false-negative rate of 60% to 70% in female cervical or urethral smears. Culture is essential in women.

LABORATORY TESTS

•

Gonorrhea culture on Thayer-Martin medium (Organism is fastidious, requires aerobic conditions with increased carbon dioxide atmosphere. Incubate ASAP.)

•

Serologic testing for syphilis on all patients

•

Chlamydia testing on all patients

•

Offer of HIV counseling and testing

TREATMENT ACUTE GENERAL Rx

Uncomplicated infections of the cervix, urethra, and rectum: •

Cefixime 400 mg PO × 1 dose or

•

Ceftriaxone 125 mg IM × 1 dose or

•

Ciprofloxacin 500 mg PO × 1 dose or

•

Ofloxacin 400 mg PO × 1 dose plus azithromycin 1 g PO × 1 dose or

•

Doxycycline 100 mg PO bid × 7 days

•

Dual treatment with azithromax and doxycycline may prevent the development of antimicrobial resistant N. gonorrhoeae.

Alternatives: Spectinomycin 2 g IM × 1 dose Quinolones: •

Gatifloxacin 400 mg PO × 1 dose

•

Norfloxacin 800 mg PO × 1 dose

•

Lomefloxacin 400 mg PO × 1 dose

•

Not recommended for person 10 lesions), subcutaneous (occurring primarily in children 2 to 5 years of age), and perforating (rare form manifesting with 1- to 4-mm papules with a central crust).

•

Localized granuloma annulare starts as a small ring of colored skin or pale erythematous papules.

•

Lesions coalesce and evolve into annular plaques over several weeks.

•

Plaques undergo central involution and increase in diameter over several months (0.5 to 5 cm) ( Fig. 1-111 ).

•

Most frequently found on the lateral and dorsal surfaces of the hands and feet.

•

Most lesions resolve spontaneously after several months.

•

The generalized form of GA is characterized by hundreds to thousands of small, flesh-colored papules in a symmetric distribution on the trunk and extremities.

•

Deep dermal (subcutaneous GA) presents as a large, painless, skin-colored nodules that are frequently mistaken for rheumatoid nodules.

FIGURE 1-111 Granuloma annulare. (From Callen JP [ed]: Color atlas of dermatology, ed 2, Philadelphia, 2000, WB Saunders.)

ETIOLOGY

Unknown, but may be related to vasculitis, trauma, monocyte activation, or delayed hypersensitivity.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Tinea corporis

•

Lichen planus

•

Necrobiosis lipoidica diabeticorum

•

Sarcoidosis

•

Rheumatoid nodules

•

Late secondary or tertiary syphilis

•

Arcuate and annular plaques of mycosis fungoides

•

Papular GA can simulate insect bites, secondary syphilis, xanthoma

•

Annular elastolytic giant cell granuloma

WORKUP

•

Diagnosis is based on clinical appearance and presentation.

•

Biopsy when diagnosis is unclear

LABORATORY TESTS

There are no laboratory tests that will help confirm the diagnosis. Biopsy shows focal degeneration of collagen and elastic fibers, mucin deposition, and perivascular and interstitial lymphohistiocytic infiltrate in the upper and mid dermis.

TREATMENT NONPHARMACOLOGIC THERAPY

Reassurance, given the self-limited and benign nature of GA CHRONIC Rx

High potency topical corticalsteroids with or without occlusion and intralesional steroid injection into elevated border with triamcinolone 2.5 to 10 mg/ml are useful first-line local therapies.

•

Cryosurgery, PUVA or UVA-1 therapy, and CO2 laser treatment can also be used.

•

Systemic agents (e.g., niacinamide, hydroxychloroquine, chloroquine, cyclosporine, dapsone) are generally reserved for severe cases. Recent case reports indicate positive outcomes with tacrolimus and pimecrolimus and with the use of the tumor necrosis factor infliximab.

DISPOSITION

Most lesions will resolve spontaneously within 2 yr. REFERRAL

Dermatology referral recommended for symptomatic, disseminated disease

PEARLS & CONSIDERATIONS COMMENTS

GA has been described as a paraneoplastic granulomatous reaction to Hodgkin's disease, NHL, solid organ tumors, and mycosis fungoides. SUGGESTED READINGS Cyr PR: Diagnosis and management of granuloma annulare. Am Fam Physician 2006; 74:1729-1734.

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Granuloma Inguinale GEORGE T. DANAKAS, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Granuloma inguinale is caused by a gram-negative bacterium, Calymmatobacterium granulomatis, that may be sexually transmitted, possibly by anal intercourse. It can also be spread through close, chronic nonsexual contact. SYNONYMS

Donovanosis

ICD-9CM CODES

099.2 Granuloma inguinale EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: Rare in the U.S. (21 yr of age and younger patients who have not achieved remission after 1 yr of ATD therapy

2.

Contraindicated during pregnancy and lactation

•

Surgery: near-total thyroidectomy is rarely performed; indications: obstructing goiters despite RAI and ATD therapy, patients who refuse RAI and cannot be adequately managed with ATDs, and pregnant women inadequately managed with ATDs

•

Adjunctive therapy: propranolol (20 to 40 mg q6h) to alleviate the ß-adrenergic symptoms of hyperthyroidism (tachycardia, tremor); contraindicated in patients with CHF and bronchospasm

•

Graves' ophthalmopathy: methylcellulose eye drops to protect against excessive dryness, sunglasses to decrease photophobia, systemic high-dose corticosteroids for severe exophthalmos; worsening of ophthalmopathy after RAI therapy often transient and can be prevented by the administration of prednisone

CHRONIC Rx

Patients undergoing treatment with ATDs should be seen every 1 to 3 mo until euthyroidism is achieved and every 3 to 4 mo while they are receiving ATDs. DISPOSITION

•

ATDs induce sustained remission in 50% within first year and 2%/yr thereafter.

•

Complications of surgery include hypothyroidism (28% to 43% after 10 yr), hypoparathyroidism, and vocal cord paralysis (1%).

•

Successful treatment of hyperthyroidism requires lifelong monitoring for the onset of hypothyroidism or the recurrence of thyrotoxicosis.

•

RAI therapy is followed by the appearance or worsening of ophthalmopathy more often than is therapy with methimazole, particularly in patients who are cigarette smokers. It can be prevented with the administration of prednisone 0.5 mg/kg of body weight per day starting 2 to 3 days post RAI, continued for 1 mo, then tapered off over 2 mo.

•

Mild to moderate ophthalmopathy often improves spontaneously. Severe cases can be treated with highdose glucocorticoids, orbital irradiation, or both. Orbital decompression may be used in patients with optic neuropathy and exophthalmos (see “Hyperthyroidism”).

SUGGESTED READINGS Weetman AP: Graves' disease. N Engl J Med 2000; 343:1236.

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Guillain-Barré Syndrome MICHAEL BENATAR, M.B.C.H.B., D.PHIL., EROBOGHENE UBOGU, M.D.

BASIC INFORMATION DEFINITION

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy (affects nerve roots and peripheral nerves), with predominant motor involvement. It is the most common cause of acute flaccid paralysis in the Western hemisphere and probably worldwide. By definition, maximal clinical weakness occurs within 4 wk of disease onset. SYNONYMS

GBS consists of several clinical variants based on the pattern of clinical involvement and electrophysiologic findings. These include: •

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)—most common form in Europe and North America

•

Acute motor axonal neuropathy (AMAN)—most prevalent form in China and Japan

•

Acute motor and sensory axonal neuropathy (AMSAN)—has more severe sensory involvement and is associated with more severe clinical course and poorer prognosis

•

Miller Fisher syndrome (MFS)—triad of ophthalmoplegia, ataxia, and areflexia

•

Acute pandysautonomia—rapid onset of parasympathetic and sympathetic failure without motor or sensory involvement

•

Regional variants such as pharyngeal-cervical-brachial and a pure ataxic form

ICD-9CM CODES

357.0 Guillain-Barré EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 0.6 to 1.9 cases/100,000 persons annually without geographic variation. Incidence increases with age. PREDOMINANT SEX: There is a slight male preponderance (1.25:1). PEAK INCIDENCE: A slight peak in incidence occurs between late adolescence and early adulthood. PREDISPOSING FACTORS: Viral (HIV, CMV, EBV, influenza) and bacterial (Campylobacter jejuni,

Mycoplasma pneumonia) infections; systemic illness (Hodgkin's lymphoma), immunizations PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symmetric weakness, most commonly involving proximal muscles initially, subsequently involving both proximal and distal muscles

•

Depressed or absent deep tendon reflexes in both arms and legs

•

“Glove and stocking” pattern paresthesias/dysesthesia/anesthesia (often mild relative to severity of weakness)

•

Pain, often paraspinal (caused by involvement of posterior nerve roots)

•

Autonomic abnormalities (bradyarrhythmias or tachyarrhythmias, hypotension or hypertension)

•

Respiratory insufficiency (caused by weakness of diaphragm and/or intercostal muscles

•

Facial weakness

•

Diplopia due to ophthalmoparesis

•

Dysphagia due to pharyngeal weakness

ETIOLOGY

•

Unknown

•

Preceding infectious illness 1 to 4 wk before disease onset in approximately two thirds of patients

•

Immune-mediated attack directed primarily against peripheral nerve myelin and/or Schwann cell antigens; secondary axonal loss may occur

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Toxic peripheral neuropathies: heavy metal poisoning (lead, thallium, arsenic), medications (vincristine, disulfiram), organophosphate poisoning, hexacarbon (glue sniffer's neuropathy)

•

Nontoxic peripheral neuropathies: acute intermittent porphyria, vasculitic polyneuropathy, infectious (polio myelitis, diphtheria, Lyme disease, West Nile virus); tick paralysis

•

Neuromuscular junction disorders: myasthenia gravis, botulism, snake envenomations

•

Myopathies such as polymyositis, acute necrotizing myopathies caused by drugs

•

Metabolic derangements such as hypermagnesemia, hypokalemia, hypophosphatemia

•

Acute central nervous system disorders such as basilar artery thrombosis with brainstem infarction, brainstem encephalomyelitis, transverse myelitis, or spinal cord compression

•

Hysterical paralysis or malingering

WORKUP

1.

Exclude other causes based on clinical history, examination, and laboratory tests.

2.

Lumbar puncture (may be normal in the first 1 to 2 wk of the illness). •

3.

Typical findings include elevated CSF protein with few mononuclear leukocytes (albuminocytologic dissociation) in 80% to 90% of patients. CSF pleocytosis is expected in cases associated with HIV seroconversion.

Electromyography/nerve conduction studies may be normal in the first 10-14 days of the disease. The earliest electrodiagnostic abnormalities are prolongation or absence of H-reflexes and reduced recruitment of motor units with normal morphology. EMG/NCS evidence of demyelination (prolonged distal latency, conduction velocity slowing, conduction block, temporal dispersion, and prolonged F-waves) in two or more motor nerves confirms diagnosis of AIDP in the appropriate clinical context.

LABORATORY TESTS

•

CBC may reveal early leukocytosis with left shift. Electrolytes to exclude metabolic causes of weakness.

•

Heavy metal testing, urine porphyria screen, creatine kinase, HIV titers, and neuroimaging of the brain and spinal cord if diagnosis uncertain. Nerve root enhancement may be seen on MRI of the lumbosacral spine.

•

Antibodies against ganglioside GQ1b may be present in up to 90% of patients with MFS. IgG antibodies against ganglioside GM1 may be associated with AMAN. There are no antiganglioside antibodies commonly associated with AIDP.

•

In equivocal cases (especially if peripheral nerve vasculitis is a concern), nerve biopsy may aid in confirming a diagnosis of GBS. Sensory nerve biopsy demonstrates segmental demyelination with infiltration of monocytes and T cells into the endoneurium. Axonal loss is commonly seen in sensory nerve biopsy specimens in GBS.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Close monitoring of respiratory function (frequent measurements of vital capacity, negative inspiratory force, and pulmonary toilet), because respiratory failure is the most serious (and sometimes lifethreatening) complication in GBS

•

Frequent repositioning of immobile patients to minimize formation of pressure sores

•

Prevention of thromboembolism with antithrombotic stockings and SC heparin (5000 U q12h) in nonambulatory patients

•

Emotional support and social counseling

ACUTE GENERAL Rx

•

Infusion of IV immunoglobulin (IVIg 0.4 g/kg/day for 5 days). Always check serum IgA levels before infusion to prevent anaphylaxis in deficient patients.

•

Plasma exchange (PE): 200 to 250 ml/kg over five sessions every other day.

•

IVIg and PE are equally effective. The selection of one or the other is determined by availability and risk of particular complications. For example, PE should be avoided in patients with prominent autonomic dysfunction.

•

There is no proven benefit from combining IVIg and PE.

•

Mechanical ventilation may be needed if FVC is >12 to 15 ml/kg, vital capacity is rapidly decreasing or is >1000 ml, negative inspiratory force 70, or if the patient is having significant difficulty clearing secretions or is aspirating.

CHRONIC Rx

•

Ventilatory support may be necessary in 10% to 20% of patients. Adequate fluid/electrolyte support and nutrition is necessary, especially in patients with dysautonomia or bulbar dysfunction.

•

Aggressive nursing care is required to prevent decubiti, infections, fecal impactions, and pressure nerve palsies.

•

Monitor and treat autonomic dysfunction (bradyarrhythmias or tachyarrhythmias, orthostatic hypotension, systemic hypertension, altered sweating).

•

Treat back pain and dysesthesia with low-dose tricyclics, gabapentin, etc. Opiate narcotics can be used cautiously in the short term, but may compound dysautonomia.

•

Stress ulcer prevention in patients receiving ventilator support.

•

Discuss physical and occupational therapy rehabilitation, including supportive devices.

DISPOSITION

•

Mortality is approximately 5% to 10%. Causes of death include cardiac arrest, pulmonary embolism, and fulminant infections.

•

Full motor recovery occurs in approximately 60% of patients. There is mild residual weakness in 15%, moderately severe residual weakness in 10%, and 5% may remain in bed 1 year after the onset of symptoms.

•

Predictors for poor recovery (inability to walk independently at 1 yr): age >60 yr, preceding diarrheal illness, recent CMV infection, fulminant or rapidly progressing course, ventilatory dependence, reduced motor amplitudes (>20% normal), or inexcitable nerves on NCS.

•

Outcomes may also be influenced by complications of medical therapy.

•

GBS is typically a monophasic illness. Recurrence may occur in >5% of patients following full recovery.

REFERRAL

•

To ENT for tracheostomy if prolonged ventilatory support is required.

•

To surgery for percutaneous endoscopic gastrostomy (PEG) if temporary nutritional support is required.

PEARLS & CONSIDERATIONS

•

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis.

•

Close monitoring of ventilatory function with respiratory mechanics (FVC and NIF) is of paramount importance in all patients with suspected Guillain-Barré syndrome.

COMMENTS

Patient education information may be obtained from the Guillain-Barré Foundation International, Box 262, Wynnewood, PA 19096; phone: (610) 667-0131.

EVIDENCE

There is evidence from six randomized controlled trials (RCTs) that plasma exchange is of benefit to patients with GBS.[[1]] There is evidence from six RCTs that IVIg is equally effective in the management of patients with GBS.[[2]]

The evidence does not support the combined use of IVIg and PE.[[3]] The evidence does not support the use of steroids in the treatment of GBS.[[4]]

Evidence-Based References 1. Rapha'l JC, et al: Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev 2002; 2:CD001798 2. Hughes RAC, et al: Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev 2006; 1:CD002063 3. Hughes RAC, et al: Corticosteroids for Guillain-Barré Syndrome. Cochrane Database Syst Rev 2006; 2:CD001446 4. Hughes RAC, van der Meché FGA: Cortico steroids for Guillain-Barré syndrome. Cochrane Database Syst Rev 2006; 2:CD001446

SUGGESTED READINGS Bernsen RA, et al: How Guillain-Barré patients experience their functioning after 1 year. Acta Neurol Scand 2005; 112:51. Garssen MP, et al: Physical training and fatigue, fitness, and quality of life in Guillain-Barré syndrome and CIDP. Neurology 2004; 63:2393. Hughes RA, et al: Guillain-Barré syndrome. Lancet 2005; 366(9497):1653. Hughes RA, et al: Multidisciplinary Consensus Group: supportive care for patients with Guillain-Barré syndrome. Arch Neurol 2005; 62:1194. Hughes RA, et al: Practice Parameter: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003; 61(6):746. Kuwabara S: Guillain-Barré syndrome: epidemiology, pathophysiology and management. Drugs 2004; 64:597.

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H Hand-Foot-Mouth Disease JAMES J. NG, M.D., JENNIFER JEREMIAH, M.D.

BASIC INFORMATION DEFINITION

Hand-foot-mouth (HFM) disease is a viral illness that is characterized by superficial lesions of the oral mucosa and of the skin of the extremities. HFM is transmitted primarily by the fecal-oral route and is highly contagious. Although children are predominantly affected, adults are also at risk. This disease is usually self-limited and benign. SYNONYMS

Vesicular stomatitis with exanthem Coxsackievirus infection

ICD-9CM CODES

074.0 Hand-foot-mouth disease EPIDEMIOLOGY & DEMOGRAPHICS

•

Children under the age of 5 yr are at the highest risk and have the most severe cases.

•

HFM is usually found in children below the age of 10 yr.

•

HFM is moderately contagious. Close contacts of affected children, including family members and health care workers, are the most commonly affected adults.

•

Infection is spread from person to person by direct contact with nasal discharge or stool.

•

A person is most contagious during the first wk of illness.

•

Outbreaks tend to occur during the summer.

•

Infection leads to immunity, but a second episode may occur after infection with a different agent.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms:

•

After a 4- to 6-day incubation period, patients may complain of odynophagia, sore throat, malaise, and fever (38.3 to 40° C).

•

One to 2 days later the characteristic oral lesions appear.

•

In 75% of cases, skin lesions on the extremities accompany these oral manifestations.

•

11% of adults have cutaneous findings.

•

Lesions appear over the course of 1 or 2 days.

Physical findings: •

Oral lesions, usually between five and ten, are commonly found on the tongue, buccal mucosa, gingivae, and hard palate.

•

Oral lesions initially start as 1- to 3-mm erythematous macules and evolve into gray vesicles on an erythematous base.

•

Vesicles are frequently broken by the time of presentation and appear as superficial gray ulcers with surrounding erythema.

•

Skin lesions of the hands and feet start as linear erythematous papules (3 to 10 mm in diameter) that evolve into gray vesicles that may be mildly painful ( Fig. 1-113 ). These vesicles are usually intact at presentation and remain so until they desquamate within 2 wk.

•

Involvement of the buttocks and perineum is present in 31% of cases.

•

In rare cases, encephalitis, meningitis, myocarditis, poliomyelitis-like paralysis, and pulmonary edema may develop. Sporadic acute paralysis has been reported with Enterovirus 71.

•

Although information is limited, there is not clear evidence that pregnancy outcomes are affected.

ETIOLOGY

FIGURE 1-113 Hand-foot-mouth disease. Note oval lesions on an erythematous base. (From Goldstein B [ed]: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

ETIOLOGY

•

Coxsackievirus group A, type 16, was the first and is the most common viral agent isolated.

•

Coxsackieviruses A5, A7, A9, A10, B1, B2, B3, B5, and enterovirus 71 have also been implicated.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Aphthous stomatitis

•

Herpes simplex infection

•

Herpangina

•

Behçet's disease

•

Erythema multiforme

•

Pemphigus

•

Gonorrhea

•

Acute leukemia

•

Lymphoma

•

Allergic contact dermatitis

WORKUP

The diagnosis is usually made on the basis of history and characteristic physical examination. LABORATORY TESTS

•

Not indicated unless the diagnosis is in doubt

•

Throat culture or stool specimen may be obtained for viral testing but may take from 2 to 4 wk for results

TREATMENT ACUTE GENERAL Rx

•

Palliative therapy is given for this usually self-limited disease.

•

Limited data suggest acyclovir may have a role in treatment of certain cases.

DISPOSITION

Prognosis is excellent except in rare cases of CNS or cardiac involvement. Most are managed as outpatients.

REFERRAL

Not usually needed

PEARLS & CONSIDERATIONS

•

Frequent hand washing, disinfection of contaminated surfaces, and washing of soiled articles of clothing can help reduce transmission.

•

HFM has no relationship to hoof and mouth disease in cattle.

SUGGESTED READINGS Chang LY, et al: Transmission and clinical features of Enterovirus 71 infections in household contacts in Taiwan. JAMA 2004; 291(2):222. Chang LY, et al: Clinical features and risk of pulmonary edema after enterovirus-related hand, foot, and mouth disease. Lancet 1999; 354(9191):1682. Weir E: Foot-and-mouth disease in animals and humans. Can Med Assoc J 2001; 164(9):1338.

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Hantavirus Pulmonary Syndrome CATHERINE SHAFTS, D.O.

BASIC INFORMATION DEFINITION

Hantavirus pulmonary syndrome (HPS) is a severe infectious cardiopulmonary illness usually caused by the Sin Nombre virus (SNV) whose main vector is the deer mouse. SYNONYMS

Four Corners disease Hantavirus cardiopulmonary syndrome

ICD-9CM CODES 079.81 EPIDEMIOLOGY & DEMOGRAPHICS

•

First identified in the U.S. in 1993, hantavirus has been found throughout the Continental U.S. and the Americas.

•

As of 2005, 396 cases have been identified in 31 states with a mortality rate of 37%.

•

The peak incidence to date was in June and July 1993 in the Four Corners region of the U.S.

•

HPS is more common in the spring and summer.

•

HPS is more prevalent among males likely due to increased environmental exposure.

•

Mean age is 38 years.

•

HPS has not been found at the extremes of age.

•

Risk factors include exposure to rodent populations, rural locales, occupations with increased exposure to rodents, and entering infrequently opened structures.

CLINICAL PRESENTATION

The most common symptoms are fever, headache, nausea, vomiting, cough, shortness of breath, and myalgia. It is not associated with rhinorrhea or nasal congestion. The most common signs on physical exam include fever, hypoxemia, and tachypnea. Rash, mucosal bleeding, or peripheral edema are not found with HPS. There are two phases of HPS, the prodromal phase and the cardiopulmonary phase. The prodromal phase is characterized by: •

Fever, chills, headache, and myalgias especially in the legs and back

•

Cough, nausea, vomiting, and general malaise

•

Tachypnea, tachycardia, hypoxemia

The cardiopulmonary phase has the following characteristics: •

Cough and dyspnea

•

Acute pulmonary edema

•

Hypotension

•

Decreased cardiac output

ETIOLOGY

•

HPS is most often caused by the Sin Nombre virus.

•

The main vector is the deer mouse.

•

It is transmitted by inhalation of aerosolized feces, urine, or saliva from infected rodents.

•

No cases of person-to-person transmission.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

ARDS

•

Pneumonia

•

CHF

•

Pulmonary edema

•

Acute bacterial endocarditis

•

Gastroenteritis

•

Plague

•

Tularemia—“rabbit fever”

•

Histoplasmosis

•

Coccidioidomycosis

•

Cardiogenic shock

•

HIV/AIDS

•

Myocardial infarction

•

Goodpasture's syndrome—an autoimmune pulmonary disease

WORKUP

•

CBC q8h. 1.

All patients manifest thrombocytopenia and its progression is the most consistent indicator heralding the cardiopulmonary phase of HPS.

2.

Differential usually reveals a left shift. WBC counts are an unreliable indicator of severity of infection.

•

Lactate level greater than 4 mg/dl is associated with a high mortality rate.

•

Rapid immunoblot strip assay (RIBA) for SNV antibodies.

•

Diagnosis is confirmed by identification of IgM and IgG antibodies to SNV.

IMAGING STUDIES

Chest x-ray: pulmonary edema

TREATMENT NONPHARMACOLOGIC THERAPY

•

ICU admission in tertiary care center

•

Mechanical ventilation with high PEEP and high FiO2

•

Pulmonary artery catheterization

•

Extracorporeal membrane oxygenation (ECMO)

ACUTE GENERAL Rx

•

Supportive measures

•

Supplemental oxygen

•

Intubation when indicated

•

Fluid resuscitation

•

Hemodynamic monitoring

•

Initial broad-spectrum antibiotics

•

Pressors

•

No medication is effective against SNV.

DISPOSITION

•

Patients that survive cardiopulmonary phase of HPS have rapid clinical improvement.

•

There are no serious sequelae.

REFERRAL

University of New Mexico Hospital is the only facility with experience in ECMO for treatment of HPS and is only for hemodynamically unstable critically ill patients failing conventional therapies.

PEARLS & CONSIDERATIONS

COMMENTS

Although rare, HPS should be a consideration in those with acute respiratory illness and a history suggestive of HPS exposure. The combination of thrombocytopenia, left shift, circulating immunoblasts, and hemoconcentration is rare in other viral illnesses. PREVENTION

Rodent control is the primary way to prevent hantavirus infection. SUGGESTED READINGS Graziano KL, et al: Hantavirus pulmonary syndrome: a zebra worth knowing. Am Fam Physician 2002; 66(b):1015-1020. Mertz GJ, et al: Diagnosis and treatment of new world hantavirus infections. Curr Opin Infect Dis 2006; 19(5):437. Mills JN, et al: Hantavirus pulmonary syndrome—United States: updated recommendations for risk reduction. MMWR Recomm Rep 2002; 51(b):1-12. National Center for Infectious Diseases, Special Pathogens Branch: All about hantaviruses, http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/generalinfoindex.htm Accessed Sept 2005.

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Headache, Cluster CHUN LIM, M.D., PH.D.

BASIC INFORMATION DEFINITION

The term cluster headache refers to attacks of severe, strictly unilateral pain that is orbital, supraorbital, temporal, or in any combination of these sites, lasting 15 to 180 minutes, and occurring from once every other day to 8 times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis, eyelid edema. Most patients are restless or agitated during an attack. SYNONYMS

Ciliary neuralgia Erythro-melalgia of the head Erythroprosopalgia of Bing Horton's headache

ICD-9CM CODES

346.2 Variants of migraine EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE:Estimated to occur in 0.05% to 1% of the population PREDOMINANT SEX: Occurs in males at least 5 times more commonly than in females PREDOMINANT AGE: Peak age of onset between 20 and 40 yr GENETICS: May be inherited (autosomal dominant) in about 5% of cases PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

During attack: ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial sweating, Horner's syndrome.

•

In contrast to migraine sufferers, patients are agitated and active during an attack.

•

Permanent partial Horner's syndrome in 5% of patients; otherwise examination normal.

ETIOLOGY

Activation of the posterior hypothalamic grey matter resulting in trigeminal activation coupled with parasympathetic activation.

DIAGNOSIS

•

Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15 to 180 minutes

•

Frequency of every other day to 8 per day

•

Headache is accompanied by at least one of the following (ipsilateral): 1.

conjunctival injection and/or lacrimation

2.

nasal congestion and/or rhinorrhea

3.

eyelid edema

4.

forehead and facial sweating

5.

miosis and/or ptosis

6.

restlessness or agitation

DIFFERENTIAL DIAGNOSIS

•

Migraine

•

Trigeminal neuralgia

•

Temporal arteritis

•

Postherpetic neuralgia

•

Other trigeminal autonomic cephalagias

•

Section II describes the differential diagnosis of headaches

WORKUP

Diagnosis is usually established by characteristic history. IMAGING STUDIES

None, unless history or examination suggests focal neurological deficit

TREATMENT NONPHARMACOLOGIC THERAPY

Avoidance of alcohol, histamine, nitroglycerine, or tobacco during clusters ABORTIVE Rx

•

Inhalation of 100% oxygen by face mask at 6 L/min for 15 min often aborts an attack.

•

Triptans, cafergot, or dihydroergotamine may abort an attack or prevent one if given just before a predictable episode. Acute episode is typically resolved before oral analgesics become effective, although indomethacin and other NSAIDS may also be effective in prolonged attacks.

PROPHYLAXIS Rx

Various medications have been tried without great success, although good responses may be obtained in up to 50% of cases. Examples include: •

Verapamil: up to 480 mg/day as tolerated (the drug of choice)

•

Lithium: 200 mg tid with frequent monitoring and adjustment to maintain therapeutic serum level of 0.4 to 1 mEq/L. Equally effective as verapamil, but more side effects

•

Ergotamine tartrate: 3 to 4 mg/day during clusters

•

Prednisone: 60 mg po qd × 1 wk followed by taper. Headaches can return during taper

DISPOSITION

Headache-free periods tend to increase with increasing age. REFERRAL

Refractory cluster headaches

PEARLS & CONSIDERATIONS COMMENTS

•

Cluster headaches are divided into episodic (attacks lasting up to 1 yr with greater than 1 mo pain-free periods) and chronic (>1 yr without remission).

•

Cluster headaches now classified as a trigeminal autonomic cephalalgia (TAC). Other TAC includes paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).

EVIDENCE

There is a randomized controlled trial (RCT) indicating that sumatriptan is an effective treatment for acute cluster headaches. [[1]] There is evidence from a small RCT indicating that intranasal oxygen can provide significant pain relief from acute cluster headaches.[[2]] There are two RCTs that suggest that verapamil is effective in episodic cluster headache prophylaxis. [10] [11]

A small RCT showed oral prednisone was effective in treating cluster headaches.[[5]]

Evidence-Based References 1. Ekbom K, et al: Treatment of acute cluster headache with sumatriptan. N Engl J Med 1991; 325:322. 2. Fogan L: Treatment of cluster headache. Arch Neurol 1985; 42:362. 3. Leone M, et al: Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo. Neurology 2000; 54:1382. 4. Bussone G, et al: Double blind comparison of lithium and verapamil in cluster headache prophylaxis. Headache 1990; 30:411. 5. Jammes JL: The treatment of cluster headaches with prednisone. Dis Nerv Syst 1975; 36:375.

SUGGESTED READINGS Headache Classification Committee of the International Headache Society: The International Classification of Headache Disorders. Cephalgia 2004; 24:s1. May A: Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005; 366:843.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Headache, Migraine CHUN LIM, M.D., PH.D.

BASIC INFORMATION DEFINITION

Migraine headaches are recurrent headaches that are preceded by a focal neurological symptom (migraine with aura), occur independently (migraine without aura), or have atypical presentations (migraine variants). Migraine with aura is characterized by visual or sensory symptoms that typically develop or march over a period of 5 to 20 min. In both migraine with and without aura, the headache is typically unilateral, pulsatile, and associated with nausea and vomiting, photophobia and phonophobia.

ICD-9CM CODES

346 Migraine EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE:Increases from infancy, peaks during the third decade of life then decreases PREVALENCE (IN U.S.): Females: 18%; males: 6% GENETICS: •

Familial predisposition, with over 50% of migraine sufferers having an affected family member

•

Autosomal dominant transmission for some rare migraine variants (familial hemiplegic migraine, CADASIL)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Normal between episodes

•

Normal for migraine without aura. Focal motor or sensory abnormalities possible with migraine with aura or migraine variants

•

Common aura types include scintillating scotomata, bright zigzags, homonymous visual disturbance such as paraethesias, speech disturbances, or hemiparesis (familial or sporadic hemiplegic migraine)

ETIOLOGY

A primary neuronal event resulting in a trigeminovascular reflex causing neurogenic inflammation. Serotonin, nitric oxide, and calcitonin-gene-related peptide also play a role but exact mechanism is unknown. Cortical spreading depression is responsible for the aura.

DIAGNOSIS Migraine without aura •

5 attacks fulfilling criteria

•

Headache attacks lasting 4 to 72 hours

•

Headache has at least two of the following characteristics:

•

1.

Unilateral location

2.

Pulsating quality

3.

Moderate or severe pain intensity

4.

Aggravation by or causing avoidance of routine physical activity

During headache at least one of the following: 1.

Nausea and/or vomiting

2.

Photophobia and phonophobia

Migraine with aura •

At least two attacks

•

Aura consisting of at least one of the following, but no motor weakness:

•

•

1.

Fully reversible visual symptoms including positive features and/or negative features.

2.

Fully reversible sensory symptoms including positive and/or negative features.

At least two of the following: 1.

Homonymous visual symptoms and/or unilateral sensory symptoms.

2.

At least one aura symptom develops gradually over >5 minutes and/or different aura symptoms occur in succession over >5 minutes.

A migraine occurring during or within 60 minutes of the aura.

DIFFERENTIAL DIAGNOSIS

•

Subarachnoid hemorrhage

•

Cluster headache

•

Chronic daily headaches (drug rebound headaches)

•

Tension headaches

•

Tumor

•

Section II describes the differential diagnosis of headaches

WORKUP

•

Generally no additional investigation is needed with recurrent, typical attacks with usual age of onset, family history, and a normal physical examination.

•

If there is an unusual presentation and/or unexpected findings on examination, investigation for other causes is required.

LABORATORY TESTS

Lumbar puncture for history of abrupt onset headaches and uncertain diagnosis of migraine IMAGING STUDIES

•

Imaging should be done in patients with headaches and an unexplained abnormal finding on the neurological examination.

•

Imaging should be considered in patients with rapidly increasing headache frequency, history of dizziness or incoordination, headache causing wakening from sleep, or headaches worsening with Valsalva maneuver.

TREATMENT Consider the use of a headache log/diary to identify triggers of headaches, to record efficacy of treatments, and to track history of the headaches. NONPHARMACOLOGIC THERAPY

•

Avoid any identifiable provoking factors: caffeine, tobacco, and alcohol may trigger attacks, as may dietary or other environmental precipitants (less common)

•

Avoid stressors in life and minimize variations in daily routine with regular sleep, meals, and exercise

•

Relaxation training and biofeedback

ACUTE ANALGESIC Rx

•

Many oral agents are ineffective because of poor absorption secondary to migraine-induced gastric stasis. Nonoral route of administration should be selected in patients with severe nausea or vomiting

•

Nonspecific treatment for pain.

•

Acetaminophen, NSAIDS, combination analgesics, benzodiazepines, opioids, barbiturates

ACUTE ABORTIVE Rx

•

Intravenous antiemetics (prochlorperazine, metoclopramide). Acute dystonic reactions and akathisia are rare side effects. Generally not used as monotherapy

•

Ergotamine and ergotamine combinations (PO/PR), and dihydroergotamine (DHE 45) all have efficacy against migraines. DHE 45 usually administered in combination with an antiemetic drug ( Table 1-17 )

•

Triptans (SC, PO, and intranasal) now considered drug of choice for abortive therapy. Meta-analysis suggests that 10 mg rizatriptan, 80 mg eletriptan, and 12.5 mg almotriptan are most effective

•

Early administration improves effectiveness

TABLE 1-17 -- Treatment for Acute Attacks of Migraine[*] Drug Route

Dose

Triptans (serotonin agonists) Sumatriptan

Subcutaneous

6 mg, repeat in 2 hr (max 2 doses/day)

Sumatriptan

Oral

25 mg, 50 mg, repeat in 2 hr (max 200 mg/day)

Sumatriptan

Nasal spray

5 mg and 20 mg, repeat in 2 hr (max 40 mg/day)

Drug

Route

Dose

Zolmitriptan

Oral

1.25, 2.5 mg, 5 mg, repeat in 2 hr (max 10 mg/day)

Zolmitriptan

Nasal spray

5 mg, repeat in 2 hr (max 10 mg/day)

Zolmitriptan

Orally disintegrating tab

2.5, 5 mg, repeat in 2 hr (max 10 mg/day)

Naratriptan

Oral

1 mg, 2.5 mg, repeat in 4 hr (max 5 mg/day)

Rizatriptan

Oral

5 mg, 10 mg, repeat in 2 hr (max 30 mg/day)

Almotriptan

Oral

6.25 mg, 12.5 mg, may repeat in 2 hr (max 25 mg/day)

Eletriptan

Oral

20 mg, 40 mg, may repeat in 2 hr (max 80 mg/day)

Frovatriptan

Oral

2.5 mg, may repeat in 2 hr (max 7.5 mg/day)

Ergotamine preparations Ergotamine and caffeine

Oral

2 tablets, may repeat 1 tab q30 min; max 6/day

Ergotamine and caffeine

Rectal

1 suppository, repeat in 1 hr; max 2/day

Ergotaminel

Sublingual

1 tablet, repeat in 1 hr; max 2/day

Dihydroergotamine

Intramuscular Subcutaneous Intravenous Nasal spray

0.5-1.0 mg, repeat twice at 1-hr intervals (max 3 mg/attack)

Oral

50-125 mg

Antiemetics Promethazine

Intramuscular Prochlorperazine

Chlorpromazine

Trimetobenzamide

Metoclopramide

D imenhydrinate

Oral

1-25 mg

Rectal

2.5-25 mg (suppository)

Intramuscular

5-10 mg

Oral

10-25 mg

Rectal

50-100 mg (suppository)

Intravenous

Up to 35 mg

Oral

250 mg

Rectal

200 mg

Oral

5-10 mg

Intramuscular

10 mg

Intravenous

5-10 mg

Oral

50 mg

Modified from Wiederholt WC: Neurology for non-neurologists, ed 4, Philadelphia, 2000, WB Saunders. * For side effects and contraindications, consult the manufacturer's drug insert before prescribing any of these drugs.

PROPHYLAXIS Rx

•

Prophylactic treatment is generally indicated when headaches occur more than once a week or when symptomatic treatments are contraindicated or not effective. They are most effective when initiated during headache-free period. All prophylaxis should be maintained for at least 3 mo before deeming the medication a failure.

•

Well-established options for prophylactic treatment include ß-blockers (propanolol, timolol), tricyclic antidepressants (amitriptyline), and the antiepileptic drugs valproic acid and topiramate.

•

Less established options include Ca-channel blockers, SSRIs, and the anti-epileptic drug gabapentin.

DISPOSITION

After age 30 yr, 40% of patients are migraine free. REFERRAL

If uncertain about diagnosis or treatment not effective

PEARLS & CONSIDERATIONS Avoid overuse of narcotics, barbiturates, caffeine, and benzodiazepines, as they are habit-forming and can result in drug-induced or rebound headaches.

EVIDENCE

Several randomized controlled trials (RCTs) have found that IV antiemetics are effective for acute treatment of migraine both as monotherapy or as adjunctive therapy. [15] [16] Many RCTs have reported on the efficacy and safety of DHE nasal spray for the treatment of moderate to severe migraine.[[3]] Many RCTs show that triptans are an appropriate and effective treatment choice for use in patients with moderate-to-severe migraine who have no contraindications for its use. [18] [19] [20] Many RCTs have shown that sodium valproate, topiramate, amitriptyline, and propanolol are the most effective medications in preventing migraine or reducing the frequency, severity, and duration of the attacks. [21] [22] [23] [24]

Evidence-Based References 1. Tek DS, et al: A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine attacks. Ann Emerg Med 1990; 19:1083. 2. Coppola M, et al: Randomized, placebo-controlled evaluation of prochlorperazine versus metroclopramide for emergency department treatment of migraine headache. Ann Emerg Med 1995; 24:541. 3. Ziegler D, et al: Dihydroergotamine nasal spray for the acute treatment of migraine. Neurology 1994; 44:447. 4. Subcutaneous Sumatriptan International Study Group: Treatment of migraine attacks with sumatriptan. N Engl J Med 1991; 325:316. 5. Solomon GD, et al: Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. The 042 clinical trial study group. Neurology 1997; 49:1219. 6. Visser WH, et al: Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Dutch/US rizatriptan study group. Arch Neurol 1996; 53:1132. 7. Hering R, Kuritzky A: Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia 1992; 12:81. 8. Couch JR, Hassanein RS: Amitriptyline in migraine prophylaxis. Arch Neurol 1979; 36:695. 9. Borgesen SE, et al: Prophylactic treatment of migraine with propranolol. A clinical trial. Acta Neurol Scand 1974; 50:651. 10. Brandes JL, et al: Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004; 291:965.

SUGGESTED READINGS Ferrari MD, et al: Oral triptans (serotonin 5-HT1B/1D agonist) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001; 358:1668. Ferrari MD, et al: Migraine—current understanding and treatment. N Engl J Med 2002; 346:257. Silberstein SD: Practice parameter: evidence-based guidelines for migraine headache. Neurology 2000; 55:754.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Headache, Tension-Type RICHARD S. ISAACSON, M.D.

BASIC INFORMATION DEFINITION

Tension-type headaches (TTH) are recurrent headaches lasting 30 min to 7 days without nausea or vomiting and with at least two of the following characteristics: pressing or tightening quality (nonthrobbing), mild or moderate intensity, bilateral, and not aggravated by routine physical activity. The International Classification of Headache Disorders (ICHD-2) criteria include three subtypes: infrequent episodic TTH ( males PHYSICAL FINDINGS & CLINICAL PRESENTATION

Pressure or “bandlike” tightness all around the head, may be worse at the vertex. Cervical, paracervical and trapezius muscle spasm and/or tenderness on palpation may be present. Scalp tenderness or hypersensitivity to pain also occurs. Symptoms suggestive of migraine are usually not present (e.g., throbbing pain, nausea/vomiting, visual complaints, aura). Either one symptom of photo or phonophobia does not exclude the

diagnosis of TTH. ETIOLOGY

•

Unclear; little data to support postulated muscle contraction component. More recently has been thought of as a multifactorial disorder with several possible concurrent pathophysiological mechanisms. Functional neuroimaging suggests gray matter decrease in regions known to be involved in pain processing.

•

No recent data to support the long-standing belief that these headaches arise from stress or other psychologic factors. However, components of stress, sleep deprivation, hunger, and eyestrain may exacerbate symptoms.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Migraine (would expect associated symptoms, see “Headache, Migraine”)

•

Cervical spine disease

•

Intracranial mass (may present with focal neurologic signs, seizures, or headache awakening patient from sleep)

•

Idiopathic intracranial hypertension (found more often in obese women of child-bearing age, may have papilledema, visual loss, or diplopia)

•

Rebound headache from overuse of analgesics

•

Secondary headache (e.g., temporomandibular joint syndrome, thyrotoxicosis, polycythemia, drug sideeffects)

•

Migraine and tension-type headache may often coexist and may be difficult to differentiate (suggest headache calendar)

•

Section II describes the differential diagnosis of headaches

WORKUP

•

Thorough history and physical examination for any new-onset headache

•

Neuroimaging should be performed when unexplained neurologic findings are present on exam or in cases of atypical new-onset sudden and severe headaches.

LABORATORY TESTS

•

No routine tests

•

ESR in elderly patients suspected of having cranial arteritis

IMAGING STUDIES

CT scan and/or MRI may be used to exclude intracranial pathology. MRI is better for imaging the posterior fossa. Contrast should be used if mass lesion is suspected.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Relaxation and cognitive behavioral therapy (especially in adolescents and children), Schultz-type autogenic training (relaxation technique based on passive concentration and body awareness of specific sensations), transcutaneous electrical nerve stimulation (TENS), heat

•

Physical therapy including stretching exercises, massage, and ultrasound

ACUTE GENERAL Rx

Nonnarcotic analgesics with limited frequency to prevent drug-induced and/or rebound headache CHRONIC Rx

•

Tricyclic antidepressants (e.g., amitriptyline 10 to 150 mg hs) and SSRIs

•

Avoid narcotics, limit NSAIDs, consider indomethacin; if related to cervical muscle spasm, may consider trial of muscle relaxants (e.g., Skelaxin 400 to 800 mg TID)

DISPOSITION

•

May not respond fully to treatment

•

Prognosis is fairly favorable for episodic forms; chronic forms, coexisting migraine, sleep difficulty, and not being married confer a less favorable prognosis

REFERRAL

If uncertain about diagnosis or unexplained focal neurologic findings on examination

PEARLS & CONSIDERATIONS It is imperative to avoid overuse of caffeine- and barbiturate-containing medications because of the risk of rebound headaches

EVIDENCE

There is a paucity of high quality trials in the treatment of TTH. Various randomized controlled trials (RCT) have showed amitriptyline and cognitive therapy were more effective than placebo in various measures (e.g., headache-free days, symptom reduction). A small, double-blind cross-over trial of mirtazapine significantly reduced headache frequency. Systematic reviews have found that acupuncture is probably effective, although a small RCT did not show statistical benefit. SUGGESTED READINGS Bendtsen L, Jensen R: Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache. Neurology 2004; 62:1706. Bendtsen L, Jensen R: Tension-type headache: the most common, but also the most neglected, headache disorder. Curr Opin Neurol 2006; 19(3):305. Bronfort G, et al: Non-invasive physical treatments for chronic/recurrent headache. Cochrane Database Syst Rev 2004; 3:

Goadsby P: Headache (chronic tension-type). BMJ 2004; 12:1808. Headache Classification Committee of the International Headache Society: The International Classification of Headache Disorders. Cephalalgia 2004; 24:1. Holroyd KA, et al: Management of chronic tension-type headache with tricyclic anti-depressant medication, stress management therapy, and their combination: a randomized controlled trial. JAMA 2001; 285(17):2208. Jensen R: Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies. Cephalalgia 1999; 19(6):602. Lipton RB, et al: Classification of primary headaches. Neurology 2004; 63:427. May A: A review of diagnostic and functional imaging in headache. J Headache Pain 2006; 7(4):174.Epub ahead of print. Russell MB: Genetics in primary headaches. J Headache Pain 2007; 8(3):190. Silver N: Headache (chronic tension-type). Am Fam Physician 2007; 76:114. Zsombok T, et al: Effect of autogenic training on drug consumption in patients with primary headache: an 8month follow-up study. Headache 2003; 43:251.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Heart Block, Complete FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

In complete heart block, there is complete blockage of all AV conduction. The atria and ventricles have separate, independent rhythms. SYNONYMS

Third-degree AV block

ICD-9CM CODES

426.0 Complete heart block EPIDEMIOLOGY & DEMOGRAPHICS

Over 100,000 permanent pacemakers are implanted worldwide each year for complete heart block. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Physical examination may be normal. Patients may present with the following clinical manifestations: •

Dizziness, palpitations

•

Stokes-Adams syncopal attacks

•

CHF

•

Angina

ETIOLOGY

•

Degenerative changes in His-Purkinje system

•

Acute anterior wall MI

•

Calcific aortic stenosis

•

Cardiomyopathy

•

Trauma

•

Cardiovascular surgery

•

Congenital

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

The differential diagnosis involves only the etiology. ECG will confirm diagnosis. WORKUP

ECG: •

P waves constantly change their relationship to the QRS complexes ( Fig. 1-114 ).

•

Ventricular rate is usually 37.8° C but =40° C. HEAT STROKE: A life-threatening heat illness characterized by extreme hyperthermia, dehydration, and neurologic manifestations (core temperature >40° C). SYNONYMS

Heat illness Hyperthermia

ICD-9CM CODES

992.0 Heat stroke 992.5 Heat exhaustion EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.):Incidence of heat stroke is approximately 20 cases/100,000 population. PREDOMINANT AGE: Heat exhaustion and stroke occur more frequently in elderly patients, especially those taking diuretics or medications that impair heat dissipation (e.g., phenothiazines, anticholinergics, antihistamines, ß-blockers). PHYSICAL FINDINGS & CLINICAL PRESENTATION

HEAT EXHAUSTION: •

Generalized malaise, weakness, headache, muscle and abdominal cramps, nausea, vomiting, hypotension, and tachycardia

•

Rectal temperature is usually normal

•

Sweating is usually present

HEAT STROKE: •

Neurologic manifestations (seizures, tremor, hemiplegia, coma, psychosis, and other bizarre behavior)

•

Evidence of dehydration (poor skin turgor, sunken eyeballs)

•

Tachycardia, hyperventilation

•

Skin is hot, red, and flushed

•

Sweating is often (not always) absent, particularly in elderly patients

ETIOLOGY

•

Exogenous heat gain (increased ambient temperature)

•

Increased heat production (exercise, infection, hyperthyroidism, drugs)

•

Impaired heat dissipation (high humidity, heavy clothing, neonatal or elderly patients, drugs [phenothiazines, anticholinergics, antihistamines, butyrophenones, amphetamines, cocaine, alcohol, ßblockers])

•

Diuretics, laxatives

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Infections (meningitis, encephalitis, sepsis)

•

Head trauma

•

Epilepsy

•

Thyroid storm

•

Acute cocaine intoxication

•

Malignant hyperthermia

•

Heat exhaustion can be differentiated from heat stroke by the following: 1.

Essentially intact mental function and lack of significant fever in heat exhaustion

2.

Mild or absent increases in CPK, AST, LDH, ALT in heat exhaustion

WORKUP

•

Heat stroke: comprehensive history, physical examination, and laboratory evaluation

•

Heat exhaustion: in most cases, laboratory tests are not necessary for diagnosis

LABORATORY TESTS

Laboratory abnormalities may include the following: •

Elevated BUN, creatinine, Hct

•

Hyponatremia or hypernatremia, hyperkalemia or hypokalemia

•

Elevated LDH, AST, ALT, CPK, bilirubin

•

Lactic acidosis, respiratory alkalosis (secondary to hyperventilation)

•

Myoglobinuria, hypofibrinogenemia, fibrinolysis, hypocalcemia

TREATMENT

•

•

Treatment of heat exhaustion consists primarily of placing the patient in a cool, shaded area and providing rapid hydration and salt replacement. 1.

Fluid intake should be at least 2 L q4h in patients without history of CHF.

2.

Salt replacement can be accomplished by using one-quarter teaspoon of salt or two 10-grain salt tablets dissolved in 1 L of water.

3.

If IV fluid replacement is necessary, young athletes can be given normal saline IV (3 to 4 L over 6 to 8 hr); in elderly patients, consider using D5½ NS IV with rate titrated to cardiovascular status.

Patients with heat stroke should undergo rapid cooling. 1.

Remove the patient's clothes and place the patient in a cool and well-ventilated room.

2.

If unconscious, position patient on his or her side and clear the airway. Protect airway and augment oxygenation (e.g., nasal O2 at 4 L/min to keep oxygen saturation >90%).

3.

Monitor body temperature every 5 min. Measurement of the patient's core temperature with a rectal probe is recommended. The goal is to reduce the body temperature to 39° C (102.2° F) in 30 to 60 min.

4.

Spray the patient with a cool mist and use fans to enhance airflow over the body (rapid evaporation method).

5.

Immersion of the patient in ice water, stomach lavage with iced saline solution, intravenous administration of cooled fluids, and inhalation of cold air are advisable only when the means for rapid evaporation are not available. Immersion in tepid water (15° C, 59° F) is preferred over ice water immersion to minimize risk of shivering.

6.

Use of ice packs on axillae, neck, and groin is controversial because they increase peripheral vasoconstriction and may induce shivering.

7.

Antipyretics are ineffective because the hypothalamic set point during heat stroke is normal despite the increased body temperature.

8.

Intubate a comatose patient, insert a Foley catheter, and start nasal O2. Continuous ECG monitoring is recommended.

9.

Insert at least two large-bore IV lines and begin IV hydration with NS or Ringer's lactate.

10. Draw initial lab studies: electrolytes, CBC, BUN, creatinine, AST, ALT, CPK, LDH, glucose, INR, PTT, platelet count, Ca2+ , lactic acid, ABGs. 11. Treat complications as follows: a.

Hypotension: vigorous hydration with normal saline or Ringer's lactate.

b.

Convulsions: diazepam 5 to 10 mg IV (slowly).

c.

Shivering: chlorpromazine 10 to 50 mg IV.

d.

Acidosis: use bicarbonate judiciously (only in severe acidosis).

12. Observe for evidence of rhabdomyolysis, hepatic, renal, or cardiac failure and treat accordingly. DISPOSITION

Most patients recover completely within 48 hr. CNS injury is permanent in 20% of cases. Mortality can exceed 30% in patients with prolonged and severe hyperthermia. SUGGESTED READINGS

Glazer JL: Management of heat stroke and exhaustion. Am Fam Physician 2005; 71:2133.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Helicobacter Pylori Infection MARGARET TRYFOROS, M.D.

BASIC INFORMATION DEFINITION

Infection of the human gastric mucosa with the organism Helicobacter pylori, a spiral-shaped gram-negative organism with unique features that allow it to survive in the hostile gastric environment. SYNONYMS

The organism was previously known as Campylobacter pylori.

ICD-9CM CODES

041.86 Helicobacter pylori (H. pylori) EPIDEMIOLOGY & DEMOGRAPHICS

H. pylori is the most common chronic bacterial infection in humans, with worldwide distribution, likely affecting 50% of the earth's population in all age groups, and probably 30% to 40% of the U.S. population. Infection is acquired at an earlier age and occurs more frequently in developing nations. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

H. pylori causes histologic gastritis in all affected individuals. However, the majority of cases are asymptomatic and unlikely to proceed to serious consequences.

•

H. pylori is a causative agent in peptic ulcer disease (PUD), gastric adenocarcinoma, and gastric MALT (mucosa-associated lymphoid tissue) lymphoma, and may be a risk factor for iron deficiency anemia and chronic idiopathic thrombocytopenic purpura (ITP). Presenting signs and symptoms of these disorders may include abdominal pain, bloating, anorexia, and early satiety.

•

Weight loss, dysphagia, protracted nausea or vomiting, anemia, melena, and palpable abdominal mass are “alarm signs and symptoms” and should prompt more immediate and aggressive workup.

ETIOLOGY

•

Route of acquisition is unknown, but is presumed to be person to person, via oral-oral or fecal-oral exposure.

•

The majority of cases are acquired in childhood. Socioeconomic status and living conditions in childhood affect risk of acquisition of infection. These factors include housing density, number of siblings, overcrowding, sharing a bed, and lack of running water.

•

H. pylori does not invade gastroduodenal tissue, but disrupts the mucous layer, causing the underlying mucosa to be more vulnerable to acid peptic damage.

•

It remains unclear what differentiates the subset of patients with H. pylori who go on to develop ulcers or cancer.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Infection with H. pylori should be considered in the face of peptic ulcer disease, gastric cancer, gastritis, and gastric MALT lymphoma.

•

Upper GI tract disease, including non-ulcer dyspepsia, reflux esophagitis, biliary tract disease, gastroparesis, pancreatitis, and ischemic bowel, may be considered in the differential diagnosis of H. pylori.

WORKUP

•

Workup is indicated in patients with active peptic ulcer disease, a past history of documented peptic ulcer, or with gastric MALT lymphoma. A test-and-treat strategy may be employed in patients under age 55 who have no alarm symptoms.

•

The role of routine screening in high-risk population is not clear. However, there are numerous studies suggesting that H. pylori eradication is protective against progression of premalignant lesions. Consider a test-and-treat approach in asymptomatic first-degree relatives of gastric cancer patients.

•

Routine identification and treatment of H. pylori in cases of non-ulcer dyspepsia, GERD, NSAID use, and of asymptomatic individuals in populations at high risk for gastric cancer is considered controversial although may be indicated in specific cases.

•

Efficacy of testing is related to the individual patient's likelihood of H. pylori infection based on demographic risk factors. In the U.S. population, increased probability of infection exists in African Americans, Hispanics/Latinos, immigrants from developing nations, patients with poor socioeconomic status, Native Americans from Alaska, and persons older than 50.

•

Routine screening for H. pylori in asymptomatic individuals is not indicated in low-risk patients.

•

There is no evidence that H. pylori causes symptoms of nonulcer dyspepsia.

LABORATORY TESTS

•

Testing may be invasive or noninvasive, depending on the need for endoscopy. There is no indication for endoscopy solely to diagnose H. pylori.

•

Tests for H. pylori may be differentiated as active or passive tests. Active tests provide direct evidence that H. pylori infection is currently present and include urea breath testing and stool antigen testing. Passive testing, which includes all serologic testing for H. pylori, gives indirect evidence of its presence, by detecting the presence of antibodies to the organism. Serologic testing is limited by its inability to distinguish between current, active infection, and prior infection that has resolved.

•

Where diagnostic endoscopy is indicated (for suspicion of or follow-up of PUD or gastric MALT), antral biopsy should be tested for urease activity, or for histologic exam, if false negative on urease testing is likely (see following section).

•

In cases where biopsy is not indicated, urea breath testing or stool antigen testing are indicated to evaluate for active infection. The sensitivities and specificities of these two tests are similar, above 90%. Urea breath testing is slightly more expensive than stool antigen testing, but both costs are in a modest range. Choice can be made based on patient preference and availability.

•

Tests that use urease as a marker (urea breath and stool antigen tests, and biopsy for urease activity) may result in false negatives in patients on antibiotics, bismuth, or antisecretory therapy as well as those with active ulcer bleeding. Patients should be off antibiotics for 4 weeks, and off protein pump inhibitors for 2 weeks, before urea breath or stool antigen testing.

•

Serologic testing may be useful in cases where the pretest probability of infection is high or where it is impractical or contraindicated to stop antisecretory medication for the required duration. It cannot be used to document eradication of infection.

TREATMENT ACUTE GENERAL Rx

•

Test only those patients whom you intend to treat if positive (indications for workup discussed at length in previous “Workup” section). At this time, the value of eradicating H. pylori infection is proven in patients with peptic ulcer disease or gastric MALT lymphoma.

•

The optimal antibiotic regimen has not been defined. In addition to efficacy, one must take into account side effects, cost, and ease of administration.

•

The following regimens are effective in 85% of patients (see first “Suggested Reading” for specific dosages): PPI twice daily, with twice-daily clarithromycin and amoxicillin. In cases of PCN allergy, metronidazole may be substituted for amoxicillin. This may reduce effectiveness of treatment because metronidazole resistance has increased. PPI twice daily, combined with bismuth 4 times daily, as well as tetracycline and metronidazole 4 times daily.

•

Current data support 2-week treatment regimens. Although there are encouraging data regarding the use of 1-week regimens, recommendation for optimal treatment duration has not yet been changed.

•

Prior exposure to a macrolide or metronidazole, for any reason, is associated with increased resistance. A preferable regimen would include medications the patient has not been previously exposed to.

•

Diarrhea and abdominal cramping are observed commonly with many of the regimens. Other side effects may include metallic taste with metronidazole or clarithromycin, neuropathy, seizures, and disulfiram-like reaction with metronidazole, diarrhea with amoxicillin, photosensitivity with tetracycline, and Clostridium difficile infection with any antibiotic exposure. Bismuth may cause black stool and constipation. Tetracycline is contraindicated in pregnant patients.

•

20% of patients may fail initial therapy. Optimal retreatment regimes are under investigation. Use either an alternative regimen with a different combination of medications, or quadruple therapy consisting of twice daily PPI and bismuth-based triple therapy. Levofloxacin-based triple therapy for persistent infections appears effective in international studies, but has not been evaluated in U.S. studies. It is important to reinforce compliance.

CHRONIC Rx

•

Data do not yet support routinely testing for cure. Accepted indications for testing to prove eradication include H. pylori associated ulcers, MALT lymphoma, and early gastric cancer, as well as those with persistent dyspepsia despite a test-and-treat management strategy.

•

Serology does not reliably revert to undetectable levels after treatment and should not be used to determine eradication.

•

Active tests (urea breath test and stool antigen testing) are preferable. They are equally accurate in confirming eradication, and either may be used depending on availability and patient preference. To reduce the likelihood of false-negative results, testing should be performed 4 weeks after eradication therapy with PPI and antibiotics or 2 weeks after the cessation of PPI therapy.

DISPOSITION

Consider further evaluation in patients with recurrent symptoms after appropriate treatment. REFERRAL

•

Patients with gastric MALT lymphoma should be followed by a gastroenterologist and oncologist with expertise in the care of lymphoid neoplasms.

•

Patients with dyspepsia who have tested positive for H. pylori and been treated, without resolution of symptoms, should be referred for endoscopy.

•

Consider referral for biopsy for culture and sensitivity in patients who have failed two attempts at treatment.

PEARLS & CONSIDERATIONS COMMENTS

•

It is not clear if H. pylori eradication reduces the risk of gastric cancer.

•

Outcomes in PUD and gastric MALT lymphoma are improved with treatment of associated H. pylori infection.

•

Tests that provide direct evidence of active H. pylori infection (urea breath and stool antigen testing) are preferred, but may result in false negatives in patients on antibiotics, bismuth, or antisecretory testing.

•

Serologic testing is unable to differentiate active from prior infection, but may be useful in the above situations, particularly in high-risk situations.

•

Be aware of high-risk populations in low-prevalence settings, including immigrants from Mexico, South America, Southeast Asia, and Eastern Europe.

SUGGESTED READINGS Chey W, Wong B: American College of Gastroenterology Guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007; 102:1808-1825. Malfertheiner P, et al: Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56:772-781.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

HELLP Syndrome SONYA S. ABDEL-RAZEQ, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

The HELLP syndrome is a serious variant of preeclampsia. HELLP is an acronym for Hemolysis, Elevated Liver function, and Low Platelet count. It is the most frequently encountered microangiopathy of pregnancy. There are three classes of the syndrome based on the degree of maternal thrombocytopenia as a primary indicator of disease severity. Class 1: platelets 50,000/mm 3 Class 2: platelets >50,000/mm3 to 100,000/mm3 Class 3: platelets >100,000/mm3

ICD-9CM CODES

642.50 HELLP, episode of care 642.51 HELLP, delivered 642.52 HELLP, delivered with postpartum complications 642.53 HELLP, antepartum complications 642.54 HELLP, postpartum complications EPIDEMIOLOGY & DEMOGRAPHICS

•

Among women with severe preeclampsia, 6% will manifest with one abnormality suggestive of HELLP syndrome, 12% will develop two abnormalities, and approximately 10% will develop all three.

•

The HELLP Syndrome, like preeclampsia, is rare before 20 wk gestation.

•

One third of all cases occur postpartum; of these, only 80% were diagnosed with preeclampsia before delivery.

RISK FACTORS:Women older than 35 yr, Caucasian, multiparity RECURRENCE RATE: 3% to 25% PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Definitive laboratory criteria remain to be validated prospectively.

•

Most commonly used criteria include hemolysis defined by the presence of an abnormal peripheral smear with schistocytes, lactate dehydrogenase (LDH) >600 U/L, and total bilirubin >1.2 mg/dl; elevated liver enzymes as serum aspartate aminotransferase (AST) >70 U/L and LDH >600 U/L; low platelet count as less than 100,000/mm3.

•

Although many women with HELLP syndrome will be asymptomatic, 80% report right upper quadrant pain and 50% to 60% present with excessive weight gain and worsening edema.

ETIOLOGY

As with other microangiopathies, endothelial dysfunction, with resultant activation of the intravascular coagulation cascade, has been proposed as the central pathogenesis of HELLP syndrome.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Appendicitis

•

Gallbladder disease

•

Peptic ulcer disease

•

Enteritis

•

Hepatitis

•

Pyelonephritis

•

Systemic lupus erythematosus

•

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

•

Acute fatty liver of pregnancy

WORKUP

Because the HELLP syndrome is a disease entity based on laboratory values, initial assessment is detailed as follows. LABORATORY TESTS

•

Initial assessment of suspected HELLP syndrome should include a complete blood count (CBC) to evaluate platelets, urinalysis, serum creatinine, LDH, uric acid, indirect and total bilirubin levels, and AST/ALT.

•

Tests of prothrombin time, partial thromboplastin time, fibrinogen and fibrin split products are reserved for those women with a platelet count well below 100,000/mm3.

IMAGING STUDIES

There are none to aid in diagnosis.

TREATMENT

Treatment is dependent on gestational age of the fetus, severity of HELLP, and maternal status. Stabilization of the mother is the first priority. ACUTE GENERAL Rx

•

Assess gestational age thoroughly. Fetal status should be monitored with nonstress tests, contraction stress tests, and/or biophysical profile

•

Maternal status should be evaluated by history, physical examination, and laboratory testing

•

Magnesium sulfate is administered for seizure prophylaxis regardless of blood pressure

•

Blood pressure control is achieved with agents such as hydralazine or labetalol

•

Indwelling Foley catheter to monitor maternal volume status and urine output

CHRONIC Rx

•

In those pregnancies 34 wk or class 1 HELLP syndrome, delivery, either vaginal or abdominal, within 24 hr is the goal.

•

In the preterm fetus, corticosteroid therapy to enhance fetal lung maturation is indicated.

•

Some reports have shown temporary amelioration of HELLP severity with the administration of high dose of steroids measured by increased urine output, improvement in platelet count and LFTs.

•

Judicious use of blood products, especially in those requiring surgery.

•

The patient requires intensive observation for 48 hr postpartum; laboratory levels should begin to improve during this time.

DISPOSITION

The natural history of this disorder is a rapidly deteriorating condition requiring close monitoring of maternal and fetal well-being. REFERRAL

Preterm patients with the HELLP syndrome should be stabilized hemodynamically and transferred to a tertiary care center. Term patients can be treated at a local hospital depending on the availability of obstetric, neonatal, and blood banking services.

PEARLS & CONSIDERATIONS Not all women with HELLP have hypertension or proteinuria. SUGGESTED READINGS Magann EF, Martin JN: Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol 1999; 42(3):532. Norwitz ER, Hsu CD, Repke JT: Acute complications of preeclampsia. Clin Obstet Gynecol 2002; 45(2):308.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hemochromatosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Hemochromatosis is an autosomal recessive disorder characterized by increased accumulation of iron in various organs (adrenals, liver, pancreas, heart, testes, kidneys, pituitary) and eventual dysfunction of these organs if not treated appropriately. SYNONYMS

Bronze diabetes

ICD-9CM CODES

275.0 Hemochromatosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE:In whites, approximately 1 in 300 persons. PREDOMINANT SEX AND AGE: Generally diagnosed in males in their fifth decade. Diagnosis in females is generally not made until 10 to 20 yr after menopause. GENETICS: Most common genetic disorder in North European ancestry. Homozygosity for the C282Y mutation is now found in approximately 5 of every 1000 persons of European descent. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Examination may be normal; patient with advanced case may present with the following: •

Increased skin pigmentation

•

Hepatomegaly, splenomegaly, hepatic tenderness, testicular atrophy

•

Loss of body hair, peripheral edema, gynecomastia, ascites

•

Amenorrhea (25% of females)

•

Loss of libido (50% of males)

•

Arthropathy

•

Joint pain (44%)

•

Fatigue (45%)

ETIOLOGY

Autosomal recessive disease linked to the region of the short arm of chromosome 6 encoding HLA-A*3; the gene HFE, which contains two missense mutations (C 282Y and H 63D), was recently identified.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hereditary anemias with defect of erythropoiesis

•

Cirrhosis

•

Repeated blood transfusions

WORKUP

Medical history, physical examination, and laboratory evaluation should be focused on affected organ systems (see Physical Findings). Liver biopsy is the gold standard for diagnosis; it reveals iron deposition in hepatocytes, bile ducts, and supporting tissues. LABORATORY TESTS

•

Transferrin saturation is the best screening test. Values >45% are an indication for further testing. When using transferring saturation to screen individuals 40%). Genetic testing should not be performed as part of initial routine evaluation for hereditary hemochromatosis. Once a patient has been identified, first-degree relatives of the index patient should also be screened. The HFE gene test is a PCR-based test usually performed on whole blood sample. Cost is approximately $150 to $200.

IMAGING STUDIES

CT scan or MRI of the liver is useful to exclude other etiologies and may in some cases show iron overload in the liver.

TREATMENT NONPHARMACOLOGIC THERAPY

Weekly phlebotomies of one or two units of blood (each containing approximately 250 mg of iron) should be continued for several weeks until depletion of iron stores is achieved (ferritin level 5%, moderate: levels are 1% to 5%, severe: levels are 2 cm that shows characteristic arterial vascularization that is seen on two imaging modalities or

•

Single positive imaging method with AFP >200 µg/ml

SCREENING

Screening high-risk patients with US and AFP q6 months may identify hepatocellular carcinoma at an early stage. Patients on transplant waiting lists should be screened for HCC because in the U.S. the development of HCC gives increased priority for liver transplantation. Screening at 6- to 12-mo intervals may be acceptable for

healthy hepatitis B virus carriers without cirrhosis. STAGING

According to the Barcelona-Clinic Liver Cancer (BCLC) staging classification, treatment is determined according to stage: •

Early stage: asymptomatic single tumor =5 cm or 3 nodules, each =3 cm (known as Milan criteria)

•

Intermediate stage: patients with tumors that exceed early criteria but do not yet show cancer-related symptoms, vascular invasion, or metastases

•

Advanced stage: patients with cancer-related symptoms

•

End-stage: patients with advanced, symptomatic disease

TREATMENT

•

Early stage: curative treatment (surgical resection or liver transplantation). Patients who have a single lesion can be offered surgical resection if they are noncirrhotic or have cirrhosis but still have well preserved liver function. Liver transplantation is an effective option for patients with HCC corresponding to the Milan criteria. Local ablation is safe and effective therapy for patients who cannot undergo resection, or as a bridge to transplantation.

•

Intermediate stage: optimal therapeutic approach is controversial. Outcome may be improved with chemoembolization.

•

Advanced stage: no curative treatment. In the absence of metastatic disease or portal invasion, chemoembolization is reasonable. Entry into clinical trials should be considered.

•

End-stage: palliative care.

•

For patients with unresectable HCC, chemoembolization using cisplatin or doxorubicin has been shown to improve 2-yr survival rates.

DISPOSITION

For unresectable tumors, prognosis is poor; 5-yr survival following surgical resection ranges from 30% to 50%. REFERRAL

Referral to GI for treatment planning

PEARLS & CONSIDERATIONS Prevention:

•

Universal hepatitis B vaccination in children in endemic areas has been shown to decrease the incidence of HCC.

•

Treatment of patients with chronic hepatitis B–associated cirrhosis with lamivudine reduces the incidence of HCC.

•

For hepatitis C virus–associated HCC, postoperative treatment with interferon-alpha may decrease the rate of tumor recurrence.

•

Eliminate aflatoxin from food.

•

Decrease alcohol consumption.

•

Identify and treat hemochromatosis.

SUGGESTED READINGS Bruix J, Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases. Hepatology 2005; 42(5):1208. Cheng BQ, et al: Chemoembolization combined with radio frequency abalation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. JAMA 2008; 299(b):1669-1677. El-Serag H, Rudolph K: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007; 132(7):2557. El-Serag HB, et al: The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003; 139:817. Liaw YF, et al: Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521. Llovet JM, Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003; 37(2):429.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hepatorenal Syndrome FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Hepatorenal syndrome (HRS) is a condition of intense renal vasoconstriction resulting from loss of renal autoregulation occurring as a complication of severe liver disease. Criteria for hepatorenal syndrome are: 1.

Serum creatinine concentration >1.5 mg/dl or 24 hr creatinine clearance 70% by age 70 yr); antivirals reduce the risk of postherpetic neuralgia.

•

Incidence of disseminated herpes zoster is increased in immunocompromised hosts (e.g., 15% to 50% of patients with active Hodgkin's disease).

•

Immunocompromised hosts are also more prone to neurologic complications (encephalitis, myelitis, cranial and peripheral nerve palsies, acute retinal necrosis). The mortality rate is 10% to 20% in immunocompromised hosts with disseminated zoster.

•

Motor neuropathies occur in 5% of all cases of zoster; complete recovery occurs in >70% of patients.

REFERRAL

•

Hospitalization for IV acyclovir in patients with disseminated herpes zoster

•

Patients with herpes zoster ophthalmicus should be referred to an ophthalmologist

VACCINATION: Immunocompetent adults 60 years of age or older are appropriate candidates for a single dose of varicella zoster vaccine (VZV) whether or not they have had a previous episode of herpes zoster. Immunization with VZV (Zostavax) boosts waning immunity in older adults and reduces the severity and duration of pain caused by herpes zoster by 61%. Adults who are VZV seronegative (never had varicella) should be immunized against varicella with 2 doses of varicella vaccine (Varivax). SUGGESTED READINGS

Kimberlin DW, Whitley RJ: Varicella-Zoster vaccine for the prevention of herpes zoster. N Engl J Med 2007; 356:1338.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hiatal Hernia ABDULBAKI ABDULRAHMAN, M.D.

BASIC INFORMATION DEFINITION

A hiatal hernia is the herniation of a portion of the stomach into the thoracic cavity through the diaphragmatic esophageal hiatus. SYNONYMS

Diaphragmatic hernias

ICD-9CM CODES

750.6 Hiatal hernia EPIDEMIOLOGY & DEMOGRAPHICS

•

Found in 50% of patients over the age of 50.

•

Increases with age.

•

More prevalent in Western countries than in Africa and Asia.

•

Sliding hiatal hernias are more common in women than men (4:1).

•

Associated with diverticulosis (25%), esophagitis (25%), duodenal ulcers (20%), and gallstones (18%).

•

More than 90% of patients with endoscopic documentation of esophagitis have hiatal hernias.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Most patients are asymptomatic. If symptoms are present, it resembles those of gastroesophageal reflux disease (GERD).

•

Heartburn

•

Dysphagia

•

Regurgitation of gastric contents

•

Chest pain

•

Postprandial fullness

•

GI bleed

•

Dyspnea

•

Hoarseness

•

Wheezing with bowel sounds heard over the left lung base

ETIOLOGY

•

Imbalance between normal pulling forces of the esophagus through the diaphragmatic hiatus during swallowing and the supporting structures maintaining normal gastroesophageal (GE) junction positioning. The repetitive stretching and pulling of the GE junction causes widening of the hiatus, rupture of the phrenoesophageal ligament, and onset of the hernia.

•

Hiatal hernias are classified as: 1.

Type I: Sliding ( Fig. 1-121, A ), axial, or concentric hiatal hernia (most common type, 99%). Only the GE junction protrudes into the thoracic cavity.

2.

Type II: Paraesophageal or rolling hernia ( Fig. 1-121, B ) (1%). The GE junction stays at the level of the diaphragm, but part of the stomach bulges into the thoracic cavity.

3.

Type III: Mixed (rare), a combination of type I and type II.

4.

Type IV: Large defect in hiatus that allows other intraabdominal organs to enter the hernia sac.

FIGURE 1-121 Types of esophageal hiatal hernia. A, Sliding hiatal hernia, the most common type. B, Paraesophageal hiatal hernia. From Behrman RE: Nelson textbook of pediatrics, ed 17, Philadelphia, 2004, WB Saunders.)

DIAGNOSIS Imaging studies DIFFERENTIAL DIAGNOSIS

•

Peptic ulcer disease

•

Unstable angina

•

Esophagitis (caused by Candida, herpes, NSAIDs, etc.)

•

Esophageal spasm

•

Barrett's esophagus

•

Schatzki's ring

•

Achalasia

•

Zenker's diverticulum

•

Esophageal cancer

WORKUP

•

Exclude conditions noted in the differential diagnosis and documenting the presence of a hiatal hernia. Upper endoscopy may also be needed to exclude abnormal metaplasia, dysplasia, or neoplasia.

•

A clinical algorithm for evaluation of heartburn is described in Section III.

LABORATORY TESTS

•

Blood tests are not specific.

•

Esophageal manometry, although not commonly done, can be used in establishing a diagnosis (low sensitivity, but high specificity when compared with endoscopy).

IMAGING STUDIES

•

Barium contrast upper gastrointestinal (UGI) series best defines the anatomic abnormality: demonstration that the gastric cardia is herniated 2 cm above the hiatus. UGI may reveal a tortuous esophagus ( Fig. 1122 ). If endoscopy is performed preoperatively, a barium swallow is generally not necessary.

•

Upper GI endoscopy: documents the presence of a hiatal hernia and also excludes common associated findings of esophagitis and Barrett's esophagus (recommended at least once during the workup). Greater than 2 cm of gastric rugal fold seen above the margins of the diaphragmatic crura is diagnostic.

•

Abdominal ultrasonography: simple, well tolerated; a transdiaphragmatic esophageal diameter of more than or equal to 18 mm is highly suggestive of the presence of a sliding hiatal hernia.

FIGURE 1-122 A sliding hiatal hernia confirmed by the presence of an incisural notch (arrow) on the greater curve aspect. From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger & Allison's diagnostic radiology, ed 4, Philadelphia, 2001, Churchill Livingstone.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Lifestyle modifications: avoidance of foods and drugs that decrease lower esophageal pressure (e.g. caffeine, chocolate, mint, calcium channel blockers, and anticholinergics)

•

Weight loss

•

Avoid large quantities of food with meals

•

Sleep with the head of the bed elevated to 6 inches

ACUTE GENERAL Rx

•

Antacids may be useful to relieve mild symptoms.

•

H2 antagonists (e.g., cimetidine 400 mg bid, ranitidine 150 mg bid, or famotidine 20 mg bid).

•

If significant GERD is present with documented esophagitis, proton pump inhibitors (e.g., omeprazole 20 mg qd or lansoprazole 30 mg qd) are used. Refractory symptoms may require higher doses (e.g., bid dosing).

•

Prokinetic agents (e.g., metoclopramide 10 mg taken 30 min before each meal) can be added to an H2 antagonist or proton pump inhibitor.

CHRONIC Rx

•

When indicated, surgery (laparoscopic or open) can be done in patients with refractory symptoms impairing quality of life, or causing intestinal (e.g., recurrent GI bleeds) or extraintestinal complications (e.g., aspiration pneumonia, asthma, or ear-nose-throat complications).

•

Prophylactic surgery is a consideration in all paraesophageal hernias because they have a higher incidence of strangulation.

DISPOSITION

•

More than 90% of patients having GERD symptoms respond well to medical therapy.

•

Complications of hiatal hernias are similar to complications occurring in patients with GERD: 1.

Erosive esophagitis

2.

Ulcerative esophagitis

3.

Barrett's esophagus

4.

Peptic stricture

5.

GI hemorrhage

6.

Extraintestinal complications

7.

Lung collapse or heart failure (severe cases)

REFERRAL

Gastroenterologist: symptoms refractory to conventional therapy (H2 antagonists, antacids, and proton pump inhibitors) or having complications mentioned above

PEARLS & CONSIDERATIONS COMMENTS

•

Gastric ulceration and erosions (Cameron's lesion) can occur in the hernia pouch and account for uncommon cause of upper GI bleeding.

•

May cause iron deficiency anemia.

•

Gastric volvulus or torsion can also occur and presents as dysphagia and postcibal pain.

•

High incidence of esophagitis even after the eradication of Helicobacter pylori.

•

The appearance of hiatal hernia may simulate left atrial mass by echocardiography.

SUGGESTED READINGS

Andujan JJ, et al: Laparoscopic repair of large paraesophageal hernia is associated with low incidence of recurrence and reoperations. Surg Endosc 2004; 18(3):444. Christensen J, Miftakhnr R: Hiatus hernia: a review of evidence for its origin in esophageal longitudinal muscle dysfunction. Am J Med 2000; 108(Suppl 4a):35. Linke GR, Borovicka J, Schneider P, et al: Is a barium swallow complementary to endoscopy essential in the preoperative assessment of laparoscopic antireflux and hiatal hernia surgery?. Surg Endosc. Epub 2007;May 24. Rosen M, Ponsky J: Laparoscopic repair of giant paraesophageal hernia: an update for internists. Clev Clin J Med 2003; 70(6):511. Stylopoulos N, Rattner DW: Paraesophageal hernia: when to operate?. Adv Surg 2003; 37:213.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hidradenitis Suppurativa RICHARD LONG, M.D.

BASIC INFORMATION DEFINITION

Hidradenitis suppurativa is a chronic, relapsing condition that occurs within the terminal follicular epithelium of the apocrine glands. Keritinous materials occlude the follicles causing secondary inflammation of the apocrine glands resulting in chronic infection and draining abscess that lead to scarring. SYNONYMS

Suppurative hidradentis Acne inversa Verneuil's disease Apocrinitis Hidradenitis axillaris

ICD-9CM CODES 705.83 EPIDEMIOLOGY & DEMOGRAPHICS

•

HS occurs more commonly in women in the U.S.

•

It usually begins in the postpubertal age group, with an average age of onset of 23 yr.

•

Its overall prevalence in the U.S. is approximately 1% to 2%.

•

An increased frequency of this disease is seen in people of African American descent, though this has not been fully studied. The suspicion is that it is due to a greater density of apocrine glands.

•

Predisposing factors thought to be involved are the following: hyperandrogenism, obesity, and familial predilection.

•

HS has been associated with other endocrine disorders such as diabetes, Cushing's disease, and acromegaly.

PHYSICAL FINDINGS & Clinical Presentation

The diagnosis is primarily clinical based on the development of typical lesions. There are three key elements to typical lesions: typical lesions, characteristic distribution, and relapsing nature.

•

Typical lesions can be as follows: Painful and/or tender erythematous papules and nodules Painful or tender abscesses and inflamed discharging papules or nodules Dermal contractures and ropelike elevation of the skin Comedones in the apocrine, gland-bearing skin

•

Characteristic sites are: Axilla ( Fig. 1-123 ) Inguinal perineal region Areola of the breast Submammary folds

•

There is a strong tendency toward relapse and recurrence.

•

Other characteristics of the disease are: Poor response to conventional antibiotics Often no pathogens from routine cultures of pus from boils Personal or family history of acne or pilonidal cysts

FIGURE 1-123 Hidradenitis suppurativa (HS). A, HS of the axilla. This is the classic appearance with inflammatory nodules and scarred areas. This condition is commonly misdiagnosed as a bacterial infection. B, HS of the axilla; a close-up view of the draining pus. When intact, the lesions represent sterile abscesses. Once open, they may become secondarily infected. From White GM, Cox NH [eds]: Diseases of the skin: a color atlas and text, ed 2, St Louis, 2006, Mosby.)

ETIOLOGY

The exact cause of hidradentis suppurativa has not been determined, though a number of theories have been proposed: 1.

Folliculitis is observed in almost all patients with HS, though whether or not this is causative has not been determined.

2.

Local friction trauma could be a cause.

3.

Infectious agents such as Streptococcus, Staphylococcus, and E. coli have been identified in cultures, but it is uncertain whether these are cause or result.

4.

Low levels of estrogen are implicated, as are high levels of androgen.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Follicular pyodermas such as folliculitis, furuncles, carbuncles, and pilonidal cysts

•

Granuloma inguinale

•

Perianal and vulvular manifestations of Crohn's disease

•

Abscess

•

Infection of a Bartholin's cyst

•

Actinomycosis

•

Lymphogranuloma venereum

•

Infection of an epidermoid cyst

•

Lymphadenitis

•

Cat scratch disease

•

Tularemia

•

Erysipelas

•

Ulcerative colitis

WORKUP

This is primarily a clinical diagnosis based on typical lesion (see “Physical Findings & Clinical Presentation”). LABORATORY TESTS

•

Patients with acute lesions may have an elevated erythrocyte sedimentation rate or WBC. They also may have serum protein abnormalities on electrophoresis.

•

Any pus should be sampled for bacterial culture and sensitivity.

AUTHOR: CHRISTINE HARTLEY, M.D. Hirsutism

BASIC INFORMATION DEFINITION

The development of stiff, pigmented (terminal) facial and body hair in women as a result of excess androgen production. SYNONYMS

Hypertrichosis Acquired lanuginosa

ICD-9CM CODES

704.1 Hirsutism EPIDEMIOLOGY & DEMOGRAPHICS

•

Overall prevalence unknown, estimated 1% to 2% in women 18 to 38 years.

•

Race and genetics should be considered as some distinct ethnic populations have minimal body hair and others have moderate to large amounts of body hair while serum androgen levels are similar.

•

Social norms and culture also determine how much body hair is cosmetically acceptable.

•

Incidence and presentation of hirsutism dependent on underlying cause of androgen excess (see “Differential Diagnosis”).

CLINICAL PRESENTATION

•

Timing of symptoms—abrupt onset, short duration, rapid progression, progressive worsening, more severe signs of virilization, or later age of onset suggest androgen-producing tumor, late-onset congenital adrenal hyperplasia, or Cushing's syndrome. Weight increases may produce increased androgen production.

•

Menstrual history—menarche, cycle regularity and symptoms of ovulation, fertility, and contraception use. Anovulatory cycles are the most common underlying cause of androgen excess.

•

Medication use history—some drugs cause hirsutism or produce androgenergic effects (donazol, phenytoin, androgenic progestins e.g., norgestrel, cyclosporin, minoxidil, metoclopramide, phenothiazines, methyldopa, diazoxide, penicillamine).

•

Family history—known or suspected family history of hirsutism, congenital adrenal hyperplasia, insulin resistance, polycystic ovary syndrome (PCOS), infertility, obesity, menstrual irregularity.

•

Physical exam—voice, body habitus, galactorrhea, abdominal and pelvic exam.

•

Associated cutaneous manifestations—acne, acanthosis nigricans, striae, hair distribution, location and quantity, frontotemporal balding, muscle mass, clitoromegaly.

ETIOLOGY

•

Presence of hirsutism indicates androgen excess. Total testosterone may be normal, but free testosterone is elevated.

•

Anovulatory ovaries are usual source of excess androgens through thecal cell steroidogenesis and conversion of androstenedione to testosterone.

•

Conditions that decrease hepatic production of sex hormone binding globulin (SHBG) decrease proteinbound testosterone and increase free testosterone fraction (e.g., low estrogen, high androgen, and hyperinsulinemic states).

•

Late-onset, congenital adrenal hyperplasia enzyme deficiency (most commonly 21-hydroxylase deficiency) produces excess 17 alpha-hydroxyprogesterone (17-OHP) and overproduction of androstenedione.

•

Rare ovarian tumors primarily derived from Sertoli-Leydig cells, granulosa theca cells, or hilus cells produce excess androgens.

•

Rare adrenal tumors produce excess androgens.

•

Rare pituitary or hypothalamic tumors produce excess prolactin and can lead to anovulation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Androgen-independent vellus hair—soft, unpigmented hair that covers entire body.

•

Hypertrichosis—diffusely increased total body hair often an adverse response to a medication or systemic illness.

•

PCOS 75%

•

Idiopathic 5% to 15%

•

Congenital adrenal hyperplasia 1% to 8%

•

Insulin resistance syndrome 3% to 4%

•

Drug induced50 yr old with an associated history of COPD.

•

Presumed ocular histoplasmosis syndrome (POHS) is seen between ages of 20 and 40 yr.

PEAK INCIDENCE:Unknown PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Conidia are deposited in alveoli then converted to yeast forms where they spread to regional lymph nodes and other organs, especially liver and spleen.

•

1 to 2 wk later, a granulomatous inflammatory response begins to contain the yeast in the form of discrete granulomas.

•

Delayed-type hypersensitivity to Histoplasma antigens occurs 3 to 6 wk after exposure.

•

Clinical disease manifests in various forms, depending on host cellular immunity and inoculum size: 1.

2.

3.

Acute primary pulmonary histoplasmosis a.

Overwhelming number of patients are asymptomatic.

b.

Most clinically apparent infections manifest by complaints of fever, headache, malaise, pleuritic chest pain, nonproductive cough, and weight loss.

c.

Less than 10%, mainly women, complain of arthralgias, myalgias, and skin manifestations such as erythema multiforme or erythema nodosum.

d.

Acute pericarditis presents in smaller percentage of patients.

e.

Hepatosplenomegaly is most commonly observed in children.

f.

With particularly heavy exposure, there is severe dyspnea, marked hypoxemia, impending respiratory failure.

g.

Most patients are asymptomatic within 6 wk.

CPH a.

Presents insidiously with low-grade fever, malaise, weight loss, cough, sometimes with blood-streaked sputum or frank hemoptysis.

b.

Most patients with cavitary lesions present with associated COPD or chronic bronchitis, masking underlying fungal disease.

c.

Tends to worsen preexisting pulmonary disease and further contribute to eventual respiratory insufficiency.

PDH

•

•

•

•

a.

In both acute and subacute forms, constitutional symptoms of fever, fatigue, malaise, and weight loss are common.

b.

Acute form (seen in infants and children) presents with respiratory symptoms, fever80% occurs in males), in Caucasians, and in higher socioeconomic groups.

•

Overall incidence of Hodgkin's disease in the U.S. is approximately 4:100,000. There are >7000 new cases of Hodgkin lymphoma diagnosed annually in the U.S.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Palpable lymphadenopathy, generally painless

•

Most common site of involvement: neck region

•

See “Workup” for description of common symptoms

ETIOLOGY

Unknown; evidence implicating Epstein-Barr virus remains controversial.

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Non-Hodgkin's lymphoma

•

Sarcoidosis

•

Infections (e.g., CMV, Epstein-Barr virus, toxoplasma, HIV)

•

Drug reaction

WORKUP

Symptomatic patients with Hodgkin's disease usually present with the following manifestations: •

Fever and night sweats: fever in a cyclical pattern (days or weeks of fever alternating with afebrile periods) is known as Pel-Epstein fever

•

Weight loss, generalized malaise

•

Persistent, nonproductive cough

•

Pain associated with alcohol ingestion, often secondary to heavy eosinophil infiltration of the tumor sites

•

Pruritus

•

Others: superior vena cava syndrome and spinal cord compression (rare)

Diagnosis can be made with lymph node biopsy. There are four main histologic subtypes, based on the number of lymphocytes, Reed-Sternberg cells ( Fig. 1-125 ), and the presence of fibrous tissue: 1.

Lymphocyte predominance

2.

Mixed cellularity

3.

Nodular sclerosis

4.

Lymphocyte depletion

FIGURE 1-125 Hodgkin's disease. High-power photomicrograph demonstrates a binucleate Reed-Sternberg cell exhibiting prominent inclusion-like eosinophilic nucleoli giving it an “owl's eye” appearance. From Skarin AT: Atlas of diagnostic oncology, ed 3, St Louis, 2003, Mosby.)

Nodular sclerosis is the most common type and occurs mainly in young adulthood, whereas the mixed cellularity type is more prevalent after age 50 yr. Staging for Hodgkin's disease follows the Ann Arbor staging classification.

Stage I: Involvement of a single lymph node region Stage II: Two or more lymph node regions on the same side of the diaphragm Stage III: Lymph node involvement on both sides of diaphragm, including spleen Stage IV: Diffuse involvement of external sites Suffix A: No systemic symptoms Suffix B: Presence of fever, night sweats, or unexplained weight loss of 10% or more body weight over 6 mo Suffix X: Indicates bulky disease >1/3 widening of mediastinum or >10 cm maximum dimension of nodal mass on a chest film Proper staging requires the following: •

Detailed history (with documentation of “B symptoms” and physical examination)

•

Surgical biopsy

•

Laboratory evaluation (CBC, sedimentation rate, BUN, creatinine, alkaline phosphatase, LFTs, albumin, LDH, uric acid)

•

Chest x-ray (PA and lateral)

•

Bilateral bone marrow biopsy

•

CT scan of the chest (when abnormal findings are noted on chest x-ray examination) and of the abdomen and pelvis to visualize the mesenteric, hepatic, portal, and splenic hilar nodes

•

Positron emmision tomography (PET) scan

•

Bipedal lymphangiography may be performed only in selected patients to define periaortic and iliac lymph node involvement

•

Exploratory laparotomy and splenectomy (selected patients): 1.

Decision to perform staging laparotomy depends on the therapeutic plan; it is generally not indicated in patients who have a large mediastinal mass (these patients will generally be treated with combined chemotherapy and radiation). Staging laparotomy may also not be required in patients with clinical stage I or unlikely to have abdominal disease (e.g., females with supradiaphragmatic disease).

2.

Exploratory laparotomy and splenectomy may be used for patients with clinical stage I to IIA or IIB.

3.

It is useful in identifying patients who can be treated with irradiation alone with curative intent.

4.

Polyvalent pneumococcal vaccine should be given prophylactically to all patients before splenectomy (increased risk of sepsis from encapsulated organisms in splenectomized patients).

TREATMENT ACUTE GENERAL Rx

The main therapeutic modalities are radiotherapy and chemotherapy; the indication for each vary with pathologic stage and other factors.

•

Stage I and II: radiation therapy alone unless a large mediastinal mass is present (mediastinal to thoracic ratio =1.3); in the latter case, a combination of chemotherapy and radiation therapy is indicated.

•

Stage IB or IIB: total nodal irradiation is often used, although chemotherapy is performed in many centers.

•

Stage IIIA: treatment is controversial. It varies with the anatomic substage after splenectomy. 1.

III1A and minimum splenic involvement: radiation therapy alone may be adequate.

2.

III2 or III1A with extensive splenic involvement: there is disagreement whether chemotherapy alone or a combination of chemotherapy and radiation therapy is the preferred treatment modality.

3.

IIIB and IVB: the treatment of choice is chemotherapy with or without adjuvant radiotherapy.

Various regimens can be used for combination of chemotherapy. Most oncologists prefer the combination of doxorubicin plus bleomycin plus vincristine plus dacarbazine (ABVD). Other commonly used regimens are MOPP, MOPP-ABV, MOPP-ABVD, MOPP-BAP. •

In patients with advanced Hodgkin's disease, increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) offers better tumor control and overall survival than COPP-ABVD.

DISPOSITION

•

The overall survival at 10 yr is approximately 60%.

•

Cure rates as high as 75% to 80% are now possible with appropriate initial therapy.

•

Poor prognostic features include presence of “B symptoms,” advanced age, advanced stage at initial presentation, mixed-cellularity, and lymphocyte depletion histology.

•

Chemotherapy significantly increases the risk of leukemia.

•

The peak in risk of leukemia is seen approximately 5 yr after the initiation of chemotherapy.

•

The risk of leukemia is greater for those who undergo splenectomy and for patients with advanced stages of Hodgkin's disease; the risk is unaffected by concomitant radiotherapy.

•

Involved-field radiotherapy does not improve the outcome in patients with advanced-stage Hodgkin's lymphoma who have a complete remission after MOPP-ABV chemotherapy. Radiotherapy may benefit patients with a partial response after chemotherapy.

•

Mediastinal irradiation increases the risk of subsequent death from heart disease caused by sclerosis of coronary artery secondary to irradiation. Risk increases with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increased duration of follow-up.

•

Both chemotherapy and radiation therapy increase the risk of developing secondary solid tumors (e.g., carcinoma of the lung, breast, and stomach).

REFERRAL

•

Surgical referral for lymph node biopsy

•

Hematology/oncology referral

PEARLS & CONSIDERATIONS COMMENTS

•

Young male patients should consider sperm banking before the initiation of therapy.

•

Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, 4 courses of chemotherapy plus involved-field radiotherapy should be the standard of treatment.

EVIDENCE

For early stage Hodgkin's disease, experience and clinical trials over the last 50 years have shown the efficacy of radiotherapy alone. A retrospective study of 709 patients with early-stage disease and who were treated with primary radiation therapy revealed that 157 patients had relapsed at a median time of 2 years.[[1]] Chemotherapy alone may prove to be equally as effective. The ultimate choice of therapy modality will then depend on differences in short-term and long-term toxic effects. The long-term effects (>15 years after completion of therapy) are not yet available for patients treated with chemotherapy alone. For patients with early-stage, massive mediastinal disease, cure rates of 80% are achievable using combined modality treatments.[[2]] For advanced-stage disease, chemotherapy alone or combined radiotherapy with chemotherapy for bulky disease is efficacious. A metaanalysis of >1700 patients treated on 14 different trials showed no improvement in overall 10-year survival for patients with advanced disease who received combined modality therapy vs. chemotherapy alone.[[3]] In patients with advanced-stage disease with massive mediastinal involvement, relapse rates were lower in the group of patients treated with combined modalities than in the group treated with chemotherapy alone (20% vs. 50%).[[4]]

Evidence-Based References 1. Torrey PJ, Poen C, Hoppe RT: Detection of relapse in early-stage Hodgkin's disease: role of routine follow-up studies. J Clin Oncol 1997; 17:253. 2. Leopold KA, et al: Stage IA-11B Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy. J Clin Oncol 1989; 7:1059. 3. Leoffler M, et al: Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. J Clin Oncol 1998; 16:818. 4. Longo DL, et al: Treatment of advanced-stage mediastinal Hodgkin's disease: the case for combined modality treatment. J Clin Oncol 1991; 9:227.

SUGGESTED READINGS Aleman B, et al: Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med 2003; 348:2396. Ansell S, Armitage JO: Management of Hodgkin Lymphoma. Mayo Clin Proc 2006; 81(3):419. Diehl V, et al: Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for

advanced Hodgkin's disease. N Engl J Med 2003; 348:2386. Ferme C, et al: Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med 2007; 357:1916-1927.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hookworm STEVEN M. OPAL, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Hookworm is a parasitic infection of the intestine caused by helminths. SYNONYMS

Ground itch Ancylostoma duodenale infection Necator americanus infection

ICD-9CM CODES

126.35 Hookworm EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.):

•

Varies greatly in different areas of the U.S.

•

Most common in rural areas of southeastern U.S.

•

Poor sanitation and increased rainfall increase likelihood

PREVALENCE (IN U.S.):Varies from 10% to 90% in regions where it is found PREDOMINANT AGE: Schoolchildren PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Nonspecific abdominal complaints

•

Because these organisms consume host RBCs, symptoms related to iron-deficiency anemia, depending on the amount of iron in the diet and the worm burden

•

Fatigue, tachycardia, dyspnea, and high-output failure

•

Hypoproteinemia and edema from loss of proteins into the intestinal tract

•

Unusual for pulmonary manifestations to occur when the larvae migrate through the lungs

•

Skin rash at sites of larval penetration in some individuals without prior exposure

ETIOLOGY

Two species can cause this disease: N. americanus and A. duodenale. N. americanus is the predominant cause of hookworm in the U.S. They are soil nematodes (Geohelminthic infections) that are acquired by skin contact (i.e., bare feet) with contaminated soils in moist, warm climate. •

Infection occurs via penetration of the skin by the larval form, with subsequent migration via the blood stream to the alveoli, up the respiratory tract, then into the GI tract

•

Ancylostoma spp infection can also occur via the oral route through ingestion of contaminated water supplies

•

Sharp mouth parts allow for attachment to intestinal mucosa

•

Ancylostoma spp are more likely to cause iron deficiency anemia because they are larger and remove more blood daily from the bowel wall than the other hookworm species N. americanus

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Strongyloidiasis

•

Ascariasis

•

Other causes of iron deficiency anemia and malabsorption

WORKUP

Examine stool for hookworm eggs. LABORATORY TESTS

CBC to show hypochromic, microcytic anemia; possible mild eosinophilia and hypoalbuminemia IMAGING STUDIES

Chest x-ray examination: occasionally shows opacities

TREATMENT NONPHARMACOLOGIC THERAPY

Prevention of disease by not walking barefoot and by improving sanitary conditions

ACUTE GENERAL Rx

•

Albendazole 400 mg once by mouth has become preferred treatment

•

Mebendazole 100 mg PO bid for 3 days is also effective

•

Iron supplementation may be helpful in patients with iron deficiency

DISPOSITION

Easily treated REFERRAL

If diagnosis uncertain

PEARLS & CONSIDERATIONS COMMENTS

•

Appropriate disposal of human wastes is important in controlling the disease in areas with a high prevalence of hookworm infestation.

•

Wearing shoes will avoid contact with contaminated soils, and the provision of safe water and sanitation for disposing human excreta is important in control of hookworm.

SUGGESTED READINGS Brooker S, Bethony J, Hotez PJ: Human hookworm infection in the 21st century. Adv Parasitol 2004; 58:197. Brooker S, et al: Epidemiologic, immunologic and practical considerations in developing and evaluating a human hookworm vaccine. Expert Rev Vaccines 2005; 4(1):35. Hotez PJ, et al: Hookworm infection. N Engl J Med 2004; 351(8):799. Quinnell RJ, Bethony J, Pritchard DI: The immunoepidemiology of human hookworm infection. Parasite Immunol 2004; 26(11–12):443.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hordeolum (Stye) GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

A hordeolum is an acute inflammatory process affecting the eyelid and arising from the meibomian (posterior) or Zeis (anterior) glands. It is most often infectious and usually caused by Staphylococcus aureus. SYNONYMS

Stye

ICD-9CM CODES

373.11 External hordeolum 373.12 Internal hordeolum EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.):Unknown PEAK INCIDENCE: May occur at any age PREVALENCE (IN U.S.): Unknown PREDOMINANT SEX: No gender predilection PREDOMINANT AGE: May occur at any age NEONATAL INFECTION: Rare in the neonatal period PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Abrupt onset with pain and erythema of the eyelid

•

Localized, tender mass in the eyelid ( Fig. 1-126 )

•

May be associated with blepharitis

•

External hordeolum: points toward the skin surface of the lid and may spontaneously drain

•

Internal hordeolum: can point toward the conjunctival side of the lid and may cause conjunctival inflammation

FIGURE 1-126 External stye. From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

•

75% to 95% of cases are caused by S. aureus.

•

Occasional cases are caused by Streptococcus pneumoniae, other streptococci, gram-negative enteric organisms, or mixed bacterial flora.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Eyelid abscess

•

Chalazion

•

Allergy or contact dermatitis with conjunctival edema

•

Acute dacryocystitis

•

Herpes simplex infection

•

Cellulitis of the eyelid

LABORATORY TESTS

•

Generally, none are necessary.

•

If incision and drainage are performed, specimens should be sent for bacterial culture.

TREATMENT NONPHARMACOLOGIC THERAPY

Usually responds to warm compresses ACUTE GENERAL Rx

•

Systemic antibiotics generally not necessary

•

In refractory cases, an oral antistaphylococcal agent (e.g., dicloxacillin 500 mg PO qid) possibly helpful

•

Topical erythromycin ophthalmic ointment applied to the lid margins two to four times daily until resolution

•

Incision and drainage: rarely needed but should be considered for progressive infections

DISPOSITION

•

Usually sporadic occurrence

•

Possible relapse if resolution is not complete

REFERRAL

•

For evaluation by an ophthalmologist if visual acuity or ocular movement is affected or if the diagnosis is in doubt

•

For surgical drainage if necessary

PEARLS & CONSIDERATIONS COMMENTS

Seborrheic dermatitis may coexist with hordeolum. SUGGESTED READINGS Hirunwiwatkul P, Wachirasereechai K: Effectiveness of combined antibiotic ophthalmic solution in the treatment of hordeolum after incision and curettage: a randomized, placebo-controlled trial: a pilot study. J Med Assoc

Thai 2005; 88(5):647. Kiratli HK, Akar Y: Multiple recurrent hordeola associated with selective IgM deficiency. J AAPOS 2001; 5(1):60. Miller J: Acinetobacter as a causative agent in preseptal cellulitis. Optometry 2005; 76(3):176.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Horner's Syndrome SUDEEP K. AULAKH, M.D., F.R.C.P.C.

BASIC INFORMATION DEFINITION

Horner's syndrome is the clinical triad of ipsilateral ptosis, miosis, and sometimes anhidrosis. Disruption of any of the three neurons in the oculosympathetic pathway (central, preganglionic, or postganglionic) can cause Horner's syndrome. SYNONYMS

Oculosympathetic paresis Raeder's paratrigeminal syndrome: Horner's syndrome of the postganglionic neuron associated with pain in the trigeminal nerve distribution

ICD-9CM CODES

337.9 Horner's syndrome EPIDEMIOLOGY & DEMOGRAPHICS

Congenital or acquired PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Ptosis is usually mild. It results from loss of sympathetic tone to Müller's muscle, which contributes about 2 mm of upper eyelid elevation. Weakness of the corresponding muscle in the lower eyelid causes it to elevate slightly. This combination causes narrowing of the palpebral fissure. Levator function of the eyelid is preserved.

•

Miosis results from loss of sympathetic pupillodilator activity of the iris ( Fig. 1-127 ). The affected pupil reacts normally to bright light and accommodation. Anisocoria is greater in darkness. Dilation lag: Horner's pupil dilates more slowly than the normal pupil when lights are dimmed (20 vs. 5 seconds) because it dilates passively due to relaxation of the iris sphincter.

•

Presence of facial anhidrosis is variable and depends on the site of injury. It occurs with lesions affecting central or preganglionic neurons.

•

Congenital Horner's syndrome may result in heterochromia. The affected eye has a lighter colored iris.

•

Acute cases may also present with conjunctival injection due to the loss of sympathetic vasoconstriction.

FIGURE 1-127 Horner's syndrome.The mild ptosis (1 to 2 mm) and the smaller pupil (in room light) can be seen on the affected right side. From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

Lesions affecting any neuron in the oculosympathetic pathway. Central lesions are least common but usually due to pathology in hypothalamus, brainstem, or cervical spinal cord. Preganglionic lesions are often caused by disease involving the cervicothoracic spinal cord, lung apex, or anterior neck. Postganglionic lesions are usually seen with disease in superior cervical ganglion, internal carotid artery, or cavernous sinus or with vascular headaches. Location is often suggested by the presence of other findings. Vascular disease and neoplasms must be considered. Mechanical: •

Syringomyelia

•

Trauma

•

Tumors: benign, malignant (thyroid, Pancoast, metastatic)

•

Lymphadenopathy

•

Neurofibromatosis

•

Cervical rib

•

Cervical spondylosis

Vascular (ischemia, hemorrhage or AVM): •

Brainstem lesion: commonly occlusion of the posterior inferior cerebellar artery but other arteries may be responsible (vertebral; superior, middle or inferior lateral medullary arteries; superior or anterior inferior cerebellar arteries)

•

Carotid artery aneurysm or dissection. Can also be from injury to other major vessels (internal carotid artery, subclavian artery, ascending aorta)

•

Cluster headache, migraine

Miscellaneous:

•

Idiopathic

•

Congenital

•

Demyelination (multiple sclerosis)

•

Infection (apical TB, herpes zoster, Lyme)

•

Pneumothorax

•

Iatrogenic (angiography, internal jugular/subclavian catheter, chest tube, surgery, epidural spinal anesthesia)

•

Radiation

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Causes of anisocoria (unequal pupils): •

Normal variant

•

Mydriatic use

•

Prosthetic eye

•

Unilateral cataract

•

Iritis

Causes of ptosis described in Section II. WORKUP

History, physical examination, imaging IMAGING STUDIES

Imaging the entire three neuron sympathetic pathway is usually warranted

•

MRI head and neck: evaluate the central and cervical sympathetic pathway

•

MR angiography (or ultrasound, CT angiography): assess the vessels in head and neck

•

CT chest and neck: evaluate lung apex, perivertebral areas

TREATMENT

•

Treatment depends on underlying cause.

•

Ptosis can be surgically corrected or treated with medication (phenylephrine drops)

DISPOSITION

•

Prognosis depends on underlying cause.

•

Horner's syndrome is an uncommon presentation for malignancy.

•

In one study, 40% of cases were idiopathic.

REFERRAL

•

Ophthalmologist to confirm diagnosis and localize lesion. Topical cocaine test: failure of pupillary dilation after cocaine eye drops confirms presence of sympathetic denervation (drops dilate normal pupil but not Horner's pupil). Topical hydroxyamphetamine test: distinguishes central and preganglionic from postganglionic sympathetic lesions (drops dilate normal pupil but not postganglionic Horner's pupil).

PEARLS & CONSIDERATIONS

•

May be the presentation of a life-threatening condition.

•

Anisocoria greater in bright light is likely due to a defect in parasympathetic innervation, and anisocoria greater in dim light is likely due to a sympathetic defect.

•

Normal variant anisocoria Occurs in 20% of people Usually600 cases identified in the U.S. since 1990 PEAK INCIDENCE: Occurs throughout the year, with peak incidence between May and July and again in November PREDOMINANT SEX: Males outnumber females by 2 to 1 PREDOMINANT AGE: Most severe disease 50 to 70 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

Most common initial symptoms 1.

Fever

2.

Chills, rigor

3.

Headache

4.

Myalgia

Subsequent symptoms 1.

Anorexia, nausea

2.

Arthralgia

3.

Cough

4.

Confusion

5.

Abdominal pain

6.

Rash (erythematous to pustular) rare (90% of patients, with approximately 60% reporting tick bite

•

Mammalian host: deer, horses, dogs, white-footed mice, cattle, sheep, goats, bison

•

Host inflammatory and immune responses define final spectrum of disease beyond granulocytes, including hepatitis, interstitial pneumonitis, and nephritis with mild azotemia

•

Between 6% and 21% of patients with HGE also have serologic evidence of other Ixodes spp. tick-borne diseases: Lyme disease or babesiosis

•

Recovery is usual outcome; fatality rate of HGE is 80 or fourfold increase in titer to E. equi antigen

•

Polymerase chain reaction (PCR) to facilitate early diagnosis

•

Culture on the first 7 days of illness; not readily available in most clinical laboratories

IMAGING STUDIES

•

Chest x-ray examination to show interstitial pneumonitis (unusual)

•

MRI of the brain

TREATMENT ACUTE GENERAL Rx

•

Immediate therapy to limit extent of acute illness and complication

•

Doxycycline: 100 mg twice a day for 10 days is therapy of choice for adults and children >8 years (4 mg/kg/day in 2 divided doses)

•

Rifampin: 300 mg twice a day for 7 to 10 days can be used in pregnancy and for children 1000 copies/ml despite appropriate ARV, cesarean section may further lower risk of transmission. Zidovudine (AZT) should also be given to the newborn for the first 6 wk of life, and mothers should completely avoid nursing. Efavirenz (Sustiva) should be avoided because of its potential teratogenic effects.

DISPOSITION

•

Ongoing care consisting of frequent medical evaluations and T-lymphocyte subset analysis along with the plasma HIV load

•

Long-term care focused on providing up-to-date antiretroviral therapy and prophylaxis of PJP and other opportunistic infections, as well as early detection of complications (See Section III.)

REFERRAL

To a physician knowledgeable and experienced in the management of HIV infection and its complications

PEARLS & CONSIDERATIONS COMMENTS

•

HIV chemoprophylaxis after occupational exposure is described in Section V.

•

A recent analysis of the impact of the HAART era indicates that antiretroviral therapy has saved at least 3 million years of life since the introduction of HAART into medicine over 10 yr ago.

SUGGESTED READINGS Bozzette SA: Routine screening for HIV infection—timely and cost-effective. N Engl J Med 2005; 352:620-621. Danel C, et al: CD4-guided antiretroviral treatment interruption strategy in HIV-infected adults in West Africa (Trivacan ANRS 1269 trial): A randomized trial. Lancet 2006; 367(9527):1981. Gallant JE, et al: Tenofir DF, emtricitabine, and efavirenz vs. zidovidine, lamivudine, and efaverenz for HIV. N Engl J Med 2006; 354(3):251. Gulick RM, et al: Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA 2006; 296(7):769. Hammer SM, et al: Treatment for adult HIV infection: 2006 recommendations of the International AIDS SocietyUSA panel. JAMA 2006; 296(7):827. Kantor R, et al: Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy. AIDS 2004; 18(11):1503. Klein MB, et al: The impact of initial highly active antiretroviral therapy on future treatment sequences in HIV infection. AIDS 2004; 18(14):1895. Walensky RP, et al: The survival benefits of AIDS treatment in the United States. J Infect Dis 2006; 194(1):11.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Huntington's Chorea CINDY ZADIKOFF, M.D.

BASIC INFORMATION DEFINITION

Huntington's chorea is an inherited neurodegenerative disorder characterized by involuntary movements, psychiatric disturbance, and cognitive decline. SYNONYMS

Huntington's disease

ICD-9CM CODES

333.4 Huntington's chorea EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE:Late 30s and 40s, with onsets from age 2 to 70 yr PREVALENCE (IN U.S.): 4.1 to 5.4 cases/100,000 persons PREDOMINANT SEX: Female = male PREDOMINANT AGE: Adulthood GENETICS: Autosomal dominant PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Chorea (irregular rapid, flowing, nonstereotyped involuntary movements). When there is a writhing quality, it is referred to as choreoathetosis. Chorea is present early on and tends to decrease in end stages of disease.

•

Dancelike, lurching gait, often caused by chorea.

•

Westphal variant: cognitive dysfunction, bradykinesia, and rigidity. This variant is more commonly seen in juvenile onset Huntington's disease.

•

Oculomotor abnormalities are common early on and include increased latency of response and insuppressible eye blinking.

•

Psychiatric disorders (can be present early on): depression is commonly seen. Also, obsessive-compulsive behaviors and aggression associated with impaired impulse control.

ETIOLOGY

•

Trinucleotide repeat disorder.

•

The responsible gene is the Huntington gene located on chromosome 4. Its function is not known.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Drug-induced chorea—dopamine, stimulants, anticonvulsants, antidepressants, and oral contraceptives have all been known to cause chorea.

•

Sydenham's chorea—decreased incidence with decline of rheumatic fever.

•

Benign hereditary chorea—autosomal dominant with onset in childhood. There is no progression of symptoms and no associated dementia or behavioral problems.

•

Senile chorea—probably vascular in origin.

•

Wilson's disease—autosomal recessive; tremor, dysarthria, and dystonia are more common presentations than chorea. 95% of patients with neurologic manifestations will have Keyser-Fleischer rings.

•

Postinfectious.

•

Systemic lupus erythematosus—can be the presenting feature of lupus. Rare.

•

Chorea gravidarum—presents during first 4 to 5 mo of pregnancy and resolves after delivery.

•

Paraneoplastic—seen most commonly in small cell lung cancer and lymphoma.

WORKUP

Onset of symptoms in an individual with an established family history requires no additional investigation. LABORATORY TESTS

•

Genetic testing.

•

If normal, obtain CBC with smear, ESR, electrolytes, serum ceruloplasmin, 24-hr urinary copper excretion, TFTs, ANA, LFTs, HIV, and ASO titer. Consider paraneoplastic markers.

IMAGING STUDIES

CT scan or MRI scan will show atrophy most notably in the caudate and putamen. Cortex is involved to a lesser

extent. A normal scan does not exclude the diagnosis.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Supportive counseling

•

Physical and occupational therapy

•

Home health care

•

Genetic counseling

CHRONIC Rx

•

Chorea does not need to be treated unless disabling

•

Chorea may be diminished by low doses of neuroleptics (e.g., haloperidol 1 to 10 mg/day)

•

Amantadine (up to 300 to 400 mg divided tid)

•

Tetrabenazine. This is a dopamine depletor that is not currently available in the United States. Side effects include parkinsonism and depression

•

Depression with suicidal ideation is common; may improve with tricyclic or SSRI antidepressants

DISPOSITION

Relentless course of variable duration leading to progressive disability and death REFERRAL

•

Should refer to psychiatry and neurology for treatment of mood disorders and movement disorders

•

Genetic counselors

PEARLS & CONSIDERATIONS

•

Suicide rate is fivefold that of the general population.

•

The number of repeats does correlate with age of onset but does not clearly correlate with disease severity. Interpretation of number of repeats is still difficult at this time and therefore it is debatable whether to disclose this information to patients.

EVIDENCE

Large placebo-controlled studies showing improved outcomes in patients with Huntington's disease are not available. Many drug trials have been undertaken but suffer either from small sample sizes, lack of blinding and placebo control, or negative results. However, amantadine, [160] [161] tetrabenazine, [162] [163] and fluphenazine[[5]] have fair (mediocre quality) evidence for symptomatic treatment of chorea when needed. Selective serotonin reuptake inhibitors are used most commonly for depression although there are small case reports and open label studies suggesting the use of risperidone and olanzapine,[[6]] especially if there is aggression or anxiety.

Evidence-Based References 1. Verhagen Metman L, et al: Huntington's disease: a randomized, controlled trial using NMDAantagonist amantadine. Neurology 2002; 59(5):694. 2. Heckmann JM, et al: IV amantadine improves chorea in Huntington's disease: an acute randomized, controlled study. Neurology 2004; 10(3):63.597 3. Swash M, et al: Treatment of involuntary movement disorders with tetrabenazine. J Neurol Neurosurg Psychiatry 1972; 35:186. 4. Asher SW, Aminoff MJ: Tetrabenazine and movement disorders. Neurology 1981; 31:1051. 5. Terrence CF: Fluphenazine decanoate in the treatment of chorea: a double-blind study. Curr Ther Res Clin Exp 1976; 20:177. 6. Bonelli RM, et al: Olanzapine for Huntington's disease: an open label study. Clin Neuropharmacol 2002; 25:263.

SUGGESTED READINGS Biglan K, Shoulson I: Huntington's disease. In: Jankovic J, Tolosa E, ed. Parkinson's disease and movement disorders, Philadelphia: Lippincott Williams & Wilkins; 2002. Bonelli RM, et al: Huntington's disease: present treatments and future therapeutic-modalities. Intnl Clin Psychopharm 2004; 19:51. Higgins D: Chorea and its disorders. Neuro Clin 2001; 19(3):707.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hydrocele TAMARA G. FONG, M.D., PH.D.

BASIC INFORMATION DEFINITION

A hydrocele is a fluid collection in a serous scrotal space usually between the layers of the tunica vaginalis (Figs. 1-130 and 1-131 [18] [19]). A hydrocele that fills with fluid from the peritoneum is termed communicating. This is distinguished from a noncommunicating hydrocele by history of variation in size throughout the day and palpation of a thickened cord above the testicle on the affected side. A communicating hydrocele is basically a small inguinal hernia in which fluid, but not peritoneal structures, traverses the processus vaginalis.

FIGURE 1-130 A hydrocele is a fluid collection in the serous space between the layers of the tunica vaginalis. The tunica vaginalis may or may not remain patent, allowing the hydrocele to communicate with the peritoneum.

FIGURE 1-131 Newborn with large right hydrocele. From Behrman RE: Nelson textbook of pediatrics, ed 16, Philadelphia, 2000, WB Saunders.)

ICD-9CM CODES

603.9 Hydrocele PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms:

•

Scrotal enlargement

•

Scrotal heaviness or discomfort radiating to the inguinal area

•

Back pain

Physical findings: •

Scrotal distention (testicle may be impossible to palpate)

•

Transillumination

ETIOLOGY

Hydroceles may occur as a congenital abnormality where the processus vaginalis fails to close. In this case, an inguinal hernia is virtually always associated with the malformation. Congenital hydroceles are most common in infants and children. In adults, hydroceles are more frequently caused by infection, tumor, or trauma. Infection of the epididymis often results in the development of a secondary hydrocele. Tropical infections such as filariasis may produce hydroceles.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Spermatocele

•

Inguinoscrotal hernia

•

Testicular tumor

•

Varicocele

•

Epididymitis

IMAGING studies

Scrotal ultrasound (useful to rule out a testicular tumor as the cause of the hydrocele). The acute development of a hydrocele might be associated with the onset of epididymitis, testicular tumor, trauma, and torsion of a testicular appendage. An ultrasound of the scrotum may provide important diagnostic information.

TREATMENT

•

No treatment if asymptomatic and testicle is thought to be normal.

•

Surgical repair. Communicating hydroceles should be repaired in the same manner as an indirect hernia. The indications for repair of a noncommunicating hydrocele include failure to resolve and increase in size to one that is large and tense.

AUTHOR: FRED F. FERRI, M.D., TOM J. WACHTEL, M.D. Hydrocephalus, Normal Pressure

BASIC INFORMATION DEFINITION

Normal pressure hydrocephalus (NPH) is a syndrome of symptomatic hydrocephalus in the setting of normal CSF pressure. The classic clinical triad of NPH includes gait disturbance, cognitive decline, and incontinence. SYNONYMS

Occult hydrocephalus Extraventricular obstructive hydrocephalus Chronic hydrocephalus

ICD-9CM CODES

331.3 Communicating hydrocephalus EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 1 per 100,0000; may account for 5% of dementia PREDOMINANT SEX: Males = females PREDOMINANT AGE: Fourth to sixth decades, but can occur at any age PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Gait difficulty: patients often have difficulty initiating ambulation, and the gait may be broad-based and shuffling, with the appearance that the feet are stuck to the floor (i.e., “magnetic gait” or “frontal gait disorder”).

•

Cognitive decline: mental slowing, forgetfulness and inattention without agnosia, aphasia, or other “cortical” disturbances.

•

Incontinence: initially may have urinary urgency; later incontinence develops. Occasionally fecal incontinence also occurs.

•

On physical examination, look for signs of disease that may mimic NPH.

ETIOLOGY

•

Approximately 50% of cases are idiopathic; remaining cases are from secondary causes, including prior subarachnoid hemorrhage, meningitis, trauma, or intracranial surgery.

•

Symptoms are presumed to result from stretching of sacral motor and limbic fibers that lie near the ventricles, as dilation occurs.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Alzheimer's disease with extrapyramidal features

•

Cognitive impairment in the setting of Parkinson's disease or parkinsonism-plus syndromes

•

Diffuse Lewy body disease

•

Frontotemporal dementia

•

Cervical spondylosis with cord compromise in setting of degenerative dementia

•

Multifactorial gait disorder

•

Multi-infarct dementia

WORKUP

•

•

Large-volume lumbar puncture 1.

Mental status testing and time to walk a prespecified distance (usually 25 feet) are measured, followed by removal of 40 to 50 ml of CSF.

2.

Retest of mental status and timed walking are done at 1 and 4 hr. Patients who have significant improvement in gait or mental status tend to have better surgical outcome; those with mild or negative response can have variable outcomes.

3.

Opening and closing pressure are measured; if pressure is elevated, alternative etiologies must be considered.

Measurement of CSF outflow resistance by an infusion test, CSF pressure monitoring, or prolonged external lumbar drainage are sometimes used to help predict surgical outcome.

LABORATORY TESTS

CSF should be sent for routine fluid analyses to exclude other pathology. IMAGING STUDIES

•

CT scan or MRI can be used to document ventriculomegaly. The distinguishing feature of NPH is ventricular enlargement out of proportion to sulcal atrophy.

•

MRI has advantages over CT, including better ability to visualize structures in the posterior fossa, visualize transependymal CSF flow, and to document extent of white matter lesions. On MRI, a flow void in the aqueduct and third ventricle (“jet sign”) may be seen.

•

Isotope cisternography and dynamic MRI studies have not been shown to be superior in predicting shunt outcome.

TREATMENT There is no evidence that NPH can be effectively treated with medications. NONPHARMACOLOGIC THERAPY

Response to ventriculoperitoneal shunting is variable. Some patients (30% of those with idiopathic NPH and 60% of patients with a known etiology) show significant improvement from shunting. Factors that may predict positive outcome with surgery:

•

NPH secondary to prior trauma, subarachnoid hemorrhage, or meningitis

•

History of mild impairment in cognition200 mg/dl. A cholesterol level of 200 to 239 mg/dl is considered borderline high, and a level of >240 mg/dl is considered to be a high cholesterol measurement. SYNONYMS

Hypercholesteremia Hypercholesterinemia Type II familial hyperlipoproteinemia

ICD-9CM CODES

272.0 Hypercholesterolemia EPIDEMIOLOGY & DEMOGRAPHICS

•

More than one-half of all U.S. adults have dyslipidemia; 50.4% of men and 50.9% of women.

•

Only about 12% of people with high cholesterol are being treated.

•

Elevated cholesterol requires drug therapy in about 60 million Americans.

•

Incidence of heterozygous familial hypercholesterolemia: about 1:500.

•

Incidence of homozygous familial hypercholesterolemia: about 1:1 million.

•

Prevalence of hypercholesterolemia increases with increasing age.

•

Familial hypercholesterolemia: autosomal dominant disorder.

•

Familial combined hyperlipidemia: possibly an autosomal dominant disorder.

•

Multifactorial predilection: apparent in majority of affected individuals.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most patients: no physical findings

•

Possible findings particularly in the familial forms 1.

Tendon xanthomas

2.

Xanthelasma

3.

Arcus corneae

4.

Arterial bruits (young adulthood)

ETIOLOGY

Primary 1.

Genetics

2.

Obesity

3.

Dietary intake

Secondary 1.

Diabetes mellitus

2.

Alcohol

3.

Oral contraceptives

4.

Hypothyroidism

5.

Glucocorticoid use

6.

Most diuretics

7.

Nephrotic syndrome

8.

Hepatoma

9.

Extrahepatic biliary obstruction

10. Primary biliary cirrhosis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

No real differential diagnosis; however, consider underlying secondary causes/etiologies for the elevated cholesterol. LABORATORY TESTS

PRIMARY PREVENTION WITHOUT ATHEROSCLEROSIS or diabetes mellitus:

1.

Recommended to get a complete lipoprotein profile (total cholesterol, HDL, LDL, and triglycerides) on all adults 20 years and older.

2.

Risk assessment to modify LDL goals: cigarette smoking, hypertension (BP >140/90 on medication), family history of premature CHD (first-degree relative with CHD in male 190 mg/dl with no risk factors, LDL >130 mg/dl with two or more risk factors, or HDL 400 mg/dl

Relative: TG >200 mg/dl

Nicotinic acid

Flushing

Absolute: Chronic liver disease

Immediate release LDL (crystalline) nicotinic acid (1.5-3 g), extended-release nicotinic acid (Niaspan) 1-2 g, sustained release nicotinic acid (1-2 g)

5%-25%

Hyperglycemia

HDL

l5%-35%

Hyperuricemia (or gout)

TG

20%-50%

Upper GI distress Relative: Hepatotoxicity

•

Severe gout

Diabetes Hyperuricemia Peptic ulcer disease

Fibric acids

Gemfibrozil (600 mg bid)

LDL

5%-20%

Fenofibrate (160 mg qd)

(may be increased in Gallstones patients with high TG)

Clofibrate (1000 mg bid)

Cholesterol absorption inhibitors

Ezetimibe (10 mg QD)

Dyspepsia

Myopathy

HDL

10%-20%

TG

20%-50%

LDL

l8%

HDL

l%

TG

.7%-8%

Abdominal pain myalgias

Absolute: Severe renal disease

•

Severe hepatic disease

Severe renal disease

Severe hepatic disease

Modified from The National Cholestrol Education Program, JAMA 285:2486, 2001. CoA, Coenzyme A; GI, gastrointestinal; HDL, high-density lipoprotein; HMG, 3-hydroxy-3 methylglutanyl; LDL, low-density lipoprotein; TG, triglyceride.

* Cyclosporine, macrolide antibiotics, various antifungal agents, and cytochrome P-450 inhibitors (hbrates and niacin should be used with appropriate caution).

DISPOSITION

•

After initiation of therapy, repeat laboratory tests in 4 to 6 wk, with modifications as necessary.

•

Once goal is achieved, lifelong medication and monitoring are needed at least three to four times a year.

•

Dietary modification is needed to continue with drug therapy.

•

Repeat review for additional CAD risk factors.

PEARLS & CONSIDERATIONS COMMENTS

See “Hyperlipoproteinemia.” SUGGESTED READINGS de Lemos JA, et al: Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292:1307. La Rosa JC, et al: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. NEJM 2005; 352:1425. Mosca L, et al: National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation 2005; 111:499. National Cholesterol Education Program: Second Report on the Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (adult treatment panel IV). JAMA 2001; 285:2486. Safeer R, Ugalat P: Cholesterol treatment guidelines update. Am Fam Physician 2002; 65:871.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hypercoagulable State SUDEEP K. AULAKH, M.D., F.R.C.P.C.

BASIC INFORMATION DEFINITION

A hypercoagulable state is an inherited or acquired condition associated with an increased risk of thrombosis. SYNONYM

Thrombophilia

ICD-9CM CODES

289.8

Hypercoagulable syndrome

795.79 Antiphospholipid antibody syndrome EPIDEMIOLOGY & DEMOGRAPHICS

See Table 1-20 . •

Risk of thrombosis increases with age and with multiple risk factors.

•

Most people with a genetic defect will not suffer thrombotic disease. When thrombosis occurs it is often associated with an acquired risk factor (surgery, pregnancy, oral contraceptive pill [OCP] use, etc.). Annual risk of thrombosis is 600 mg/dl, serum/urine ketones absent or “small.”

•

Hyperosmolarity: serum osmolarity usually >320 mOsm/L.

•

Serum sodium: may be low, normal, or high; if normal or high, the patient is severely dehydrated, because an elevated glucose draws fluid from intracellular space decreasing the serum sodium; the corrected sodium can be obtained by increasing the serum sodium concentration by 1.6 mEq/dl for every 100 mg/dl increase in the serum glucose level over normal.

•

Serum potassium: may be low, normal, or high; regardless of the initial serum level, the total body deficit is approximately 5 to 15 mEq/kg.

•

Serum bicarbonate: usually >15 mEq/L (average is 17 mEq/L).

•

Arterial pH: usually >7.3; both serum bicarbonate and arterial pH may be lower if lactic acidosis is present.

•

BUN: azotemia (prerenal) is usually present (BUN generally ranges from 60 to 90 mg/dl).

•

Phosphorus: hypophosphatemia (average deficit is 70 to 140 mm).

•

Calcium: hypocalcemia (average deficit is 50 to 100 mEq).

•

Magnesium: hypomagnesemia (average deficit is 50 to 100 mEq).

•

CBC with differential, urinalysis, blood and urine cultures should be performed to rule out infectious etiology.

IMAGING STUDIES

•

Chest x-ray is useful to rule out infectious process. The initial chest x-ray may be negative if the patient has significant dehydration. Repeat chest x-ray examination after 24 hr of hydration if pulmonary infection is suspected.

•

CT scan of head should be performed in patients with suspected CVA.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Monitor mental status, vital signs, urine output qh until improved, then monitor q2 to 4h.

•

Monitor electrolytes, renal function, and glucose level (see “Acute General Rx”).

ACUTE GENERAL Rx

•

Vigorous fluid replacement: the volume and rate of fluid replacement are determined by renal and cardiac function. Typically, infuse 1000 to 1500 ml/hr for the initial 1 to 2 L; then decrease the rate of infusion to 500 ml/hr and monitor urinary output, blood chemistries, and blood pressure; use 0.9% NS (isotonic solution) if the patient is hypotensive or serum osmolarity is 12 mg/dl.

•

A high level of urinary cyclic AMP is also suggestive of primary hyperparathyroidism.

•

Parathyroid hormone–like protein (PLP) is increased in hypercalcemia associated with solid malignancies.

•

ECG may reveal shortening of the QT interval secondary to hypercalcemia.

LABORATORY TESTS

•

Elevated serum ionized calcium level, low serum phosphorus, and normal or elevated alkaline phosphatase

•

Elevated urine calcium level (in contrast with very low urinary calcium levels seen in patients with familial hypocalciuric hypercalcemia)

•

Possibly elevated serum chloride levels, decreased serum CO2, hyperchloremic metabolic acidosis

•

A serum albumin level should be obtained when measuring serum calcium and the calcium level should be adjusted (see previous) in hypoalbuminemic patients

•

The differential diagnosis of hypercalcemia is described in Section II

IMAGING STUDIES

•

A bone survey may show evidence of subperiosteal bone resorption suggesting PTH excess ( Fig. 1-132 ). The classic bone disease of primary hyperparathyroidism is osteitis fibrosa cystica.

•

Parathyroid localization with technetium-99m sestamibi has been shown to have a high sensitivity and specificity for single adenomas.

•

Screen for osteopenia with measurement of bone mineral density in all postmenopausal women.

FIGURE 1-132 Radiograph of hand from a patient with severe primary hyperparathyroidism. Note the dramatic remodeling associated with the intense region of high bone turnover in the third metacarpal in addition to widespread evidence of subperiosteal, and trabecular resorption. (Courtesy Fuller Albright Collection, Masschusetts General Hospital. From Larsen PR, Kronenburg HM, Melmed S, Polonsky KS [eds]: Williams textbook of endocrinology, ed 10, Philadelphia, 2003, Saunders.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Unless contraindicated, patients should maintain a high intake of fluids (3 to 5 L/day) and sodium chloride (>400 mEq/day) to increase renal calcium excretion. Calcium intake should be 1000 mg/day.

•

Potential hypercalcemic agents (e.g., thiazide diuretics) should be discontinued.

•

Surgery is the only effective treatment for primary hyperparathyroidism. It is generally indicated in all patients under age 50 and patients with complications from hyperthyroidism, such as nephrolithiasis and osteopenia. The conventional surgical approach is bilateral neck exploration under general anesthesia. Minimally invasive adenomectomy guided by preoperative technetium-99-m sestamibi scanning or ultrasound plus spiral CT is an alternative to conventional neck exploration. With the minimally invasive approach, the solitary adenoma is excised through a small unilateral incision with the patient under local cervical block anesthesia.

•

Percutaneous ethanol injection into the parathyroid gland should be considered in selected patients who have undergone a subtotal parathyroidectomy for multigland disease and have recurrent hyperparathyroidism as a result of remnant gland. Percutaneous alcohol ablation of the parathyroid gland may also be a suitable treatment for patients who are unwilling or unable to undergo parathyroidectomy.

•

Asymptomatic elderly patients can be followed conservatively with periodic monitoring of serum calcium level and review of symptoms. Serum creatinine and PTH levels should also be obtained at 6- to 12-mo intervals, bone density (cortical and trabecular) yearly. Criteria for medical monitoring of patients with asymptomatic primary hyperparathyroidism are as follows:

•

1.

Serum calcium level only mildly elevated

2.

Asymptomatic patient

3.

Normal bone status (no osteoporosis)

4.

Normal kidney function and no urolithiasis or nephrocalcinosis

5.

No previous episode of life-threatening hypercalcemia

Nearly 25% of asymptomatic patients develop indications for surgery during observation.

ACUTE GENERAL Rx

Acute severe hypercalcemia (serum calcium >13 mg/dl) or symptomatic patients can be treated with the following: •

Vigorous IV hydration with NS followed by IV furosemide. Use NS with caution in patients with cardiac or renal insufficiency to avoid fluid overload.

•

Biphosphonates are effective agents. Zoledronate (4 mg IV over a 15-min period in a solution of 50 ml of NS or D5W) or pamidronate (60 to 90 mg IV infusion over a 2-hr period in a solution of 50 to 200 ml of saline or D5W) are both very effective.

•

Cinacalcet (Sensipar) is an oral calcimimetic agent that directly lowers PTH levels by increasing the Calcium-sensing receptor to extracellular calcium. The reduction in PTH is associated with a concomitant decrease in serum calcium levels. It is indicated in treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and hypercalcemia in parathyroid carcinoma. Initial dose is 30 mg po qd.

PEARLS & CONSIDERATIONS COMMENTS

•

Patients should understand the importance of diet and exercise and be familiar with symptoms of disease progression.

•

All patients with hyperparathyroidism should undergo further evaluation for the presence of MEN I or II.

•

Decreased bone mineral density and nephrolithiasis are the major sequelae of untreated hyperparathyroidism.

•

Treatment with alendronate or raloxifene should be considered in patients with hyperparathyroidisminduced osteoporosis.

•

An experienced endocrine surgeon cures more than 95% of patients undergoing bilateral neck exploration and incurs 50%) of predominantly CD 8+ suppressor cells. In acute stages neutrophils predominate but as the disease progresses to chronic form the ratio of CD 4+ to CD 8+ cells increase. When fibrosis is present the number of neutrophils increase.

•

Lung biopsy: the histopathologic features of HP are distinctive but not pathognomonic. Typically bronchiolitis and interstitial pneumonitis with granuloma formation is seen. Variable degrees of interstitial fibrosis are seen in the chronic form.

•

Laboratory inhalation challenge: testing to prove a direct relationship between a suspected antigen and disease; extract of antigen is inhaled via a nebulizer.

PEARLS & CONSIDERATIONS A clinical prediction rule using six features has high specificity and sensitivity for the diagnosis of acute and subacute HP: •

Exposure to a known offending agent

•

Positive specific precipitating AB

•

Recurrent episodes of symptoms

•

Inspiratory crackles

•

Symptoms occurring 4 to 8 hr after exposure

•

Weight loss

No diagnostic gold standards, requires combination of clinical, environmental, radiologic, physiologic, and pathologic findings that represent a diagnostic challenge. HP occurs more frequently in smokers than nonsmokers (likely due to an immunosuppressive effect). SUGGESTED READINGS

Churg A: Chronic hypersensitivity pneumonitis. Am J Surg Path 2006; 30(2):201. Fink JN, et al: Needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med 2005; 171:792-798. Fraser , et al: Synopsis of diseases of the chest, ed 2. Philadelphia, WB Saunders, 1994. Lacasse Y, et al: Clinical diagnosis of active hypersensitivity pneumonitis. Am J Respir Crit Care Med 2003; 168:952-958. Morrell F, Roger A, Cruz MJ: Usefulness of specific skin tests in the diagnosis of hypersensitivity pneumonitis. J Allergy Clin Immunol 2002; 110(6):939. Patel AM, Ryu JH, Reed CE: Hypersensitivity pneumonitis: current concepts and further questions. J Allergy Clin Immunol 2001; 108:661. Schuyler M, Cormier Y: The diagnosis of hypersensitivity pneumonitis. Chest 1997; 111:534. Selman M: Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med 2004; 25:3.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hypersplenism SUDEEP K. AULAKH, M.D., F.R.C.P.C.

BASIC INFORMATION DEFINITION

Hypersplenism is a syndrome characterized by splenomegaly, cytopenia (decrease of one or more peripheral cell lines), and compensatory hyperplastic bone marrow. The cytopenias are correctable with splenectomy.

ICD-9CM CODES

289.4 Hypersplenism EPIDEMIOLOGY & DEMOGRAPHICS

Most often seen in patients with liver disease, hematologic malignancy, infection. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms depend on the size of the spleen, rate of growth, and underlying disease. •

History: early satiety, abdominal discomfort/fullness, left upper quadrant pleuritic pain (abscess, infarction), episodes of acute left upper quadrant pain (sequestration crisis), referred pain to left shoulder

•

Physical examination: splenomegaly, presence of a rub in left upper quadrant (suggestive of a splenic infarct), stigmata of cytopenias

ETIOLOGY

The spleen is an important component of cellular and humoral immunity: antigen recognition, antibody production, clearance of antibody-coated particles, and bacteria from circulation. It is also responsible for the modification (removal of particles and parasites) and removal of old red blood cells from circulation. The spleen is a platelet reservoir, storing 30% of platelet mass. It can become the site of extramedullary hematopoiesis in certain disease states. The spleen's normal activities are augmented when it is enlarged. •

Splenomegaly increases the proportion of blood channeled through the red pulp (cords of Billroth), causing inappropriate splenic pooling of both normal and abnormal blood cells. The size of the spleen determines the amount of cell sequestration. Up to 90% of platelets may be pooled in an enlarged spleen.

•

Splenomegaly leads to increased destruction of RBCs. Platelets and WBCs have about normal survival time even when sequestered and may be available if needed.

•

Splenomegaly causes plasma volume expansion, exacerbating cytopenias by dilution.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Hypersplenism can be caused by splenomegaly of almost any cause. •

Splenic congestion: cirrhosis, CHF, portal, splenic or hepatic vein thrombosis

•

Hematologic causes: hemolytic anemia, sickle cell anemia, thalassemia, spherocytosis, elliptocytosis, extramedullary hematopoiesis

•

Infections: viral (hepatitis, infectious mononucleosis, CMV, HIV), bacterial (abscess, endocarditis, tuberculosis, salmonella, brucellosis, Lyme), parasitic (babesiosis, malaria, leishmaniasis, schistosomiasis, toxoplasmosis), fungal

•

Malignancy: acute and chronic leukemia, lymphoma, polycythemia vera, myeloproliferative diseases, metastatic tumors

•

Inflammatory diseases: rheumatic fever, Felty syndrome, SLE, sarcoid, serum sickness

•

Infiltrative diseases: amyloidosis, Gaucher's disease, Niemann-Pick disease, glycogen storage disease

•

Anatomic abnormalities: cyst, pseudocyst, hemangioma, hamartoma

WORKUP

History (including travel), physical examination, laboratory tests, imaging studies LABORATORY TESTS

•

CBC with differential: cytopenia, neutrophilia (infection)

•

Peripheral smear: RBC and WBC morphology (abnormal cells may suggest infection, malignancy, bone marrow disease, rheumatologic disease), organisms (bacteria, malaria, babesiosis)

•

Bone marrow biopsy: hyperplasia of cytopenic cell lines, hematologic, infiltrative disorders

•

Tests to diagnose suspected cause of splenomegaly: LFT, hepatitis serology, HIV, RF, ANA, etc.

•

Note: red cell mass (51Cr assay) may be used to assess severity of anemia. If considering splenectomy secondary to severe anemia, RBC mass measurement will differentiate true anemia (decrease in red cells) from dilutional anemia (plasma volume expansion).

IMAGING STUDIES

•

Ultrasound: splenic size, presence of cyst or abscess

•

CT: estimate volume, obtain structural information: cyst, abscess, tumor, infarct

•

MRI: most useful for assessing vascular lesions and infections

•

Liver-spleen scan: assess anatomy and function; may suggest presence of portal hypertension

•

Consider other studies as suggested by history and exam: CXR, echocardiogram, etc.

TREATMENT ACUTE GENERAL Rx

•

Treat underlying disease

•

Splenectomy is considered if: 1.

Indicated for the management of the underlying cause

2.

Persistent symptomatic disease (severe cytopenia) not responding to therapy

3.

Necessary for diagnosis

Risks: •

Infections (especially encapsulated organisms): risk greatest in the first 2 yr after splenectomy. Mortality from sepsis is fiftyfold greater in asplenic patients. Attempts to decrease risk include: Immunization with pneumococcal, meningococcal, and hemophilus vaccines 3 wk before splenectomy. Revaccination with pneumococcal every 10 yr. Prophylactic antibiotics post splenectomy in highest risk patients. Patient education regarding the importance of rapid initiation of antibiotics at the first sign of infection.

•

Rapid increase in platelet count may cause thromboembolic complications.

•

Possible increased risk of atherosclerotic heart disease.

•

Splenectomy should not be performed if the spleen is the main site of hematopoiesis secondary to bone marrow failure (i.e., myelofibrosis).

•

Other options include partial splenectomy, partial splenic embolization, portosystemic shunting (for congestive splenomegaly).

DISPOSITION

•

Cytopenias are usually correctable with splenectomy, cell counts return to normal within a few weeks.

•

Splenectomy may alleviate portal hypertension.

•

Prognosis depends on the underlying disease.

REFERRAL

Hematology

PEARLS & CONSIDERATIONS

•

Thrombocytopenia in hypersplenism is usually moderately severe (>50 × 109/L) and asymptomatic; severe thrombocytopenia (10 mm

2.

Microadenomas 10 µg/dl.

2.

Serum insulin-like growth factor I can also be measured after provocative testing.

Hyperprolactinemia: 1.

•

Prolactin levels may be elevated in prolactin-secreting pituitary adenomas.

Vasopressin deficiency:

1.

Urinalysis shows low specific gravity.

2.

Urine osmolality is low.

3.

Serum osmolality is high.

4.

Fluid deprivation test over 18 hr with inability to concentrate the urine.

5.

Serum vasopressin level is low.

6.

Electrolytes may show hyponatremia and exclude hyperglycemia.

IMAGING STUDIES

•

When hypopituitarism has been established clinically and biochemically, imaging of the pituitary gland is necessary to identify the specific lesion.

•

MRI is more sensitive than CT scan of the head in visualizing the pituitary fossa, sella turcica, optic chiasm, pituitary stalk, and cavernous sinuses. It is also more sensitive in detecting pituitary microadenomas.

•

CT scan with coronal cuts through the sella turcica gives better images of bony structures.

TREATMENT Hormone replacement therapy and either surgery, radiation, or medications in patients with pituitary tumors. NONPHARMACOLOGIC THERAPY

•

IV fluid resuscitation with normal saline to maintain hemodynamic stability may be needed in some circumstances

•

Correction of electrolyte and metabolic abnormalities with potassium, bicarbonate, and oxygen therapy

ACUTE GENERAL Rx

Acute situations like adrenal crisis or myxedema coma can occur in untreated hypopituitarism and should be treated accordingly with IV corticosteroids (e.g., hydrocortisone 100 mg IV q6h for 24 hr) and levothyroxine (e.g., 5 to 8 µg/kg IV over 15 min, then 100 µg IV q24h). CHRONIC Rx

Treatment is lifelong and requires the following hormone replacement therapy:

ACTH deficiency: •

Hydrocortisone 20 mg PO qam and 10 mg PO qpm or prednisone 5 mg PO qam and 2.5 mg PO qpm. Dexamethasone or prednisone are often preferred due to longer duration of action.

LH and FSH deficiency: •

In men, testosterone enanthate or propionate 200 to 300 mg IM q2 to 3 wk or transdermal testosterone scrotal patches can be tried.

•

In women who are not interested in fertility, conjugated estrogen 0.3 to 1.25 mg/day and held the last 5 to 7 days of each month with the addition of medroxyprogesterone 10 mg/day given during days 15 to 25 of the normal menstrual cycle. In those who have secondary hypogonadism and wish to become pregnant, pulsatile GnRH may be of benefit.

TSH deficiency: •

Levothyroxine 0.05 to 0.15 mg/day.

GH deficiency: •

Growth hormone is not used in adults; however, can be given at 0.04 to 0.08 mg/kg/day subcutaneously in children.

ADH deficiency: •

Desmopressin (DDAVP) 10 to 20 µg via intranasal spray or 0.05 to 0.1 mg PO bid is used in patients with diabetes insipidus.

DISPOSITION

•

Hormone replacement therapy is adjusted according to serum hormone blood monitoring.

•

Hypopituitarism if untreated can lead to adrenal crisis, severe hyponatremia and hypothyroidism, metabolic abnormalities, and death.

•

The prognosis for patients with hypopituitarism is excellent, and life expectancy can be normal in patients with eradication of the pituitary disease and adequate hormone replacement therapy that is closely monitored in long-term follow-up.

REFERRAL

Anyone suspected of having hypopituitarism should have an endocrine consultation. For patients with pituitary tumors, a radiation oncologist and neurosurgeon consultation should be consulted.

PEARLS & CONSIDERATIONS

•

Hyperprolactinemia resulting in galactorrhea or hypogonadism may be associated with hypopituitarism in cases where the pituitary stalk is transected by tumor or trauma/surgery. In these cases, inhibitory dopaminergic effects on the prolactin-secreting cells of the anterior pituitary from neurons in the hypothalamus is disrupted.

•

Thyroxine supplementation increases the rate of cortisol metabolism and can lead to adrenal crisis. It is therefore recommended to supplement corticosteroids first before administering thyroid hormone replacement therapy.

•

All patients receiving glucocorticoid replacement therapy should wear proper identification stating the need for this therapy.

•

Stress doses of corticosteroids are indicated before surgery or for any medical emergency (e.g., sepsis, acute myocardial infarction, etc.).

COMMENTS

•

Mineralocorticoid replacement is not necessary in secondary adrenal insufficiency because the renninangiotensin-aldosterone system is unaffected by pituitary failure.

•

Patients with adult acquired GH deficiency must meet at least two criteria before replacement therapy: a poor GH response to at least two standard stimuli and hypopituitarism due to pituitary or hypothalamic damage. The criteria are different in children in whom GH is required for normal growth.

EVIDENCE

Medical therapy should precede surgical therapy. The order to replace treatment is cortisol, thyroxine, androgen/estrogen, and then in some cases, growth hormone.[[1]] Transsphenoidal approach compared with the transcranial approach during surgery allowed for significantly more tumor to be removed, reduced hypothalamic dysfunction, and reduced visual complications. [236] [237] It is important to take account of the experience of the surgeon and maximize perioperative medical management to improve the safety of the pituitary surgery.[[4]] The following features are poor prognostic indicators for pituitary surgery: large tumor size, infiltrating tumor, and very elevated levels of hypersecreted hormones. There is a small but significant risk of surgical complications including nasal perforation and loss of vision with transsphenoidal surgery.

Evidence-Based References 1. Orrego , et al: Pituitary disorders: drug treatment options. Drugs 2000; 59(1):93.Medline. 2. Czepko , et al: Early results of treating pituitary adenomas by means of transcranial and transsphenoidal approach. Przegl Lek 1999; 56(10):638.Medline. 3. Woolons , et al: Complications of trans-sphenoidal surgery: the Wellington experience. Aust NZJ Surg 2000; 70(6):405.Medline. 4. Giovenelli , et al: Surgical therapy of pituitary adenoma. Metab 1996; 45(8):115.Medline.

SUGGESTED READINGS American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children—2003 update. Endocr Pract 2003; 9:64. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients—2002 update. Endocr Pract 2002; 8:439. Hanberg A: Common disorders of the pituitary gland: hyposecretion versus hypersecretion. J Infus

Nurs 2005; 28(1):36. Sheehan JP, et al: Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. J Neurosurg 2005; 102(4):678.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hypospadias PHILIP J. ALIOTTA, M.D., M.S.H.A., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Hypospadias is a developmental abnormality of the penis characterized by

•

Abnormal ventral opening of the urethral meatus anywhere from the ventral aspect of the glans penis to the perineum

•

Ventral curvature of the penis (chordee)

•

Dorsal foreskin hood

ICD-9CM CODES ICD-9CM: 752.61 Congenital Chordee: 752.63 EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE:1 in 250 GENETICS: Pertinent familial aspects of hypospadias include the finding of hypospadias in 6.8% of fathers of affected boys and in 14% of male siblings •

An 8.5-fold higher rate of hypospadias is reported in monozygotic twins suggesting that there is insufficient production of human chorionic gonadotropin by the single placenta

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Genetics: normal karyotypes are seen with glandular hypospadias; abnormal karyotypes are noted in more severe forms of hypospadias

•

Cryptorchidism: 8% to 9% occurrence

•

Inguinal hernia: 9% to 10% occurrence

•

Hydrocele: 9% to 16% occurrence

PENILE CURVATURE (CHORDEE): Three theories

•

Abnormal development of the urethral plate

•

Abnormal fibrotic mesenchymal tissue at the urethral meatus

•

Corporal disproportion

ETIOLOGY

Multifactorial •

•

Endocrine factors 1.

Abnormal androgen production

2.

Limited androgen sensitivity in the target tissues

3.

Premature cessation of androgenic stimulation secondary to Leydig cell dysfunction

4.

Insufficient testosterone-dihydrotestosterone synthesis as a result of deficient 5-alpha reductase enzyme activity

Arrested development

DIAGNOSIS WORKUP

Made by observation and examination LABORATORY TESTS

Intersex evaluation should be undertaken if there is associated cryptorchidism. The evaluation should include: ultrasound, genitographic studies, chromosomal, gonadal, biochemical, and molecular studies.

TREATMENT ACUTE GENERAL Rx

DESIGNATION/CLASSIFICATION: Anterior: 33% Middle: 25% Posterior: 41% SPECIAL CONSIDERATION: •

The only reason for operating on any hypospadias patient is to correct deformities that interfere with the function of urination and procreation

•

Other reasons for interventions: Cosmetic concerns

•

The American Academy of Pediatrics recommends the best time for surgical intervention as 6 to 12 mo

HORMONAL MANIPULATION:

•

Controversial

•

hCG administration is given before repair of proximal hypospadias

•

The effect of the hCG administration is decreased hypospadias and chordee severity in all patients, increased vascularity and thickness of the proximal corpus spongiosum

•

Application of topical testosterone increased mean penile circumference and length without any lasting side effects

•

Prepubertal exogenous testosterone does not adversely effect ultimate penile growth

CHRONIC Rx

SURGICAL PROCEDURES: •

Orthoplasty (correcting penile curvature)

•

Urethroplasty

•

Meatoplasty

•

Glanuloplasty

•

Skin coverage

There is no single universally acceptable applicable technique for hypospadias repair. TYPES OF REPAIR: •

Anterior hypospadias: MAGPI, Thiersch-Duplay urethroplasty, glans approximation procedure (GAP), tubularized incised plate (TIP) urethroplasty, Mathieu perimeatal flap, Mustarde technique, megameatus intact prepuce (MIP), pyramid procedure

•

Midlevel hypospadias: TIP, Mathieu, onlay island flap (OIF), King procedure

•

Posterior hypospadias: 1.

One-stage repair: OIF, double onlay preputial flap, pedicled preputial flap, transverse preputial island flap (TPIF)

2.

Two-stage repair: Orthoplasty to correct chordee followed 6 mo later or longer by ThierschDuplay, bladder and/or buccal mucosal hypospadias repair

COMPLICATIONS OF REPAIR: Hematoma, meatal stenosis, fistula, urethral stricture, urethral diverticulum, wound infection, impaired healing, balanitis xerotica obliterans, penile curvature

PEARLS & CONSIDERATIONS

•

It must be kept in mind that apparent simple isolated hypospadias may be the only visible indication of an underlying abnormality.

•

The dorsal hood of redundant foreskin is used in the repair of hypospadias, and the patient with hypospadias and a dorsal hood should not be circumcised.

SUGGESTED READINGS American Academy of Pediatrics: Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. Pediatrics 1996; 97:590. Belman AB: Hypospadias update. Urology 1997; 49:166.

Borer JG, Retik AB: Current trends in hypospadias repair. Urol Clin North Am 1999; 26(1):15. Retik AB, Borer JG: In: Walsh PC, et al ed. Campbell's urology, ed 8. Philadelphia: WB Saunders; 2002. Zaontz MR, Packer MG: Abnormalities of the external genitalia. Pediatr Clin North Am 1997; 44:1267.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Hypothermia FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Hypothermia is a rectal temperature 6 months) of exertional dyspnea and nonproductive cough. Progressive dyspnea is usually the most prominent symptom.

•

Tachypnea to compensate for stiff noncompliant lung.

•

Fine bibasilar inspiratory crackles in >80% of patients, with progression upward as the disease advances.

•

Clubbing in 25% to 50% of patients.

•

Cyanosis, cor pumonale, right ventricular heave, peripheral edema may occur late in the disease course.

•

Extrapulmonary involvement does not occur. Fever is rare and suggests alternative diagnosis.

ETIOLOGY

•

Unknown.

•

Numerous hypotheses, including environmental insults such as metal and wood dust, infectious causes, chronic aspiration, or exposure to certain drugs (antidepressants).

•

New research suggests important role of aberrant tissue repair and fibrosis, and downplays the importance of generalized inflammation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Sarcoidosis

•

Drug-induced lung diseases

•

Connective tissue disease with similar clinical and pathologic presentations

•

Other idiopathic interstitial pneumonias: Desquamative interstitial pneumonia Respiratory bronchitis interstitial lung disease Acute interstitial pneumonia Nonspecific interstitial pneumonia Cryptogenic organizing pneumonia Bronchiolitis obliterans organizing pneumonia Occupational exposures (e.g., asbestos, silica) may cause pneumoconiosis that mimics IPF

WORKUP

•

Almost all patients have abnormal CXR at presentation with bilateral reticular opacities most prominent in the periphery and lower lobes. Peripheral honeycombing may be seen.

•

High-resolution CT scan shows patchy peripheral reticular abnormalities with intralobular linear opacities, irregular septal thickening, subpleural honeycombing, and ground glass appearance.

•

Pulmonary function tests show restrictive impairment with reduced vital capacity and total lung capacity. Obstructive picture only seen in smokers with IPF. Reduced DLCO.

•

Laboratory abnormalities (nondiagnostic): mild anemia; increases in ESR, LDH, CRP; low titer ANA seen in up to 30% of patients.

•

Limited role for bronchioalveolar lavage either in diagnosis or monitoring IPF.

•

Gold standard for diagnosis is lung biopsy (open thoracotomy or video-assisted thorascopy). Hallmark features: heterogeneous distribution of parenchymal fibrosis against background of mild inflammation (UIP).

•

Transbronchial lung biopsies do not provide a large enough sample to make diagnosis.

•

Lung biopsy is critical to distinguish IPF from diseases with better prognosis and treatment options, especially in patients with any atypical features.

•

In absence of or contraindication to lung biopsy, the combination of the clinical and radiographic features are often enough to establish the diagnosis.

TREATMENT

•

No proven treatment for IPF and little evidence to support the routine use of any specific therapy.

•

Conventional treatment includes a trial of corticosteroids at 0.5 mg/kg × 4 wk, 0.25 mg/kg × 8 wk, then tapered down combined with azathioprine or cyclophosphamide for 3 to 6 mo; 10% to 30% of patients may respond.

•

Treatment is continued for up to 24 months if the patient improves or is stable. Long-term treatment only with objective evidence of continued improvement or stabilization.

•

Single lung transplantation is the only therapy shown to prolong survival in IPF. Posttransplant 5-year survival for IPF patients is about 40%.

•

Treatment agents designed to target the fibrotic process include N-Acetylcysteine, pirfenidone, interferongamma 1b, coumadin, and etanercept. These are under investigation and show some initial promise.

DISPOSITION

•

Spontaneous remissions do not occur.

•

The course is progressive.

•

No difference in clinical course, pathology, or prognosis in younger patients.

•

Mean survival after the diagnosis of biopsy-confirmed IPF is 3 yr.

•

40% die of respiratory failure.

•

The incidence of bronchiogenic carcinoma is increased.

REFERRAL

To pulmonologist for review of abnormal chest imaging and establishing diagnosis

PEARLS & CONSIDERATIONS

•

The course is progressive with a high mortality rate.

•

Critical to differentiate IPF from other interstitial lung diseases since prognosis and response to treatment differs.

•

There is no proven treatment for IPF. A course of steroids combined with azathioprine or cyclophosphamide is often tried.

•

Consider early referral for lung transplant.

SUGGESTED READINGS American Thoracic Society: Idiopathic Pulmonary Fibrosis: Diagnosis and Treatment: International Consensus Statement. Am J Respir Crit Care Med 2000; 61:646. Gross TJ, Hunninghake GW: Idiopathic pulmonary fibrosis. N Engl J Med 2001; 345(7):517. Strieter RM: Pathogenesis and natural history of usual interstitial pneumonia. Chest 2005; 128(5):526S. Walter N, et al: Current perspectives on the treatment of idiopathic pulmonary fibrosis. Proc Am Thorac Soc 2006; 3:3308.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

IgA Nephropathy HEMANT K. SATPATHY, M.D.

BASIC INFORMATION DEFINITION

IgA nephropathy is a proliferative glomerulonephritis associated with predominant deposition of IgA in the mesangium. SYNONYMS

Berger's disease

ICD-9-CM CODES 583.81 EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: It is the most common type of glomerulonephropathy worldwide. PREVALENCE: Prevalence rate is lower in the U.S. (10% to 15%) compared to Asian countries. Lower rates could be explained by conservative approach by nephrologists in the U.S. who are reluctant to do renal biopsy in asymptomatic patients with minimal renal abnormalities. In most reports, prevalence rates are expressed as a percentage of cases of primary glomerulonephritis or as a percentage of total series of renal biopsies. PREDOMINANT SEX AND AGE: It is most prevalent in the second and third decade of life with a male:female ratio of 6:1 in the U.S. GENETICS: Although it is considered to be a sporadic disease, genetic linkage to locus called IgAN1 on 6q22 and 6q23 has been shown. RISK FACTORS: It has a higher association with Asians, Caucasians, and Native Americans and is rarely seen in African Americans. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Two common presentations include (1) recurrent macroscopic hematuria often associated with upper respiratory infection or (2) persistent microscopic hematuria.

•

Loin pain may be associated with macroscopic hematuria.

•

Physical findings are usually unremarkable except hypertension seen in 20% to 30% of patients with chronic disease and edema in 5% of patients with nephrotic range proteinuria.

•

Mild proteinuria is common.

•

Rarely, IgA nephropathy could present as acute renal failure in 5% of patients and chronic renal failure in 10% to 20% of patients.

ETIOLOGY

•

Most cases are idiopathic/primary.

•

Secondary causes of IgA nephropathy include Henoch-Schönlein purpura, hepatitis B, alcoholic cirrhosis, celiac disease, inflammatory bowel disease, psoriasis, sarcoidosis, cystic fibrosis, cancer of lungs/larynx/pancreas, HIV infection, systemic lupus erythematosus (SLE), rheumatoid arthritis, diabetic nephropathy, Sjögren's syndrome, Reiter's syndrome, and so on.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Henoch-Schönlein purpura

•

Hereditary nephritis

•

Thin glomerular basement membrane disease

•

Lupus nephritis

•

Poststreptococcal nephritis

•

Above mentioned secondary causes associated with IgA nephropathy

WORKUP

•

The diagnosis is suspected based on clinical history and laboratory data, but is confirmed by renal biopsy showing IgA deposits in the mesangium.

•

Renal biopsy is restricted to patients with sustained proteinuria more than 1 gm/day or worsening renal function.

LABORATORY TESTS

•

Urine analysis showing protein, RBC, WBC, and RBC casts.

•

Serum creatinine may be elevated.

•

24-hour urine assay for quantifying proteinuria and to check creatinine clearance.

•

Serum IgA is elevated in only 50% of patients. It has no clinical utility.

TREATMENT Although initially considered to be a benign disease, IgA nephropathy is now recognized as a common cause of renal failure. Currently there is no cure for it.

NONPHARMACOLOGIC THERAPY

•

Moderate dietary protein restriction

•

Discourage smoking

ACUTE/CHRONIC GENERAL Rx

•

Aggressive therapy for hypertension preferably with ACE inhibitors. Goal BP is less than 125/75 in presence of proteinuria over 1 gm/day.

•

Patients with recurrent gross hematuria or isolated microscopic hematuria, no or minimal proteinuria ( female (3:1); more common in white than black population PREDOMINANT AGE: Older than 50 years of age; rare before the age of 30 PEAK INCIDENCE: Fifth decade

GENETICS: •

•

Two forms: 1.

Acquired sporadic: the majority of cases (discussed here)

2.

Familial: differs from the acquired form by the age of onset (early childhood), distribution of muscle weakness (spares quadriceps), and biopsy findings (lack of inflammation and less amyloid deposits). It is linked to chromosome 9 and can be expressed in an autosomal dominant or recessive fashion.

HLA types: DR_1*0301, DR_3*0101 (or DR_3*0202) and DQ_1*0201

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Insidious onset (>6 yr from the onset of symptoms to diagnosis).

•

Steadily progressive asymmetric and painless muscle weakness and atrophy of the finger or wrist flexors (commonly the flexor pollicis longus), knee extensor (quadriceps), and foot dorsiflexion. Over time weakness spreads to involve other muscles.

•

A common complaint is difficulty with ambulation and frequent falls (due to buckling of knees caused by knee extensor weakness).

•

Fatigue and reduced tolerance of exertion are common.

•

Dysphagia (up to 60%).

•

Weakness of the diaphragm resulting in subacute respiratory failure.

•

Classic appearance is a scooped-out medial aspect of forearms and thin, atrophic quadriceps muscles.

•

Facial and neck weakness can be seen.

•

Early loss of patellar reflexes.

•

Up to 15% of patients have other autoimmune diseases (systemic lupus erythematosus, Sjögren's syndrome, scleroderma, interstitial pneumonitis, psoriasis, and sarcoidosis), diabetes, and mild polyneuropathy.

•

Cardiovascular abnormalities have been documented in some reports.

•

There is no documented association with malignancies.

•

Diagnostic criteria of either definite or possible IBM based on muscle biopsy, clinical features, and laboratory findings have been published.

ETIOLOGY

•

Cell-mediated immune response: CD8 cytotoxic T-cell endomysial infiltration

•

Of patients with sporadic form, 20% to 33% have a concomitant systemic or neurologic autoimmune disease

•

Monoclonal gammopathies are found at higher frequency in these patients

•

A strong association with a susceptibility gene in the central major histocompatibility (MHC) region (butyrophilin-like MHC class II–associated gene)

•

Abundant proinflammatory and regulatory cytokines, chemokines, and chemokine receptors are upregulated

•

Abnormal protein processing: accumulation of Alzheimer-type proteins (prion protein, beta amyloid protein, neuronal microtubule-associated protein, amyloid precursor protein, alpha-1 antichymotrypsin, phosphorylated tau, apolipoprotein E, ubiquitin, and presenilin) within the degenerating muscle fibers

•

Deletion of mitochondrial DNA

•

Nitric oxide induced oxidative stress

•

Possible viral pathogenesis: filamentous inclusions resembling myxovirus nucleocapsids. Also seen in patients with chronic viral infection (HIV, HTLV-1, hepatitis C)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Amyotrophic lateral sclerosis

•

Polymyositis

•

Polyneuropathy

•

Oculopharyngeal dystrophy

•

Emery-Dreifuss muscular dystrophy

•

Vitamin E deficiency

•

Chronic atrophic sarcoid myopathy

•

Myasthenia gravis

•

Acid maltase deficiency

•

Chronic inflammatory demyelinating polyradiculoneuropathy

WORKUP

•

Good history and physical exam demonstrating the characteristic pattern of weakness in a male who is older than 50.

•

Electromyography: active myopathic changes (fibrillation potentials, positive sharp waves and short duration, low-amplitude, polyphasic motor unit action potentials). Mixed myopathic and neurogenic changes can also be seen.

•

Nerve conduction studies: occasionally sensory nerve conduction studies are abnormal (if there is an associated neuropathy).

•

Muscle biopsy: small angular atrophic and denervated fibers. CD8 cytotoxic T-cell endomysial infiltration. Intracytoplasmic rimmed vacuoles and cytoplasmic tubofilamentous inclusions on electromicrosopic examination of the affected muscle fiber.

•

MRI has been used to visualize inflamed or atrophic muscles.

LABORATORY TESTS

•

CPK (normal to increased 3 to 5 times normal)

•

Thyroid function test to rule out thyroid disease

•

Antinuclear antigen (ANA), rheumatoid factor (RF), double stranded DNA (ds-DNA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rapid plasma reagin (RPR), scl-70, anti-SS-A (Ro), and anti-SS-B (La) to rule out other autoimmune diseases

•

Standard serum studies (hemogram and electrolytes)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Exercise therapy: isotonic training program of the weak muscles

•

Nutritional assessment if dysphagia is present

•

Cricopharyngeal myotomy for dysphagia

•

Braces/orthotics for weakness of tibialis anterior or quadriceps

•

Routine follow-up visits

GENERAL Rx

•

Resistant to treatment.

•

Although there is no effective treatment, all available medical and nonmedical treatment should be discussed with the patient and considered.

•

Corticosteroids, cyclophosphamide, chlorambucil, azathioprine, cyclosporine, methotrexate, anabolic steroid oxandrolone, and IVIG have been used but without evidence of benefit.

•

IVIG might provide some benefit for patients with dysphagia (Cherin P et al.).

•

IVIG in combination with prednisone results in reduction of endomysial inflammation but no clinical improvement (Dalakas, 2001).

•

Beta interferon-1a at 30 and 60 mg IM/wk regimens did not result in significant improvement in muscle strength or muscle mass (Muscle Study Group, 2001 and 2004).

•

Oxandrolone (a synthetic anabolic steroid) use resulted in muscle strength improvement but further studies are needed (Rutkow SB et al.).

•

Several months' trial of prednisone (0.6 mg/kg) is recommended by some (Lotz et al., Alexandrescu et al.).

•

Botulinum toxin A injection into the upper esophageal sphincter (Liu et al.).

•

Patients should be given a trial of immunosuppressive therapy if a connective tissue disease coexists.

DISPOSITION

•

The progression of the disease is very slow.

•

The rate of decline in strength (based on handheld myometry or manual muscle testing) is 0.66%-1.4%/mo.

•

The rate of functional decline from the onset of symptoms to use of a walker varies depending on the age of onset of symptoms (17 yr and 3.2 yr for age of onset 40 to 49 and 70 to 79, respectively).

•

Periods of stabilization (3 to 6 mo) can be seen in 25% to 50% of patients.

REFERRAL

•

Surgical evaluation for muscle biopsy

•

A neurologist or a neuromuscular specialist

•

Physical therapy

PEARLS & CONSIDERATIONS COMMENTS

•

Risk of falls should be assessed by a physical therapist.

•

Quantitative measures of muscle strength (myometry) should be used to assess response to treatment and disease activity.

EVIDENCE

There is no strong evidence to support the benefit of corticosteroids in producing sustained or quantitatively demonstrated improvement. At best, short-term stabilization was noted. [30] [31] Azathioprine resulted in a slight improvement in some patients with IBM.[[3]] Methotrexate might provide long term remission in some patients[[3]] and minor response in others.[[3]] Cyclosporin might provide some stability or short-term benefit in selected patients.[[4]] Total body irradiation, plasma exchange, IVIG, cyclophosphamide, and Chlorambucil did not show any significant benefit.

Evidence-Based References 1. Barohn RJ, et al: Inclusion body myositis: explanation for poor response to immunosuppressive therapy. Neurology 1995; 45:1302-1304. 2. Dalakas MC, et al: A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology 2001; 56(3):323. 3. Love LA, et al: A new approach to the classification of idiopathic inflammatory myopathy: myositis specific autoantibodies define useful homogenous patient groups. Medicine (Baltimore) 1991; 70:360. 4. Leff RL, et al: The treatment of inclusion body myositis: a retrospective review and a randomised prospective trial of immunosuppressive therapy. Medicine (Baltimore) 1993; 72:225-235.

SUGGESTED READINGS Alexandrescu DT, et al: Steroid-responsive inclusion body myositis associated with endometrial cancer. Clin

Exp Rheumatol 2005; 23(b):93-96. Cherin P, et al: Intravenous immunoglobulin for dysphagia of inclusion body myositis. Neurology 2002; 58:326. Dalakas MC: Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies. Nat Clin Pract Neurol 2006; 2(8):437. Katirji B, et al: Neuromuscular disorders in clinical practice, Boston: Butterworth-Heinemann; 2002:1169-1190. Liu LW, Tarnopolsky M, Armstrong D: Injection of botulinum toxin A to the upper esophageal sphincter for oropharyngeal dysphagia in two patients with inclusion body myositis. Can J Gastroenterol 2004; 18(b):397399. Lotz BP, et al: Inclusion body myositis: observation in 40 patients. Brain 1989; 112:727. Muscle Study Group: Randomized pilot trial of betaINF1a (Avonex) in patients with inclusion body myositis. Neurology 2001; 57(9):1566. Muscle Study Group: Randomized pilot trial of high-dose beta INF-1a in patients with inclusion body myositis. Neurology 2004; 63(4):718. Rutkove SB, et al: A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology 2002; 58:1081. Sayers ME, et al: Inclusion body myositis: analysis of 32 cases. J Rheumatol 1992; 19:1385. Tawil R, Griggs RC: Inclusion body myositis. Curr Opin Rheumatol 2002; 14:653-657. Toepfer M, et al: Expression of chemokines in normal muscle and inflammatory myopathies. Neurology 1998; 50:A413.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Incontinence (Urinary) PHILIP J. ALIOTTA, M.D., M.S.H.A., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Incontinence is the involuntary loss of urine.

ICD-9CM CODES

788.3

Incontinence

625.6

Stress incontinence

788.33 Mixed stress and urge incontinence 788.32 Male incontinence 788.39 Neurogenic incontinence 307.6

Nonorganic origin

EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE/PREVALENCE: In the general population between the ages of 15 and 64 yr, 1.5% to 5% of men and 10% to 25% of women will suffer from incontinence. In the nursing home population, 50% of the population suffers some degree of incontinence. Nearly 20% of children through the midteenage years have episodes of urinary incontinence. CLINICAL, PSYCHOLOGIC, & SOCIAL IMPACT

Less than 50% of the individuals with incontinence living in the community consult health care providers, preferring to “suffer silently,” turning to “home remedies,” commercially available absorbent materials, and supportive aids. As their condition worsens, they become depressed, sacrifice their independence, suffer from recurrent urinary tract infection and its sequelae, limit their social interaction, refrain from sexual intimacy, and become homebound. In terms of costs, for all ages living in the community, it is estimated that $7 billion is spent for incontinence annually. MAJOR TYPES OF INCONTINENCE

TRANSIENT INCONTINENCE: Incontinence occurring as a result or reaction to an acute medical problem affecting the lower urinary tract. Many of these problems can be reversed with treatment of the underlying problem. URGE INCONTINENCE: Involuntary loss of urine associated with an abrupt and strong desire to void. It is

usually associated with involuntary detrusor contractions on urodynamic investigation. In neurologically impaired patients, the involuntary detrusor contraction is referred to as detrusor hyperreflexia. In neurologically normal patients the involuntary contraction is called detrusor instability. STRESS INCONTINENCE: The involuntary loss of urine with physical activities that increase abdominal pressure in the absence of a detrusor contraction or an overdistended bladder. Classification of stress incontinence: Type 0: Complaint of incontinence without demonstration of leakage Type I: Incontinence in response to stress but little descent of the bladder neck and urethra Type II: Incontinence in response to stress with >2 cm descent of the bladder neck and urethra Type III: Bladder neck and urethra wide open without bladder contraction; intrinsic sphincter deficiency; and denervation of the urethra. The most common causes: urethral hypermobility and displacement of the bladder neck with exertion, intrinsic sphincter deficiency from failed antiincontinence surgery, prostatectomy, radiation, cord lesions, epispadias, or myelomeningocele OVERFLOW INCONTINENCE: Loss of urine resulting from overdistention of the bladder with resultant “overflow” or “spilling” of the urine. Causes: hypotonic-to-atonic bladder resulting from drug effect, fecal impaction, or neurologic conditions such as diabetes, spinal cord injury, surgery, vitamin B12 deficiency. It is also caused by obstruction at the bladder neck and urethra. In this situation, prostatism, prostatic cancer, urethral stenosis, antiincontinence surgery, pelvic prolapse, and detrusor-sphincter dyssynergia cause the incontinence. FUNCTIONAL INCONTINENCE: Involuntary loss of urine resulting from chronic impairments of physical and/or cognitive functioning. This is a diagnosis of exclusion. The condition can sometimes be improved or cured by improving the patient's functional status, treating comorbidities, changing medications, reducing environmental barriers, etc. MIXED STRESS AND URGE INCONTINENCE SENSORY URGENCY INCONTINENCE: Involuntary loss of urine as a result of decreased bladder compliance and increased intravesical pressures accompanied by severe urgency and bladder hypersensitivity without detrusor overactivity. This is seen with radiation cystitis, interstitial cystitis, eosinophilic cystitis, myelomeningocele, and radical pelvic surgery. Nephropathy can occur as a complication of this vesicoureteral reflux. SPHINCTERIC INCONTINENCE: Urethral Hypermobility: The basic abnormality is a weakness of pelvic floor support. Because of this weakness, during increases in abdominal pressure there is rotational descent of the vesical neck and proximal urethra. If the urethra opens concomitantly, stress urinary incontinence ensues. Urethral hypermobility is often present in women who are not incontinent. Its mere presence is not sufficient evidence to make the diagnosis of sphincteric abnormality unless incontinence is shown. Intrinsic Sphincter Deficiency: There is an intrinsic malfunction of the sphincter itself. It is characterized by an open vesical neck at rest and a low leak point pressure (10 yr and adults 65 yr) and rimantadine (same dose schedule as amantadine)

•

1.

Further dose adjustments needed with renal insufficiency

2.

Fewer CNS side effects with rimantadine

Neuraminidase inhibitors block release of virions from infected cells, resulting in shortened duration of symptoms and decrease in complications; effective against both influenza A and B 1.

Zanamivir, administered via inhaler, 10 mg bid

2.

Oseltamivir, administered orally, 75 mg by mouth bid for 5 days

•

Placebo-controlled studies have suggested that antiviral therapy with any of the above mentioned agents must be initiated within 1 to 2 days of the onset of symptoms and reduces the duration of illness by approximately 1 day

•

Oseltamivir resistance has developed on therapy in individuals with avian flu (H5, N1) in Asia, and this is associated with poor outcome.

DISPOSITION

Patients are hospitalized if signs of pneumonia are present. REFERRAL

Infectious disease and/or pulmonary consultation when influenza pneumonia is suspected

PEARLS & CONSIDERATIONS COMMENTS

•

Prevention of influenza in patients at high risk is an important goal of primary care.

•

Vaccines reduce the risk of infection and the severity of illness.

•

1.

Antigenic composition of the vaccine is updated annually.

2.

Vaccination should be given at the start of the flu season (October) for the following groups: a.

Adults =50 yr

b.

Adults and children with chronic cardiac or pulmonary disease, including asthma

c.

Adults and children with illness requiring frequent follow-up (e.g., hemoglobinopathies, diabetes mellitus)

d.

Children ages 6 to 59 mo and all those receiving long-term aspirin therapy

e.

Immunocompromised patients (including HIV-infected persons)

f.

Household contacts and caregivers of persons in the previous groups

g.

Health care workers, pregnant women

3.

Only contraindication to vaccination is hypersensitivity to hen's eggs.

4.

Special efforts should be made to vaccinate high-risk patients 60 yr. GENETICS: Insomnia can run in families and may be genetically influenced. Sleep characteristics in monozygous twins are more similar than in dizygote twins. Some sleep disorders, such as circadian rhythm disorders and narcolepsy, have been traced to specific genes. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Difficulty falling asleep, difficulty staying asleep, early morning awakening, restless or nonrestorative sleep, or difficulty sleeping at desired times.

•

May have daytime sleepiness or fatigue.

•

Symptoms may be acute and self-limited, chronic but intermittent, or chronic and frequent.

ETIOLOGY

•

•

Transient insomnia: 1.

Stress

2.

Illness

3.

Travel (across time zones)

4.

Environmental disruptions (noise, heat, cold, poor bedding, unfamiliar surroundings, etc.)

Persistent insomnia: 1.

Mood and anxiety disorders (depression, hypomania/mania, PTSD)

2.

Primary or psychophysiologic insomnia (with or without poor sleep hygiene)

3.

Sleep-related breathing disorders (e.g., obstructive apnea and hypopnea, increased upper airway resistance)

4.

Chronobiologic (also known as circadian rhythm) disorder (delayed sleep phase, advanced sleep phase, shift work, free-running rhythm secondary to blindness)

5.

Drug and alcohol abuse

6.

Restless legs syndrome and periodic leg movements

7.

Neurodegenerative (Alzheimer's disease, Parkinson's disease, etc.)

8.

Medical (pain, GERD, nocturia, orthopnea, medications, etc.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Primary or psychophysiologic insomnia is diagnosed when other etiologies (see “Etiology”) are ruled out. Primary insomnia may be related to counterproductive sleep hygiene, hyperarousal, or insufficient sleep drive. WORKUP

•

History (with bed partner interview, if possible)

•

Sleep diary for 2 wk to document nightly sleep quality and daytime sleepiness or fatigue (sample sleep diary can be downloaded from the National Sleep Foundation website: www.sleepfoundation.org )

•

Validated sleep-quality rating scale (optional) 1.

Pittsburgh Sleep Quality Index or Insomnia Severity Index

2.

Epworth Sleepiness Scale (see Daytime Sleepiness Test at www.sleepfoundation.org

)

LABORATORY TESTS

•

Evaluate for anemia, uremia (for restless legs), thyroid function (if other signs present).

•

Polysomnography (in home or in sleep lab) for symptoms suggesting something other than primary insomnia: daytime sleepiness (obstructive sleep apnea, narcolepsy), nonrestorative sleep (periodic leg movements), or sleep behavior suggesting parasomnia (somnambulism, REM sleep behavior).

IMAGING STUDIES

•

Not generally helpful for insomnia

•

Brain CT or MRI for severe daytime sleepiness or acute onset

TREATMENT NONPHARMACOLOGIC THERAPY

•

Sleep hygiene measures ( Box 1-8 )

•

Cognitive-behavioral therapy (CBT) can address anxiety and insomnia-perpetuating behaviors. CBT has been shown to reduce time to fall asleep and time awake during the night in placebo-controlled trials and can reduce reliance on sleep medications.

•

The cognitive component of CBT involves education about sleep and insomnia to address concerns that might increase anxiety around sleeplessness. The behavioral component attempts to change habits that may perpetuate insomnia. The four components are relaxation techniques; stimulus control to address the conditioned cues that create arousal when attempting to sleep; bed restriction to sleep and sex and not tossing and turning, watching TV, reading, etc.; and improved sleep hygiene practices such as increased daytime exercise, avoiding heavy meals at night, and reduce or eliminate caffeine, nicotine, and alcohol intake.

•

Increased daytime activity improves sleep, especially in people (of any age) who were previously sedentary. Improvements are seen in total sleep duration, in sleep-onset latency, and in scores on a scale of global sleep quality.

•

Insomnia secondary to circadian rhythm disturbances, as in shift workers, many blind individuals (lack of light-dark cycle to synchronize body-clock), adolescents and young adults with delayed sleep phase syndrome, and jet lag can be treated with chronobiological therapies such as bright light exposure, melatonin, or melatonin agonists. These therapies have to be given at specific times of the day or night, and referral to a sleep specialist may be necessary.

BOX 1-8

Sleep Habits (Sleep Hygiene Measures) That May Improve Insomnia 1.

Reduce caffeine, alcohol, or tobacco late in the day or evening.

2.

Avoid heavy meals at night.

3.

Increase daytime activity.

4.

Increase daytime exposure to natural light.

5.

Take warm bath as part of bedtime ritual.

6.

Restrict bed to sleep and sex.

7.

Get out of bed if not asleep after 30 minutes and return when drowsy.

8.

Repeat above if awakened during the night.

9.

Maintain regular sleep and wake times.

10. Go to bed with calm mind; resolve arguments or deal with problems earlier in day. ACUTE GENERAL Rx

•

Benzodiazepine sedative-hypnotics (e.g., temazepam 7.5 to 30 mg, triazolam 0.125 to 0.25 mg).

•

In critical care: lorazepam 0.25 to 0.5 mg po, SL, or IV as needed for sleep. In patients with acute delirium, haloperidol 0.25 to 0.5 mg IV as needed up to 2 mg daily may be less likely to worsen confusion.

•

Benzodiazepine receptor agonists zolpidem 5 to 10 mg and zaleplon 5 to 10 mg for sleep-onset insomnia, and zolpidem continuous release formulation 6.25 to 12.5 mg and eszopiclone 1 to 3 mg for maintenance insomnia.

•

Melatonin agonist ramelteon 8 mg for sleep-onset insomnia when a mild agent without benzodiazepine side effects is desired.

•

Avoid antihistamines except for occasional use.

•

Optimize treatment of medical symptoms, especially pain.

CHRONIC Rx

•

Controlled trials suggest that CBT is superior to medication for chronic insomnia. Long-term management of insomnia needs ongoing attention to sleep hygiene and other cognitive behavioral approaches for best results.

•

Three sedative-hypnotics—zolpidem-continuous release, eszopiclone, and ramelteon—have been studied in 6-mo controlled trials and are FDA approved for chronic use.

•

There is some evidence that benzodiazepines and benzodiazepine receptor agonists can be used for chronic insomnia on either intermittent or nightly use with moderate risk of tolerance and dependence but low risk of addiction.

•

Sedating antidepressants (e.g., trazodone 25 to 150 mg, mirtazapine 7.5 to 30 mg, amitriptyline 25 to 50 mg) are in widespread use but there are limited data on safety and efficacy for insomnia. Amitriptyline should be avoided if possible in older adults.

•

Sedating antipsychotics (e.g., quetiapine 25 to 200 mg, olanzapine 2.5 to 10 mg at night) for severe mood or psychotic disorders associated with insomnia.

COMPLEMENTARY & ALTERNATIVE MEDICINE

Melatonin is the only substance that has been studied in larger controlled trials. It may shorten sleep-onset latency in some individuals but not most. Valerian has been studied in small trials, but like melatonin, appears to be of minimal benefit for insomnia in most people.

DISPOSITION

•

Transient insomnia: usually self-limited, but may require follow-up if stressrelated or illness-related because of risk of depression or persistent insomnia.

•

Persistent insomnia: patients have a chronic and recurrent disorder and will need periodic follow-up to reinforce good sleep hygiene measures and to reassess need for pharmacologic therapies. Increasingly, there is evidence that insomnia is associated with significant negative health effects over time.

REFERRAL

•

Excessive daytime sleepiness not obviously due to insomnia (e.g., narcolepsy, sleep-related breathing disorder)

•

Nighttime behavior suggestive of a parasomnia (e.g., somnambulism, REM behavior disorder)

•

Severe insomnia not responsive to basic interventions

PEARLS & CONSIDERATIONS COMMENTS

Treatment of insomnia should focus on reducing daytime sleepiness and improving daytime function, rather than trying to achieve the elusive goal of uninterrupted nighttime sleep. PREVENTION

Not much is known about prevention of insomnia. Effective treatment of transient insomnia may reduce the risk of developing persistent insomnia. PATIENT/FAMILY EDUCATION

The National Sleep Foundation (www.sleepfoundation.org providers and patients.

EVIDENCE

) is a comprehensive resource for health care

The effects of CBT on reduced time to fall asleep are comparable to sleep medication, although may take several weeks to develop. CBT may be superior to pharmacotherapy for chronic insomnia. [76] [77] Regular, moderate-intensity exercise improves sleep in adults 60 years of age or older with primary insomnia. Improvements are seen in total sleep duration, in sleep-onset latency, and in scores on a scale of global sleep quality.[[3]] Melatonin is effective in the prevention and reduction of jet lag, and occasional short-term use appears to be safe.[[4]] A systematic review found inconsistent and contradictory evidence for the efficacy of valerian in the treatment of insomnia. [[5]]

Evidence-Based References 1. Jacobs GD, et al: Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Int Med 2004; 164(17):1888. 2. Silber MH: Chronic insomnia. N Engl J Med 2005; 353:803. 3. Montgomery P, Dennis J: Physical exercise for sleep problems in adults aged 60$1. Cochrane Database Syst Rev 2002; 4: 4. Herxheimer A, Petrie KJ: Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002; 2: 5. Stevinson C, Ernst E: Valerian for insomnia: a systematic review of randomized clinical trials. Sleep Medicine 2000; 1:91.

SUGGESTED READINGS Carney PR, Berry RB, Geyer JD: Clinical sleep disorders, Philadelphia, Lippincott Williams & Wilkins, 2005. 2005. Ramakrishnan K, Scheid DC: Treatment options for insomnia. Am Fam Phys 2007; 76(4):517.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Insulinoma FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Insulinoma is a pancreatic insulinsecreting tumor that causes symptoms associated with hypoglycemia.

ICD-9CM CODES

M8151/0 Insulinoma EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 1 case/250,000 persons/yr. Ninety percent of insulinomas are benign. PREDOMINANT SEX/AGE: Insulinomas occur in both sexes (approximately 60% in women) and at all ages. In the Mayo Clinic series, the median age at diagnosis was 50 yr in sporadic cases but 23 yr in patients with multiple endocrine neoplasia (MEN), type 1. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms occur typically in the morning before breakfast (i.e., fasting hypoglycemia as opposed to reactive hypoglycemia, which is not commonly associated with insulinoma)

Neuroglycopenic symptoms

%

Various combinations of diplopia, blurred vision, sweating, palpitations, or weakness 85 Confusion or abnormal behavior

80

Unconsciousness or amnesia

53

Grand mal seizures

12

Adrenergic symptoms

%

Sweating

43

Tremulousness

23

Hunger, nausea

12

Palpitations

10

ETIOLOGY, PATHOLOGY, PATHOPHYSIOLOGY

•

Insulinomas are almost always solitary. Malignant insulinomas account for 5% of the total; they tend to be larger (6 cm). Metastases are usually to the liver (47%), regional lymph nodes (30%), or both.

•

Insulinomas are evenly distributed in the head, body, and tail of the pancreas; ectopic insulinomas are rare (1% to 3%). Tumor size: 5% 0.5 cm or less, 34% 0.5 to 1 cm, 53% 1 to 5 cm, 8% >5 cm.

•

Histologic classification includes insulinoma in 86% of patients, adenomatosis in 5% to 15%, nesidioblastosis in 4%, and hyperplasia in 1%. Adenomatosis consists of multiple macroadenomas or microadenomas and occurs especially in patients with MEN-1. Nesidioblastosis is also a diffuse lesion, in which islet cells form as buds on ductular structures.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS (of fasting hypoglycemia)

HYPERINSULINISM: •

Insulinoma

•

Nonpancreatic tumors

•

Severe congestive heart failure

•

Severe renal insufficiency in non-insulin-dependent diabetes

HEPATIC ENZYME DEFICIENCIES OR DECREASED HEPATIC GLUCOSE OUTPUT (primarily in infants, children): •

Glycogen storage diseases

•

Endocrine hypofunction

•

Hypopituitarism

•

Addison's disease

•

Liver failure

•

Alcohol abuse

•

Malnutrition

EXOGENOUS AGENTS: •

Sulfonylureas, biguanides

•

Insulin

•

Other drugs (aspirin, pentamidine)

FUNCTIONAL FASTING HYPOGLYCEMIA: Autoantibodies to insulin receptor or insulin LABORATORY TESTS

•

An overnight fasting blood sugar level combined with a simultaneous plasma insulin, proinsulin, and/or C peptide level will establish the existence of fasting organic hypoglycemia in 60% of patients.

•

If single overnight fasting glucose and insulin levels are nondiagnostic, a 72-hr fast is usually done with blood glucose and insulin levels determined at 2- to 4-hr intervals: 75% of patients with insulinoma develop symptoms and a blood sugar level of less than 40 mg/dl by 24 hr, 92% to 98% develop these by 48 hr, and virtually all patients develop them by 72 hr. The test is considered positive for insulinoma if the plasma insulin/glucose ratio is more than 0.3. If, at any point, the patient becomes symptomatic, plasma insulin and glucose values should be obtained and intravenous glucose should be administered.

•

Plasma proinsulin, C-peptide, antibodies to insulin, and plasma sulfonylurea levels may be used to rule out factitious use of insulin or hypoglycemic agents or autoantibodies against the insulin receptor or insulin.

•

See Section III, “Hypoglycemia,” for a description of the diagnostic approach to patients with documented hypoglycemia and elevated insulin.

IMAGING STUDIES

•

Abdominal CT scan or MRI detects half to two thirds of insulinomas (abdominal ultrasound is not effective). Should be done only after laboratory tests for insulinoma have confirmed the diagnosis

•

Intraoperative ultrasound

•

Arteriography

•

Octreotide scan

TREATMENT NONPHARMACOLOGIC THERAPY

•

Enucleation of single insulinoma

•

Partial pancreatectomy for multiple adenomas

ACUTE GENERAL Rx

•

Carbohydrate administration

•

Diazoxide directly inhibits insulin release and has an extrapancreatic, hyperglycemic effect that enhances glycogenolysis

•

Lanreotide and octreotide (somatostatin analogs)

•

Streptozotocin

REFERRAL

At some point in the workup the patient will probably be referred to an endocrinologist and then to a surgeon. A combination of fasting hypoglycemia and elevated insulin level is probably a good point at which to refer. SUGGESTED READINGS Axelrod L: Insulinoma: cost-effective care in patients with rare disease. Ann Intern Med 1995; 123:311. Service FJ: Hypoglycemic disorders. Endocrinol Metab Clin North Am 1999; 28:467. Service FJ, et al: Functioning insulinoma—incidence, recurrence and long-term survival of patients. Mayo Clin Proc 1991; 66:711.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Interstitial Cystitis HEMANT K. SATPATHY, M.D.

BASIC INFORMATION DEFINITION

The International Continence Society defines interstitial cystitis (IC), otherwise known as painful bladder syndrome (PBS), as a clinical syndrome consisting of suprapubic pain related to bladder filling and accompanied by other symptoms such as increased daytime and nighttime frequency in the absence of proven infection or other obvious pathology. SYNONYMS

Painful bladder syndrome Tic douloureux of bladder

ICD-9-CM CODES 595.1 EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 21 cases/100,000 women per yr, and 4 cases/100,000 men per yr PREVALENCE: •

197 per 100,000 women and 41 per 100,000 men in U.S.

•

Because the disease is substantially underdiagnosed, it may actually affect 1 in 5 women and 1 in 20 men.

•

More than 81% of women diagnosed with chronic pelvic pain (CPP) and up to 84% of men initially diagnosed with chronic prostatitis actually have IC.

•

More than 90% of patients diagnosed with overactive bladder who do not respond to anticholinergics are subsequently diagnosed with IC.

PREDOMINANT SEX AND AGE: •

Caucasian women constitute 95% of patients with IC.

•

Female:male ratio of 5 to 10:1.

•

Most prevalent in fourth and fifth decades of life.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Urinary urgency, frequency (>8 in daytime), nocturia (>2 at night), and suprapubic pain are the most common symptoms.

•

Suprapubic pain is worse with bladder filling or urinating, and relieved after emptying.

•

Dyspareunia.

•

Symptoms lasting longer than 6 months.

•

Intensity of symptoms waxes and wanes.

•

Insidious onset and worsens to the final stage within 5 to 15 yr.

•

Exercise, stress, sexual activity, ejaculation, certain foods with high potassium and acids (beer, spices, banana, tomatoes, chocolate, strawberries, artificial sweeteners, oranges, cranberries, caffeine, etc.), menstruation, prolonged sitting, activation of allergies, and so on exacerbates the symptoms.

•

Often associated with irritable bowel syndrome, migraine, endometriosis, skin sensitivities, multiple drug allergies, other allergies, vulvodynia, fibromyalgia, chronic fatigue syndrome, systemic lupus erythematosus (SLE), mood disorders, and so on.

•

Dysphoric mood.

•

Lower abdominal tenderness.

•

Tender prostate in digital rectal examination.

•

Levator ani tenderness in female.

•

Tenderness of anterior vaginal wall/bladder neck in female.

ETIOLOGY

Unknown

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Chronic pelvic pain

•

Overactive bladder

•

Recurrent UTI

•

Endometriosis

•

Pelvic adhesions

•

Vulvar vestibulitis

•

Vulvodynia

•

Urethral pain syndrome

•

Chronic nonbacterial prostatitis

•

Frequent vaginitis

•

Benign prostatic hyperplasia

WORKUP

•

A clinical diagnosis should be a diagnosis of inclusion.

•

There is no definite diagnostic test.

•

Validated questionnaires such as Pelvic Pain and Urgency/Frequency scale (PUF), O'Leary-Sant symptoms and problem index, and Wisconsin IC scale. PUF is the most commonly used.

•

Voiding diary shows low volume (1 cm in diameter. Intralesional injection of interferon alfa-2b has also been reported as effective and well tolerated.

•

Radiation therapy is effective in non-AIDS KS and for large tumor masses that interfere with normal function.

•

Systemic therapy with interferon is also effective in AIDS-related KS and is often used in combination with AZT.

•

Systemic chemotherapy (vinblastine, bleomycin, doxorubicin, and dacarbazine) can be used for rapidly progressive disease and for classic and African endemic KS.

•

Sirolimus (rapamycin), an immunosuppressive drug, is effective in inhibiting the progression of dermal Kaposi's sarcoma in kidney transplant recipients.

•

Oral etoposide is also effective and has less myelosuppression than vinblastine.

•

Paclitaxel is also effective in patients with advanced KS and represents an excellent second-line therapy.

DISPOSITION

•

Prognosis is poor in AIDS-related KS. Death is often a result of other AIDS-defining illnesses.

•

Prognosis is better in African cutaneous KS and classic sarcoma (patients usually die of unrelated causes).

PEARLS & CONSIDERATIONS COMMENTS

Immunosuppression-associated Kaposi's sarcoma usually regresses with the cessation, reduction, or modification of immunosuppression therapy in most patients. Similarly in HIV patients, Kaposi's sarcoma responds concurrently with the decrease in serum HIV RNA and increase in the CD4 count. SUGGESTED READINGS Stallone , et al: Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Eng J Med 2005; 352:1317.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Kawasaki Disease PRANAV M. PATEL, M.D.

BASIC INFORMATION DEFINITION

Kawasaki disease (also known as the mucocutaneous lymph node syndrome) is an acute, febrile, multisystem disease usually involving children, and is usually manifested by self-limited generalized vasculitis of unknown etiology. SYNONYMS

Kawasaki syndrome Mucocutaneous lymph node syndrome

ICD-9CM CODES

446.1 Kawasaki disease EPIDEMIOLOGY & DEMOGRAPHICS

•

Kawasaki disease is a leading cause of acquired heart disease in children.

•

Commonly occurs under the age of 5 yr (80%). Peak age is 18 to 24 months.

•

More prevalent in boys than in girls (1.5:1).

•

The highest incidence is found in Japan (approximately 150 cases/100,000 children).

•

Incidence of Kawasaki disease in the U.S. is 10 to 15 cases/100,000 children 5 days and the presence of at least four of the following five principal features: 1.

Predominantly unilateral cervical lymphadenopathy (>1.5 cm in diameter)

2.

Changes in extremities: (i) Acute: erythema and edema of hands and feet ( Fig. 1-141, A ); (ii) convalescent: membranous desquamation of fingertips

3.

Polymorphous exanthema (usually in truncal region)

4.

Bilateral, painless bulbar conjunctival injection without exudate

5.

Erythema and cracking of lips, strawberry tongue ( Fig. 1-141, B ), diffuse injection of the oral and pharyngeal mucosae

•

The fever of Kawasaki disease is usually higher than 102.2°F (39°C) and often above 104.0°F (40°C); if untreated, it lasts for an average of 11 days.

•

Coronary-artery aneurysms (>8 mm in diameter) develop in as many as 25% of untreated children and can lead, over time, to ischemic heart disease, myocardial infarction, congestive heart failure and occasionally, death.

•

Children with Kawasaki disease who are less than 1 yr of age are more likely to develop the cardiac sequelae and are most likely to fail treatment.

•

Patients with fever and fewer than four principal symptoms but evidence of coronary artery disease are diagnosed as having atypical Kawasaki disease.

•

Mucous membrane changes involving the hands are the most common manifestation of Kawasaki disease (either typical or atypical).

•

Cervical adenopathy is the most common physical manifestation in atypical Kawasaki disease.

•

On rare occasions aneurysms of peripheral arteries (e.g., axillary) may be seen.

•

Beau's lines (transverse grooves of the nails), diarrhea, dyspnea, arthralgia, and myalgia may also been seen.

FIGURE 1-141 A, Erythema of the hands, to be followed by desquamation. B, Strawberry tongue in a patient with Kawasaki syndrome. (A Courtesy Department of Dermatology, University of North Carolina at Chapel Hill. In Goldstein B [ed]: Practical dermatology, ed 2, St Louis, 1997, Mosby. B Courtesy Marshall Guill, M.D. In Goldstein B [ed]: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

ETIOLOGY

The cause of Kawasaki disease is not known, although evidence substantiates an infectious etiology precipitating an immune-mediated reaction.

DIAGNOSIS There is no diagnostic test for this acute vasculitis. The illness begins with the abrupt onset of fever. Typically, the clinical signs appear over the course of several days. The clinical criteria (listed in “Physical Findings & Clinical Presentation”) can be used to aid in the diagnosis of Kawasaki disease. DIFFERENTIAL DIAGNOSIS

•

Scarlet fever

•

Stevens-Johnson syndrome

•

Drug eruption

•

Henoch-Schönlein purpura

•

Toxic shock syndrome

•

Measles

•

Rocky Mountain spotted fever

•

Infectious mononucleosis

WORKUP

Clinical findings in addition to laboratory and imaging studies are useful in searching for multiorgan system involvement and complications (e.g., cardiac, lung, liver). LABORATORY TESTS

Clinical and laboratory findings observed in patients with this disease are frequently helpful in diagnosis. They include the following: •

CBC commonly shows a normochromic normocytic anemia, elevated platelet count, elevated white blood cell count with neutrophil predominance.

•

Elevated liver function tests.

•

Elevated erythrocyte sedimentation rate (often above 40 mm/hour and, not uncommonly, is elevated to levels of at least 100 mm/hour).

•

Elevated C-reactive protein (levels of 3 mg/dl or more).

•

Urinalysis may show sterile pyuria.

IMAGING STUDIES

•

Chest x-ray may reveal pulmonary infiltrates.

•

Echocardiogram is very helpful and may show depressed left ventricular function with regional wall motion abnormalities, pericardial effusion (30%), and mitral valve regurgitation. The echocardiogram is also useful in the long-term follow-up of patients with Kawasaki disease.

•

Coronary angiogram and MRI can be used to visualize the coronary arteries and for the presence of coronary artery aneurysms. Echocardiography may be able to visualize these aneurysms in infants.

•

Intravascular ultrasound can assess for luminal irregularities of the coronary arteries.

•

Exercise testing with myocardial perfusion studies can be done to assess for coronary blood flow and the presence of myocardial ischemia.

•

ECG changes (arrhythmias, abnormal Q waves, prolonged PR and/or QT intervals, occasionally low voltage, or ST-T wave changes) can be seen. Chest x-ray abnormalities (cardiomegaly) may also be evident.

TREATMENT Consists of treatment of the acute phase and long-term management of patients with Kawasaki disease. Treatment of Kawasaki disease in the acute phase is directed at reducing inflammation in the coronary artery wall and preventing coronary thrombosis, whereas long-term therapy in individuals who develop coronary aneurysms is aimed at preventing myocardial ischemia or infarction. NONPHARMACOLOGIC THERAPY

•

Oxygen in selected patients

•

Salt restriction in patients with congestive heart failure

ACUTE GENERAL Rx

•

Without treatment, coronary artery abnormalities develop in about 15% to 25% of patients with Kawasaki disease.

•

Intravenous immunoglobulin (IVIG) 2 g/kg over 8 to 12 hr is the treatment of choice in children diagnosed with Kawasaki disease and ideally should be given within the first 10 days of the illness.

•

Aspirin 80 to 100 mg/kg/day given in four divided doses until the patient is no longer febrile. Thereafter, aspirin 3 to 5 mg/kg/day is continued until lab studies (e.g., sedimentation rate) return to normal, generally within 6 to 8 wk.

•

In patients that do not defervesce within 48 hr or have recrudescent fever after initial IVIG treatment, a second dose of IVIG 2 g/kg IV over 8 to 12 hr should be considered.

•

Non steroidal anti-inflammatory drugs are not effective in the treatment of Kawasaki disease.

•

The effect of corticosteroids on coronary artery aneurysms is unclear. Therefore, most experts recommend withholding steroids unless fever persists after at least two courses of IVIG.

•

Other therapies, including pentoxifylline, infliximab (monoclonal antibody against tumor necrosis factor A), plasma exchange, abciximab (platelet glycoprotein IIb/IIIa receptor inhibitor), and cytotoxic agents (cyclophosphamide), have been used but there is limited data on their success.

•

Acute management of patients with coronary artery abnormalities depends on the severity of the lesion.

•

Most patients with large or giant coronary artery aneurysms (diameter >8 mm) are maintained on aspirin (or clopidogrel) and warfarin to prevent thrombosis within the aneurysm and myocardial infarction

CHRONIC Rx

Interventional and surgical procedures can be tried in children who have developed cardiac complications of Kawasaki disease: •

Percutaneous transluminal coronary angioplasty

•

Coronary bypass graft surgery using the internal mammary artery or the gastroepiploic artery has met with greater patency success than saphenous vein grafts

•

Cardiac transplantation is an option and is indicated in patients with: 1.

Severe left ventricular failure

2.

Malignant arrhythmias

3.

Multivessel coronary artery disease

DISPOSITION

•

Mortality rate of children with Kawasaki disease is 0.5% to 2.8%, usually from coronary artery aneurysm, coronary thrombosis, and myocarditis.

•

Death usually occurs in the third to fourth week of the illness.

•

Before the use of IVIG, approximately 20% of all patients with Kawasaki disease developed coronary artery aneurysms.

•

Treatment with IVIG has reduced the incidence of coronary aneurysms by 80%.

•

IVIG has also been shown to improve left ventricular function during the acute stages of the disease.

•

Risk factors for the development of coronary aneurysms or giant coronary aneurysms (>8 mm) are:

•

1.

Fever lasting >10 days

2.

Age 60% of blacks have some form of lactose intolerance. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Abdominal tenderness and cramping, bloating, flatulence

•

Diarrhea

•

Symptoms are directly related to the osmotic pressure of substrate in the colon and occur about 2 hr after ingestion of lactose

•

Physical examination: may be entirely within normal limits

ETIOLOGY

•

Congenital lactase deficiency: common in premature infants; rare in full-term infants and generally inherited as a chromosomal recessive trait

•

Secondary lactose intolerance: usually a result of injury of the intestinal mucosa (Crohn's disease, viral gastroenteritis, AIDS enteropathy, cryptosporidiosis, Whipple's disease, sprue)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

IBD

•

IBS

•

Pancreatic insufficiency

•

Nontropical and tropical sprue

•

Cystic fibrosis

•

Diverticular disease

•

Bowel neoplasm

•

Laxative abuse

•

Celiac disease

•

Parasitic disease (e.g., giardiasis)

•

Viral or bacterial infections

WORKUP

•

The diagnosis can usually be made on the basis of the history and improvement with dietary manipulation.

•

Diagnostic workup may include confirming the diagnosis with hydrogen breath test and excluding other conditions listed in the differential diagnosis that may also coexist with lactase deficiency.

LABORATORY TESTS

•

Lactose breath hydrogen test: A rise in breath hydrogen >20 ppm within 90 min of ingestion of 50 g of lactose is positive for lactase deficiency. This test is positive in 90% of patients with lactose malabsorption. Common causes of false-negative results are recent use of oral antibiotics or recent high colonic enema.

•

The lactose tolerance test is an older and less accurate testing modality (20% rate of false positive and negative results). The patient is administered an oral dose of 1 to 1.5 gm of lactose/kg body weight. Serial measurement of blood glucose level on an hourly basis for 3 hr is then performed. The test is considered positive if the patient develops intestinal symptoms and the blood glucose level rises 0 WORKUP

•

Laboratory: none

•

Endoscopic laryngeal inspection

•

After (and only after) diagnosis of the malignancy, imaging with CT or MRI should be undertaken to stage the disease

HISTOLOGIC CLASSIFICATION: Epithelial cancers •

Squamous cell carcinoma in situ

•

Superficially invasive cancer

•

Verrucous carcinoma

•

Pseudosarcoma

•

Anaplastic cancer

•

Transitional cell carcinoma

•

Lymphoepithelial cancer

•

Adenocarcinoma

•

Neuroendocrine tumors, including small cell and carcinoid

Sarcomas Metastatic malignancies

TREATMENT ACUTE GENERAL Rx

•

•

•

Early stage (T or T2): two options 1.

Conservative surgery (partial laryngectomy) with neck dissection

2.

Primary radiation

Intermediate stage: four options 1.

Primary radiation alone

2.

Supraglottic laryngectomy with neck dissection

3.

Supraglottic laryngectomy with postoperative radiation

4.

Chemotherapy with radiation

Advanced stage

Chemotherapy and radiation with total laryngectomy reserved for treatment failure Glottis

•

•

•

•

Carcinoma in situ 1.

Microexcision

2.

Laser vaporization

3.

Radiation

Early stage (T or T2): two options 1.

Voice conservation surgery

2.

Radiation

Intermediate stage (T3) 1.

Combined radiation and chemotherapy (cisplatin and 5FU)

2.

Total laryngectomy for treatment failure

Advanced stage (T 4) 1.

Combined radiation and chemotherapy

2.

Total laryngectomy and neck dissection followed by postoperative radiation in unfavorable lesion or treatment failure

Subglottis Total laryngectomy and approximate neck surgery to excise the tumor, followed by radiation Unresected cancers •

Induction chemotherapy and radiation followed by neck dissection in chemosensitive tumors, or by laryngectomy and neck dissection in chemoresistant tumors

•

If hypopharyngeal involvement exists: laryngopharyngectomy, neck dissection, and postoperative radiation

DISPOSITION

Supraglottis 5-yr control •

T1 95% to 100%

•

T2 80% to 90%

•

T3 65% to 85%

•

T4 40% to 55%

Glottis 5-yr control •

T1 95% to 100%

•

T2 50% to 85%

•

T3 35% to 85%

•

T4 20% to 65%

EVIDENCE

Expert opinion supports the use of surgery in the management of laryngeal cancer.

Although there have been no definitive studies that compare the primary treatment options for oral cancer, there is a consensus that surgery is effective as a primary treatment of oral cancer.[[1]] Expert opinion supports the use of radiation therapy in the treatment of cancer of the head and neck, including laryngeal cancer. Although there have been few definitive studies that compare the primary treatment options for laryngeal cancer, there is a consensus that radiation therapy is effective as a primary treatment of cancer of the larynx. It is also effective as an adjunctive treatment where surgical resection has been carried out as the primary treatment.[[1]] There is evidence that, in patients at high risk for local recurrence following surgical resection, the use of postoperative radiation therapy significantly improves treatment outcomes. A nonrandomized study compared the effects of secondary surgery alone or with radiotherapy in patients with positive resection margins or evidence of extracapsular spread following primary radical neck resection. The study found that patients receiving the surgery/radiotherapy combination had significantly better rates of locoregional control and survival compared with those patients who were treated with further surgery alone.[[2]] There is evidence that delays in initiating radiation therapy, both as the primary treatment and as an adjunct to surgical resection, has a detrimental effect on locoregional control and survival. A systematic review identified 12 case series that, retrospectively, assessed the relationship between delay in initiating radiation therapy and outcomes in patients with head and neck cancer.[[3]] In one study where radiation was the primary therapy the review found that patients in whom treatment was initiated more than 30 days after diagnosis had significantly higher rates of locoregional failure and significantly poorer 5-year survival than those patients treated within 30 days of diagnosis.[[3]] The same review also assessed the impact of timing of postoperative radiation therapy. It found that delays in initiating postoperative radiotherapy had a detrimental effect on locoregional control and survival. Patients treated with postoperative radiation therapy started 30 days after surgery had significantly poorer rates of locoregional control and 5-year survival compared with those patients where radiation therapy was started earlier.[[3]] There is limited evidence that patients with head and neck cancer who cease smoking during radiation therapy have better rates of response and survival than patients who continue to smoke. One study evaluated the role of cigarette smoking during radiation therapy on the efficacy of treatment in 115 patients with head and neck cancer. The study found that the 53 patients who continued to smoke during treatment had significantly poorer response and 2-year survival compared with those patients who did not smoke or stopped before treatment.[[4]] There is limited evidence that the concomitant use of chemotherapy with surgery/radiation therapy is of benefit in the treatment of head and neck cancer. A metaanalysis study of 69 trials comparing the impact on survival of chemotherapy added to locoregional

treatment found that the use of concomitant chemotherapy had a small but significant overall benefit in survival.[[5]] Two recent randomized controlled trials (RCTs) each compared the use of concomitant cisplatin with postoperative radiotherapy vs. radiotherapy alone following surgical resection of mucosal squamous cell cancer of the head and neck. Both studies found that the use of cisplatin concurrent to postoperative radiotherapy significantly reduced the incidence of locoregional failure. Both RCTs, however, reported that the use of cisplatin was associated with a greater incidence of adverse effects. [18] [19] One RCT also demonstrated that the concomitant use of cisplatin significantly improved 5-year survival rates compared with radiotherapy alone.[[6]] There is evidence that the combined use of chemotherapy with radiation therapy allows preservation of the larynx in patients with advanced carcinoma of the larynx. A randomized controlled trial (RCT) compared induction chemotherapy (cisplatin plus fluorouracil) followed by radiation therapy vs. surgery followed by radiation therapy in 332 patients with stage III/IV laryngeal cancer. Patients initially assigned for nonsurgical treatment were evaluated during the initial treatment phase and those patients in whom there was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy. This study reported that the 2-year survival was similar for both treatment groups (68%) and of the patients initially assigned for laryngeal preservation, by treatment with chemotherapy and radiation therapy, the larynx was preserved in 64% of cases.[[8]] A recent RCT compared induction chemotherapy (cisplatin plus fluorouracil) followed by radiation therapy vs. concomitant chemotherapy (cisplatin plus fluorouracil) plus radiation therapy vs. radiation therapy alone in 547 patients with stage III/IV laryngeal cancer, the surgical treatment for which would require total laryngectomy. In all patients who had either an inadequate response to chemotherapy or tumor recurrence following therapy, laryngectomy was performed. This study found that the use of concomitant chemotherapy (cisplatin plus fluorouracil) with radiation therapy resulted in significantly greater rates of locoregional control and laryngeal preservation than either induction chemotherapy followed by radiation therapy or radiation therapy alone. Survival rates were similar for all three regimens; 2 year (75%); 5 year (55%).[[9]] There is some evidence that the use of conventional analgesia is effective in the treatment of pain associated with cancer of the head and neck. A systematic review found that morphine is effective in the management of moderate to severe cancer pain.[[10]] A systematic review found that single doses of NSAIDs are as equally effective as weak opioids in shortterm symptomatic relief from cancer pain.[[11]] There is some evidence that pilocarpine is effective in the symptomatic management of xerostomia associated with radiation therapy for head and neck cancer. A systematic review found that pilocarpine produced significant improvements in patient symptoms associated with postirradiation xerostomia.[[12]] There is some evidence that topical therapies are effective in the reduction and prevention of oral mucositis in patients undergoing treatment for cancer of the head and neck.

A systematic review found that, of a variety of topical measures, the use of ice chips was most effective in preventing or reducing the severity of mucositis.[[13]] A systematic review of patients undergoing radiation treatment, with or without chemotherapy, for squamous cancers of the head and neck found that there is some benefit from the use of prophylactic topical antibiotics in reducing the clinical severity of mucositis.[[14]] There is limited evidence that the use of retinoic acid is effective in preventing the development of a new second primary tumor of the aerodigestive tract. A randomized controlled trial compared the use of the retinoid, 13-cis-retinoic acid, vs. placebo in 103 patients who were disease free after primary treatment of squamous cell carcinoma of the head and neck. Although no differences were observed in recurrence rates of the original tumor, the use of 13-cis-retinoic acid significantly reduced the incidence of new second primary tumors of the aerodigestive tract compared with placebo.[[15]] However, a recent large randomized controlled trial comparing the vitamin A analogue, retinyl palmitate, vs. placebo in the prevention of new second primaries in patients with head and neck cancer found no significant difference in the incidence of such tumors after 4 years' follow-up.[[16]] Another recent RCT involving 151 patients with primary head and neck cancer compared isotretinoin (at high or moderate doses) vs. placebo over a 3-year period. The study found that there were no significant differences in the incidence of new second primary carcinomas between the treatment groups.[[17]]

Evidence-Based References 1. American Head and Neck Society: Los Angeles, CA. 2. Huang DT, et al: Postoperative radiotherapy in head and neck carcinoma with extracapsular lymph node extension and/or positive resection margins: a comparative study. Int J Radiat Oncol Biol Phys 1992; 23:737. 3. Huang J, et al: Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol 2003; 21:555. 4. Browman GP, et al: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 1993; 328:159. 5. Pignon JP, et al: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. Lancet 2000; 355:949. 6. Bernier J, et al: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350:1945. 7. Cooper JS, et al: Postoperative concurrent radiotherapy and chemotherapy in high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004; 350:1937. 8. The Department of Veterans Affairs Laryngeal Cancer Study Group: Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991; 324:1685. 9. Forastiere AA, et al: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349:2091.

10. Wiffen PJ, et al: Oral morphine for cancer pain. Cochrane Database Syst Rev 2003; 4: 11. Eisenberg E, et al: Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis. J Clin Oncol 1994; 12:2756.Reviewed in: Bandolier: Knowledge Library. 12. Hawthorne M, Sullivan K: Pilocarpine for radiation-induced xerostomia in head and neck cancer. Int J Palliat Nurs 2000; 6:228.Reviewed in: DARE Document 20005206, York, UK. 13. Clarkson JE, Worthington HV, Eden OB: Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 2003; 3: 14. Sutherland SE, Browman GP: Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a proposed classification scheme of interventions and meta-analysis of randomized controlled trials. Int J Radiat Oncol Biol Phys 2001; 49:917. 15. Hong WK, et al: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 1990; 323:795. 16. van Zandwijk N, et al: EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the European Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000; 92:977. 17. Perry CF, et al: Chemoprevention of head and neck cancer with retinoids: a negative result. Arch Otolaryngol Head Neck Surg 2005; 131:198.

AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Laryngitis

BASIC INFORMATION DEFINITION

Laryngitis is an acute or chronic inflammation of the laryngeal mucous membranes. SYNONYMS

Lower respiratory tract infection

ICD-9CM CODES

464.0 Acute laryngitis 476.0 Chronic laryngitis EPIDEMIOLOGY & DEMOGRAPHICS

Common illness in both genders and all age groups, but the diagnosis is imprecise and therefore, statistics are

not readily available with respect to incidence and prevalence. PHYSICAL FINDINGS AND CLINICAL PRESENTATION

ACUTE LARYNGITIS: •

Clinical syndrome characterized by the onset of hoarseness, voice breaks, or episodes of aphonia. May also have accompanying sore throat, cough, nasal congestion, and rhinorrhea

•

Usually associated with viral upper respiratory infection

•

Larynx with diffuse erythema, edema, and vascular engorgement of the vocal folds, and occasionally mucosal ulceration

•

In young children subglottis is often affected, resulting in airway narrowing with marked hoarseness, inspiratory stridor, dyspnea, and restlessness

•

Respiratory compromise rare in adults

CHRONIC LARYNGITIS: Characterized by hoarseness or dysphonia persisting for longer than 2 wk ETIOLOGY

ACUTE LARYNGITIS: •

Most often caused by viruses so treatment consists of supportive measures as outlined in nonpharmacologic therapy section.

•

Studies evaluating the use of antibiotics (erythromycin, penicillin) in acute laryngitis failed to show objective clinical benefit over placebo so they are not routinely recommended. Antibiotics and other antimicrobials may be indicated in cases where specific treatable pathogens are identified.

•

Avoid decongestants secondary to their drying effect.

•

Guaifenesin may be a useful adjunct as a mucolytic agent.

•

In GERD-associated laryngitis use acid-suppressive therapy (H2 blockers, proton pump inhibitors) and nocturnal antireflux precautions.

CHRONIC LARYNGITIS: •

Results from any of the following: tuberculosis, usually through bronchogenic spread; leprosy, from nasopharyngeal or oropharyngeal spread; syphilis, in secondary and tertiary stages; rhinoscleroma, extending from the nose and nasopharynx; actinomycosis; histoplasmosis; blastomycosis; paracoccidiomycosis; coccidiosis; candidiasis; aspergillosis; sporotrichosis; rhinosporidiosis; parasitic infections including leishmaniasis and Clinostomum infection following raw fresh-water fish ingestion

•

Noninfectious causes of both acute and chronic laryngitis include malignancy, voice abuse (singers), gastroesophageal reflux disease, and chemical or environmental irritants such as cigarettes and allergens. Other causes of inflammatory or granulomatous lesions of the larynx include relapsing polychondritis, Wegener's granulomatosis, and sarcoidosis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Young children with signs of airway obstruction:

•

Supraglottitis (epiglottitis)

•

Laryngotracheobronchitis

•

Tracheitis

•

Foreign body aspiration

Adults with persistent hoarseness consider noninfectious causes of laryngitis as listed previously WORKUP

•

History and physical examination: diagnosis is usually apparent.

•

Laryngoscopy for severe or persistent cases.

•

Laryngeal cultures should be performed if etiology other than acute viral infection is suspected.

•

Imaging not indicated unless evidence of airway compromise. Obtain plain radiographs of neck, anteroposterior and lateral views, to differentiate laryngitis from acute laryngotracheobronchitis or supraglottitis.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Rest the voice.

•

Use an air humidifier.

•

Adequate hydration. Avoid alcohol and caffeine because of diuretic effect.

ACUTE GENERAL Rx

•

Antibiotics and other antimicrobials: indicated only when a specific pathogen is isolated; commonly employed antibacterial agents are macrolides (clarithromycin 500 mg by mouth BID for 5 to 7 days or azithromycin 500 mg followed by 250 mg once daily for 4 to 5 days if the cause of laryngitis is found to be Mycoplasma pneumoniae or Chlamydiophila pneumoniae [the new name for what was formerly known as Chlamydia pneumoniae])

•

Avoid decongestants secondary to their drying effect

•

Guaifenesin may be a useful adjunct as a mucolytic agent

•

In GERD-associated laryngitis use acid-suppressive therapy (H2 blockers, proton pump inhibitors) and nocturnal antireflux precautions

DISPOSITION

Uncomplicated laryngitis is usually benign, with gradual resolution of symptoms REFERRAL

If symptoms persist for >2 wk, refer to otolaryngologist for laryngoscopy Consider referral to gastroenterologist if GERD is suspected

PEARLS & CONSIDERATIONS

•

Most cases of uncomplicated acute laryngitis are viral in origin, and bacterial agents should not be routinely administered.

•

A recent Cochrane analysis found no evidence for the use of empiric antibiotics in adults with laryngitis.

•

The most difficult clinical challenge is often convincing patients with acute laryngitis that they do not need and will not benefit from antibacterial agents.

SUGGESTED READINGS Ebell MH: Antibiotics for acute laryngitis in adults. Am Fam Phys 2005; 72:76. Mehanna HM, et al: Fungal laryngitis in immunocompetent patients. J Laryngol Otol 2004; 118(5):379. Reveiz L, Cardona AF, Ospina EG: Antibiotics for acute laryngitis in adults. Cochrane Database Syst Rev 2005;CD004783

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Laryngotracheobronchitis GLENN G. FORT, M.D., M.P.H, DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Acute laryngotracheobronchitis is a viral infection of the upper and lower respiratory tract leading to erythema and edema of the tracheal walls and narrowing of the subglottic region. SYNONYMS

Croup

ICD-9CM CODES

464.4 Croup EPIDEMIOLOGY & DEMOGRAPHICS

•

Croup is primarily a disease of children occurring between the ages of 1 and 6 yr.

•

The peak incidence of croup is the second year of life (50 cases/1000 children).

•

Most cases usually occur in the fall and represent parainfluenza type 1 viral infection.

•

Winter outbreaks usually represent infection by influenza A and B viruses.

•

Croup accounts for 10% to 15% of lower respiratory tract infections in young children.

•

Boys are affected more often than girls.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most children with croup present with symptoms of an upper respiratory infection for several days

•

Rhinorrhea

•

Cough

•

Low-grade fever

•

Barking cough that usually occurs at night and wakes the child up

•

Sore throat

•

Stridor

•

Apprehension

•

Use of accessory muscles of respiration

•

Tachypnea

•

Tachycardia

•

Wheezing

ETIOLOGY

•

Parainfluenza viruses (types 1, 2, and 3) are the most common causes of croup in the U.S.

•

Influenza A and B, although not a common cause of croup, does lead to more severe cases of the disease

•

Adenovirus

•

Respiratory syncytial virus

•

Mycoplasma pneumoniae (rare)

DIAGNOSIS The diagnosis of croup is usually based on the characteristic clinical presentation of a young child between the ages of 1 to 6 yr waking up with a barking cough (“seal's bark”) and stridor. DIFFERENTIAL DIAGNOSIS

•

Spasmodic croup

•

Epiglottitis

•

Bacterial tracheitis

•

Angioneurotic edema

•

Diphtheria

•

Peritonsillar abscess

•

Retropharyngeal abscess

•

Smoke inhalation

•

Foreign body

WORKUP

•

The workup of a child with croup is to differentiate viral laryngotracheobronchitis from noninfectious causes of stridor and epiglottitis caused by H. influenzae.

•

The clinical presentation and plain films of the soft tissues of the neck assist in differentiating viral from nonviral and noninfectious causes.

LABORATORY TESTS

•

Laboratory tests are not often used to make the diagnosis of viral tracheobronchitis.

•

CBC, viral serology, and tissue cultures can be ordered and may detect the infecting agent in up to 65% of cases.

•

Pulse oximetry and arterial blood gas determination for patients with tachypnea and respiratory distress.

IMAGING STUDIES

•

Plain (AP and lateral) films of the soft tissues of the neck may show the classic radiographic finding of subglottic stenosis or “steeple” sign.

•

CT scan of the soft tissues of the neck may be performed in the cases where the differential between croup, epiglottitis, and noninfectious is more difficult.

•

Direct visualization via laryngoscopy may be useful in some situations under a controlled setting.

TREATMENT Treatment of croup focuses on airway management. NONPHARMACOLOGIC THERAPY

•

Oxygen

•

Cool mist

•

Hot steam

ACUTE GENERAL Rx

•

Use of 0.25 to 0.75 ml of 2.25% racemic epinephrine every 20 min is used in children with severe respiratory symptoms, rest stridor, and impending intubation.

•

Corticosteroids (e.g., dexamethasone 0.6 mg/kg IV or PO, prednisone 2 mg/kg/day) have been shown to be effective.

•

Budesonide, a nebulized corticosteroid given at 4 mg, has been shown to improve symptoms in patients with moderate to severe croup.

DISPOSITION

•

Croup is usually benign and self-limited, resolving within 3 to 4 days.

•

Complications include: 1.

Airway obstruction

2.

Otitis media

3.

Pneumonia

4.

Dehydration

REFERRAL

If intubation is needed (rarely), an emergency consultation with ENT and/or anesthesiology is recommended.

PEARLS & CONSIDERATIONS COMMENTS

•

Most patients with croup can be managed at home (e.g., patients without stridor and in no respiratory distress).

•

Hospitalization and observation is required for children with moderate-to-severe croup (e.g., rest stridor, respiratory distress refractory to the above mentioned acute treatments).

EVIDENCE

Dexamethasone, budesonide, and inhaled epinephrine are effective in the management of croup in pediatric assessment units. Improvement in symptoms and reduction in hospital admissions have been noted in RCTs. [33] [34] Systemic dexamethasone and inhaled budesonide have similar efficacy in terms of symptom resolution rate and reattendance after discharge.[[1]] Although humidification has been used for decades in the inpatient and outpatient treatment of croup, there is little evidence to support its use.

Evidence-Based References 1. Osmond M: Croup. Reviewed, 6. London: BMJ Publishing Group; 2001:268. 2. Russell K, et al: Glucocorticoids for croup (Cochrane Review), Chichester, UK, John Wiley, 2004. Reviewed in: 2,

SUGGESTED READINGS Knutson D, Aring A: Viral croup. Am Fam Physician 2004; 69:535. Reveiz L, Cardona AF, Ospina EG: Antibiotics for acute laryngitis in adults. Cochrane Database Syst Rev 2005; 1:CD004783

Roe M, O'Donnell DR, Tasker RC: Acute laryngotracheobronchitis. Paediatr Respir Rev 2003; 4(3):267.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Lead Poisoning FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Lead poisoning refers to multisystem abnormalities resulting from excessive lead exposure. SYNONYMS

Plumbism

ICD-9CM CODES

984.0 Lead poisoning EPIDEMIOLOGY & DEMOGRAPHICS

•

Lead poisoning is most common in children ages 1 to 5 yr (17,000 cases/100,000 persons). The highest rates are among blacks, those with low income, and urban children.

•

In 1991 the Centers for Disease Control and Prevention (CDC) lowered the definition of a safe blood lead level to 15% of preschoolers in the U.S. have a blood lead level >15 µg/dl.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Findings vary with the degree of toxicity. Examination may be normal in patients with mild toxicity.

•

Myalgias, irritability, headache, and general fatigue may be present initially.

•

Abdominal cramping, constipation, weight loss, tremor, paresthesias and peripheral neuritis, seizures, and coma may occur with severe toxicity.

•

Motor neuropathy is common in children with lead poisoning; learning disorders are also frequent.

ETIOLOGY

Chronic repeated exposure to paint containing lead, plumbing, storage of batteries, pottery, lead soldering

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Polyneuropathies from other sources

•

Anxiety disorder, attention deficit disorder

•

Malabsorption, acute abdomen

•

Iron deficiency anemia

WORKUP

Laboratory screening: all U.S. children should be considered to be at risk for lead poisoning and should be screened routinely starting at 1 yr of age for low-risk children and 6 mo of age for high-risk ones. LABORATORY TESTS

•

Venous blood lead level: normal level: 70 µg/dl: associated with severe poisoning

•

Mild anemia with basophilic stippling on peripheral smear

•

Elevated zinc protoporphyrin levels or free erythrocyte protoporphyrin level

•

An increased body burden of lead with previous high-level exposure in patients with occupational lead poisoning can be demonstrated by measuring the excretion of lead in urine after premedication with calcium EDTA or another chelating agent

IMAGING STUDIES

•

Imaging studies are generally not necessary.

•

A plain abdominal film can visualize lead particles in the gut.

•

“Lead lines” may be noted on x-ray films of long bones.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Provide adequate amounts of calcium, iron, zinc, and protein in patient's diet

•

Family education on sources of lead exposure and potential adverse health effects

ACUTE GENERAL Rx

•

For children with blood levels of 10 to 19 µg/dl the CDC recommends nonpharmacologic interventions (see “Nonpharmacologic Therapy”).

•

For children with blood levels between 20-44 µg/dl the CDC recommendations include case management by a qualified social worker, clinical management, environmental assessment, and lead hazard control. Chelation therapy should be considered in children with refractory blood lead levels.

Chelation therapy is indicated in children with blood lead levels 45 µg/dl:

•

Succimer (DMSA) 10 mg/kg PO q8h for 5 days then q12h for 2 wk can be used in patients with levels between 45 and 70 µg/dl.

•

Edetate calcium disodium (EDTA) and dimercaprol (BAL) are effective in patients with severe toxicity.

•

Use of both EDTA and DMSA is indicated in children with blood levels >70 µg/dl.

•

d-Penicillamine (Cuprimine) can also be used for lead poisoning, but it is not FDA approved for this condition.

CHRONIC Rx

•

Reduce exposure, remove any potential lead sources.

•

Correct iron deficiency and any other nutritional deficiencies.

•

Recheck blood lead level 7 to 21 days after chelation therapy.

DISPOSITION

Patients with mild to moderate toxicity generally improve without any residual deficits. The presence of encephalopathy at diagnosis is a poor prognostic sign. Residual neurologic deficits may persist in these patients. Chelation therapy seems to slow the progression of renal insufficiency in patients with mildly elevated body lead burden. REFERRAL

If exposure to lead is work related, it should be reported to the Office of the United States Occupational Safety and Health Administration (OSHA). Follow-up testing is mandatory in all patients following an abnormal screening blood lead level.

PEARLS & CONSIDERATIONS COMMENTS

•

Even blood lead concentrations 120 mo, whereas for RAI stage 4 or Binet stage C it is approximately 30 mo). Overall 5-yr survival is 60%. Measurement of ZAP-70 intracellular protein (where available) is also a useful indicator of prognosis. SUGGESTED READINGS Nowakowski GS, et al: Using smudge cells on routine blood smears to predict clinical outcome in chronic lymphocytic leukemia: a universally available prognostic test. Mayo Clin Proc 2007; 82(4):449. Yee K, O'Brien SM: Chronic lymphocytic leukemia: diagnosis and treatment. Mayo Clin Proc 2006; 81(8):1105.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Leukemia, Chronic Myelogenous FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Chronic myelogenous leukemia (CML) is a malignant clonal stem disease caused by an acquired somatic mutation that fuses, through chromosomal translocation, the ABL and BCR genes on chromosomes 9 and 22 and is characterized by abnormal proliferation and accumulation of immature granulocytes. CML manifests with a chronic phase (CP-CML) lasting months to years, followed by an advanced phase (AP-CML) characterized by poor response to therapy, worsening anemia, or decreased platelet count; the second phase then evolves into a terminal phase (acute transformation) that degenerates into acute leukemia (mostly myeloid and approximately 20% lymphoid subtype), characterized by elevated number of blast cells and numerous complications (e.g., sepsis, bleeding). SYNONYMS

CML Chronic granulocytic leukemia Chronic myeloid leukemia

ICD-9CM CODES

201.1 Chronic myelogenous leukemia EPIDEMIOLOGY & DEMOGRAPHICS

•

CML usually affects elderly patients (median age at presentation is 65 yr) and accounts for 15% of adult leukemias

•

Incidence is 1 to 2 cases per 100,000 people every year.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The chronic phase usually reveals splenomegaly; hepatomegaly is not infrequent, but lymphadenopathy is very unusual and generally indicates the accelerated proliferative phase of the disease.

•

Common complaints at the time of diagnosis are weakness or discomfort secondary to an enlarged spleen (abdominal discomfort or pain). Splenomegaly is present in up to 40% of patients at time of diagnosis.

•

40% of patients are asymptomatic and diagnosis is based solely on an abnormal blood count.

ETIOLOGY

Current evidence strongly implicates the chromosome translocation t (9;22) (q34;q11.2) as the cause of chronic granulocytic leukemia. This translocation is present in >95% of patients. The remaining patients have a complex or variant translocation involving additional chromosomes that have the same end result (fusion of the BCR [break point cluster region] gene on chromosome 22 to ABL [Ableson leukemia virus] gene on chromosome 9).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Splenic lymphoma

•

CLL

•

Myelodysplastic syndrome

LABORATORY TESTS

•

Elevated WBC count (generally >100,000/mm3) with broad spectrum of granulocytic forms.

•

Bone marrow demonstrates hypercellularity with granulocytic hyperplasia, increased ratio of myeloid cells to erythroid cells, and increased number of megakaryocytes. Blasts and promyelocytes constitute 95% of patients with CML; its presence (Ph1) is a major prognostic factor because survival rate of patients with Philadelphia chromosome is approximately eight times better than that of those without it. Some believe that Ph+ defines CML and that those who are Ph- have another disease.

•

Leukocyte alkaline phosphatase (LAP) markedly decreased (used to distinguish CML from other myeloproliferative disorders).

•

Anemia and thrombocytosis are often present.

•

Additional laboratory results are elevated vitamin B12 levels (caused by increased transcobalamin 1 from granulocytes) and elevated blood histamine levels (because of increased basophils).

IMAGING STUDIES

Chest x-ray and CT scan of abdomen/pelvis

TREATMENT ACUTE GENERAL Rx

Treatment with a potential to either cure CML or prolong survival should be used during the chronic phase of the disease because it is often futile when administered during the advanced phase. Imatinib mesylate (Gleevec), an oral tyrosine kinase inhibitor, is effective and indicated as first-line treatment for CML myeloid blast crisis, accelerated phase, or CML in its chronic phase. More than 75% of patients have major cytogenetic response (90% of cases) secondary to tumor cell infiltration

•

Pallor, ecchymosis, and evidence of infection if the pancytopenia is severe

•

Weakness, lethargy, and fatigue

•

Infections (resulting from impaired resistance secondary to neutropenia) and easy bruising (secondary to thrombocytopenia) also common

ETIOLOGY

Neoplastic disease of the lymphoreticular system of unknown etiology

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other forms of leukemia

•

Lymphoma

•

Viral syndrome

WORKUP

Comprehensive history, physical examination, and laboratory evaluation to confirm the diagnosis LABORATORY TESTS

•

Pancytopenia involving erythrocytes, neutrophils, and platelets is common; anemia is usually present and varies from minimal to severe.

•

Hairy cells ( Fig. 1-146 ) can account for 5% to 80% of cells in the peripheral blood. The cytoplasmic projections on the cells are redundant plasma membranes.

•

Leukemic cells stain positively for tartrate-resistant acid phosphatase (TRAP) stain.

•

Bone marrow may result in a “dry tap” (because of increased marrow reticulin).

FIGURE 1-146 Hairy cell leukemia. Note the lymphocytes with hairlike cytoplasmic projections surrounding the nucleus. (From Rodak BF: Diagnostic hematology, Philadelphia, 1995, WB Saunders.)

TREATMENT NONPHARMACOLOGIC THERAPY

Approximately 8% to 10% of patients are asymptomatic and have minimal splenomegaly and minor cytopenia. They are usually detected on routine laboratory evaluation and do not require initial therapy. They should, however, be frequently monitored for progression of their disease. ACUTE GENERAL Rx

•

Drugs of choice are the purine analogues 2-Chloro-2 deoxyadenosine (Cladribine) or 2-deoxycoformycin (DCF, Pentostatin). They induce complete remissions in up to 85% of patients and partial responses in 5% to 25%.

•

2-Chloro-2 deoxyadenosine (CdA) 0.14 mg/kg qd for 7 days has minimal toxicity and is able to induce complete durable responses with a single course of therapy.

•

Interferon-a produces a partial remission in 30% to 70% of patients and complete remission, often of short duration, in 5% to 10% of patients.

•

The anti-CD 22 recombinant immunotoxin BL 22 can induce complete remission in patients with hairy cell leukemia that is resistant to treatment with purine analogues.

CHRONIC Rx

Patients should be monitored with periodic examination and laboratory tests for progression of their disease. DISPOSITION

Prognosis has become increasingly favorable with the newer agents. Approximately 90% of patients who are treated have a complete or partial response. REFERRAL

Hematology consultation is recommended in all patients.

PEARLS & CONSIDERATIONS COMMENTS

The diagnosis of hairy cell leukemia is occasionally missed and subsequently made by the histopathologist following removal of the spleen for diagnostic purposes.

EVIDENCE

We are unable to cite evidence that meets our criteria for some therapies, and there is only limited evidence for some other therapies. Initial therapies of choice are cladribine or pentostatin. In a randomized controlled trial to compare pentostatin vs. interferon alpha-2a in previously untreated patients with hairy cell leukemia, 121 of 154 patients treated with pentostatin achieved confirmed complete or partial remission, compared with 60 of 159 who received interferon alpha-2a. Response rates were significantly higher and relapse-free survival was significantly longer with pentostatin than interferon.[[1]]

Evidence-Based References 1. Grever M, et al: Randomized comparison of pentostatin versus interferon alpha in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol 1995; 13:974.

SUGGESTED READINGS Kreitman RJ, et al: Efficacy of the anti-CD 22 recombinant immunotoxin BL 22 in chemotherapy resistant hairycell leukemia. N Engl J Med 2001; 345:241.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Leukoplakia, Oral Hairy SAJEEV HANDA, M.D.

BASIC INFORMATION DEFINITION

Oral hairy leukoplakia (OHL) is a painless, white, nonremovable, plaquelike lesion typically located on the lateral aspect of the tongue.

ICD-9CM CODES

528.6 Oral hairy leukoplakia EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE AND PREVALENCE: EBV seroprevalence occurs in high incidence in individuals who are HIV seropositive. However, OHL occurs in only 25% of these cases. RISK FACTORS: OHL is usually found in human immunodeficiency virus (HIV) seropositive individuals (median CD4 count is 468/µl) but may also be identified in other immunocompromised patients such as transplant recipients (particularly renal) and patients taking steroids. Diagnosing OHL is an indication to institute a workup to evaluate and manage HIV disease. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Varying morphology and appearance

•

May be unilateral or bilateral

•

White and can be small with fine vertical corrugations on the lateral margin of the tongue ( Fig. 1-147 )

•

Irregular surface; may have prominent folds or projection, occasionally markedly resembling hairs

•

May spread to cover the entire dorsal surface or spread onto the ventral surface of the tongue where they usually appear flat

•

Rarely lesions manifest on the soft palate, buccal mucosa, and in the posterior oropharynx

•

Usually asymptomatic, but some have mouth pain, soreness, or a burning sensation, impaired taste, or difficulty eating; others complain of its unsightly appearance

•

OHL may progress to oral squamous cell carcinoma, which has a poor prognosis

FIGURE 1-147 Oral hairy leukoplakia. Note white verrucoid plaques on the lateral border of the tongue. (From Noble J: Primary care medicine, ed 3, St Louis, 2001, Mosby.)

ETIOLOGY

Epstein-Barr virus (EBV) is implicated in its etiology, and OHL is a result of replication EBV in the epithelium of keratinized cells. OHL differs from most EBV-related diseases in that infection is predominantly lytic rather than latent.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Candida albicans

•

Lichen planus

•

Idiopathic leukoplakia

•

White sponge nevus

•

Dysplasia

•

Squamous cell carcinoma

WORKUP

Requires physical examination and evaluation of HIV disease

LABORATORY TESTS

The provisional diagnosis is clinical and based on: •

Visual inspection

•

Inability to scrape the lesion off the tongue with a blade

•

Failure to respond to antifungal therapy

The presumptive diagnosis requires biopsy and histologic demonstration of: •

Epithelial hyperplasia with hairs

•

Absence of inflammatory cell infiltrate

The definitive diagnosis requires: •

In situ hybridization of histologic or cytologic specimens revealing EBV DNA or

•

Electron microscopy of specimens revealing herpes-like particles

•

Measurement of the DNA content in cells of oral leukoplakia may be used to predict the risk of oral carcinoma

note: Specimens obtained from lesions may demonstrate hyphae of Candida albicans, which may coexist and potentiate EBV-induced OHL.

TREATMENT NONPHARMACOLOGIC THERAPY

OHL is usually asymptomatic and requires no specific therapy. It may resolve spontaneously and has no known premalignant potential. ACUTE GENERAL Rx

Highly active antiretroviral (HAART) therapy has considerably changed the frequency of oral lesions caused by opportunistic infections in HIV-seropositive individuals. •

Topical retinoids (0.1% vitamin A) may improve the appearance of OHL-affected oral surfaces through their dekeratinizing and immunomodulation effects; however, they are expensive and prolonged use may result in a burning sensation over the treated area.

•

Topical podophyllin resin 25% solution has been reported to induce resolution.

•

Surgical excision and cryotherapy may help, but the lesions may recur.

•

High-dose acyclovir 800 mg 5 × day, valacyclovir 1000 mg tid, famciclovir 500 mg tid, ganciclovir 1000 mg tid, or foscarnet 40 mg/kg IV tid will cause lesions to resolve but only temporarily.

PEARLS & CONSIDERATIONS

•

Oral hairy leukoplakia is a nonmalignant lesion seen in patients with AIDS.

•

Incidence has decreased significantly in the era of highly active antiretroviral therapy.

SUGGESTED READINGS Sudbo J, et al: DNA content as a prognostic marker in patients with oral leukoplakia. N Engl J

Med 2001; 344:1270.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Lichen Planus TANYA ALI, M.D.

BASIC INFORMATION DEFINITION

Lichen planus refers to a papular skin eruption characteristically found over the flexor surfaces of the extremities, genitalia, and mucous membranes. SYNONYMS

Lichen Lichen planus et atrophicus

ICD-9CM CODES

697.0 Lichen planus EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 1 in every 100 new patients seen in dermatology clinics in the U.S. is diagnosed with lichen planus PREVALENCE: 440/100,000 PREDOMINANT SEX: Found equally between males and females (1:1) PREDOMINANT AGE: Usually found in people between the ages of 30 to 60 PREDISPOSING FACTORS: 1.

Associated with other autoimmune disorders (e.g., primary biliary cirrhosis, myasthenia gravis, ulcerative colitis, and diabetes)

2.

Associated with hepatitis C infection

3.

Drug-induced form affects any area of the body surface (e.g., beta-blocker, methyldopa, penicillamine, Quinidine, NSAIDS, ACE-I, sulfonylurea agents)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

History

•

Usually starts on an extremity and may remain localized or it can spread to involve other areas over a 1- to 4-mo time period.

•

Pruritic

Physical findings •

Anatomic distribution: 1.

Flexor surface of wrists, forearms, shins, and upper thighs

2.

Neck and back area

3.

Nails

4.

Scalp (lichen planopilaris)

5.

Oral mucosa, buccal mucosa, tongue, gingiva, and lips

6.

Vulva, penis

Genital mucosa •

•

•

•

Lesion configuration: 1.

Linear

2.

Annular (more common)

3.

Reticular pattern noted on oral mucosa and genital area

Lesion morphology: 1.

Papules (flat, smooth and shiny)—most common presentation

2.

Hypertrophic

3.

Follicular

4.

Vesicular

Color: 1.

Dark red, bluish red, purplish-violaceous color is noted in cutaneous lichen planus

2.

Individual lesions characteristically have white lines visible (Wickham's striae)

3.

Oral and genital lichen planus have a reticular network of white lines that may be raised or annular in appearance

Scalp lesions may result in alopecia.

ETIOLOGY

The cause of lichen planus is unknown.

DIAGNOSIS

•

Clinical history and physical findings usually establish the diagnosis of lichen planus.

•

Skin biopsy (deep shave or punch biopsy of the most developed lesion) can be done to confirm the diagnosis.

DIFFERENTIAL DIAGNOSIS

Drug eruption, psoriasis, Bowen's disease, leukoplakia, candidiasis, lupus rash, secondary syphilis, seborrheic

dermatitis, chronic graft vs. host disease WORKUP

If the diagnosis is questionable, a skin biopsy is performed. LABORATORY TESTS

Laboratory tests are not specific for the diagnosis of lichen planus. IMAGING STUDIES

Imaging studies are not helpful in diagnosing lichen planus.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoid scratching.

•

Use mild soaps and emollients after bathing to prevent dryness.

ACUTE GENERAL Rx

For cutaneous lichen planus •

Topical steroids (e.g., triamcinolone acetonide 0.1%, fluocinonide 0.05%, clobetasol propionate 0.05% cream or ointment) with occlusion used twice daily

•

Acitretin 30 mg/day PO for 8 wk

•

Systemic prednisone 30 to 60 mg/day as a starting dose and tapered to 15 to 20 mg/day maintenance for 6 wk

•

Intradermal steroid triamcinolone acetonide 5 mg/ml can be tried for thick hyperkeratotic lesions

•

Hydroxyzine 25 mg PO q6h can be used for pruritus

For oral lichen planus •

Topical steroid fluocinonide in an adhesive base used six times/day for 9 wk

•

Topical calcineurin in steroid unresponsive cases

•

Topical or systemic retinoids 0.1% retinoic acid in an adhesive base or gel

•

Etretinate 75 mg/day for 2 mo

CHRONIC Rx

Refer to acute general treatment DISPOSITION

•

Spontaneous remissions of cutaneous lichen planus occur in over 65% of cases within the first year.

•

Spontaneous remission of oral lichen planus usually occurs by 5 yr.w

•

Approximately 10% to 20% of patients will have recurrence.

REFERRAL

Dermatology

PEARLS & CONSIDERATIONS COMMENTS

•

Lichen planus can be remembered as purple, planar, pruritic, polygonal, papules, and plaques (Ps).

•

Lesions can develop at the site of prior skin injury (Koebner's phenomenon).

•

Although transformation to skin cancer has been seen in patients with lichen planus, it remains unclear if there is a true correlation.

EVIDENCE

There are small controlled trials on the use of oral acitretin vs. placebo in cutaneous lichen planus.[[1]] There is a Cochrane review on interventions for treating oral lichen planus. This concludes that there is weak evidence for the superiority of any of the assessed interventions over placebo for palliation of symptomatic oral lichen planus.[[2]] Trials have demonstrated the efficacy of topical tacrolimus in oral disease.[ 3 , 4 ]

Evidence-Based References 1. Laurberg G, et al: Treatment of lichen planus with acitretin. A double blind placebo controlled study in 65 patients. J Am Acad Dermatol 1991; 24:434. 2. Kaliakatsou F, et al: Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus. J Am Acad Dermatol 2002; 46:35. 3. Dissemond J, et al: Pimecrolimus in an adhesive ointment as a new treatment option for oral lichen planus. Br J Dermatol 2004; 150:782. 4. Swift JC, et al: The effectiveness of 1% pimecrolimus cream in the treatment of oral erosive lichen planus. J Periodontol 2005; 76:627.

SUGGESTED READINGS Chan ES, Thornhill M, Zakrzewska J: Interventions for treating oral lichen planus. Cochrane Database Syst Rev 2000; 2:CD001168

Katta R: Lichen planus. Am Fam Physician 2000; 61(11):3319.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Lichen Sclerosus GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Chronic inflammatory condition of the skin usually affecting the vulva, perianal area, and groin

ICD-9CM CODES

701.0 Lichen sclerosus EPIDEMIOLOGY & DEMOGRAPHICS

•

Most common in postmenopausal women and men between ages 40 and 60 yr

•

More common in females

•

Can occur in children (usually prepubertal girls with involvement of the vulva and perineum)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Erythema may be the only initial sign. A characteristic finding is the presence of ivory-white atrophic lesions on the involved area.

•

Close inspection of the affected area will reveal the presence of white-to-brown follicular plugs on the surface (dells).

•

When the genitals are involved, the white parchmentlike skin assumes an hourglass configuration around the introital and perianal area (“keyhole” distribution, Fig. 1-148 ). Inflammation, subepithelial hemorrhages, and chronic ulceration may develop.

•

Dyspareunia, genital bleeding, and anal bleeding are common.

FIGURE 1-148 Lichen sclerosus. Perianal area is thinned and chalk white (keyhole distribution). (Courtesy Department of Dermatology, University of North Carolina at Chapel Hill. From Goldstein BG, Goldstein AO: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

ETIOLOGY

Unknown. There may be an autoimmune association and a genetic familial component.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Localized scleroderma (morphea)

•

Cutaneous discoid lupus erythematosus

•

Atrophic lichen planus

•

Psoriasis

WORKUP

Diagnosis is based on close examination of the lesions for the presence of ivory-white atrophic lesions and typical location. LABORATORY TESTS

Punch or deep shave biopsy can be used to confirm the diagnosis when in doubt.

TREATMENT NONPHARMACOLOGIC THERAPY

Attention to hygiene and elimination of irritants or excessive bathing with harsh soaps GENERAL Rx

•

Application of clobetasol propionate 0.05% topically bid for up to 4 wk is usually effective. Repeat courses of corticosteroids may be necessary because of the chronic nature of this disorder. Continual application of topical steroids may lead to atrophy of the vulva.

•

Use of topical testosterone (2%) has been found to be less effective than topical corticosteroids.

•

Lubricants (e.g., Nutraplus cream) are useful to soothe dry tissues.

•

Hydroxyzine 25 mg at hs is effective in decreasing nocturnal itching.

•

Use of intralesional steroids, etretinate, and surgical management are usually reserved for refractory cases.

DISPOSITION

•

The disease persists in approximately one third of patients.

•

Most prepubertal girls improve spontaneously at menarche.

•

Squamous cell carcinoma can develop within the lesions in 3% to 10% of older patients; therefore, periodic examination and biopsy of suspicious areas are indicated.

PEARLS & CONSIDERATIONS COMMENTS

•

Prepubertal lichen sclerosus may be confused with sexual abuse in prepubertal girls and may lead to false accusations and investigations.

•

Lichen sclerosus of the vulva (kraurosis vulvae) usually occurs after menopause and is generally chronic. It can be painful and interfere with sexual activity.

•

Lichen sclerosus of the penis (balanitis xerotica obliterans) is seen more commonly in uncircumcised males. It affects the glans and prepuce and may lead to stricture if it encroaches into the urinary meatus.

AUTHORS: FRED F. FERRI, M.D. Listeriosis

BASIC INFORMATION DEFINITION

Listeriosis is a systemic infection caused by the gram-positive aerobic bacterium Listeria monocytogenes. SYNONYMS

Listerial infection Granulomatosis infantisepticum

ICD-9CM CODES

027.0 Listeriosis 771.2 Congenital listeriosis 771.2 Fetal listeriosis 665.4 Suspected fetal damage affecting management of pregnancy EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Listeria meningitis: about 0.7 cases/100,000 persons (fourth most common cause of community-acquired bacterial meningitis in adults)

•

Perinatal listeriosis: 8.6 cases/100,000 persons

•

Nonperinatal listeriosis: 3 cases/1 million persons

PREDOMINANT SEX: Pregnant women are more susceptible to Listeria bacteremia, accounting for up to one third of reported cases. PREDOMINANT AGE: •

Pregnant women

•

Immunocompromised patients of any age

•

Elderly patients are susceptible even in the absence of recognized immunocompromised states

GENETICS: Congenital Infection: •

With transplacental transmission, syndrome termed granulomatosis infantisepticum in neonate

•

Characterized by disseminated abscesses in multiple organs, skin lesions, conjunctivitis

•

Mortality: 33% to 100%

Neonatal Infection: •

Infant becoming ill after 3 days of age; mother invariably asymptomatic

•

Clinical picture of sepsis of unknown origin

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

•

Infections in pregnancy 1.

More common in third trimester

2.

Usually present with fever and chills without localizing symptoms or signs of infection

Meningoencephalitis 1.

More common in neonates and immunocompromised patients, but up to 30% of adults have no underlying condition

2.

In neonates: poor appetite with or without fever possibly the only presenting signs

3.

In adults: presentation often subacute, with low-grade fever and personality change as only signs

4.

Focal neurologic signs seen without demonstrable brain abscess on CT scan

Cerebritis/rhombencephalitis: 1.

Headache and fever may be only presenting complaints

2.

Progressive cranial nerve palsies, hemiparesis, seizures, depressed level of consciousness, cerebellar signs, respiratory insufficiency may also be seen

Focal infections 1.

Ocular infections (purulent conjunctivitis) and skin lesions (granulomatosis infantisepticum) as a result of inadvertent inoculation by laboratory and veterinary personnel

2.

Others: arthritis, prosthetic joint infections, peritonitis, osteomyelitis, organ abscesses, cholecystitis

ETIOLOGY

•

Direct invasion of skin and eye has been documented, but mechanism of GI entry is unclear.

•

Organism's intracellular life cycle explanatory of: 1.

Importance of cell-mediated immunity in host defense

2.

Increased infection in neonates, pregnant women, and immunocompromised hosts

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Meningitis caused by other bacteria, mycobacteria, or fungi

•

CNS sarcoidosis

•

Brain neoplasm or abscess

•

Tuberculous and fungal (especially cryptococcal) meningitis

•

Cerebral toxoplasmosis

•

Lyme disease

•

Sarcoidosis

WORKUP

Dictated by age, end-organ involvement, and immune status LABORATORY TESTS

•

Cultures of blood and other appropriate body fluids

•

Variable CSF findings, but neutrophils usually predominate

•

Organisms uncommonly seen on Gram stain and may be difficult to identify morphologically

•

Monoclonal antibodies, polymerase chain reaction, and DNA probe techniques to detect Listeria in foods

IMAGING STUDIES

•

If focal cerebral involvement suspected: CT scan or MRI

•

MRI most sensitive for evaluation of brainstem and cerebellum

TREATMENT Empiric therapy should be administered when diagnosis is suspected because overall mortality is 23%. ACUTE GENERAL Rx

•

Drugs of choice: 1.

IV ampicillin 8 to 12 g/day in divided doses

2.

IV penicillin 12 to 24 million U/day in divided doses

•

Continuation of therapy for 2 wk

•

Alternative (if penicillin allergic): trimethoprim/sulfamethoxazole or vancomycin

•

Gentamicin added to provide synergy in meningitis or endocarditis

CHRONIC Rx

Relapses reported, especially in immunocompromised hosts, after 2 wk of therapy DISPOSITION

Long-term follow-up of immunodeficiency state REFERRAL

Infectious disease consultation for all patients

PEARLS & CONSIDERATIONS COMMENTS

•

Foodborne cases have been linked to various products: coleslaw, soft cheeses, unpasteurized milk and milk products, vegetables, undercooked chicken, hot dogs, luncheon meats, refrigerated smoked seafood, etc.

•

Complete decontamination of food products is difficult because Listeria is resistant to pasteurization and refrigeration.

SUGGESTED READINGS Gottlieb SL, et al: Multistate outbreak of Listeriosis linked to turkey deli meat and subsequent changes in US regulatory policy. Clin Infect Dis 2006; 42(1):29. Mylonakis E, et al: Listeriosis during pregnancy: a case series and review of 222 cases. Medicine 2002; 81:260. Pasche B, et al: Sex-dependent susceptibility to Listeria monocytogenes infection is mediated by differential Interleukin-10 production. Infect Immun 2005; 73(9):5952. Saunders BD, et al: Molecular epidemiology and cluster analysis of human Listeriosis cases in three U.S. states. J Food Prot 2006; 69(7):1680. Schlech WF, et al: Does sporadic listeria gastroenteritis exist? A 2-year population-based survey in Nova Scotia, Canada. Clin Infect Dis 2005; 41(6):778.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Long QT Syndrome FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Long QT syndrome is an electrocardiographic abnormality characterized by a corrected QT interval longer than 0.44 sec and associated with an increased risk of developing life-threatening ventricular arrhythmias. SYNONYMS

QT interval prolongation Congenital forms: •

Jervell and Lange-Nielsen syndrome (associated with deafness)

•

Romano-Ward syndrome (associated with normal hearing)

Sporadic forms of long QT syndrome (nonfamilial)

ICD-9CM CODES

427.9 Unspecified cardiac dysrhythmia EPIDEMIOLOGY & DEMOGRAPHICS

•

Familial associated with deafness: autosomal recessive.

•

Familial associated with normal hearing: autosomal dominant (the incidence is unknown). Although inheritance of long QT syndrome is autosomal dominant, female predominance has often been observed and has been attributed to an increased susceptibility to cardiac arrhythmias in women.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Syncope caused by ventricular tachycardia

•

Sudden death

•

Abnormal ECG (prolonged QT) in asymptomatic relatives of known case. Bazett formula; QTc5QT/vRR. Calculated QTc should be 500 ms in female with LQT3 or L QTc 30% of cancer deaths in males and >25% of cancer deaths in females. It has been the most common cancer in the world since 1985 and is the leading cause of cancer-related death.

•

Tobacco smoking is implicated in 85% of cases; second-hand smoke is responsible for approximately 20% of cases.

•

There are >180,000 new cases of lung cancer yearly in the U.S., most occurring >age 50 yr (30% or in pregnant woman and in elderly with severe malaria

MULTIDRUG-RESISTANT MALARIA: •

Mefloquine 1250 mg as a single dose, or

•

Halofantrine 500 mg every 6 hr for 3 doses, repeat same course after 1 wk

•

Combination therapy usually preferred

DISPOSITION

RISK FACTORs FOR FATAL MALARIA: •

Failure to take chemoprophylaxis

•

Delay in seeking medical care

•

Misdiagnosis

COMPLICATIONS OF MALARIA:

•

Anemia

•

Acidosis

•

Hypoglycemia

•

Respiratory distress

•

DIC

•

Blackwater fever

•

Renal failure

•

Shock

REFERRAL

•

To an infectious disease specialist or travel medicine expert for severe malaria complications

•

To an intensive care specialist if severe cerebral malaria or other major organ failure develops

PEARLS & CONSIDERATIONS HOST RESPONSE: •

The specific immune response to malaria confers protection from high-level parasitemia and disease, but not from infection

•

Asymptomatic parasitemia without illness (premunition) is common among adults in endemic area

•

Immunity is specific for both the species and the strain of infecting malarial parasites

•

Immunity to all strains is never achieved

•

Normal spleen function is an important host factor because of immunologic as well as filtering functions of the spleen

•

Both humoral and cellular immunity are necessary for protection

•

Polyclonal increase in serum level of IgG, IgM, and IgA occur in immune individuals

•

Antibody to antigenically variant protein PfEMP1 is important for protection in case of P. falciparum malaria

•

Passively transferred IgG from immune individual has been shown protective

•

Maternal antibody confers relative protection of infants from severe disease

•

Genetic disorders (sickle cell disease, thalassemia, and G6PD deficiency) confer protection from death because parasites are unable to grow efficiently in low-oxygen tensions, thus preventing high-level parasitemias

•

Individuals deficient of Duffy factor in RBC are resistant to infection by P. vivax

•

Nonspecific defense mechanisms, cytokines (TNF-a, IL-1, 6, 8) also play an important role in protection; it causes fever (temperatures of 40° C damage mature parasites) and other pathologic effects

PREVENTION OF MALARIA: Prophylaxis should be taken 1 wk before travel, continue weekly for the duration of stay and for 4 wk after leaving endemic area NON-FALCIPARUM MALARIA: Chloroquine 300 mg base (500 mg chloroquine phosphate) PO/wk

FALCIPARUM MALARIA: •

Mefloquine 250 mg (228 mg base) PO/wk, or

•

Doxycycline 100 mg PO/day, or

•

Primaquine 0.5 mg base/kg/day, or

•

Chloroquine (300 mg base) plus proguanil (200 mg) PO/day

SPECIAL CONSIDERATIONs: •

Long-term visitors or travelers

•

Children M1)

* a, Without ulceration; b, with ulceration † a, Micrometastasis; b, macrometastases; c, intransit metastases with metastatic lymph nodes

LABORATORY TESTS

The pathology report should indicate the following: •

Tumor thickness (Breslow microstage).

•

Tumor depth (Clark level): The depth of invasion is the most important histologic prognostic parameter in evaluating the primary tumor.

•

Mitotic rate: tabulated as mitosi per mm2 in the dermal part of the tumor in which most mitoses are identified.

•

Radial growth rates vs. vertical growth rate: Radial growth phase describes the growth of melanoma within the epidermis and along the dermal-epidermal junction.

•

Tumor infiltrating lymphocytes: They have a strong predictive value in vertical growth phase melanomas and are defined as brisk, nonbrisk, and absent.

•

Histologic regression: characterized by the absence of melanoma in the epidermis and dermis flanked on one or both sides by melanoma.

•

Reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosine messenger RNA is a useful marker for the presence of melanoma cells. It is performed on sentinel lymph node biopsy and is useful for detection of submicroscopic metastases.

TREATMENT

•

Initial excision of the melanoma

•

Reexcision of the involved area after histologic diagnosis:

•

1.

The margins of reexcision depend on the thickness of the tumor.

2.

Low-risk or intermediate-risk tumors require excision of 1 to 3 cm.

3.

Melanomas of moderate thickness (0.9 to 2.0 mm) can be excised safely with 2-cm margins.

4.

A 1-cm margin of excision for melanoma with a poor prognosis (as defined by a tumor thickness of at least 2 mm) is associated with a significantly greater risk of regional recurrence than is a 3cm margin, but with a similar overall survival rate.

Lymph node dissection: recommended in all patients with enlarged lymph nodes. Lymph node evaluation is important in patients with melanoma 1 mm in depth because it determines the overall prognosis and need for therapeutic lymph node dissection or adjuvant treatment. 1.

Elective lymph node dissection remains controversial.

2.

It is indicated with positive sentinel node. It may be considered in those with a primary melanoma that is between 1 and 4 mm thick (especially in patients 60 yr

•

There are currently more than 8 million persons in the U.S. who are at risk for mesothelioma because of prior asbestos exposure

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Dyspnea

•

Nonpleuritic chest pain

•

Fever, weight loss, sweats, fatigue, loss of appetite

•

Dysphagia, superior vena cava syndrome, Horner's syndrome in advanced stages

•

Auscultation may reveal unilateral loss of breath sounds

•

Dullness on percussion may be present

ETIOLOGY

•

Asbestos exposure

•

Other reported potentially causal factors include prior radiation therapy and extravasated thorotrast, zeolite, and erionite fibers

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Metastatic adenocarcinomas (from lung, breast, ovary, kidney, stomach, prostate) WORKUP

•

Staging evaluation includes complete history (including occupational history), physical examination, and testing to determine potential operability (CT, bone scan, PFTs)

•

Thoracoscopy, pleuroscopy, and open lung biopsy are useful in obtaining adequate tissue samples for diagnosis

•

Pulmonary function tests

•

Staging: the UICC staging uses the TNM categories to organize mesothelioma in stages I to IV in a manner similar to that used for non–small cell lung cancer

LABORATORY TESTS

•

Diagnostic thoracentesis is generally insufficient for diagnosis because pleural effusions may only reveal atypical mesothelial cells

•

Immunohistochemistry is useful to distinguish adenocarcinoma from epithelial malignant mesothelioma (mesotheliomas are generally CEA negative and cytokeratin positive)

•

Thrombocytosis and anemia may be found on initial lab evaluation

•

Serum osteopontin levels (where available) can be used to distinguish persons with exposure to asbestos who do not have cancer from those with exposure to asbestos who have pleural mesothelioma

IMAGING STUDIES

•

Chest radiographs may reveal pleural plaques or calcifications in the diaphragm

•

CT scan of the chest/abdomen and bone scan are used to assess the extent of disease

TREATMENT GENERAL Rx

•

Operable patient (epithelial type, no positive nodes, confined to pleura, adequate PFTs): the two surgical techniques for therapeutic intervention are decortication (pleurectomy) and extrapleural pneumonectomy. Postoperative chemotherapy with cisplatin, doxorubicin, and cyclophosphamide and subsequent external beam radiation are used in some centers with limited success.

•

Inoperable patient (disease too extensive, sarcomatous or mixed histology type, poor PFTs): supportive care plus/minus radiation therapy for symptoms or supportive care plus chemotherapy. Combined modality therapies (surgery, radiation therapy, chemotherapy, and biologics) have also been used to reduce both local and distant recurrences. The combination of pemetrexed (an antimetabolite that inhibits enzymes involved in folate metabolism) and cisplatin is used for chemotherapy of unresectable malignant pleural mesothelioma.

•

Intrapleural instillation of cisplatin or biologics (e.g., interferons, interleukin-2) is generally limited to very early disease because it can only penetrate a very limited depth of the tumor and there is a propensity of the pleural space to become progressively obliterated with advancing disease.

•

The role of radiation therapy in the treatment of mesotheliomas remains uncertain. It is often used for palliation of local pain despite lack of trials to prove its utility.

•

Obliteration of the pleural space (pleurodesis) with instillation of tetracycline, bleomycin, or biologic substances such as C. parvum into the pleural cavity is often tried in attempting to treat recurrent symptomatic pleural effusions.

DISPOSITION

Median survival for patients undergoing pleurectomy ranges from 6.7 to 21 mo, for extrapleural pneumonectomy 4 to 21 mo. Survival is better for patients with epithelial form.

PEARLS & CONSIDERATIONS COMMENTS

•

Patients with early disease should be referred to treatment centers specializing in mesothelioma treatment before attempts are made to obliterate the pleural space with pleurodesis.

•

An approach to the evaluation and treatment of mesothelioma is described in Section III.

SUGGESTED READINGS Pass H, et al: Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med 2005; 353:1564. Robinson B, Lake R: Advances in malignant mesothelioma. N Engl J Med 2005; 353:1591.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Metabolic Syndrome GEETHA GOPALAKRISHNAN, M.D.

BASIC INFORMATION DEFINITION

Guidelines define the metabolic syndrome as the presence of any three of the following: •

Abdominal waist circumference >102 cm (40 inches) in men and >88 cm (35 inches) in women

•

Serum hypertriglyceridemia =150 mg/dl (1.7 mmol/L) or drug treatment for elevated triglycerides

•

Serum high-density lipoprotein (HDL) cholesterol 102 cm (40 inches) in men and >88 cm (35 inches) in women Triglycerides: =150 mg/dl (1.7 mmol/L) HDL: 35 kg/m 2 and comorbidities (hypertension, impaired glucose tolerance, diabetes mellitus, dyslipidemia, sleep apnea) are also potential surgical candidates.

ACUTE GENERAL Rx

•

Treat obesity (see “Obesity”) Pharmacologic treatment: consider sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion in individuals who have failed diet and exercise if BMI >30 kg/m2 or a BMI of 27 to 30 kg/m2 with comorbid conditions.

•

Treat hypertension (see “Hypertension”) Systolic blood pressures >130/80: consider angiotensin converting-enzyme inhibitors, angiotensin II receptor blocker, or thiazide-type diuretics as first line.

•

Treat hyperlipidemia Serum LDL cholesterol of 55 mm and fractional shortening 4 hr before antiemetic effect is required.

•

Over-the-counter oral preparations (e.g., Dramamine) are less effective.

•

Meclizine (Antivert) 12.5 to 25 mg q6h may be effective.

CHRONIC Rx

•

Rarely chronic

•

Symptoms generally resolve completely with cessation of motion exposure

DISPOSITION

Follow-up is not needed. REFERRAL

If another diagnosis is suspected (e.g., purulent ear, fever, cranial nerve abnormalities)

PEARLS & CONSIDERATIONS

COMMENTS

•

Many patients with migraine report having severe motion sickness as a child.

•

Improved ventilation, avoidance of large meals before travel, semirecumbent sitting, and avoidance of reading while in motion will minimize the risk of motion sickness.

EVIDENCE

A systematic review concluded that scopolamine was more effective than placebo in the prevention of motion sickness but no conclusions could be drawn from the comparative studies with other agents such as antihistamines and calcium channel antagonists.[[1]] Limited evidence suggests that dimenhydrinate and cyclizine are equally effective in preventing motion sickness, but cyclizine is associated with less drowsiness and lower gastrointestinal symptom scores.[[2]]

Ginger may be effective in preventing seasickness, but evidence is still limited by the size of the trials.[[3]]

Evidence-Based References 1. Spinks AB, et al: Scopolamine for preventing and treating motion sickness. Reviewed. Cochrane Library, 3, Chichester, UK, John Wiley, 2004. 2. Weinstein SE, Stern RM: Comparison of Marezine and Dramamine in preventing symptoms of motion sickness. Aviat Space Environ Med 1997; 68:890. 3. Ernst E, Pittler MH: Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth 2000; 84:367.Reviewed in: Does ginger prevent nausea and vomiting? Bandolier: Knowledge Library.

SUGGESTED READINGS Koch KL: Illusory self-motion and motion sickness: a model for brain-gut interacting and nausea. Dig Dis Sc 1999; 48(8 Suppl):53S. Yates BJ, Miller AD, Lacot JB: Physiological basis and pharmacology of motion sickness: an update. Brain Res Bull 1998; 45(5):395.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Mucormycosis FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Mucormycosis is a fungal infection by Zygomycetes fungi, which include Mucorales spp. (Mucor, Rhizopus, Absidia, Cunninghamella, Mortierella, Saksenaea, Syncephalastrum, Apophysomyces, and Thamnidium) and Entomophthorales spp. (Conidiobolus and Basidiobolus).

ICD-9CM CODES

117.7 Mucormycosis EPIDEMIOLOGY & DEMOGRAPHICS

•

Infection by these ubiquitous organisms occurs in association with underlying conditions including diabetes mellitus, lymphoma, severe burns or trauma, prolonged postoperative course, multiple myeloma, hepatitis, cirrhosis, renal failure, steroid treatment, immunodeficiency states (e.g., AIDS), and use of contaminated Elastoplast bandages. Immunocompetent hosts may become infected in tropical climates.

•

Most commonly the fungus gains entry to the body through the respiratory tract. The spores are deposited in the nasal turbinates and may be inhaled into the pulmonary alveoli. In cases of cutaneous mucormycosis, the spores are introduced directly into the skin lesion.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Rhinocerebral-rhinoorbital-paranasal syndrome may present with fever, facial and orbital pain, headache, diplopia, loss of vision, facial or orbital cellulitis, facial anesthesia, cranial nerve dysfunction, black nasal discharge, epistaxis, and seizure. Physical findings in this situation include proptosis, chemosis, nasal, palatal or pharyngeal necrotic ulcerations, and retinal infarction. Thrombosis of the cavernous sinus or internal carotid artery may occur. This form of mucormycosis is found most commonly in diabetics, primarily in the presence of acidosis, and in patients with leukemia and neutropenia.

•

Pulmonary mucormycosis can present with pneumonia, lung abscess, pulmonary infarction, pleurisy, pleural effusion, hemoptysis, chills, and fever. This form of mucormycosis is found most commonly in immunocompromised neutropenic hosts following chemotherapy for hematologic malignancies.

•

Gastrointestinal zygomycosis presents with abdominal pain, diarrhea, GI hemorrhage, ulcers, peritonitis, and bowel infarction. This form of mucormycosis is found most commonly in patients with extreme malnutrition and is believed to arise from ingestion of the fungi.

•

Cutaneous zygomycosis presents as nodular lesions (hematogenous seeding) or a wound infection. It involves primarily the epidermis and dermis following use of occlusive dressings that have not been properly sterilized.

•

Cardiac mucormycosis is a form of endocarditis.

•

Septic arthritis and osteomyelitis.

•

Brain abscess occurs most often from extension of the fungus from the nose or paranasal sinuses through adjacent bones in severely debilitated patients.

•

Disseminated zygomycosis (rare but uniformly fatal).

•

Physical findings depend on the location of the infection.

ETIOLOGY & PATHOGENESIS

The cause of mucormycosis is infection by a fungus of the Zygomycetes class (see “Definition”). Normal host defenses include leukocytes and pulmonary macrophages. Quantitative (e.g., neutropenia) or qualitative (e.g., diabetes mellitus or steroid treatment) disruption in the host defenses predisposes the patient to infection.

DIAGNOSIS The hallmark of mucormycosis is vascular invasion and tissue necrosis. Black eschars and discharges should be closely evaluated. Diagnosis depends on the demonstration of the organism in the tissue of a biopsy specimen. DIFFERENTIAL DIAGNOSIS

•

Infection of the sites described previously by other organisms (bacterial [including TB and leprosy], viral, fungal, or protozoan)

•

Noninfectious tissue necrosis (e.g., neoplasia, vasculitis, degenerative) of the sites described previously

WORKUP

•

Biopsy of infected tissue with direct light microscopy examination establishes the diagnosis within minutes of the biopsy in the case of nasopharyngeal infection. Typically the fungi appear as broad (10 to 20 micrometers in diameter) nonseptate hyphae with branches occurring at right angles.

•

Bronchoalveolar lavage or bronchoscopy with biopsy for smear, culture, and histologic examination.

•

X-rays and other imaging studies of symptomatic sites may be required before infection is suspected and tissue specimens are obtained.

TREATMENT Aggressive correction of underlying disease (e.g., hyperglycemia, academia, high steroid doses, use of immunosuppressive drugs) should be undertaken. Standard therapy for invasive mucormycosis is treatment with amphotericin B given IV at a daily dose of 1.0 to 1.5 mg/kg infused over 2 to 4 hr for a total of 1 to 4 g. Adverse reactions may be managed as follows: •

Fever, chills, headache, myalgias, nausea, and vomiting: premedicate with aspirin (650 mg po), acetaminophen (650 mg po), diphenhydramine (25 to 50 mg IV), hydrocortisone (25 to 100 mg IV), or meperidine (25 to 50 mg IV).

•

Hypokalemia and hypomagnesemia are treated with potassium and magnesium replacement.

•

Nephrotoxicity and renal tubular acidosis can be mitigated to some extent with 500 ml of normal saline infusion 30 min before and after each dose of amphotericin. Amphotericin dose reduction may also be necessary.

•

Renal function and electrolytes should be monitored twice a week during the entire course of amphotericin.

•

Lipid preparations of amphotericin B may be less toxic (i.e., amphotericin B lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B).

•

The role of flucytosine, rifampin, and tetracycline is controversial.

•

Surgical debridement or radical resection.

•

The role of colony-stimulating factors remains unclear, beyond that of increasing the neutrophil count in patients with neutropenia.

PROGNOSIS

•

Sinus infection with no underlying disease: 75% survival.

•

Sinus infection with diabetes: 60% survival.

•

Sinus infection with renal disease: 25% survival.

•

Surgery may increase survival by 5% to 20%.

•

Early diagnosis improves survival as well as control of the underlying condition.

SUGGESTED READINGS Larsen K, et al: Unexpected expansive paranasal sinus mucormycosis. J Otorhinolaryngol Relat Spec 2003; 65:57-60. Paydas S, et al: Mucormycosis of the tongue in a patient with acute lymphoblastic leukemia: a possible relation with use of tongue depressor. Am J Med 2003; 114:618-620.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Multifocal Atrial Tachycardia FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Multifocal atrial tachycardia is a supraventricular, moderately rapid arrhythmia (rate 100 to 140 bpm) with P waves having at least three or more different morphologies. SYNONYMS

Chaotic atrial rhythm The term wandering pacemaker is used for a similar arrhythmia associated with a normal or slow heart rate

ICD-9CM CODES

427.89 Multifocal atrial tachycardia EPIDEMIOLOGY & DEMOGRAPHICS

Same as chronic lung disease (obstructive or restrictive), which the arrhythmia may complicate PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms:

•

Palpitation

•

Lightheadedness

•

Syncope

•

Symptoms of the underlying pulmonary disease

•

Physical findings associated with the underlying pulmonary disease

ETIOLOGY

•

Exact mechanism unknown

•

Associated abnormalities include hypoxia, hypercarbia, acidosis, electrolyte disturbances, digitalis toxicity

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Atrial fibrillation

•

Atrial flutter

•

Sinus tachycardia

•

Paroxysmal atrial tachycardia

•

Extrasystoles

WORKUP

•

ECG ( Fig. 1-163 )

•

Pulmonary function tests

•

Electrolytes

•

Arterial blood gases

•

Digoxin level (if patient on digoxin)

FIGURE 1-163 The P waves show variable shapes, variable PR intervals, or both. (From Goldberger AL: Clinical electrocardiography, ed 5, St Louis, 1994, Mosby.)

TREATMENT

•

Improve the pulmonary or metabolic dysfunction if possible

•

Calcium blockers

•

ß-Blockers if not contraindicated by obstructive lung disease

•

If the arrhythmia is asymptomatic, it can be left untreated

AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D.

Multiple Myeloma

BASIC INFORMATION DEFINITION

Multiple myeloma is a malignancy of plasma cells characterized by overproduction of intact monoclonal immunoglobulin or free monoclonal kappa or lambda chains. Diagnostic criteria require the following: 1.

Presence of 10% are immature.

•

Serum beta-2 microglobulin has little diagnostic value; it is useful for prognosis because levels >8 mg/L indi-cate high tumor mass and aggressive disease.

•

Elevated serum levels of LDH at the time of diagnosis define a subgroup of myeloma patients with very poor prognosis.

•

Increased interleukin-6 in serum during active stage of myeloma.

•

The production of DKK1, an inhibitor of osteoblast differentiation, by myeloma cells is associated with the presence of lytic bone lesions in patients with multiple myeloma.

•

Nearly all patients with myeloma present with abnormal chromosomes identified by fluorescence in situ hybridization (FISH). The Mayo Clinic Stratification of Myeloma, for purposes of therapy, identifies high-risk patients (~25% of patients at diagnosis) as those who have any of the following: FISH deletion 17p, FISH translocation 4;14, FISH translocation 14;16, cytogenetic deletion 13q, cytogenetic hypodiploidy, or plasma cell labeling index whites (2:1).

•

Usually found in males 40 to 60 yr of age.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Mycosis fungoides characteristically progresses through three phases: •

A premycotic phase featuring scaly, erythematous patches that can last from months to years. During this stage the diagnosis can only be suspected, because the histopathologic features are not definitive for mycosis fungoides. Lesions are pruritic and can appear anywhere but are usually found in sun-shielded areas. Parapsoriasis en plaques, poikilodermatous parapsoriasis, parapsoriasis lichenoides, and variegata are skin lesions suspicious of representing premycotic cutaneous T-cell lymphoma.

•

The infiltrative plaque phase features raised, indurated erythematous palpable plaques that are pruritic and may be associated with alopecia. Stage IA disease is defined as a patch or plaque skin disease involving 500 cases/100,000 persons.

•

>500,000 MIs in the U.S. yearly.

•

More prominent in males between the ages of 40 and 65 yr; no predominant sex after age 65 yr.

•

Women experience more lethal and severe first acute MIs than men, regardless of comorbidity, previous angina, or age.

•

At least one fourth of all myocardial infections are clinically unrecognized.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Clinical presentation: •

Crushing substernal chest pain usually lasts longer than 30 min.

•

Pain is unrelieved by rest or sublingual nitroglycerin or is rapidly recurring.

•

Pain radiates to the left or right arm, neck, jaw, back, shoulders, or abdomen and is not pleuritic in character.

•

Pain may be associated with dyspnea, diaphoresis, nausea, or vomiting.

•

There is no pain in approximately 20% of infarctions (usually in diabetic or elderly patients).

Physical findings: •

Skin may be diaphoretic, with pallor (because of decreased oxygen).

•

Rales may be present at the bases of lungs (indicative of CHF).

•

Cardiac auscultation may reveal an apical systolic murmur caused by mitral regurgitation secondary to papillary muscle dysfunction; S3 or S 4 may also be present.

•

Physical examination may be completely normal.

ETIOLOGY

•

Coronary atherosclerosis

•

Coronary artery spasm

•

Coronary embolism (caused by infective endocarditis, rheumatic heart disease, intracavitary thrombus)

•

Periarteritis and other coronary artery inflammatory diseases

•

Dissection into coronary arteries (aneurysmal or iatrogenic)

•

Congenital abnormalities of coronary circulation

•

MI with normal coronaries (MINC syndrome): more frequent in younger patients and cocaine addicts. The risk of acute MI is increased by a factor of 24 during the 60 min after the use of cocaine in persons who are otherwise at relatively low risk. Most patients with cocaine-related MI are young, nonwhite, male cigarette smokers without other risk factors for ASHD who have a history of repeated cocaine use. Blood and urine toxicology screen for cocaine is recommended in all young patients who present with acute MI.

•

Hypercoagulable states, increased blood viscosity (polycythemia vera).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

The various causes of myocardial ischemia are described in Section II along with the differential diagnosis of chest pain. LABORATORY TESTS

•

Cardiac troponin levels: cardiac-specific troponin T (cTnT) and cardiac-specific troponin I (cTnl) are generally indicative of myocardial injury. Increases in serum levels of cTnT and cTnI may occur relatively early after muscle damage (3 to 12 hr), peak within 24 hr, and may be present for several days after MI (up to 7 days for cTnI and up to 10 to 14 days for cTnT). Troponin T tests can be falsely positive in patients with renal failure. The threshold level of troponin T considered positive for MI is 0.1 ng/ml in patients with normal renal function or 0.5 ng/ml in patients with renal impairment. Although troponin is a sensitive biomarker to “rule out” NSTMI, it is less useful to “rule in” this event because many other diseases such as sepsis, hypovolemia, atrial fibrillation, CHF, pulmonary embolism, myocarditis, myocardial contusion, and renal failure can be associated with an increase in troponin level.

•

Creatine kinase MB isoenzyme is a useful marker for MI. It is released in the circulation in amounts that correlate with the size of the infarct.

•

Neither CK-MB nor troponin consistently appear in the blood within 6 hr after an ischemic event; therefore serial testing (e.g., on presentation and after 8 hr) is necessary to definitely rule out MI.

•

ECG:

1.

2.

In STEMI, there is development of: a.

Inverted T waves, indicating an area of ischemia.

b.

Elevated ST segment, indicating an area of injury. Significant ST-segment elevation of =0.10 mV measured 0.02 sec after the J point is evident in two contiguous leads. The presence of this finding in leads V1-V6 indicates anterior or anterolateral MI, in leads I and aVL a lateral MI, and its presence in leads II, III, or aVF is diagnostic of inferior wall MI.

c.

Q waves ( Fig. 1-166 ), indicating an area of infarction (usually develop over 12 to 36 hr).

In NSTEMI: a.

History and myocardial enzyme elevations are compatible with MI.

b.

ECG shows no ST-segment elevation and sometimes shows a small depression of the ST segment.

FIGURE 1-166 Evolving interoposterolateral infarction. Note the prominent Q waves in II, III, and aV 1, along with ST elevation and T wave inversion in these leads, as well as V3 through V6. ST depression in I, aV1, V1, and V2 is consistent with a reciprocal change. Relatively tall R waves are also present in V1 and V2. (From Zipes DP, Libby P, Bonow RO, Braunwauld E [eds]: Braunwald's heart disease, ed 7, Philadelphia, 2005, Elsevier.)

IMAGING STUDIES

•

Chest radiography is useful to evaluate for pulmonary congestion and exclude other causes of chest pain.

•

Echocardiography can evaluate wall motion abnormalities and identify mural thrombus or mitral regurgitation, which can occur acutely after MI.

RISK ASSESSMENT

Several risk assessment models are available. The TIMI risk score uses the seven following variables: age =65, at least three conventional risk factors for coronary artery disease, prior coronary stenosis =50%, STsegment deviation on ECG at presentation, =2 anginal events in the preceding 24 hr, use of aspirin in the prior 7 days, and elevated serum cardiac markers.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Limit patient's activity: bed rest for the initial 12 to 24 hr; if the patient remains stable, gradually increase activity.

•

Diet: NPO until stable, then no added salt and a low-cholesterol diet.

•

Patient education to decrease the risk of subsequent cardiac events (proper diet, cessation of smoking, regular exercise) should be initiated when the patient is medically stable.

ACUTE GENERAL Rx

•

Any patient with suspected acute MI should immediately receive the following: 1.

Antiplatelet therapy: aspirin, 160 to 325 mg po unless true aspirin allergy is suspected. If the first dose is chewed, a blood level is achieved more rapidly than if it is swallowed. Clopidogrel 75 mg qd may be substituted if true allergy is present or given in addition to aspirin. Clopidogrel pretreatment in patients with STEMI significantly reduces the incidence of cardiovascular death or ischemic complications both before and after PCI and without a significant increase in major or minor bleeding. For patients taking clopidogrel for whom CABG is planned, the drug should be withheld for at least 5 days unless the urgency of revascularization outweighs the risk of bleeding.

2.

Nitrates: they increase the supply of oxygen by reducing coronary vasospasm and decrease consumption of oxygen by reducing ventricular preload. Sublingual nitroglycerin (0.4 mg) can be administered immediately on suspicion of MI (unless systolic blood pressure is 18 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

DM and PM:

•

Most patients have a subacute onset, over weeks to months.

•

Symmetric proximal muscle weakness involving the neck flexors, shoulder, and pelvic girdles.

•

Difficulty getting up from a chair, climbing stairs, reaching for objects above head, or combing hair.

•

Distal muscle and ocular involvement is uncommon.

•

Sensation and reflexes are preserved.

•

Dysphagia and dysphonia result from pharyngeal muscle involvement.

•

Esophageal dysmotility often occurs in DM.

•

Respiratory failure may be seen from associated pulmonary fibrosis, weakness of respiratory accessory muscles, or a combination of both.

•

Cardiac conduction abnormalities can be seen with DM.

•

Systemic autoimmune disease occurs frequently in PM, and rarely in DM.

•

Skin findings in DM: 1.

Heliotrope rash on the upper eyelids ( Fig. 1-167 )

2.

Erythematous rash on the face (see Fig. 1-167 )

3.

May also involve the back and shoulders (shawl sign), neck and chest (V-shape), knees and elbows

4.

Photosensitivity

5.

Gottron's papules (violaceous papules overlying dorsal interphalangeal or metacarpophalangeal areas, elbow or knee joints; Fig. 1-168 )

6.

Nail cracking, thickening, and irregularity with periungual telangiectasia (see Fig. 1-168 )

7.

Mechanic's hand: fissured, hyperpigmented, scaly, and hyperkeratotic; also associated with increased risk of interstitial lung disease

FIGURE 1-167 The facial rash of juvenile dermatomyositis. There is erythema over the bridge of the nose and malar areas, with violaceous (heliotropic) discoloration of the upper eyelids. (From Behrman RE: Nelson textbook of pediatrics, 3. ed 17, Philadelphia, 2004, WB Saunders.)

FIGURE 1-168 Dermatomyositis (Gottron's papules). Note erythematous papules over joints and periungual telangiectasias. (From Noble J [ed]: Textbook of primary care medicine, ed 2, St Louis, 1996, Mosby.)

ETIOLOGY

•

DM: complex, immune-mediated vasculitic microangiopathy 1.

•

Adaptive immune response via humorally mediated complement attack.

PM: unknown 1.

Cell-mediated immune major histocompatibility-I (MHC-1) process directed against muscle fibers is likely, given biopsy features.

2.

A viral etiology has been proposed secondary to the presence of autoantibodies to histidyl transferase antibody, anti-Jo-1 antibody, and signal recognition particle.

DIAGNOSIS

•

Characteristic pattern of muscle weakness for each type.

•

EMG and nerve conduction studies should be consistent with myopathic features.

•

Laboratory tests listed below.

•

Biopsy is required for diagnosis and should confirm inflammation before treatment is started: myopathic features (variation in fiber size, fiber splitting, fatty replacement of muscle tissue, and increased endomysial connective tissue) should be seen in addition to the following: 1.

DM: perifascicular atrophy, MAC deposition along capillaries

2.

PM: endomysial infiltrates composed of CD8+ T cells and macrophages invading nonnecrotic muscle fibers that express MHC-I antigen.

DIFFERENTIAL DIAGNOSIS

•

Muscular dystrophies

•

Amyloid myoneuropathy

•

Amyotrophic lateral sclerosis (ALS)

•

Myasthenia gravis

•

Lambert-Eaton myasthenic syndrome

•

Drug-induced myopathies (e.g., quinidine, NSAIDs, penicillamine, HMG CoA-reductase inhibitors)

•

Diabetic amyotrophy

•

Guillain-Barré syndrome

•

Hyperthyroidism or hypothyroidism

•

Lichen planus

•

Amyopathic DM (rash without weakness)

•

SLE

•

Contact atopic or seborrheic dermatitis

•

Psoriasis

LABORATORY TESTS

•

Creatine kinase is the most sensitive muscle enzyme test for muscle breakdown and can be elevated as much as 50 times above normal in DM and PM.

•

Aldolase, AST, ALT, alkaline phosphatase, and LDH can be elevated.

•

Anti-Jo-1 antibodies are seen in myositis with associated interstitial lung disease, but are not specific for either DM or PM.

•

Electrolytes, TSH, Ca, and Mg should be requested to exclude other causes of weakness.

•

ECG for cardiac involvement.

IMAGING STUDIES

•

Chest x-ray to rule out pulmonary involvement. If suspicious for pulmonary interstitial disease, a highresolution CT scan of the chest may be helpful.

•

Video fluoroscopy or barium swallow study to look for upper esophageal dysfunction in patients with dysphagia and DM.

TREATMENT Goal: maintain strength, muscle function, and minimize disease/iatrogenic sequelae. NONPHARMACOLOGIC THERAPY

•

Sun-blocking agents with SPF 15 or greater for skin protection in patients with DM.

•

Physical therapy is beneficial for gait training and increasing muscle tone and strength.

•

Occupational therapy to assist with activities of daily living.

•

Speech therapy for dysphagia and swallowing problems.

ACUTE GENERAL Rx

•

Prednisone 1 to 2 mg/kg per day up to 100 mg/day. Continue dose until muscle strength improves or muscle enzymes have returned to normal for 4 wk. Begin taper by 10 mg/mo until 60 mg/day, then taper by 5 mg/mo. Consider every-other-day prednisone treatment at same dose (may decrease side effects).

•

Use intravenous immunoglobulin or cyclophosphamide if patient fails to improve on prednisone, or muscle enzymes begin rising when tapering off prednisone. See “Chronic Rx” for specific dosage.

•

Hydroxychloroquine can be used to treat the cutaneous lesions of DM.

CHRONIC Rx

•

Chronic prednisone therapy may be needed for years, but other immunosuppressive agents should be added early to decrease long-term steroid side effects.

•

Azathioprine 2 to 3 mg/kg per day tapered to 1 mg/kg per day once steroid is tapered to 15 mg/day. Reduce dosage monthly by 25-mg intervals. Maintenance dosage is 50 mg/day.

•

Methotrexate 7.5 to 10 mg po/wk, increased by 2.5 mg/wk to total of 25 mg/wk; consider IM dosing if oral administration ineffective.

•

IVIg 2 g/kg total dose over 2 to 5 days can be used before azathioprine/methotrexate use. If initial improvement seen, repeat if relapse occurs.

•

IV cyclophosphamide 1 g/M2 monthly × 6 is preferred to oral dosing for refractory cases. However, oral dosing of cyclophosphamide is 1 to 3 mg/kg per day po or 2 to 4 mg/kg per day in conjunction with prednisone.

•

Cyclosporin A: initial: 2.0 to 2.5 mg/kg bid; long-term maintenance is lowest effective dose.

•

Mycophenolate mofetil 500 mg po bid, titrate to 1500 mg po bid over 1 to 2 mo.

•

Hydroxychloroquine 200 mg po daily; monitor for visual changes.

DISPOSITION

•

As treatment is initiated, the muscle enzymes should return to normal before symptoms improve.

•

During exacerbations, enzymes may rise first before symptoms appear.

•

Approximately 50% of the patients will go into remission and stop therapy within 5 yr. The remaining will have either active disease requiring ongoing treatment or inactive disease with permanent muscle atrophy and contractures.

•

Poor prognostic indicators include delay in diagnosis, older age, recalcitrant disease, malignancy, interstitial pulmonary fibrosis, dysphagia, leukocytosis, fever, and anorexia.

•

Infection, malignancy, cardiac and pulmonary dysfunction are the most common causes of death.

•

With early treatment, 5- and 8-yr survival rates of 80% and 73%, respectively, have been reported.

REFERRAL

Neurology or rheumatology referral should be made to help establish the diagnosis and implement treatment.

PEARLS & CONSIDERATIONS

•

Do not implement treatment before muscle biopsy.

•

When assessing response to treatment, it is best to follow clinical muscle strength over muscle enzyme tests.

•

The concern of malignancies (ovary, lung, breast, GI) associated with dermatomyositis is legitimate and merits screening in patients older than age 40 at time of diagnosis and every 2 to 3 yr thereafter.

•

There does not appear to be any association between juvenile dermatomyositis and malignancy.

•

Overlap syndrome refers to patients with dermatomyositis who also meet criteria for other connective tissue disorders (e.g., rheumatoid arthritis, scleroderma, SLE).

•

If patient is taking steroids chronically, be sure to monitor for development of: 1.

Diabetes (oral glucose tolerance test)

2.

Osteopenia/osteoporosis (DEXA scan q6 mo)

3.

Cataracts (yearly ophthalmologic appointment)

4.

Hypertension

5.

Psychiatric side effects including depression or psychosis

6.

Poor sleep

7.

Peptic ulcer disease (prescribe H2 antagonist or proton pump inhibitor)

EVIDENCE

Double-blind (DB), randomized (R), placebo-controlled (PC) trial of DM patients suggested intravenous immunoglobulin (IVIg) 2 gm/kg per month for 3 months was beneficial.[[1]] DBRPC trial (PM patients) suggested trend toward benefit with 60 mg of prednisone per day plus azathioprine (2 mg/kg/day) for 3 months.[[2]] DBRPC trial (DM, PM patients) suggested plasma exchange and leukapheresis offer no benefit.[[3]] DBR trial (DM, PM patients) of prednisolone plus either methotrexate 15 mg weekly or azathioprine 2.5 mg/kg/daily showed equivalent efficacy; however, methotrexate was better tolerated.[[4]] Randomized controlled trial (RCT) (DM, PM patients) suggested cyclo-sporin A 3.0 to 3.5 mg/kg/day vs. 7.5-15 mg weekly oral methotrexate showed no difference between groups.[[5]] R, crossover, open label trial (DM, PM patients) of intramuscular methotrexate (50 mg/m2 every 6 hours for 4 doses every 2 weeks for 12 doses) vs. oral methotrexate plus azathioprine (up to 25 mg/week and 150 mg/day) for 6 months showed trend favoring combination therapy.[[6]]

Evidence-Based References 1. Dalakas MC, et al: A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993; 329(b):1993-2000. 2. Bunch TW, et al: Azathioprine with prednisone for polymyositis. Ann Int Med 1980; 92(b):365-369. 3. Miller FW, et al: Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis. N Engl J Med 1992; 326(b):1380-1384. 4. Miller J, et al: Randomised double blind controlled trial of methotrexate and steroids compared with azathioprine and steroids in the treatment of idiopathic inflammatory myopathy. J Neurol Sci 2002; 199(suppl 1):S53. 5. Vencovsky J, et al: Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. Scand J Rheumatol 2000; 29(b):95-102. 6. Villalba L, et al: Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. Arthritis Rheum 1998; 41(b):392-399.

AUTHOR: GREGORY J. ESPER, M.D. Myotonia

BASIC INFORMATION DEFINITION

Myotonia is a type of muscular dystrophy in which relaxation of a muscle after contraction is delayed or prolonged. The most common type of muscular dystrophy with myotonia is myotonic dystrophy, which is

described below. SYNONYMS

Myotonic dystrophy

ICD-9CM CODES

359.2

Myotonic disorders

728.85 Muscle spasm EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 3 to 5 cases/100,000 persons

•

Genetic disorder inherited as an autosomal dominant illness

•

Symptoms usually manifest during adolescence or early adulthood. Cases of infantile myotonic dystrophy have been described.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usual first complaint is distal extremity weakness sometimes associated with muscle stiffness, cramps, or difficulty relaxing the grasp.

•

Weakness spreads to eventually involve all muscle groups. Flexor neck muscle weakness and masseter and temporal wasting are often prominent features, as is dysarthria.

•

Percussion of a muscle produces a slow contraction followed by prolonged relaxation. The “myotonic reflex” is best tested by percussing the thenar muscles and observing a slow flexion followed by slow relaxation of the thumb.

•

As the disease progresses, generalized weakness becomes more pronounced and myotonia becomes less evident.

•

Extramuscular involvement: Mental retardation of variable severity (may be absent) Frontal baldness ( Fig. 1-169 ) Cataracts Diabetes mellitus Hypogonadism Adrenal failure Cardiomyopathy

•

Infantile myotonic dystrophy presents as neonatal extreme hypotonia with “shark mouth” deformity (upper lip forming an inverted V).

FIGURE 1-169 Myotonic dystrophy with typical myopathic facies, frontal balding, and sunken cheeks. (From Dubowitz V: Muscle disorders in childhood, 3. London, 1995, WB Saunders.)

ETIOLOGY & PATHOGENESIS

Genetic disorder encoded on chromosome 19 leading to sustained firing of the muscle membrane, causing prolonged muscle contraction. Myotonic dystrophy 1 (the more common form) is caused by an expanded CTG repeat within the noncoding 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The less common form (myotonic dystrophy 2) is due to an expanded CCTG repeat in the first intron of the zinc finger protein 9 (ZNF9) gene.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Myotonia congenita (Thomsen's disease) May be autosomal dominant or recessive (two distinct varieties) The disease is limited to muscles and causes hypertrophy and stiffness after rest. Muscle function normalizes with exercise. There is no weakness. Symptoms are exacerbated by exposure to cold.

•

Paramyotonia congenita Autosomal dominant disease Weakness and stiffness of facial muscles and distal upper extremities, especially or exclusively on cold exposure

•

Muscular dystrophies

•

Inflammatory myopathies (polymyositis)

•

Metabolic muscle diseases

•

Myasthenic syndromes

•

Motor neuron disease

WORKUP

•

History and physical examination usually sufficient

•

Muscle enzymes usually abnormal (CPK, aldolase, AST)

•

EMG: typical myotonic “dive bomber” bursts

•

Muscle biopsy: type I fiber atrophy, ring fibers, and increased central nucleation

TREATMENT

•

Phenytoin

•

Quinine

•

Quinidine

•

Procainamide

•

Acetazolamide

•

Genetic counseling

•

Assistive devices, orthotics

DISPOSITION

In myotonic dystrophy, death is usually caused by the wasting of skeletal muscle and defects in cardiac function. REFERRAL

To neurologist SUGGESTED READINGS Cooper TA: A reversal of misfortune for myotonic dystrophy. N Engl J Med 2006; 355:17. Kanadia RN, et al: Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse

poly (CUG) model for myotonic dystrophy. Proc Natn Acad Sci USA 2006; 103:11748.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Myxedema Coma FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Myxedema coma is a life-threatening complication of hypothyroidism characterized by profound lethargy or coma and usually accompanied by hypothermia.

ICD-9CM CODES

244.8 Myxedema, pituitary 244.1 Myxedema, primary PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Profound lethargy or coma

•

Hypothermia (rectal temperature 3.5 g/1.73 m3/24 hr.

•

Abnormalities of blood chemistries include serum albumin 40%. Children under the age of 1 yr have a cure rate as high as 90%.

•

Approximately 70% of patients with neuroblastoma have metastases at diagnosis.

•

Age, stage, and molecular abnormalities are important prognostic factors that are also used for riskstratification and for determination of therapy. Children with localized disease and infants 95% in stage I), age >1 year at diagnosis, increased number of N-myc copies, adrenal tumor, chronic 1p deletion.

•

Children with neuroblastoma may be at risk for second malignancies, including renal cell carcinoma.

REFERRAL

Multidisciplinary oncology team with experience in treating cancers of childhood and adolescence.

PEARLS & CONSIDERATIONS

•

Predominantly a tumor of early childhood that originates in the sites where the sympathetic nervous system tissue is present.

•

Most common symptoms due to tumor mass or bone pain from metastases.

•

Children can present with paraneoplastic neurologic symptoms including cerebellar ataxia and opsoclonus/myoclonus.

EVIDENCE

For patients with high-risk neuroblastoma, myoablative chemotherapy with hematopoetic stem-cell transplant is an effective treatment strategy. A large randomized controlled trial evaluated the role of conventional chemotherapy or myoablative therapy with stem-cell transplant. Event free survival was greater in those who received myoablative therapy plus hematopoietic cell transplantation (HCT) (34% vs. 22%). [[1]] In most cases of stage IV, neuroblastoma is a favorable disease with minimal therapy achieving an excellent outcome. Infants 104°F (40°C).

•

Late neuropsychiatric sequelae.

•

Monitor closely for future complications of pharmacologic therapy.

REFERRAL

If patient's condition is critical, patient is preferably treated in a medical/neurologic ICU.

PEARLS & CONSIDERATIONS COMMENTS

Early detection and diagnosis lead to a more favorable outcome. Treatment is a medical emergency.

EVIDENCE

There is no evidence from randomized controlled trials to guide therapy in neuroleptic malignant syndrome. SUGGESTED READINGS Adityanjee Sajatovic M, Munshi KR: Neuropsychiatric sequelae of neuroleptic malignant syndrome. Clin Neuropharmacol 2005; 28:197-204. Chandran GJ, Mikler JR, Keegan DL: Neuroleptic malignant syndrome: case report and discussion. CMAJ 2003; 169:439. Kipps CM, et al: Movement disorder emergencies. Mov Disord 2005; 20:322-334. Sueman VL: Clinical management of neuroleptic malignant syndrome. Psychiatr Q 2001; 72(4):825. Ty EB, Rothner AD: Neuroleptic malignant syndrome in children and adolescents. J Child Neurol 2001; 16(3):157.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Neuropathic Pain GREGORY ESPER, M.D.

BASIC INFORMATION DEFINITION

Neuropathic pain is not a disease. It is a symptom, and at most, a syndrome. It may result from multiple illnesses, and it is not enough to define its presence without searching for its cause. It is defined as the sensation derived from the abnormal discharges of impaired or injured neural structures in either the peripheral or central nervous system. Descriptors include: •

Hyperalgesia: extreme sensitivity to painful stimuli, or reduced threshold to feel pain

•

Hyperesthesia: abnormal acuteness of sensitivity to touch, pain, or other sensory stimuli

•

Allodynia: a nonpainful stimulus is perceived as painful

ICD-9CM CODES

782.0 Numbness, paresthesias 729.1 Myositis/myalgia, not otherwise specified 729.2 Neuralgia, neuritis, or radiculitis, not otherwise specified SYNONYMS

Neuralgia EPIDEMIOLOGY & DEMOGRAPHICS

•

Neuropathic pain affects at least 1.5% of the U.S. population.

•

Demographics vary widely depending on etiology, for example: 1.

Postherpetic neuralgia: affects elderly, and pain seen in almost 100% of cases

2.

AIDS: 33% of patients affected

3.

Diabetes mellitus: 33% affected

4.

Fabry's disease: affects mostly children, pain in almost 90% of patients

PHYSICAL FINDINGS & CLINICAL PRESENATION

History: localize the disease with questions.

•

Type of pain: burning, lancinating, shooting, sharp, hot or cold pain, pins and needles, broken glass, stinging, etc., can occur in any part of the body (e.g., V1 to V3 in trigeminal neuralgia).

•

Identify if symptoms occur along a nerve distribution (i.e., superficial peroneal nerve) or plexus distribution (acute brachial neuritis or lumbosacral plexus in diabetic amyotrophy).

•

Generalized small fiber neuropathy: dysesthesias without numbness common, but many etiologies (e.g., diabetes) cause both small and large fiber dysfunction.

•

Large fiber neuropathy: coexisting numbness or weakness can be seen, usually worse distally than proximally.

•

Nerve root: coexisting neck or low back pain that radiates along a specific dermatome; most common cause is structural compression.

•

Spinal cord symptoms: coexisting spasticity, bowel or bladder involvement, sensory level.

•

Past history of stroke in thalamic distribution.

•

Family history suggests genetic cause.

Examination: see Table 1-31 and Section III, “Neuropathic Pain.”

TABLE 1-31 -- Examination Exam Finding

Localization

Pinprick/temperature loss alone

Small fibers only

Pinprick/temperature loss + vibratory/proprioceptive loss

Small and large fibers

Sensory loss and motor dysfunction worse distally than proximal

Large fiber neuropathy

Sensory loss and motor dysfunction along single nerve distribution

Single nerve

Sensory loss and motor dysfunction along multiple single nerves

Multiple mononeuropathies (i.e., mononeuropathy multiplex)

Motor and sensory loss involving multiple nerves belonging to specific region of brachial or lumbar plexus

Plexopathy

Sensory loss along dermatome with multiple myotomal muscles affected

Nerve root lesion

Asymmetric sensory loss without weakness and pseudoathetosis

Dorsal root ganglion

Vibratory/proprioceptive loss without pinprick/temperature Dorsal column dysfunction (from compressive lesion, loss B12 deficiency, or tabes dorsalis from neurosyphilis) Sensory level with weakness below the level of lesion and Spinal cord lesion long tract signs (spasticity/Babinski's sign) Hemisensory hyperalgesia ETIOLOGY & LABORATORY EVALUATION ( Table 1-32 )

Contralateral thalamus

•

Metabolic—diabetes mellitus; porphyria; Fabry's disease; thiamine deficiency, commonly seen in malnutrition and alcoholism; vitamin B12 deficiency

•

Inflammatory—immune vasculitides (lupus, Sjögren's syndrome, polyarteritis nodosa, etc.), acute inflammatory demyelinating polyneuropathy (also classically presents with ascending weakness or numbness), chronic inflammatory demyelinating polyneuropathy, sarcoid, multiple sclerosis (common cause of trigeminal neuralgia), arachnoiditis

•

Infiltrative—amyloidosis, paraproteinemias (e.g., MGUS)

•

Infectious—postviral (brachial neuritis), HIV/AIDS, HSV, VZV, Lyme disease, leprosy (thickened nerves and skin lesions), syphilis

•

Neoplastic and paraneoplastic—carcinomatous infiltration of nerve/nerve root, anti-Hu

•

Drugs/toxins: determined by his-tory—alcohol; chemotherapeutic agents: paclitaxel, vincristine; isoniazid; met-ronidazole; gold; thallium

TABLE 1-32 -- Clinical Presentation and Laboratory Findings Neuropathy Type Predisposition Examination Findings Idiopathic small fiber PN

Age >50

Strength: normal

EMG/NCS

Laboratory Analysis

Normal

Serum studies: normal

Reflexes: normal

Skin biopsy: abnormal

Pos/Vib: normal

Sudomotor studies: abnormal

Pain/Temp: decreased distally Diabetic PN

Long-standing disease Strength normal to reduced, sensation reduced distally Family history

Abnormal

Inherited PN

Family history

Pes cavus, hammer toes, reduced reflexes, sensation reduced distally

Abnormal

Familial amyloid PN

Family history

Pain/temp loss Reduced reflexes Orthostasis

Abnormal if large Transthyretin genetic fibers affected; study also carpal tunnel syndrome

Pain/temp loss

Abnormal if large SPEP, UPEP, fibers affected; immunofixation also carpal tunnel abnormal syndrome

Acquired amyloid Monoclonal PN gammopathy

Reduced reflexes Orthostasis

Fabry's disease

Age children.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

Inhalation of Nocardia organisms is the most common mode of entry, and pneumonia is the most common presentation, with 75% manifesting with fever, chills, dyspnea, and a productive cough ( Fig. 1-174 ). 1.

Presentation can be acute, subacute, or chronic.

2.

Nocardiosis should be suspected if soft tissue abscesses or CNS tumors or abscesses form in conjunction with the pulmonary infection.

3.

Pulmonary infection may spread into the pericardium, mediastinum, and superior vena cava.

Cutaneous disease usually occurs via direct inoculation of the organism as a result of skin puncture by a thorn or splinter, surgery, IV catheter use, or animal scratches or bites manifesting in: 1.

Cellulitis

2.

Lymphocutaneous nodules appearing along lymphatic sites draining the infected puncture wound

3.

Mycetoma (Madura foot), a chronic deep nodular infection usually involving the hands or feet that can cause skin breakdown, fistula formation, and spread along the fascial planes to infect surrounding skin, subcutaneous tissue, and bone

•

The CNS system is infected in approximately one third of all cases. Brain abscesses is the most common pathologic finding.

•

Dissemination of nocardiosis may infect other tissues and organs including kidney, heart, skin, and bone.

FIGURE 1-174 Right lower lobe Nocardia pneumonia in a renal transplant recipient. (From Gorbach SL: Infectious diseases, ed 2, Philadelphia, 1998, WB Saunders.)

ETIOLOGY

•

•

The most common Nocardia species leading to infection in humans are: 1.

N. asteroides (causing more than 80% of the cases of pulmonary nocardiosis)

2.

N. brasiliensis (most common cause of mycetoma)

3.

N. otitidiscaviarum

N. asteroides has two subgroups 1.

N. farcinica

2.

N. nova

DIAGNOSIS The diagnosis of nocardiosis requires a high index of suspicion in the proper clinical setting and is confirmed by bacteriologic staining and growth of the organism in culture. DIFFERENTIAL DIAGNOSIS

There are no pathognomonic findings separating nocardiosis pneumonia from other infectious etiologies of the lung. Diagnoses presenting in a similar manner and often confused for nocardiosis are: 1.

Tuberculosis

2.

Lung abscess

3.

Lung tumor

4.

Other causes of pneumonia

5.

Actinomycosis

6.

Mycosis

7.

Cellulitis

8.

Coccidioidomycosis

9.

Histoplasmosis

10. Aspergillosis 11. Kaposi's sarcoma WORKUP

All patients with suspected nocardiosis need laboratory identification of the microorganism by obtaining sputum in the case of pneumonia, cultures of the infected skin lesions in mycetoma or lymphocutaneous disease, or the sampling of any purulent material (e.g., brain abscess, lung abscess, and pleural effusion). LABORATORY TESTS

•

Blood tests are not very sensitive in the diagnosis of nocardiosis.

•

Gram stain shows gram-positive beaded filaments with multiple branches ( Fig. 1-175 ).

•

Gomori methenamine silver staining may detect the organism.

•

Nocardia species are acid-fast on a modified Ziehl-Neelsen stain.

•

Nocardia are slow-growing organisms and colony growth in cultures may take up to 2 to 3 wk.

FIGURE 1-175 Nocardia pneumonia. Thin, branching, irregularly staining Gram-positive bacilli course through necrotic pulmonary tissue (Brown-Hopps Gram, ×1000). (From Silverberg SG, Delellis RA, Frable WJ, LiVolsi VA, Wick MR [eds]: Silverberg's principles and practice of surgical pathology and cytopathology, ed 4, Philadelphia, 2006, Churchill Livingstone.)

IMAGING STUDIES

•

Chest x-ray may demonstrate infiltrates, densities, nodules, cavitary masses, or multiple abscesses.

•

CT scan of the brain is indicated in the appropriate clinical setting to exclude CNS brain abscesses.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Supportive therapy with oxygen in patients with pneumonia

•

Chest physiotherapy

•

For any abscess formation, surgical drainage indicated (e.g., skin, lung, or brain)

ACUTE GENERAL Rx

•

There are no prospective randomized trials to date highlighting the most effective treatment of nocardiosis. Nevertheless, sulfonamides are considered the treatment of choice. Sulfadiazine 6 to 10 g is given in 4 to 6 divided oral doses.

•

For cutaneous infection Trimethoprim-sulfamethoxazole (TMX-SMX) (5 mg/kg/day divided in 2 doses)

•

Severe infection—life-threatening pulmonary or disseminated disease, CNS disease, immunocompromised patients—two-drug therapy: TMP-SMX 15 mg/kg/day divided into 4 to 6 doses and amikacin 7.5 mg/kg/IVevery 12 hours. In patients with CNS disease, ceftriaxone 2 g/IV daily is substituted for amikacin.

•

Sulfonamide-resistant disease: any of the following two-drug regimen: amikacin plus one of the following: ampicillin/sulbactam, imipenem, meropenem, ceftriaxone, or cefotaxime.

•

Alternative drug treatment includes: 1.

Imipenem

2.

Third-generation cephalosporin

3.

Minocycline 100 to 200 mg bid

4.

Extended spectrum fluoroquino-lones (moxifloxacin)

5.

Linezolid (use of linezolid >4 wks is associated with hematologic toxicity)

CHRONIC Rx

•

Although the optimal duration of therapy has not been determined, long-term therapy is generally recommended for all infections caused by Nocardia.

•

Patients with cellulitis and lymphocutaneous syndrome are treated for 2 to 4 mo depending on whether there is bone involvement or not.

•

Mycetomas are best treated with antibiotics for 6 to 12 mo but may require surgical drainage.

•

Pulmonary and systemic nocardiosis excluding the CNS is treated for 6 to 12 mo.

•

CNS involvement is treated with drainage and antibiotics for 12 mo.

•

All immunosuppressed patients should receive 12 mo of antibiotic therapy.

DISPOSITION

•

Patients with pulmonary nocardiosis have a mortality rate of 15% to 30%.

•

CNS involvement carries a >40% mortality rate.

•

Isolated skin lesions have a low mortality rate.

REFERRAL

Whenever the diagnosis of nocardiosis is suspected, consultation with infectious disease is indicated. Pulmonary evaluation and assistance may be needed in pulmonary nocardiosis. Neurosurgery consultation is indicated in patients with single or multiple brain abscesses.

PEARLS & CONSIDERATIONS

•

Nocardiosis does not spread from animal to animal.

•

Nocardiosis is not transmitted from person to person.

•

Nocardiosis is distinguished by its ability to disseminate to any organ and its tendency to relapse despite appropriate antibiotic therapy.

COMMENTS

Tuberculosis and nocardiosis may coexist in the same patient. SUGGESTED READINGS Chapman S: Diagnosis and treatment of nocardiosis. UpToDate 2007; 15.2:www.uptodateonline.com Corti ME, Villafane-Fioti MF: Nocardiosis: a review. Int J Infect Dis 2003; 7(4):243. Torres HA, et al: Nocardiosis in cancer patients. Medicine 2002; 81(5):388.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Nonalcoholic Fatty Liver Disease FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Spectrum of diseases based on histiopathologic findings and representing a morphologic rather than a clinical diagnosis. It is liver disease occurring in patients who do not abuse alcohol and manifesting histologically by mononuclear cells and/or polymorphonuclear cells, hepatocyte ballooning, and spotty necrosis. SYNONYMS

•

Nonalcoholic steatohepatitis (NASH)

•

NAFLD

•

Fatty liver hepatitis

•

Diabetes hepatitis

•

Alcohol-like liver disease

•

Laënnec's disease

ICD-9CM CODES

571.8 Fatty liver EPIDEMIOLOGY & DEMOGRAPHICS

•

Nonalcoholic fatty liver disease (NAFLD) affects 10% to 24% of general population

•

Increased prevalence in obese persons (57% to 74%), type 2 diabetes mellitus, and hyperlipidemia (primarily hypertriglyceridemia)

•

Most common cause of abnormal liver test results in adults in the U.S. (accounts for up to 90% of cases of asymptomatic ALT elevations)

•

30 million obese adults have steatosis, 8.6 million may have steatohepatitis

•

There is a 3:1 female-to-male predominance

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most patients are asymptomatic

•

Patients may report a sensation of fullness or discomfort on the right side of the upper abdomen

•

Nonspecific complaints of fatigue or malaise may be reported

•

Hepatomegaly is generally the only positive finding on physical examination

•

Acanthosis nigricans may be found in children

ETIOLOGY

•

Insulin resistance is the most reproducible factor in the development of nonalcoholic fatty liver disease

•

Risk factors are obesity (especially truncal obesity), diabetes mellitus, hyperlipidemia

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Alcohol-induced liver disease (a daily alcohol intake of 20 g in females and 30 g in males [three 12-oz beers or 12 oz of wine] may be enough to cause alcohol-induced liver disease)

•

Viral hepatitis

•

Autoimmune hepatitis

•

Toxin or drug-induced liver disease

WORKUP

Diagnosis is usually suspected on the basis of hepatomegaly, asymptomatic elevations of transaminases, or “fatty liver” on sonogram of abdomen in obese patients with little or no alcohol use. Liver biopsy will confirm diagnosis and provide prognostic information. It should be considered in patients with suspected advanced liver fibrosis (presence of obesity or type 2 diabetes, AST/ALT ratio 1, age 45 yr). LABORATORY TESTS

•

Elevated ALT, AST: AST/ALT ratio is usually $5 to 10 billion to health care in the U.S. PREVALENCE (IN U.S.):2 to 4 million cases/yr PREDOMINANT SEX: •

Overall, approximately equal

•

Elderly women: predominantly nosocomial urinary tract infections

PREDOMINANT AGE: Elderly patients (>60 yr old) at highest risk RISK FACTORS: Patients with the following conditions may develop NI at any age. 1.

ICU

2.

Intubation

3.

Chronic lung disease

4.

Renal disease

5.

Comatose

6.

Chronic urethral or vascular catheterization

7.

Malnutrition

8.

Postoperative state

PEAK INCIDENCE:Varies widely with infection site PHYSICAL FINDINGS & CLINICAL PRESENTATION

Vary with specific NI ETIOLOGY

•

Bacteria

•

Fungi

•

Viruses

DIAGNOSIS MOST COMMON NOSOCOMIAL INFECTIONS: •

Urinary tract infections (40% to 45%)

•

Surgical wound and other soft tissue infections (25% to 30%)

•

Pneumonia (15% to 20%)

•

Bacteremia (5% to 12%)

NOSOCOMIAL URINARY TRACT INFECTIONS:

•

•

•

General associations: 1.

Foley catheters

2.

Inappropriate catheter care (including opening catheter junctions)

3.

Female sex

4.

Absence of systemic antibiotics

Physical findings: 1.

Fever

2.

Dysuria

3.

Leukocytosis

4.

Pyuria

5.

Flank or costovertebral angle tenderness

Usual organisms: 1.

E. coli

2.

Klebsiella

3.

Enterobacter

4.

Pseudomonas

5.

Enterococcus

•

Sepsis in 1% to 3% of nosocomial UTIs

•

Prevention: 1.

Meticulous technique during insertion and daily perineal care

2.

Never open the catheter-collection tubing junction

3.

Obtain all specimens using sterile syringe

4.

Substitute intermittent catheterization for Foley catheters

NOSOCOMIAL BACTEREMIAS: •

General associations: 1.

IV lines

2.

Arterial lines

3.

CVP lines

4.

Phlebitis

5.

Hyperalimentation

•

Fever possibly only presenting sign

•

Exit site of all vascular lines carefully evaluated for:

•

1.

Erythema

2.

Induration

3.

Tenderness

4.

Purulent drainage

Usual organism for device-associated bacteremia

1.

S. aureus (including MRSA)

2.

Staphylococcus epidermidis for long-term IV lines

3.

Enterobacter

4.

Klebsiella

5.

Candida spp.

6.

Pseudomonas aeruginosa may come from a water source or reflect cutaneous bacteria

•

Phlebitis in 1.3 million patients yearly

•

Approximately 10,000 annual deaths from IV sepsis

•

Prevention: 1.

Meticulous sterile technique during IV insertion

2.

Emphasis should be placed on attention to detail, including handwashing, adherence to guidelines for catheter insertion and maintenance, appropriate use of antiseptic solutions such as chlorhexidine or iodine to prepare the skin around the catheter insertion site, and use of sterile technique for central catheter insertion

3.

Modified catheter may reduce risk for endoluminal colonization and catheter-related sepsis in subclavian lines

4.

Decrease use of routine IVs (patients would rather drink)

NOSOCOMIAL PNEUMONIAS: •

More common in ICUs

•

General associations:

•

•

•

1.

Aspiration

2.

Intubation

3.

Altered consciousness

4.

Old age

5.

Chronic lung disease

6.

Postsurgery

7.

Antacids

Signs of pneumonia common among patients on general wards: 1.

Cough

2.

Sputum

3.

Fever

4.

Leukocytosis

5.

New infiltrate on chest x-ray examination

Signs more subtle in ICUs, because many patients have purulent sputum because of chronic intubation 1.

Change in sputum character or volume

2.

Small changes on chest x-ray examination

Usual organisms:

•

1.

Klebsiella

2.

Acinetobacter

3.

Enterobacter

4.

Pseudomonas aeruginosa

5.

S. aureus (including MRSA)

Less common organisms: 1.

Stenotrophomonas spp.

2.

Legionella, Flavobacterium

3.

Respiratory syncytial virus (infants)

4.

Adenovirus

•

1% of hospitalized patients affected

•

Mortality rate high (40%)

•

Prevention: 1.

Meticulous sterile technique during suctioning and handling airway

2.

Do not routinely change ventilator breathing circuits and components more frequently than q48h

3.

Drain respirator tubing without allowing fluid to return to respirator

4.

Handwashing routinely to prevent colonization of patients and transfer of organisms among patients

NOSOCOMIAL SOFT TISSUE INFECTIONS: •

•

•

Associations: 1.

Decubitus ulcers

2.

Surgical wound classification (contaminated or dirty-infected)

3.

Abdominal surgery

4.

Presence of drain

5.

Preoperative length of stay

6.

Duration of surgery >2 hr

7.

Surgeon

8.

Presence of other infection

Physical findings: 1.

Decubitus ulcer with fluctuance at margin or under firm eschar

2.

Erythema extending >2 cm beyond margin of surgical wound

3.

Tenderness

4.

Induration

5.

Erythema

6.

Fluctuance

7.

Purulent drainage

8.

Dehiscence of sutures

Usual organisms:

•

1.

S. aureus (including MRSA)

2.

Enterococcus

3.

Enterobacter

4.

Acinetobacter

5.

E. coli

Prevention: 1.

Careful skin care and frequent, proper positioning of patient to prevent decubitus ulcer

2.

Meticulous sterile surgical technique

3.

Handwashing to decrease colonization when handling postoperative wound

4.

Limit prophylactic antibiotics to 24 hr perioperatively

5.

Double-wrap contaminated dressings (hold in gloved hand and evert gloves over dressings) before disposal

LABORATORY TESTS

•

Appropriate to specific NI and specific patient's condition

•

Cultures generally indicated for proper confirmation of responsible pathogens

•

1.

Urine

2.

Blood

3.

Sputum

4.

Soft tissue infection

Molecular analysis of nosocomial epidemics 1.

Plasmid fingerprinting

2.

Restriction endonuclease digestion (plasmid and genomic DNA)

3.

Peptide analysis by SDS-PAGE

4.

Immunoblotting

5.

Ribosomal (rRNA) typing

6.

DNA probes

7.

Multilocus enzyme electrophoresis

8.

Restriction fragment length polymorphism (RFLP)

9.

Polymerase chain reaction (PCR)

10. Provide confirmation of point-source or common strains and corroboration of hypotheses reached utilizing classic epidemiology IMAGING STUDIES

Rarely needed for diagnosis of NI

TREATMENT ACUTE GENERAL Rx

•

•

Appropriate to etiologic organism: 1.

Antibiotic

2.

Antifungal

3.

Antiviral

Specific therapy determined after careful consideration of resident flora within the microenvironment in which the patient was hospitalized 1.

2.

Empiric therapy a.

Frequently difficult to fashion accurately

b.

Often undesirable, unless the patient's clinical condition requires urgent treatment

Consultation for expert advice regarding antibiotic selection in view of known epidemiologic risks within the hospital a.

Nosocomial infection control nurses

b.

Hospital epidemiologist

•

Avoid unnecessary treatment for organisms that are colonizing but not infecting patients

•

Prevention of spread of communicable diseases often requiring Isolation or Precautions

•

•

1.

Classic Schema (Strict, Respiratory Isolation and Contact [Skin and Wound] Precautions) being replaced by more streamlined Revised Guidelines (Airborne, Droplet, Contact Isolation Precautions)

2.

Less careful response to some diseases (e.g., hemorrhagic fevers) inadvertently induced by removal of strict isolation category

3.

Universal/Standard Precautions and Body Substance Isolation continue within a new Standard Isolation Precautions Guideline

Universal Precautions used for all patients during all contacts with blood, body fluids, or secretions 1.

Gloves

2.

Goggles

3.

Impermeable gowns if aerosol or splash is likely

Consider aggressive isolation to restrict spread of resistant organisms and their plasmids 1.

MRSA

2.

VREF

3.

Highly resistant Gram-negative organisms, including ESBL (extended sprectrum ß-lactamases) Gram-negative rods

DISPOSITION

The infection control service and/or hospital epidemiologist should be notified when infectious complications occur in hospital setting; most, but not all, nosocomial infections are potentially avoidable, and every effort should be taken to minimize the risk of infections associated with health care. REFERRAL

•

To nosocomial infection control nurses

•

To hospital epidemiologist

PEARLS & CONSIDERATIONS COMMENTS

•

Sharps and splash injuries to staff relatively are rare, but nearly all are preventable. 1.

Nurses incur most injuries.

2.

Usual causes:

3.

•

a.

Needle sticks

b.

Scalpel and surgical needle injuries

c.

Blood splashes

Prevention: a.

Never recap needles

b.

Needle disposal only in rigid, impermeable plastic containers

c.

Clearly announce instrument passes in operating room or during procedures and use passing trays

d.

Use needleless systems for vascular access and connectors whenever possible to limit health care workers' use of sharp medical devices

e.

Gloves, masks, and goggles if aerosol or splash is likely

f.

Never leave needles or other sharp items in beds

g.

Never dispose of sharp items in regular trash bags

4.

Infection control staff should be consulted immediately after exposure to determine need for prophylaxis for hepatitis B or HIV.

5.

All staff should be immune to hepatitis B (natural or vaccine).

Fungi previously considered to be contaminants now risks for patients with cancer and organ transplantation 1.

Candida spp. a.

C. guilliermondii

b.

C. krusei

c.

C. parapsilosis

d.

C. tropicalis

2.

Aspergillus spp.

3.

Curvularia spp.

4.

Bipolaris spp.

5.

Exserohilum spp.

6.

Alternaria spp.

7.

Fusarium spp.

8.

Scopulariopsis spp.

9.

Pseudallescheria boydii

10. Trichosporon beigelii

11. Malassezia furfur 12. Hansenula spp. 13. Microsporum canis •

Focused, committed efforts by the entire health care staff continuously directed toward prevention 1.

Each NI addressed as an opportunity to improve the organization and delivery of care

2.

Essential that individual staff members understand that small risks applied to large populations result in a large number of total events (i.e., NI)

SUGGESTED READINGS Brossette SE, et al: A laboratory-based, hospital-wider, electronic marker for nosocomial infection: the future of infection control surveillance?. Am J Clin Pathol 2006; 125(1):34. Eriksen HM, Iversen BG, Aavitsland P: Prevalence of nosocomial infections and use of antibiotics in long-term care facilities in Norway, 2002 and 2003. J Hosp Infect 2004; 57(4):316. Gastmeier P: Nosocomial infection surveillance and control policies. Curr Opin Infect Dis 2004; 17(4):295. Merle V, et al: Knowledge and opinions of surgical patients regarding nosocomial infections. J Hosp Infect 2005; 60(2):169. Won SP, et al: Handwashing program for the prevention of nosocomial infections in a neonatal intensive care unit. Infect Control Hosp Epidemiol 2004; 25(9):742.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

O Obesity PRANAV M. PATEL, M.D.

BASIC INFORMATION DEFINITION

Obesity refers to having an excess amount of body fat in relation to lean body mass, or a body mass index (BMI) of =30 kg/m2. Overweight is defined as BMI of 25 to 29.9 kg/m2. These conditions result from a problem of imbalance between energy intake and expenditure. SYNONYMS

Overweight

ICD-9CM CODES

278.0 Obesity EPIDEMIOLOGY & DEMOGRAPHICS

•

The Behavioral Risk Factor Surveillance System (BRFSS) of the Centers for Disease Control and Prevention (CDC) has suggested that during the past 20 years there has been a dramatic increase in obesity in the U.S.

•

In 1990, four states in the U.S. had obesity prevalence rates of 15% to 19%, and no states had rates of 20% or more. By 2005, all but four states had obesity prevalence rates of 20% or more.

•

The prevalence of obesity has increased from 23% to 31% over the recent past in the U.S, and 66% of adults are overweight.

•

Approximately 33% of all U.S. women and 28% of all U.S. men are obese.

•

The prevalence of overweight and obesity increases with advancing age until the sixth decade, after which it begins to decline.

•

The Third National Health and Nutrition Examination Survey (NHANES III) estimated that 13.7% of children and 11.5% of adolescents are overweight.

•

The present costs of obesity in the U.S. population are estimated to run at 5% to 8% of total health care spending, which equates to $92.6 to $99.2 billion annually.

•

For persons with a BMI of =30 kg/m2, all-cause mortality is increased by 50% to 100% above that of persons with BMI in the range of 20 to 25 kg/m2.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Obese individuals are at increased risk of morbidity/mortality from type 2 diabetes, hypertension, coronary artery disease (CAD), cancer (particularly colon, prostate, and breast cancer), sleep apnea, degenerative joint disease, thromboembolic disorders, digestive tract diseases (gallstones), and dermatologic disorders.

•

The effects of obesity on health outcome appear to be reversible with weight loss.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination should assess the degree and distribution of body fat and signs of secondary causes of obesity.

•

Increased waist circumference is apparent. Excess abdominal fat is clinically defined as a waist circumference >40 inches (>102 cm) in men and >35 inches (>88 cm) in women.

•

Symptoms associated with hypertension, CAD, and diabetes (e.g., polyuria, polydipsia, retinopathy, and neuropathy) may be present.

•

Joint pain and swelling are associated with degenerative joint disease and obesity.

ETIOLOGY

•

The cause of obesity is multifactorial, involving social, nutritional, physiological, psychological, environmental, and genetic factors.

•

Environmental factors such as a sedentary lifestyle and the chronic ingestion of excess calories can cause obesity in some cases.

•

Most human obesity may be related to genetic factors. It is thought that obesity may be polygenic. Genetic studies with adopted children have demonstrated that they have similar BMIs to their biologic parents, but not to their adoptive parents. Twin studies also demonstrate a genetic influence on BMI.

•

Current data also suggest that obesity may spread in social networks in a quantifiable and discernable pattern that depends on the nature of social ties. Moreover, social distance appears to be more important than geographic distance within these networks.

DIAGNOSIS

•

BMI will help to establish the diagnosis of obesity. BMI is a measure of an adult's weight in relationship to his or her weight: more specifically, the adult's weight in kilograms divided by the square of his or her height.

•

BMI values can categorize patients into three classes of obesity: Class I (mild)

BMI = 30.0 to 34.9 kg/m2

Class II (moderate) BMI = 35.0 to 39.9 kg/m2 Class III (severe)

BMI = 40 kg/m2

•

Although BMI is commonly used to define obesity, it is not a very accurate indicator of body fat composition in children, who are undergoing rapid changes in height, or in bodybuilders or athletes who have large amounts of muscle tissue.

•

Measure waist circumference because the health risks of overweight and obesity are independently associated with excess abdominal fat.

DIFFERENTIAL DIAGNOSIS

It is important to rule out specific causative medical disorders in obese patients. Metabolic syndrome, hypothalamic disorders, hypothyroidism, Cushing's syndrome, insulinoma, depression, diabetes mellitus, drugs

(corticosteroids, antidepressants, antipsychotics, antihistamine agents, antihypertensive agents, and HIV protease inhibitors) can cause obesity. WORKUP

History should be obtained regarding weight change, family history of obesity, social circles, and eating and exercise behavior. Assessment for eating disorders and depression should be made. Attention should be directed to the use of nutritional supplements, over-the-counter medications, hormones, diuretics, and laxatives. The workup of an obese patient typically requires laboratory work to assess for risks and complications as well as to rule out underlying causative medical conditions. LABORATORY TESTS

•

Obese patients should be assessed for medical consequences of their obesity by screening for metabolic syndrome (measure high density lipoprotein [HDL], triglycerides, blood pressure, fasting glucose, and waist circumference).

•

In the proper clinical setting, thyroid function studies, dexamethasone suppression testing, a.m. cortisol level, and insulin level with C-peptide measurements will exclude hypothyroidism, Cushing's syndrome, and insulinoma as underlying causes of obesity.

IMAGING STUDIES

•

Several methods are available for determining or calculating total body fat but offer no significant advantage over the BMI. These include measurement of total body water, total body potassium, bioelectrical impedance, and dual-energy x-ray absorptiometry.

•

Buoyancy testing is an accurate method for determining total body fat composition.

TREATMENT

•

The National Heart, Lung, and Blood Institute (NHLBI) has developed guidelines for selecting treatment strategies for overweight and obese patients based on BMI and comorbidities. They recommend a combination of dietary management, physical activity management, and behavior therapy for any patient with a BMI =30 and for those with a BMI between 25 and 29.9 with comorbidities. Pharmacotherapy should be considered for patients with a BMI between 27 and 29.9 with comorbidities and for any patient with a BMI =30.

•

Surgery is indicated for patients with a BMI between 35 and 39.9 with comorbidities and for any patient with a BMI =40.

NONPHARMACOLOGIC THERAPY

•

The major principle of dietary management for weight loss is calorie reduction.

•

The NHLBI guidelines recommend an initial diet to produce a calorie deficit of 500-1000 kcal/day. This has been shown to reduce total body weight by an average of 8% over 3 to 12 months.

•

These guidelines recommend the use of a food diary to focus on dietary substitutes.

•

Thirty minutes of moderate intensity activity on 5 or more days of the week results in health benefits for obese individuals. Today several studies also indicate that 60 to 80 minutes of moderate to vigorous physical activity can be more beneficial.

•

Behavioral therapy is also necessary.

ACUTE GENERAL Rx

•

According to the NHLBI Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults and the U.S. Food and Drug Administration (FDA), pharmacotherapy is indicated for: Obese patients with a BMI =30 or Overweight patients with a BMI of =27 and concomitant obesity related risk factors or diseases, such as hypertension, diabetes, or dyslipidemia

•

There are three general classes of medications currently approved by the FDA for treating obesity: 1.

Sympathomimetic medications approved for long-term use

2.

Gastrointestinal (GI) lipase inhibitors

3.

Sympathomimetic medications approved for short-term use

•

Sibutramine (Meridia) acts as a serotonin norepinephrine reuptake inhibitor (SNRI) and suppresses appetite primarily by increasing satiation.

•

Orlistat (Xenical) blocks the digestion and absorption of ingested dietary fat. It is a reversible inhibitor of pancreatic, gastric, and carboxylester lipases and phospholipase A2, which are required for the hydrolysis of dietary fat in the gastrointestinal tract.

•

Phentermine is an amphetamine derivative that increases the amount of norepinephrine (NE) in the neuronal cleft, resulting in appetite suppression. Similar drugs include diethylpropion, benzphetamine, and phendimetrazine.

•

In 1997 both dexfenfluramine and fenfluramine were withdrawn from the market secondary to side effects of valvular heart lesions and pulmonary hypertension.

•

Other medications in clinical trials include bupropion (Wellbutrin), topiramate (Topamax), and metformin (Glucophage).

CHRONIC Rx

•

According to the NHLBI guidelines surgical intervention is an option for selected patients with clinically severe obesity (a BMI =40 or a BMI =35 with co-morbid conditions), when patients are at high risk for obesity-associated morbidity or mortality and when less invasive methods of weight loss have failed.

•

Bariatric surgery for weight loss falls into one of two categories: 1.

Restrictive surgeries that limit the amount of food the stomach can hold and slow the rate of gastric emptying. These include vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding.

2.

Restrictive malabsorptive bypass procedures combine the elements of gastric restriction and selective malabsorption. These include Roux-en-Y gastric bypass and biliopancreatic diversion.

DISPOSITION

•

Obesity increases the risk of developing hypertension, hyperlipidemia, type 2 diabetes, coronary artery disease, cerebrovascular disease, degenerative joint disease, digestive tract disease, sleep apnea, and endometrial, breast, prostate, and colon cancers.

•

Obesity accelerates the progression of coronary atherosclerosis.

•

All-cause mortality is increased in obese patients as increased body fat corresponds to increased health risks.

REFERRAL

Obesity is commonly seen in the primary care setting. If pharmacologic therapy is considered, consultation with physicians specializing in obesity and experienced with the use of the drug is recommended. In addition, consultation with nutritionists and behavioral therapists is also helpful. A consultation with general surgery is

indicated in patients being considered for surgical intervention.

PEARLS & CONSIDERATIONS COMMENTS

•

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) launched the Obesity Education Initiative (OEI) in January 1991. The overall purpose of the initiative is to help reduce the prevalence of overweight along with the prevalence of physical inactivity in order to reduce the risk of coronary heart disease (CHD) and overall morbidity and mortality from CHD.

•

The American Medical Association produced, with support from the Robert Wood Johnson Foundation, and developed, in collaboration with the U.S. Department of Health and Human Services, a primer for the assessment and management of adult obesity. The primer consists of 10 booklets that offer practical recommendations for addressing adult obesity in the primary care setting.

PREVENTION

•

Prevention of overweight and obesity involves both increasing physical activity and dietary modification to reduce caloric intake.

•

Clinicians can help guide patients to develop personalized eating plans and help them to recognize the contributions of fat, concentrated carbohydrates, and large portion sizes.

•

Clinicians must work with patients to modify other risk factors such as tobacco use, high glycemic intake, and elevated blood pressure in order to prevent the long-term chronic disease sequelae of obesity.

•

Regular screening of body weight and BMI measurements at routine office visits can help to identify early weight gain.

PATIENT/FAMILY EDUCATION

Information can be obtained on the American Obesity Association website (http://www.obesity.org American Medical Association website (http://www.ama-assn.org ).

) and the

EVIDENCE

The prevalence of obesity has increased from 23% to 31% over the last 20 years in the United States, and 66% of adults are overweight. [1] [2] Proposed explanations for the obesity epidemic include societal changes that promote both inactivity and food consumption,[[3]] as well as genetic factors. [4] [5] Network phenomena appear to be relevant to the biologic and behavioral trait of obesity, and obesity appears to spread through social ties.[[6]] Health care professionals should be concerned about overweight and obesity because of the wellestablished relations between excess body weight and such medical conditions as type 2 diabetes, hypertension, and osteoarthritis.[[7]]

Evidence-based guidelines issued by the National Institutes of Health call for weight loss both in obese persons and in overweight persons with two or more risk factors for obesity-related diseases.[[8]] In regard to pharmacologic therapy, there is evidence that Orlistat is modestly effective in promoting weight loss in obese people. [9] [10] There is evidence that sibutramine is modestly effective at promoting weight loss in obese people, and doses of 10 to 20 mg daily results in greater weight loss than placebo after 8 weeks and after 6 months.[[11]]

A systematic review found evidence that gastric surgery results in good weight loss in very obese patients in whom all other remedies have failed, with surgical patients losing 23 to 28 kg more weight on average than nonsurgical patients after 2 years. One study with 8 years' follow-up found that surgical patients had lost an average of 21 kg, whereas nonsurgical patients had gained weight.[[12]]

Evidence-Based References 1. Chang VW, Lauderdale DS: Income disparities in body mass index and obesity in the United States, 1971-2002. Arch Intern Med 2005; 165:2122-2128. 2. Hedley AA, et al: Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004; 291:2847-2850. 3. Hill JO, et al: Environmental contributions to the obesity epidemic. Science 1998; 280:1371-1374. 4. Stunkard AJ, et al: An adoption study of human obesity. N Engl J Med 1986; 314:193-198. 5. Stunkard AJ, et al: The body-mass index of twins who have been reared apart. N Engl J Med 1990; 322:1483-1487. 6. Christakis NA, Fowler JH: The spread of obesity over a large social network over 32 years. N Engl J Med 2007; 357:370-379. 7. National Task Force on the Prevention and Treatment of Obesity: Overweight, obesity, and health risk. Arch Intern Med 2000; 160:898-904. 8. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes Res 1998; 6(Suppl 2):51S-209S. 9. O'Meara S, et al: A rapid and systematic review of the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity. Health Technol Assess 2001; 5:1.Reviewed in: Clin Evid 10:676, 2004. 10. Hill JO, et al: Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-year study. Am J Clin Nutr 1999; 69:1108.Reviewed in: Clin Evid 10:676, 2004. 11. University of York, NHS Centre for Reviews and Dissemination: A systematic review of the clinical effectiveness of sibutramine and orlistat in the management of obesity, York, UK, 2000, NHS Centre for Reviews and Dissemination. Reviewed in: Clin Evid 10:676, 2004. 12. Colquitt J, et al: Surgery for morbid obesity (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS

Chang VW, Lauderdale DS: Income disparities in body mass index and obesity in the United States, 19712002. Arch Intern Med 2005; 165:2122-2128. Li Z, et al: Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142:532. Maggard MA, et al: Meta-analysis: surgical treatment of obesity. Ann Intern Med 2005; 142:547. Ogden CL, Carroll MD, Curtin LR, et al: Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006; 295:1549. Snow V, et al: Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005; 142:525. Speakman JR: Obesity: the integrated roles of environment and genetics. J Nutr 2004; 134:2090S.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Obsessive-Compulsive Disorder (OCD) JASON M. SATTERFIELD, PH.D., MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Obsessive-compulsive disorder (OCD) involves recurrent obsessions (intrusive and inappropriate thoughts, impulses, or images) and/or compulsions (behaviors or mental acts performed in response to obsessions or rigid application of rules) that consume >1 hr/day or cause marked impairment or distress. The symptoms are perceived as excessive and unreasonable. SYNONYMS

Compulsive hoarding, washing, list-making Intrusive thoughts with ritualized and repetitive behaviors

ICD-9CM CODES

F42.8 Obsessive-compulsive disorder (DSM-IV 300.3) EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: Mean age at onset is 19.6 yr. LIFETIME PREVALENCE (IN U.S.): 2.5% of adults PREDOMINANT SEX: Approximately equal distribution between sexes. PREDOMINANT AGE: •

Modal age of onset for females is between 20 and 29 yr.

•

Modal age of onset for males is between 6 and 15 yr.

DISEASE COURSE:

•

Condition is chronic with waxing and waning.

•

Symptoms typically worsen with stress.

•

15% show progressive deterioration while 5% show an episodic course with little impairment between episodes.

GENETICS: •

There is no clear genetic pattern.

•

Rate of concordance is higher in monozygotic (33%) vs. dizygotic (7%) twins.

•

Rate of disorder is also higher in first-degree relatives of individuals with OCD and Tourette's disorder than the general population.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Persistent and recurrent intrusive and ego-dystonic obsessive ideas, thoughts, impulses, or images that are perceived as alien and beyond one's control.

•

Frequent experiencing of obsessions related to contamination (e.g., when using the telephone), excessive doubt (e.g., was the door locked?), organization (the need for a particular order), violent impulses (e.g., to yell obscenities in church), or intrusive sexual imagery.

•

Obsessions possibly leading to compulsive behaviors meant to temporarily ameliorate the anxiety caused by obsessions (e.g., repeated hand washing, checking, rearranging), or mental tasks (e.g., counting, repeating phrases).

•

Obsessions and compulsions almost always accompanied with high anxiety and subjective distress. Both are seen as excessive and unreasonable.

ETIOLOGY

•

Strong evidence of neurobiological etiology.

•

OCD may have onset after infectious illness of CNS (e.g., Von Economo's encephalitis, Sydenham's chorea).

•

OCD may follow head trauma or other premorbid neurological conditions including birth hypoxia and Tourette's syndrome.

•

Serotonergic pathways believed important in some ritualistic instinctual behaviors, with dysfunction of these pathways possibly giving rise to OCD.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Obsessive-compulsive personality disorder (OCPD) is a maladaptive personality style defined by excessive rigidity, need for order/control, preoccupation with details, and excessive perfectionism. Unlike OCD, OCPD is ego syntonic.

•

Other psychiatric disorders in which obsessive or intrusive thoughts occur (e.g., body dysmorphic disorder, phobias, posttraumatic stress disorder).

•

Other conditions in which compulsive or impulse control behaviors are seen (e.g., trichotillomania, gambling, paraphilias).

•

Major depression, hypochondriasis, and several anxiety disorders with predominant obsessions or compulsions; however, in these disorders the thoughts are not anxiety provoking or are extremes of normal concern.

•

Delusions or psychosis, which may be mistaken for obsessive thoughts; unlike OCD, these individuals do not believe their obsessions are unreal and may likely meet criteria for another psychotic spectrum disorder that fully accounts for the obsessions (e.g., schizophrenia).

WORKUP

•

Careful history leading to diagnosis

•

Neurologic examination to rule out concomitant Tourette's or other tic disorder

•

In adolescents and children: psychological testing to reveal learning disabilities

LABORATORY TESTS

No specific tests are indicated. IMAGING STUDIES

No specific studies are indicated.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Average delay between symptom onset and treatment is 17 yr.

•

Initiation of treatment will help about 50% of patients achieve partial remission within the first 6 mo.

•

Cognitive-behavioral therapy (especially exposure with response prevention) is successful in up to 70% of patients but nearly 25% drop out of treatment due to the initial anxiety the exposures create. Best results are found for contamination obsessions and washing compulsions.

ACUTE GENERAL Rx

PRN clonazapam may be helpful in patients with extreme anxiety or those with a history of seizure disorder. CHRONIC Rx

•

Antidepressants with serotonergic reuptake blockade, including fluoxetine, clomipramine, fluvoxamine, paroxetine, sertraline, venlafaxine, escitalopram, and citalopram; optimal dosages are typically at the high end of the prescription range.

•

No response in only 15% of patients.

•

Indefinite treatment.

•

It is unclear if combination cognitive-behavioral therapy and pharmacotherapy yields superior outcomes.

•

Patients with comorbid psychosis and/or tic disorders may benefit from the addition of a neuroleptic.

•

Surgical interventions (e.g., cingulotomy) are available for the most extreme, refractory cases.

DISPOSITION

•

Course is chronic with waxing and waning. Symptoms tend to worsen with stress.

•

Most mild to moderate cases can be managed on a regular outpatient basis. Treatment should typically start with SSRI monotherapy with regular follow-up to assess treatment response and side effect management. Dose should be increased to maximum tolerated.

•

Patient and family education may help improve medical adherence and support.

REFERRAL

•

If distinction from other psychiatric conditions, particularly delusional disorder, is not clear

•

If patient refractory to drug treatment and/or requests cognitive-behavioral therapy

PEARLS & CONSIDERATIONS Patients with OCD typically have insight regarding the irrationality of their obsessions and compulsions but lack the ability to control them. This may cause intense shame and avoidance of medical care unless patient education and support are provided.

EVIDENCE

Selective serotonin reuptake inhibitors (SSRIs) have been found to be more effective than placebo at reducing symptoms of obsessive-compulsive disorder (OCD). [19] [20] Systematic reviews have also found clomipramine to be more effective than SSRIs (paroxetine, fluoxetine, fluvoxamine, sertraline) in the management of OCD in children and adolescents, and more effective than desipramine, imipramine, or nortriptyline. All of the SSRIs were equally effective. [19] [21] A randomized controlled trial compared fluvoxamine vs. clomipramine and found no significant difference in symptom severity after 10 wk. Fluvoxamine was better tolerated.[[4]] A randomized controlled trial found that there was no significant difference in symptoms between treatment with venlafaxine and clomipramine at 12 wk. This trial may have been underpowered. [[5]] Both behavioral therapy and cognitive therapy have been found to be significantly more effective than relaxation therapy for the reduction of symptoms in patients with obsessive-compulsive disorder.[[6]] It is unclear if the addition of fluvoxamine to behavioral or cognitive therapy produces superior outcomes. [25] [26]

Evidence-Based References 1. Math SB, Janardhan Reddy YC: Issues in the pharmacological treatment of obsessive-compulsive disorder. Int J Clin Pract 2007; 61:1188. 2. Ackerman DL, Greenland S: Multivariate meta-analysis of controlled drug studies for obsessivecompulsive disorder. J Clin Psychopharmacol 2002; 22:309.Reviewed in: Clin Evid 10:1172, 2003. 3. Geller DA, et al: Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessivecompulsive disorder. Am J Psychiatry 2003; 160:1919. 4. Mundo E, et al: Fluvoxamine in obsessive-compulsive disorder: similar efficacy but superior tolerability in comparison with clomipramine. Hum Psychopharmacol 2001; 16:461.Reviewed in: Clin Evid 13:1297, 2005. 5. Albert U, et al: Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: A preliminary single-blind, 12-week, controlled study. J Clin Psychiatry 2002; 63:1004. 6. Abramowitz JS: Effectiveness of psychological and pharmacological treatments for obsessive compulsive disorder: a quantitative review. J Consult Clin Psychol 1997; 65:44.Reviewed in: Clin Evid 9:1073, 2003. 7. van Balkom AJ, et al: Cognitive and behavioral therapies alone versus in combination with fluvoxamine in the treatment of obsessive compulsive disorder. J Nerv Ment Dis 1998; 186:492.Reviewed in: Clin Evid 13:1297, 2005. 8. Hohagen F, et al: Combination of behaviour therapy with fluvoxamine in comparison with behaviour therapy and placebo: results of a multicentre study. Br J Psychiatry 1998; 35(suppl):718.Reviewed in: Clin Evid 13:1297, 2005.

SUGGESTED READINGS

Eddy MF, Walbroehl GS: Recognition and treatment of obsessive-compulsive disorder. Am Fam Physician 1998; 57:1623. Fineberg NA, Gale TM: Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int J Neuropsychopharmacol 2005; 8(1):107. Schruers K, et al: Obsessive-compulsive disorder: a critical review of therapeutic perspectives. Acta Psychiatr Scand 2005; 111(4):261.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ocular Foreign Body MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

The term ocular foreign body refers to a foreign body on the surface of the corneal epithelium.

ICD-9CM CODES

930 Foreign body in external eye EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Universal, with a predominance in active people PEAK INCIDENCE: Childhood through active adult years PREDOMINANT SEX: Perhaps slightly more common in men PREDOMINANT AGE: Childhood through active adult years PHYSICAL FINDINGS & CLINICAL PRESENTATION

Pain is most common symptom Most common foreign bodies: •

Grinding ( Fig. 1-176 )

•

Drilling

•

Auto mechanics

•

Working beneath cars

•

Airborne particles blown by fans and so forth

FIGURE 1-176 A small, iron foreign body may be seen on external examination. (Courtesy Department of Dermatology, University of North Carolina at Chapel Hill. In Goldstein GB, Goldstein AO: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

History of corneal foreign body seen

•

Hemorrhage, loss of vision

•

Distorted anterior chamber, soft eye

•

Corneal abrasion

•

Corneal ulceration or laceration

•

Glaucoma

•

Herpes ulcers

•

Infection

•

Other keratitis

•

Intraocular foreign body

WORKUP

•

Fluorescein stain, slit lamp examination if no foreign body is found

•

Ultrasound exam

•

Plain x-ray

LABORATORY TESTS

Intraocular pressure to make certain that eye has not been penetrated IMAGING STUDIES

Occasionally, MRI of the orbits to identify foreign bodies not found by other means. Do not do MRI if suspect metallic foreign body. Plain x-ray and ultrasound are sufficient.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Remove foreign body

•

Treat infection

•

Repair eye if ruptured

•

Treat corneal abrasion or injury

ACUTE GENERAL Rx

•

Saline irrigation

•

Removal of foreign body with moist cotton-tipped applicator after instillation of topical anesthetic drops

•

Use Burr or more aggressive treatment if needed

•

Cycloplegics, antibiotics, and pressure dressing after removal of foreign body

•

Repair corneal laceration or damaged eye

DISPOSITION

If symptoms persist 24 hr after examination, refer to an ophthalmologist. REFERRAL

To ophthalmology within 24 hr if patient not completely comfortable

PEARLS & CONSIDERATIONS COMMENTS

•

Make sure foreign body is not intraocular inside eye.

•

Alkaline or acidic chemical foreign bodies can be dangerous, and pH test must be performed if either of these is suspected (for all chemical foreign bodies).

SUGGESTED READING Ta CN, Bowman RW: Hyphema caused by a metallic intraocular foreign body during magnetic resonance imaging. Am J Ophthalmol 2000; 129(4):533.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Onychomycosis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Onychomycosis is defined as a persistent fungal infection affecting the toenails and fingernails. SYNONYMS

Tinea unguium Ringworm of the nails

ICD-9CM CODES

110.1 Onychomycosis EPIDEMIOLOGY & DEMOGRAPHICS

•

Onychomycosis is most commonly found in people between the ages of 40 to 60 yr.

•

Onychomycosis rarely occurs before puberty.

•

Incidence: 20 to 100 cases/1000 population.

•

Toenail infection is 4 to 6 times more common than fingernail infections.

•

Onychomycosis affects men more often than women.

•

Occurs more frequently in patients with diabetes, peripheral vascular disease, and any conditions resulting in the suppression of the immune system.

•

Occlusive footwear, physical exercise followed by communal showering, and incompletely drying the feet predisposes the individual to developing onychomycosis.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Onychomycosis causes nails to become thick, brittle, hard, distorted, and discolored (yellow to brown color). Eventually, the nail may loosen, separate from the nail bed, and fall off.

•

Onychomycosis is frequently associated with tinea pedis (athlete's foot).

ETIOLOGY

•

The most common causes of onychomycosis are dermatophyte, yeast, and nondermatophyte molds.

•

The dermatophyte Trichophyton rubrum accounts for 80% of all nail infections caused by fungus.

•

Trichophyton interdigitale and Trichophyton mentagrophytes are other fungi causing onychomycosis.

•

The yeast Candida albicans is responsible for 5% of the cases of onychomycosis.

•

Nondermatophyte molds Scopulariopsis brevicaulis and Aspergillus niger, although rare, can also cause onychomycosis.

•

Onychomycosis is classified according to the clinical pattern of nail bed involvement. The main types are: 1.

Distal and lateral subungual onychomycosis (DLSO)

2.

Superficial onychomycosis

3.

Proximal subungual onychomycosis

4.

Endonyx onychomycosis

5.

Total dystrophic onychomycosis

DIAGNOSIS The diagnosis of onychomycosis is based on the clinical nail findings and confirmed by direct microscopy and culture. DIFFERENTIAL DIAGNOSIS

•

Psoriasis

•

Contact dermatitis

•

Lichen planus

•

Subungual keratosis

•

Paronychia

•

Infection (e.g., Pseudomonas)

•

Trauma

•

Peripheral vascular disease

•

Yellow nail syndrome

WORKUP

The workup of suspected onychomycosis is directed at confirming the diagnosis of onychomycosis by visualizing hyphae under the microscope or by culturing the organism. LABORATORY TESTS

•

Blood tests are not specific in the diagnosis of onychomycosis

•

KOH prep

•

Fungal cultures on Sabouraud medium

IMAGING STUDIES

•

Imaging studies are not very specific in making the diagnosis of onychomycosis.

•

If an infection is present and osteomyelitis is a consideration, an x-ray of the specific area and a bone scan may help establish the diagnosis.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Surgical removal of the nail plate is a treatment option; however, the relapse rate is high.

•

Prevention of reinfection by wearing properly fitted shoes, avoiding public showers, and keeping feet and nails clean and dry.

ACUTE GENERAL Rx

•

•

Topical antifungal creams are used for early superficial nail infections. 1.

Miconazole 2% cream applied over the nail plate bid

2.

Clotrimazole 1% cream bid

Oral agents. 1.

2.

3.

Itraconazole a.

For toenails: 200 mg qd × 3 mo

b.

For fingernails: 200 mg PO bid × 7 days, followed by 3 wk of no medicine, for two pulses

Terbinafine a.

For toenails: 250 mg/day for 3 mo

b.

For fingernails: 250 mg/day for 6 wk

Fluconazole a.

For toenails: 150 to 300 mg once weekly, until infection clears

b.

For fingernails: 150 to 300 mg once weekly until infection clears

•

All oral agents used for onychomycosis require periodic monitoring of liver function blood tests. Patients should be advised to watch for symptoms of drug-induced hepatitis (anorexia, fatigue, nausea, right upper quadrant pain) while taking these oral antifungal agents. They should stop their medication and contact their physician immediately if symptoms occur.

•

Itraconazole is contraindicated in patients taking cisapride, astemizole, triazolam, midazolam, and terfenadine. Statins should be discontinued during itraconazole therapy. Itraconazole requires gastric acidity for absorption; patients should be advised not to take oral antacids, H2 blockers, or proton pump inhibitors while taking itraconazole.

•

Fluconazole is contraindicated in patients taking cisapride and terfenadine.

•

Oral antifungal agents should not be initiated during pregnancy.

•

Ciclopirox, a topical nail lacquer antifungal agent, is FDA approved for treatment of mild to moderate disease not involving the lunula.

DISPOSITION

•

Spontaneous remission of onychomycosis is rare.

•

A disease-free toenail is reported to occur in approximately 25% to 50% of patients treated with the oral antifungal agents mentioned previously.

REFERRAL

•

Podiatry consultation is indicated in diabetic patients for proper instruction in foot care, footwear, and nail debridement or surgical removal of the toenail.

•

Dermatology consultation is indicated in patients refractory to treatment or if another diagnosis is considered (e.g., psoriasis).

PEARLS & CONSIDERATIONS COMMENTS

•

The growth of fungus on an infected nail typically begins at the end of the nail and spreads under the nail plate to infect the nail bed as well.

•

Carefully consider the informational insert regarding drug-drug interactions and contraindications before initiating oral antifungal agents.

EVIDENCE

A systematic review found insufficient evidence to draw conclusions on the efficacy of topical antifungals for the treatment of nail infections.[[1]] Terbinafine is more effective than griseofulvin for the treatment of patients with dermatophyte onychomycosis. [32] [33] Continuous terbinafine was found to be more effective than intermittent itraconazole in patients with fungal toenail infections in one randomized controlled trial (RCT).[[4]] Continuous terbinafine was also found to be more effective than continuous itraconazole for fungal toenail infections, in the pooled results of two RCTs included in a systematic review.[[5]]

Evidence-Based References 1. Crawford F, et al: Topical treatments for fungal infections of the skin and nails of the foot (Cochrane Review), 4. Chichester, UK: John Wiley; 2003. 2. Haneke E, et al: Short-duration treatment of fingernail dermatophytosis: a randomized, double-blind study with terbinafine and griseofulvin. LAGOS III Study Group. J Am Acad Dermatol 1995; 32:72. 3. Faergemann J, et al: Double-blind, parallel-group comparison of terbinafine and griseofulvin in the treatment of toenail onychomycosis. J Am Acad Dermatol 1995; 32:750. 4. Evans EG, Sigurgeirsson B: Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. The LION Study Group. BMJ 1999; 318:1031. 5. Crawford F, et al: Oral treatments for toenail onychomycosis. Arch Dermatol 2002; 138:811.

SUGGESTED READINGS Baran R, Kaoukhov A: Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapy. J Eur Acad Dermatol Venereol 2005; 19(1):21. Gupta AK, et al: The use of terbinafine in the treatment of onychomycosis in adults and special populations: a review of the evidence. J Drugs Dermatol 2005; 4(3):302. Kulac M, et al: Venous insufficiency in patients with toenail onychomycosis. J Ultrasound Med 2005; 24(8):1085. Romano C, Gianni C, Difonzo EM: Retrospective study of onychomycosis in Italy: 1985–2000. Mycoses 2005; 48(1):42. Sigurgeirsson B, Steingrimsson O: Risk factors associated with onychomycosis. J Eur Acad Dermatol Venereol 2004; 18(1):48.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Opiate Addiction STEVEN PELIGIAN, D.O.

BASIC INFORMATION DEFINITION

•

Opiate addiction is defined as a cluster of cognitive, behavioral, and physiological symptoms in which the individual continues use of opiates despite significant opiate-induced problems. Opiate dependence is a chronic, relapsing disorder characterized by repeated self-administration that usually results in opiate tolerance, withdrawal, and compulsive drug use. Dependence may occur with or without the physiological symptoms of tolerance and withdrawal.

•

There are four stages of addiction: Stage I, acute drug effects: rewarding effects of drug result from neurobiological changes in response to the acute drug use. Duration varies from hours to days. Stage II, transformation to addiction: associated with changes in neuronal function that accumulate with repeated administration and diminish over days or weeks after discontinuation of drug use. Stage III, relapse after extended periods of abstinence: precipitated by an incubation of cueinduced craving (people, places, and things as triggers) and priming (relapse precipitated by drug exposure). Stage IV, end-stage addiction: vulnerability to relapse endures for years and results from prolonged changes at the cellular level.

•

Pseudoaddiction: undertreatment of pain resulting in “opiate-seeking” behaviors such as “doctor shopping” and multiple emergency room visits. These behaviors disappear with adequate treatment of pain.

SYNONYMS

Opioid addiction Opiate abuse Narcotic addiction Narcotic abuse

ICD-9-CM CODES

304.7X/304.8X Opioid dependence EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: There are 980,000 opiate addicts in the U.S.; less than one third are in treatment. PREVALENCE:

•

Approximately 6 million persons age 12 yr and older used psychotherapeutic drugs for nonmedical purposes in 2004, which represents 2.5% of the population. Most of them reported abusing opiate pain relievers.

•

In 2004, 2.4 million persons age 12 yr or older initiated nonmedical use of prescription pain relievers, surpassing for the first time those who initiated abuse of marijuana (2.1 million).

•

Opiate addiction is becoming an adolescent disease. Among twelfth-graders, in 2005, 9.5% reported past year nonmedical use of oxycodone (Vicodin) and 5.5% reported past year nonmedical use of oxycodone slow-release tablets (Oxycontin).

•

The percentage of eighth-, tenth-, and twelfth-graders who have used heroin has more than doubled since the late 1990s. This increase has largely been attributed to decreased price and increased purity in the last decade.

PREDOMINANT SEX: Males abuse opiates more commonly than females, with a male:female ratio of 3:1 for heroin and 1.5:1 for prescription opiates. PEAK INCIDENCE: The majority of new abusers of opiates are less than 26 yr old. RISK FACTORS: •

Family history

•

Prior history of addiction

•

Psychiatric disorders

GENETICS: •

Genetic epidemiologic studies suggest a high degree of heritable vulnerability for opiate dependence.

•

Gene polymorphism for dopamine receptor/transporters, opioid receptors, serotonin receptors/transporters, proenkephlin, and catachol-o-methytrasferase (COMT) all appear to be associated with vulnerability to opiate dependence. Future interventions for opiate dependence may include medications identified through genetic research.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical exam is often noncontributory.

•

Small-sized pupils may be the only observable sign of use because only mild tolerance develops for miosis.

•

Scars or tracks from chronic intravenous (IV) use may be visible in the veins of the arms, hands, ankles, neck, and breasts.

•

Inflamed nasal mucosa or respiratory wheezing may be apparent in patients who are snorting heroin or Oxycontin.

•

Patients in withdrawal may have more dramatic findings such as tachycardia, hypertension, fever, piloerection (goose flesh), mydriasis, lacrimation, central nervous system (CNS) arousal, irritability, and repeated yawning. In patients presenting with sympathetic overactivity and panic attacks, use of CNS stimulants, such as amphetamines or cocaine, should also be ruled out.

•

Although gastrointestinal symptoms of nausea, vomiting, and abdominal pain are common in opiate withdrawal, other causes such as gastroenteritis, pancreatitis, peptic ulcer disease, and intestinal obstruction need to be ruled out.

•

The history may provide relevant information in making the diagnosis. Significant findings may include:

A long history of opiate self-administration typically via the IV or intranasal route but sometimes through smoking as well. Polysubstance use. Intoxication by drugs other than narcotics (e.g., benzodiazepines, barbiturates) should be ruled out in unconscious patients. A high incidence of non–opiate related psychiatric disorders (>80%). History of problems at work, school, or relationships associated with drug use. History of legal problems associated with drug use such as arrest for possession, robberies, or prostitution. History of interpersonal violence (perpetrator or victim). History of physical problems such as skin infections, phlebitis, endocarditis, liver diseases due to acetaminophen toxicity (Vicodin/Percocet), and viral hepatitis. Hepatitis C is the most prevalent blood-borne pathogen. It is present in approximately 90% of opiate-dependant people and is often spread by sharing IV drug “works” or snorting devices. There is also a higher incidence of HIV infection. ETIOLOGY

Opiate dependence is a biopsychosocial disorder. Pharmacologic, social, genetic, and psychodynamic factors interact to influence abusive behaviors. Pharmacologic factors are especially prominent in opiate addiction because these drugs are strong reinforcing agents owing to their euphoric effects and their ability to reduce anxiety and increase self-esteem and the patient's subjective feelings of improved ability to cope with daily challenges.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Psychiatric disorders (e.g., anxiety, depression, bipolar disorder).

•

Acute medical illness (e.g., hypoglycemia, seizure disorder, sepsis, renal or hepatic insufficiency) may mimic opiate withdrawal symptoms.

WORKUP

•

The history is the most important part of the workup.

•

Observation of opiate withdrawal is indicative of opiate addiction.

•

Observation of purposeful behaviors such as complaints and manipulations directed at getting more drugs and anxiety during withdrawal is suggestive of opiate addiction.

•

Screen blood and urine for opiate metabolites.

•

Screen for communicable diseases: HIV, hepatitis B and hepatitis C, tuberculosis.

•

Screen for endocarditis in patients with newly diagnosed murmurs.

LABORATORY TESTS

•

Urine and serum toxicology screen

•

CBC

•

Chemistries (ALT, AST, serum creatinine): elevated liver function tests (LFTs) may be secondary to viral hepatitis or acetaminophen toxicity

•

Hepatitis screen: if hepatitis C antibody–positive, follow up with hepatitis C PCR (viral load) even in patients with normal LFTs

•

HIV

•

PPD

IMAGING STUDIES

Generally not helpful in routine diagnosis and treatment. Consider echocardiography in patients with heart murmurs and liver sonography or CT scan in patients with elevated LFTs or positive for hepatitis C or B (increased risk of hepatocellular carcinoma).

TREATMENT NONPHARMACOLOGIC THERAPY

•

Brief counseling interventions during a visit with their primary care physician or OB/GYN have proven efficacious in motivating patients for treatment.

•

Therapeutic communities (residential).

•

12-step or other self-help groups (e.g., Alcoholics Anonymous, Narcotics Anonymous).

•

Relapse prevention (counseling).

ACUTE Rx

•

Medical withdrawal (not overdosed).

•

Short (30 days) or long-term (30 to 180 days) protocols.

•

Buprenorphine (opioid partial agonist) or methadone (opioid agonist) is initiated in tapering doses.

•

Clonidine 0.1 mg bid-tid can be used to minimize autonomic symptoms (sweating) and craving.

•

NSAIDs for body/muscle aches.

•

The anticholinergic dicyclomine (Bentyl) can be used to minimize GI hyperactivity.

•

Nonbenzodiazepine hypnotics, low-dose atypical antipsychotics (e.g., Quetiapine [Seroquel]), or low-dose tricyclics are effective for promoting adequate sleep.

CHRONIC Rx

Opioid antagonist treatment: •

Naltrexone: does not stabilize neuronal circuitry like partial or full opioid agonists and generally results in poor outcomes, much like Antabuse for alcohol.

•

Opioid partial agonist therapy: buprenorphine.

•

Opioid agonist therapy: methadone.

NOTE: Buprenorphine and methadone are both metabolized by the cytochrome P450 3a4 and 2d6 I isoenzyme pathways. Prescribers should be aware of multiple possible drug interactions.

PATIENT SELECTION FOR BUPRENORPHINE OR METHADONE

•

Appropriate patients for buprenorphine office-based treatment: Patients interested (highly motivated) for treatment Have no major contraindications (see following) Can be expected to be reasonably compliant with treatment Understand the benefits and risks of buprenorphine treatment Willing to follow safety precautions

•

Less likely to be appropriate for office-based treatment: Have comorbid dependence on benzodiazepines or other CNS depressants (including ETOH) Have significant untreated psychiatric comorbidities Have active or chronic suicidal or homicidal ideation or attempts Have multiple previous treatments with frequent relapses Have poor response to previous treatment with buprenorphine Have significant medical complications (e.g., hepatic insufficiency, bacterial endocarditis, active TB)

•

Methadone maintenance: narcotic treatment program (clinic setting) indications

•

Evidence of opiate addiction >1 yr

•

Two failed previous treatment attempts

•

Patients not appropriate for office-based treatment

•

Eligible without active “use” if prior methadone maintenance patient within previous 2 months

•

Pregnancy

DISPOSITION

•

Opiate addiction is a chronic relapsing disease.

•

High rate of relapse after “detox.”

•

Relapse potential after medically supervised withdrawal from methadone: 90% after 1 yr stable in treatment 80% after 3 yr stable in treatment 70% after 5 yr stable in treatment

REFERRAL

Refer to addiction medicine specialist or narcotic treatment program when the neurobiological disease of opiate addiction is identified.

PEARLS & CONSIDERATIONS COMMENTS

•

Methadone maintenance is the gold standard for the pregnant opiate-addicted patient regardless of the duration of the addiction or prior treatment attempts. Detoxification is contraindicated during pregnancy.

•

Breastfeeding is encouraged in mothers on methadone maintenance (MOMS). The American Academy of Pediatrics statement regarding “Transfer of Drugs and Other Chemicals into Human Milk” has placed methadone into the “usually compatible with breastfeeding” group, based on the assumption that maternal urines are monitored to detect use of illicit drugs. The U.S. Department of Health and Human Services also recommends that mothers on methadone be encouraged to breastfeed.

•

When a physician identifies a patient as a “drug seeker,” it is imperative that the physician avoids abruptly stopping the opiate prescription because this will often result in the patient buying the drugs illegally. These patients should be counseled and referred for treatment.

•

Patients on methadone or buprenorphine who have pain resulting from an acute injury will need pain medication in addition to their daily dose of methadone or buprenorphine. They will require higher than usual doses of pain medications because of opiate receptor “blockade” secondary to their methadone or buprenorphine use.

•

Opiate-dependant patients have a lower pain threshold resulting from hyperalgesia caused by the longterm use of opiates.

PREVENTION

Education is the hallmark of prevention. •

School drug prevention education programs.

•

Educate children about their family medical history including diseases of addiction.

•

Address childhood psychiatric disorders to prevent self-medicating.

PATIENT/FAMILY EDUCATION

•

Stigma of addictions and treatment often interferes with good treatment.

•

Family needs to be educated so they can support the patient's efforts.

•

Encourage family meeting with addiction specialist, counselor.

•

Recommend support groups for family members.

SUGGESTED READINGS Daniel A: Acute pain management for patients receiving methadone or buprenorphine therapy. Ann Int Med 2006; 144:127. Kalinas PW, Volkow ND: The neural basis of addiction: a pathology of motivation and choice. Am J Psych 2005; 162:1403. Minkoff K: Best practices: developing standards of care for individuals with co-occurring psychiatric and substance abuse disorders. Psych Serv 2001; 52:597. Olsen Y, Alford D: Chronic pain management in patients with substance use disorders. Johns Hopkins Advanced Studies in Medicine 2006; 6:110. Puredes A, Zweban J: The hepatitis C epidemic: shall we remain silent. J Addict Dis 2001; 1:1. Wilford B: Principles of addiction medicine, ed 3. Chevy Chase, MD, American Society of Addiction Medicine, 2003.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Optic Atrophy RICHARD S. ISAACSON, M.D.

BASIC INFORMATION DEFINITION

Optic atrophy refers to the degeneration of the axons of the optic nerve. It is a symptom rather than a disease. SYNONYMS

Unilateral/Bilateral optic atrophy

ICD-9CM CODES

377.10 Atrophy, optic nerve EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: Varies depending on etiology PREDOMINANT SEX: Unilateral optic atrophy in women is most commonly MS; may also occur after head injury (more commonly in men) PREDOMINANT AGE: 21 to 40 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Asymmetry of disc color is often first subtle finding

•

Temporal part of optic disc is pale initially ( Fig. 1-177 ); later the entire disc becomes pale/white

•

Optic disc pallor occurs 4 to 6 wk after optic nerve injury

•

Unilateral lesion produces a relative afferent pupillary defect (RAPD): swing flashlight eye to eye; abnormal pupil dilates to direct light

•

Decreased visual acuity, blurred vision, visual field deficits (e.g., central scotoma), abnormal color vision (e.g., red desaturation)

FIGURE 1-177 Optic atrophy. Patient's right eye shows atrophy. (Courtesy John W. Payne, M.D., The Wilmer Ophthalmological Institute, The Johns Hopkins University and Hospital, Baltimore. From Seidel HM [ed]: Mosby's guide to physical examination, ed 4, St Louis, 1999, Mosby.)

ETIOLOGY

•

Optic neuritis—multiple sclerosis, sarcoidosis, infections (syphilis, CMV, HIV, Lyme, TB, bartonella, West Nile)

•

Vascular—ischemic optic neuropathy, central retinal artery occlusion, temporal arteritis

•

Compression—glaucoma, pituitary tumor, meningioma, thyroid eye disease, pseudotumor cerebri

•

Hereditary—Leber's hereditary optic neuropathy

•

Nutritional, toxic and metabolic—Amiodarone, Isoniazid, B12 deficiency, tobacco-alcohol

•

Trauma

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Nutritional, toxic, and hereditary causes are usually bilateral.

•

Unilateral optic atrophy in a young person is more commonly MS.

•

Postviral atrophy may be seen in childhood.

WORKUP

•

Depends on suspected etiology/clinical presentation. History including age of onset, risk factors, acuity of onset of symptoms, trauma, presence of pain, family history, toxic/nutritional factors, and other associated neurologic findings should be considered. When accompanied by other systemic signs and symptoms, a metabolic disorder should be considered.

•

Visual field testing may help identify etiology (e.g., centrocecal field defects may occur with nutritional/toxic causes), but specificity is low.

•

To differentiate between optic nerve vs. macular disease an Amsler chart and/or visual evoked responses may be helpful.

•

If high clinical suspicion for MS, consider MRI of brain with contrast and LP with oligoclonal bands.

•

Measure intraocular pressure (glaucoma).

•

If pseudotumor cerebri is suspected, suggest LP; if bartenellosis (catscratch disease) is suspected, check bartonella titers.

LABORATORY TESTS

•

Depends on suspected etiology: none for trauma, tumor, MS

•

Serum B12

•

Autoimmune diseases: ESR, ANA, ACE

IMAGING STUDIES

•

MRI brain with contrast, need fat suppression and special (thin) cuts through orbits to identify compressive lesions in all patients with unexplained optic atrophy; especially important in patients with positive predictive factors for abnormal imaging (e.g., young age, progression, bilateral findings)

•

If sarcoid is suspected, order chest x-ray

TREATMENT ACUTE GENERAL Rx

Treat the underlying cause—discontinue identifiable toxins, B12 replacement, neurosurgical intervention if tumor found; consider IV steroids if there is evidence for active demyelinating disease. CHRONIC Rx

The optic nerve does not regenerate although symptoms often improve.

DISPOSITION

•

Visual loss occurs over weeks to months

•

Usually follow-up by neurologist or ophthalmologist

REFERRAL

If tumor or demyelinating lesions are found or if etiology is unknown

PEARLS & CONSIDERATIONS COMMENTS

•

An experienced clinician should be able to identify pale optic discs and a relative afferent pupillary defect.

•

Pupillary dilation with mydriatic agents (e.g., Pilocarpine) may be necessary for a better funduscopic examination.

•

Patient education material can be obtained from the National Eye Institute, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, MD 20892.

EVIDENCE

Optic atrophy is a syndrome with multiple potential etiologies, rather than a single disorder, and there are no randomized, controlled clinical trials for the diagnosis or treatment of this syndrome. SUGGESTED READINGS Huizing M, et al: Optic atrophies in metabolic disorders. Mol Genet Metab 2005; 86:51. Lee AG, et al: The diagnostic yield of the evaluation for isolated unexplained optic atrophy. Ophthalmol 2005; 112(5):757. Newman NJ: Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol 2005; 140(3):517. Van Stavern GP, Newman NJ: Optic neuropathies. An overview. Ophthalmol Clin North Am 2001; 14(1):61.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Optic Neuritis ALEXANDRA DEGENHARDT, M.D.

BASIC INFORMATION DEFINITION

Optic neuritis is an inflammation of the optic nerve resulting in a reduction of visual function. SYNONYMS

Optic papillitis Retrobulbar neuritis

ICD-9CM CODES

377.3 Optic neuritis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 1 to 5/100,000 person years; rates vary according to incidence of multiple sclerosis (MS). PEAK INCIDENCE: 20 to 49 yr, mean 30. PREVALENCE (IN U.S.): Common in multiple sclerosis. PREDOMINANT SEX: Female 1.8:1 male. GENETICS: MS more common in patients with certain HLA blood types. See “Multiple Sclerosis.” PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Visual loss develops over hours or days, most often accompanied by pain and tenderness with movement of affected eye.

•

Marcus Gunn pupil (RAPD = relative afferent pupillary defect): direct and consensual responses are normal. However, when swinging the flashlight from eye to eye, the affected eye's pupil dilates transiently to direct light.

•

Decreased visual acuity.

•

Unilateral visual field abnormalities—often a central scotoma.

•

Color desaturation—red most affected.

•

Normal orbit and fundus; occasionally there is disc edema acutely ( Fig. 1-178 ), uveitis, or periphlebitis.

•

May have movement or light-induced phosphenes (flashes of light lasting 1 to 2 sec) or Uhtoff's phenomenon (see “Multiple Sclerosis”).

•

After several months the optic disc may atrophy and develop pallor.

FIGURE 1-178 A case of optic neuritis. The optic disc edema seen here is often not present. Note the otherwise normal fundus. (Courtesy of J. Barton, M.D., Beth Israel Deaconess Medical Center, Boston.)

ETIOLOGY

An inflammatory response associated with an infection, autoimmune disease (such as multiple sclerosis), or

rarely a mitochondrial disorder.

DIAGNOSIS The classic triad includes loss of vision, pain, and dyschromatopsia. Alternate ocular pathology, infection, and CNS mass lesions should be excluded. 30% of cases are bilateral. DIFFERENTIAL DIAGNOSIS

•

Inflammatory: multiple sclerosis, neuromyelitis optica, sarcoidosis, SLE, Sjögren's, Behçet's, postinfectious, postvaccination

•

Infectious: syphilis, TB, Lyme, Bartonella, HIV, CMV, herpes, orbital infection

•

Ischemic: giant cell arteritis, anterior and posterior ischemic optic neuropathies, diabetic papillopathy, branch or central retinal artery or vein occlusion (sudden onset loss of vision)

•

Mitochondrial: Leber's hereditary optic neuropathy

•

Mass lesion: pituitary tumor, aneurysm, meningioma, glioma, metastases, sinus mucocele

•

Ocular: optic drusen, retinal detachment, vitreous hemorrhage, uveitis, posterior scleritis, neuroretinitis, maculopathies and retinopathies

•

Toxic: B 12 deficiency, tobacco-ethanol amblyopia, methanol or ethambutol intoxication (painless, slowly progressive, and mostly bilateral)

•

Other: acute papilledema, retinal migraine, factitious visual loss

WORKUP

The neurologic examination should otherwise be normal. Recommend dilated ophthalmoscopy. LABORATORY TESTS

•

Recommend: CBC, ANA, ESR, CRP.

•

Consider: HIV Ab, Lyme titer, ACE, RPR, LHON mtDNA mutations.

IMAGING STUDIES

MRI of the brain and orbits (thin section fat-suppressed T2-weighted) with gadolinium to rule out compressive and infiltrative etiologies and to assess the risk of MS.

TREATMENT NONPHARMACOLOGIC THERAPY

Assure patient that in most cases there is nearly complete recovery of vision. ACUTE GENERAL Rx

Treat if the visual loss is moderate to severe or if there is an abnormal MRI (higher risk of MS). Methylprednisolone 250 mg IV every 6 hr for 3 days followed by an oral prednisone taper over 11 days.

CHRONIC Rx

None, unless at high risk to develop MS. See “Multiple Sclerosis.” DISPOSITION

Recovery over several months. In the ONTT (see below), 90% had 20/40 or better at 1 yr and 3% had 20/200 or worse. Of initial 20/200 or worse, only 5% remained in that group at 6 mo. REFERRAL

•

To neurologist if patient has other neurologic signs or an abnormal brain MRI.

•

Urgent if proptosis, ophthalmoplegia, or brain MRI demonstrates a mass lesion.

•

To ophthalmologist when atypical features, sudden onset, slowly progressive, other ocular pathology; if vision worsens or does not improve after several weeks; if severe or persistent pain; or if vision deteriorates as steroids are tapered.

PEARLS & CONSIDERATIONS

•

Bilateral ON with poor recovery suggests possible Leber's hereditary optic neuropathy or toxic optic neuropathies.

•

Consider pituitary apoplexy with severe headache or diplopia.

EVIDENCE

IV methylprednisolone hastens recovery with slight improvement in visual function tests at 6 mo. Oral prednisone may increase the risk of recurrent ON.[[1]]

Evidence-Based Reference 1. Beck RW, et al: A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med 1992; 326(9):581.

SUGGESTED READINGS Beck R, et al: High and low risk profiles for the development of MS within 10 years after optic neuritis. Arch Ophthalmol 2003; 121(7):944. Beck R, et al: Visual function more than 10 years after optic neuritis. Am J Ophthalmol 2004; 137:77.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Orchitis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Orchitis is an inflammatory process (usually infectious) involving the testicles. Infection may be viral or bacterial and can be associated with infection of other male sex organs (prostate, epididymis, bladder) or lower urogenital tract or sexually transmitted diseases often via hematogenous spread. Common causes are: •

Viral: Mumps—20% postpubertal; coxsackie B virus

•

Bacterial: Pyogenic via spread from involving epididymis; bacteria include Escherichia coli, Klebsiella pneumoniae, P. aeruginosa, Staphylococcus, Streptococcus or Rickettsia, Brucella spp.

•

Other: Viral-HIV associated, CMV Fungi 1.

Cryptococcosis

2.

Histoplasmosis

3.

Candida

4.

Blastomycosis

Mycobacterium tuberculosis and M. leprae Parasitic causes: toxoplasmosis, filiariasis, schistosomiasis SYNONYMS

Epididymiorchitis Testicular infection Testicular inflammation

ICD-9CM CODES

0.72

Mumps

098.13 Acute gonococcal orchitis 095.8

Syphilitic orchitis

016.50 Tuberculous orchitis, unspecified EPIDEMIOLOGY & DEMOGRAPHICS

PREDOMINANT SEX: Male PREDOMINANT ORGANISM: The leading cause of viral orchitis is mumps. The mumps virus rarely causes orchitis in prepubertal males but involves one or both testicles in nearly 30% of postpubertal males. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Testicular pain, unilateral or bilateral swelling

•

May have associated epididymitis, prostatitis, fever, scrotal edema, erythema cellulitis

•

Inguinal lymphadenopathy

•

Acute hydrocele (bacterial)

•

Rare development—abscess formation, pyocele of scrotum, testicular infarction

•

Spermatic cord tenderness may be present

DIAGNOSIS Clinical presentation as described previously with possible history of acute viral illness or concomitant epididymitis. DIFFERENTIAL DIAGNOSIS

•

Epididymoorchitis—gonococcal

•

Autoimmune disease

•

Vasculitis

•

Epididymyosis

•

Mumps—with or without parotitis

•

Neoplasm

•

Hematoma

•

Spermatic cord torsion

LABORATORY TESTS

•

CBC with differential

•

Urinalysis

•

Viral titer—mumps

•

Urine culture

•

Ultrasound of testicle to rule out abscess

IMAGING STUDIES

Ultrasound if abscess suspected

TREATMENT

•

Dependent on etiology

•

Viral (mumps)—observation; bed rest, ice packs, analgesics, and a scrotal sling for support may provide some relief of discomfort that accompanies mumps orchitis

•

Bacterial—empiric antibiotic treatment with parenteral antibiotic treatment until pathogen identified: ceftriaxone (250 mg IM × 1) plus doxycycline (100 mg PO bid × 10 days), ofloxacin (300 mg PO bid × 10 days), ciprofloxacin (500 mg PO bid or 400 mg IV bid)

•

Surgery for abscess, pyogenic process

DISPOSITION

Follow up for evidence of recurrence, hypogonadism, and infertility may be needed with bilateral orchitis REFERRAL

To a urologist if surgical drainage is needed To an endocrinologist if hypogonadism develops To a fertility specialist if infertility develops

PEARLS & CONSIDERATIONS Consider tuberculous orchitis if symptoms fail to respond to standard antibacterial therapy, even in the absence of chest radiographic evidence of pulmonary tuberculosis SUGGESTED READINGS Niizuma T, et al: Elevated serum C-reactive protein in mumps orchitis. Pediatr Infect Dis J 2004; 23(10):971. Rajagopal AS: Pseudomonas orchitis in puberty. Int J STD AIDS 2004; 15(10):707.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Orthostatic Hypotension TIMOTHY W. FARRELL, M.D.

BASIC INFORMATION DEFINITION

Orthostatic hypotension (OH) is defined as the presence of at least one of the following: a decrease in systolic blood pressure by greater than or equal to 20 mm Hg or a decrease in diastolic blood pressure by greater than or equal to 10 mm Hg within 5 minutes of standing. SYNONYMS

Postural hypotension

ICD-9CM CODES

458.0 Orthostatic hypotension EPIDEMIOLOGY & DEMOGRAPHICS

•

The incidence of OH is increased in the elderly, most likely due to an impaired baroreceptor response to postural changes in these patients.

•

OH may cause up to 30% of all syncopal events in the elderly.

CLINICAL PRESENTATION

•

Symptoms include dizziness, lightheadedness, syncope, visual and auditory disturbances, weakness, diaphoresis, pallor, gastrointestinal upset, and urinary dysfunction.

•

Associated with increased autonomic activity during meals (from increased splanchnic blood flow), exercise, and hot weather.

•

Supine and nocturnal hyper tension in patients with OH may be secondary to underlying autonomic dysfunction.

ETIOLOGY

•

The assumption of an upright posture results in a lower arterial pressure and decreased carotid baroreceptor activity. The consequent increase in sympathetic tone at the expense of parasympathetic tone causes arterial and venous constriction as well as positive inotropic and chronotropic effects, thereby limiting the fall in blood pressure in the upright position.

•

When OH is caused by central or peripheral autonomic dysfunction, this baroreceptor reflex is impaired, and thus decreased blood pressure cannot be counteracted by the aforementioned compensatory mechanisms.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Common: •

Medications: antihypertensives, antidepressants (tricyclics), antipsychotics (phenothiazines), alcohol, narcotics, barbiturates, insulin, nitrates

•

Reduced intravascular volume (hemorrhage, dehydration, hyperglycemia, hypoalbuminemia)

•

Postprandial effect (especially in the elderly)

•

Vasovagal syncope

•

Deconditioning

•

Peripheral autonomic dysfunction (diabetes mellitus, Guillain-Barré syndrome)

Uncommon: •

Central autonomic dysfunction (Shy-Drager syndrome)

•

Postganglionic autonomic dysfunction: impaired norepinephrine release

•

Autoimmune autonomic dysfunction: nAChR autoantibodies

•

Paraneoplastic autonomic dysfunction: anti-Hu antibodies (in small cell lung cancer)

•

POTS (postural tachycardia syndrome): usually occurs in young women; an abnormally large increase in heart rate is observed in the upright position due to increased venous pooling from autonomic dysfunction of the lower extremities, but blood pressure is not affected due to an excess of plasma norepinephrine.

•

Impaired cardiac output

•

Cerebrovascular accident

•

Adrenal insufficiency

•

Deconditioning

•

Carotid sinus hypersensitivity

•

Anxiety, panic attacks

•

Seizures

•

Idiopathic

WORKUP

•

Measure supine blood pressure, stand for 5 minutes, then measure upright blood pressure.

•

Thorough neurologic exam.

•

Rule out treatable causes (e.g., medications, volume depletion).

LABORATORY TESTS

•

Hemoglobin and hematocrit.

•

Serum erythropoietin level if anemia is suspected.

•

Consider when treatable causes of OH have been ruled out: Blood pressure and heart rate monitoring using the tilt table test. Plasma norepinephrine measurements (to distinguish postganglionic from preganglionic autonomic dysfunction). Other methods use the Valsalva maneuver or measure sweating as indirect means of evaluating the autonomic nervous system.

IMAGING STUDIES

None

TREATMENT NONPHARMACOLOGIC THERAPY

•

High-salt diet (e.g., bouillon cubes)

•

Liberal fluid intake

•

Raising the head of the bed at night

•

Compression stockings to waist (to include splanchnic circulation)

•

Multiple low-carbohydrate meals to avoid postprandial orthostatic hypotension

•

Patient education (leg crossing, prolonged sitting before first standing in the morning)

ACUTE GENERAL Rx

•

Correction of volume status

•

Discontinuation of medications that may cause OH

CHRONIC Rx

•

Fludrocortisone: 0.1 mg/d (may combine with an alpha-1 agonist to lower the dose of each)

•

Midodrine (alpha-1 agonist): 10 mg three times a day

•

Erythropoietin (if anemic)

•

Caffeine

OTHER TREATMENTS

•

Pyridostigmine (enhances renal sodium reabsorption): 0.2 to 0.6 mg/d (not FDA approved for this indication)

•

Octreotide: 300 to 600 mg/d (not FDA approved for this indication)

•

Indomethacin (prostaglandin inhibitor)

•

DdAVP (experimental)

PEARLS & CONSIDERATIONS COMMENTS

•

Orthostatic hypotension is diagnosed by observing changes in blood pressure, but not by observing changes in heart rate.

•

Volume depletion should cause an increased heart rate upon standing, but the heart rate may not change upon standing in patients with autonomic dysfunction.

•

Pharmacotherapy with mineralocorticoids may require concomitant potassium replenishment and monitoring for hypertension.

•

Suspect OH when a patient has preexisting supine hyper tension.

•

Suspect POTS in young women with a marked increase in heart rate but no change in blood pressure upon standing.

SUGGESTED READINGS Jacob G, et al: The neuropathic postural tachycardia syndrome. N Engl J Med 2000; 343:1008. Kaufman H, et al: Mechanisms and causes of orthostatic and postprandial hypotension. In: Kasper, et al ed. Harrison's principles of internal medicine, ed 16. New York, NY: McGraw Hill; 2005:2430-2434. Shannon J, et al: Orthostatic intolerance and tachycardia associated with norepinephrine transporter deficiency. N Engl J Med 2000; 342:541.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Osgood-Schlatter Disease LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Osgood-Schlatter disease is a painful swelling of the tibial tuberosity that occurs in adolescence.

ICD-9CM CODES

732.4 Osgood-Schlatter disease EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 4 cases/100 adolescents PREDOMINANT SEX: Male:female ratio of 3:1 PREDOMINANT AGE: 11 to 15 yr (bilateral in 20%) PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pain at the tibial tubercle that is aggravated by activity, especially stair-walking and squatting

•

Tender swelling and enlargement of the tibial tubercle

•

Increased pain with knee extension against resistance

ETIOLOGY

•

Unknown

•

May be traumatically induced inflammation

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Referred hip pain (any child with hip pain should have a thorough clinical hip examination)

•

Patellar tendinitis

WORKUP

In most cases, the diagnosis is obvious on a clinical basis. IMAGING STUDIES

•

Lateral roentgenogram of the upper portion of the tibia with the leg slightly internally rotated may reveal variable degrees of separation and fragmentation of the upper tibial epiphysis ( Fig. 1-179 ).

•

Occasionally, fragmented area fails to unite to the tibia and persists into adulthood.

FIGURE 1-179 A, Radiograph of Osgood-Schlatter disease demonstrating thickening of patella tendon, fragmentation of the tibial tubercle, and soft tissue swelling. B, Clinical picture of bony prominence anteriorly at the tibial tubercle. (From Scuderi G [ed]: Sports medicine: principles of primary care, St Louis, 1997, Mosby.)

TREATMENT ACUTE GENERAL Rx

•

Ice, especially after exercise

•

NSAIDs

•

Gentle hamstring and quadriceps stretching exercises

•

Abstinence from physical activity

•

Temporary immobilization in a knee splint for 2 to 4 wk in resistant cases

DISPOSITION

•

Prognosis for complete restoration of function and relief from pain is excellent.

•

Condition usually heals when the epiphysis closes.

•

Complications are rare.

•

Symptoms in the adult: 1.

Although unusual, prominence of the tibial tubercle is usually permanent

2.

May be more susceptible to local irritation, especially when kneeling

3.

Rarely, nonunion of the epiphyseal fragment, but it is usually asymptomatic

4.

Surgery rarely required

REFERRAL

For orthopedic consultation when diagnosis is uncertain or when symptoms persist.

PEARLS & CONSIDERATIONS COMMENTS

Larsen-Johansson disease is a similar disorder that can develop where either the quadriceps or patellar tendon inserts into the patella. Treatment and prognosis are the same as with Osgood-Schlatter disease. SUGGESTED READINGS Bloom OJ, Mackler L, Barbee J: What is the best treatment for Osgood-Schlatter disease?. J Fam Pract 2004; 53(2):153. Cohen DA, Hinton RY: Bilateral tibial tubercle avulsion fractures associated with Osgood-Schlatter's disease. Am J Orthop 2008; 37:92. Duri ZA, Patel DV, Aichroth PM: The immature athlete. Clin Sports Med 2002; 21(3):461. Frank JB, et al: Lower extremity injuries in the skeletally immature athlete. J Am Acad Orthop Surg 2007; 15(6):356. Gholve PA, et al: Osgood Schlatter syndrome. Curr Opin Pediatr 2007; 19(1):44. Hirano A, et al: Magnetic resonance imaging of Osgood-Schlatter disease: the course of the disease. Skeletal Radiol 2002; 31(6):334. Ross MD, Villard D: Disability levels of college-aged men with history of Osgood-Schlatter disease. J Strength Cond Res 2003; 17(4):659

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Osteoarthritis LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Osteoarthritis is a joint condition in which degeneration and loss of articular cartilage occur, leading to pain and deformity. Two forms are usually recognized: primary (idiopathic) and secondary. The primary form may be localized or generalized. SYNONYMS

Degenerative joint disease Osteoarthrosis Arthrosis

ICD-9CM CODES

715.0 Osteoarthrosis and allied disorders EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 2% to 6% of general population PREDOMINANT SEX: Female = male PREDOMINANT AGE: >50 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Similar symptoms in most forms: stiffness, pain, and crepitus

•

Joint tenderness, swelling

•

Decreased range of motion

•

Crepitus with motion

•

Bony hypertrophy

•

Pain with range of motion

•

DIP joint involvement possibly leading to development of nodular swellings called Heberden's nodes ( Fig. 1-180 )

•

PIP joint involvement possibly leading to development of nodular swellings called Bouchard's nodes

FIGURE 1-180 Osteoarthritis of the distal interphalangeal (DIP) joints. This patient has the typical clinical findings of advanced osteoarthritis of the DIP joints, including large, firm swellings (Heberden's nodes), some of which are tender and red because of associated inflammation of the periarticular tissues and the joint. (From Klippel J, Dieppe P, Ferri F [eds]: Primary care rheumatology, London, 1999, Mosby.)

ETIOLOGY

Primary osteoarthritis is of unknown cause. Secondary osteoarthritis may result from a number of disorders including trauma, metabolic conditions, and other forms of arthritis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Bursitis, tendinitis

•

Radicular spine pain

•

Inflammatory arthritides

•

Infectious arthritis

WORKUP

•

No diagnostic test exists for degenerative joint disease.

•

Laboratory evaluation is normal.

•

Rheumatoid factor, ESR, CBC, and ANA tests may be required if inflammatory component is present.

•

Synovial fluid examination is generally normal.

IMAGING STUDIES

•

When knee is involved with pain, x-rays should always be taken with the patient standing

•

Roentgenographic evaluation reveals: 1.

Joint space narrowing

2.

Subchondral sclerosis

3.

New bone formation in the form of osteophytes

TREATMENT

•

Rest, restricted use or weight bearing, and heat

•

Walking aids such as a cane (often helpful for weight-bearing joints)

•

Suitable footwear

•

Gentle range of motion and strengthening exercise

•

Local creams and liniments to provide a counterirritant effect

•

Education, reassurance

ACUTE GENERAL Rx

•

Mild analgesics for joint pain

•

NSAIDs if inflammation is present

•

Occasional local corticosteroid injections

•

Mild antidepressants, especially at night, if depression is present

•

Viscosupplementation (injection of hyaluronic acid products into the degenerative joint) is of uncertain benefit

•

Nutritional supplements (glucosamine and chondroitin) are unproven

DISPOSITION

Progression is not always inevitable, and the prognosis is variable depending on the site and extent of the disease.

REFERRAL

Surgical consultation for patients not responding to medical management

PEARLS & CONSIDERATIONS COMMENTS

Surgical intervention is generally helpful in degenerative joint disease. Arthroplasty, arthrodesis, and realignment osteotomy are the most common procedures performed. Arthroscopic debridement (of the knee) appears to be of questionable value.

EVIDENCE

Evidence for pharmacologic therapy There is some evidence for the effectiveness of acetaminophen compared with placebo in the treatment of pain caused by osteoarthritis, although NSAIDs may be slightly more effective. [66] [67] [68] Two systematic reviews found that NSAIDs were effective at reducing short-term pain from osteoarthritis vs. placebo, the first in the hip and the second in the knee. [69] [70] There is limited evidence for the efficacy of intraarticular corticosteroid injections in the short-term treatment of osteoarthritic knee pain. [71] [72] There is good evidence for the effectiveness of joint replacement as a treatment in osteoarthritis. [73] [74] [75] [76]

Evidence-Based References 1. Towheed TE, et al: Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2003; 1: 2. Zhang W, Jones A, Doherty M: Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials. Ann Rheum Dis 2004; 63:901.Reviewed in: Bandolier J 127:2004. 3. Wegman A, et al: Nonsteroidal anti-inflammatory drugs or acetaminophen for osteoarthritis of hip or knee? A systematic review of evidence and guidelines. J Rheumatol 2004; 31:344.Reviewed in: Paracetamol for osteoarthritis, Bandolier J 127:2004. 4. Towheed T, et al: Analgesia and non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the hip. Cochrane Database Syst Rev 1997; 4:(Cochrane Review). Reviewed in Clin Evid 11:1560, 2004. 5. Watson MC, et al: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee. Cochrane Database Syst Rev 1997; 1: 6. Godwin M, Dawes M: Intra-articular steroid injections for painful knees: systematic review with metaanalysis. Can Fam Physician 2004; 50:241.

7. Arroll B, Goodyear-Smith F: Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ 2004; 328:869. 8. Callahan CM, et al: Patient outcomes following tricompartmental total knee replacement. A metaanalysis. JAMA 1994; 271:1349.Reviewed in: Clin Evid 11:1560, 2004. 9. Callahan CM, et al: Patient outcomes following unicompartmental or bicompartmental knee arthroplasty. A meta-analysis. J Arthroplasty 1994; 10:141.Reviewed in: Clin Evid 11:1560, 2004. 10. Kiebzak GM, et al: SF-36 general health status survey to determine patient satisfaction at short-term follow up after total hip and knee arthroplasty. J South Orthop Assoc 1997; 6:169.Reviewed in: Clin Evid 11:1560, 2004. 11. Hawker G, et al: Health-related quality of life after knee replacement. J Bone Joint Surg Am 1998; 80:163-173.Reviewed in: Clin Evid 11:1560-1588, 2004.

SUGGESTED READINGS Callahan JJ, et al: Results of Charnley total hip arthroplasty at a minimum of thirty years. J Bone Joint Surg 2004; 86A:690. Felson DT: Hyaluronate sodium injections for osteoarthritis: hope, hype and hard truths. Arch Intern Med 2002; 162:245. Hartofilakidis G, Karachalios T: Idiopathic osteoarthritis of the hip: incidence, classification and natural history of 272 cases. Orthopedics 2003; 26:161. Hinton R, et al: Osteoarthritis: diagnosis and therapeutic considerations. Am Fam Physician 2002; 65:841. Hunt SA, Jazrawi LM, Sherman OH: Arthroscopic management of osteoarthritis of the knee. J Am Orthop Surg 2002; 10:356. Kelly MA, et al: Osteoarthritis and beyond: a consensus on the past, present and future of hyaluronans in orthopedics. Orthopedics 2003; 26:1064. Leopold S, et al: Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. J Bone Joint Surg 2003; 85:1197. Lo HG: Intra-articular hyaluronic acid in treatment of knee osteoarthritis. JAMA 2003; 290:3115. Moseley JB, et al: A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002; 347:81. O'Connor MI: Sex differences in osteoarthritis of the hip and knee. J Am Acad Orthop Surg 2007; 15(suppl 1):S22. Ottaviani RA, et al: Inflammatory and immunological responses to hyaluronan preparations: study of a murine biocompatibility model. J Bone Joint Surg 2007; 89A:148. Pollo FE, Jackson RW: Knee bracing for unicompartmental osteoarthritis. J Am Acad Orthop Surg 2006; 14:5. Ramsey DK, et al: A mechanical theory for the effectiveness of bracing for medial compartment osteoarthritis of the knee. J Bone Joint Surg 2007; 89:2398. Salk RS, et al: Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized double-blind study. J Bone Joint Surg 2006; 88A:295.

Saltzman CL, et al: Impact of comorbidities on the measurement of health in patients with ankle osteoarthritis. J Bone Joint Surg 2006; 88A:2366. Scott WN, Clarke HD: Early knee arthritis: the role of arthroscopy. Orthopedics 2003; 26:943. Wai EK, Kreder HJ, Williams JI: Arthroscopic debridement of the knee for osteoarthritis in patients fifty years of age or older. J Bone Joint Surg 2002; 84(A):17. Wang C, et al: Therapeutic effects of hyaluronic acid in osteoarthritis of the knee. J Bone Joint Surg 2004; 86A:538. Wegman A, et al: Nonsteroidal antiinflammatory drugs or acetominophen for osteoarthritis of the hip or knee? A systematic review of evidence and guidelines. J Rheumatol 2004; 31:344.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Osteochondritis Dissecans LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Osteochondritis dissecans is a disorder in which a portion of cartilage and underlying subchondral bone separates from a joint surface and may even become detached. SYNONYMS

Osteochondrosis Talar dome fracture: commonly used in describing the lesion of the talus Panners disease (capitellum)

ICD-9CM CODES

732.7 Osteochondritis dissecans EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 0.3 cases/1000 persons PREDOMINANT SEX: Male:female ratio of 3:1 PREDOMINANT AGE: Onset at 10 to 30 yr The most common joint affected is the knee, with the lateral surface of the medial femoral condyle the most frequent area involved. The capitellum of the humerus, dome of the talus, shoulder, and hip may also be affected. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pain, stiffness, and swelling

•

Intermittent locking if the fragment becomes detached

•

Occasionally palpable loose body

•

Tenderness at the site of the lesion

•

When the knee is involved, positive Wilson's sign (pain with knee extension and internal rotation)

•

Some asymptomatic cases

ETIOLOGY

Unknown

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Acute fracture

•

Neoplasm

IMAGING STUDIES

•

Plain roentgenography to confirm the diagnosis ( Fig. 1-181 )

•

“Tunnel view” helpful in knee cases

•

Typical finding: radiolucent, semilunar line outlining the oval fragment of bone (but findings variable, depending on the amount of healing and stability)

•

MRI or bone scanning usually not necessary in establishing diagnosis but helpful in determining prognosis and management, especially with regards to the stability of the lesion

FIGURE 1-181 Osteochondritis dissecans of the knee. The “tunnel” view is often helpful in visualizing the defect. This fragment may become detached and form a loose body. This area should not be confused with the normal irregularity of the distal femoral epiphysis in young children.

TREATMENT ACUTE GENERAL Rx

•

Observation every 4 to 6 mo for patients in whom the lesion is asymptomatic

•

Symptomatic patients who are skeletally immature: 1.

Observation with an initial period of non–weight bearing for 6 to 8 wk (in knee cases)

2.

When symptoms subside, gradual resumption of activities

DISPOSITION

•

Juvenile cases with open epiphyses have a favorable prognosis.

•

Cases developing after skeletal maturity are more likely to develop osteoarthritis.

•

Large fragments, especially those in weight-bearing areas, have a more unfavorable prognosis, especially if they involve the lateral femoral condyle.

•

Loose body formation and degenerative joint disease are more common when condition develops after age 20 yr.

REFERRAL

For orthopedic consultation: •

For most adults with unstable lesions

•

If a loose body is present

•

If symptomatic care has failed

PEARLS & CONSIDERATIONS COMMENTS

•

Although inflammation is suggested by the name, it has not been shown to be of significance in this disorder. Osteochondral lesion or osteochondrosis dissecans may be more appropriate terms to describe these disorders.

•

Repetitive trauma with ischemic necrosis is the most likely cause.

•

The condition is often bilateral, especially in the knee, which could suggest the possibility of an endocrine or genetic basis.

•

This condition should always be considered in the patient whose “sprained ankle” does not improve over the usual course of treatment.

SUGGESTED READINGS Bramer JA, et al: Increased external tibial torsion and osteochondritis dissecans of the knee. Clin Orthop 2004; 422:175. Crawford DC, Safran MR: Osteochondritis dissecans of the knee. J Am Acad Orthop Surg 2006; 14:90. Frank JB, et al: Lower extremity injuries in the skeletally immature athlete. J Am Acad Orthop Surg 2007; 15:356. Hanna SA, et al: Bicondylar osteochondritis dissecans in the knee: a report of two cases. J Bone Joint Surg 2008; 90:232. Kobaynsh K, Burton KJ, et al: Lateral compression injuries in the pediatric elbow. Panner's disease and osteochondritis dissecans of the capitellum. J Am Acad Orthop Surg 2004; 12:246. Peh WC: Osteochondritis dissecans. Am J Orthop 2004; 33(1):46. Perumal V, et al: Juvenile osteochondritis dissecans of the talus. J Pediatr Orthop 2007; 27:821. Takahara M, et al: Classification, treatment and outcome of osteochondritis dissecans of the humeral capitellum. J Bone Joint Surg 2007; 89A:1205.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Osteomyelitis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Osteomyelitis is an acute or chronic infection of the bone secondary to the hematogenous or contiguous source of infection or direct traumatic inoculation, which is usually bacterial. SYNONYMS

Bone infection

ICD-9CM CODES

730.1 Chronic osteomyelitis 730.2 Acute or subacute osteomyelitis EPIDEMIOLOGY & DEMOGRAPHICS

PREDOMINANT SEX: Male > female PREDOMINANT AGE: All ages PHYSICAL FINDINGS & clinical presentation

HEMATOGENOUS OSTEOMYELITIS: Usually occurs in tibia/fibula (children). •

Localized inflammation: often secondary to trauma with accompanying hematoma or cellulitis

•

Abrupt fever

•

Lethargy

•

Irritability

•

Pain in involved bone

VERTEBRAL OSTEOMYELITIS: Usually hematogenous. •

Fever: 50%

•

Localized pain/tenderness

•

Neurologic defects: motor/sensory

CONTIGUOUS OSTEOMYELITIS: Direct inoculation. •

Associated with trauma, fractures, surgical fixation

•

Chronic infection of skin/soft tissue

•

Fever, drainage from surgical site

CHRONIC OSTEOMYELITIS: •

Bone pain

•

Sinus tract drainage, nonhealing ulcer

•

Chronic low-grade fever

•

Chronic localized pain

ETIOLOGY

•

Staphylococcus aureus

•

S. aureus (methicillin-resistant)

•

Pseudomonas aeruginosa

•

Enterobacteriaceae

•

Streptococcus pyogenes

•

Enterococcus

•

Mycobacteria

•

Fungi

•

Coagulase-negative staphylococci

•

Salmonella (in sickle cell disease)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Gaucher's disease

•

Bone infarction

•

Charcot's joint

•

Fracture

WORKUP

•

ESR, C-reactive protein

•

Blood culturing

•

Bone culture

•

Pathologic evaluation of bone biopsy for acute/chronic changes consistent with necrosis or acute inflammation

IMAGING STUDIES

•

Bone x-ray examination

•

Triple-phase bone scan ( Fig. 1-182 )

•

Gallium scan

•

Indium scan

•

CT or MRI (most accurate imaging study)

FIGURE 1-182 Osteomyelitis. Intense accumulation of Tc-99m WBC in proximal phalanx of fifth digit of left foot at 4 hours after injection. (From Specht N [ed]: Practical guide to diagnostic imaging, St Louis, 1998, Mosby.)

TREATMENT Surgical debridement in biopsy-positive cases will guide direction for antibiotic therapy. This will vary with type of osteomyelitis. Duration of therapy is usually 6 wk for acute osteomyelitis; chronic osteomyelitis may need a longer course of medication. •

S. aureus: cefazolin IV, nafcillin IV, vancomycin IV (in patient allergic to penicillin)

•

S. aureus (methicillin resistant): vancomycin IV, linezolid, daptomycin, or tigecycline

•

Streptococcus spp.: cefazolin or ceftriaxone

•

P. aeruginosa: piperacillin plus aminoglycoside or cefepime plus aminoglycoside

•

Enterobacteriaceae: ceftriaxone or fluoroquinolone

•

Hyperbaric oxygen therapy: may be useful in chronic osteomyelitis

•

Surgical debridement of all devitalized bone and tissue

•

Immobilization of affected bone (plaster, traction) if bone is unstable

DISPOSITION

Acute hematogenous osteomyelitis usually resolves without recurrence or long-term complications, but contiguous focus osteomyelitis, bone infections from open fractures, or osteomyelitis frequently recur. REFERRAL

•

To an orthopedic surgeon if chronic osteomyelitis with need for bone debridement, bone grafting, or stabilization of infected tissue adjacent to a bone fracture

•

To an infectious disease specialist for appropriate treatment for difficult-to-treat or recalcitrant infections

•

To an hyberbaric oxygen chamber service for nonhealing, chronic osteomyelitis

PEARLS & CONSIDERATIONS Chronic osteomyelitis is one of the most challenging infections to treat; the high failure rate is a consequence of poor vascular supply, nondistensible bone tissue, and limited penetration of bone tissue

EVIDENCE

The use of antibiotics had a protective effect against early infection in open fractures compared with no antibiotics or placebo.[[1]] We are unable to cite evidence for the other therapies used in osteomyelitis.

Evidence-Based Reference 1. Gosselin RA, Roberts I, Gillespie WJ: Antibiotics for preventing infection in open limb fractures. Cochrane Database Syst Rev 2003; 3:

SUGGESTED READINGS Joosten U, et al: Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Biomaterials 2005; 26(25):5251. Schinabeck MK, Johnson JL: Osteomyelitis in diabetic foot ulcers. Prompt diagnosis can avert amputation. Postgrad Med 2005; 118(1):11. Yin LY, et al: Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model. J Antimicrob Chemother 2005; 55(6):995.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Osteoporosis DENNIS M. WEPPNER, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Osteoporosis is characterized by a progressive decrease in bone mass that results in increased bone fragility and a higher fracture risk. The various types are as follows: PRIMARY OSTEOPOROSIS: 80% of women and 60% of men with osteoporosis •

Idiopathic osteoporosis: unknown pathogenesis; may occur in children and young adults

•

Type I osteoporosis: may occur in postmenopausal women (age range: 51 to 75 yr); characterized by accelerated and disproportionate trabecular bone loss and associated with vertebral body and distal forearm fractures (estrogen withdrawal effect)

•

Type II osteoporosis (involutional): occurs in both men and women >70 yr of age; characterized by both trabecular and cortical bone loss, and associated with fractures of the proximal humerus and tibia, femoral neck, and pelvis

SECONDARY OSTEOPOROSIS: 20% of women and 40% of men with osteoporosis; osteoporosis that exists as a common feature of another disease process, heritable disorder of connective tissue, or drug side effect (see “Differential Diagnosis”)

ICD-9CM CODES

733.0 Osteoporosis EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE (IN U.S.): •

Approximately 25 million men and women

•

Twice as common in women

•

Results in 1.5 million fractures annually (70% women)

•

Osteoporosis-related fractures in 50% women and 20% men >65 yr

•

Results: institutionalization, mortality, and costs in excess of $10 billion annually

RISK FACTORS:

•

Age: each decade after 40 yr associated with a fivefold increase risk

•

Genetics: 1.

Ethnicity (white/Asian > black > Polynesian)

2.

Gender (female > male)

3.

Family history

•

Environmental factors: poor nutrition, calcium deficiency, physical inactivity, medication (steroids/heparin), tobacco use, ETOH, traumatic injury

•

Chronic disease states: estrogen deficiency, androgen deficiency, hyperthyroidism, hypercortisolism, cirrhosis, gastrectomy

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most commonly silent with no signs and symptoms

•

Insidious and progressive development of dorsal kyphosis (dowager's hump), loss of height, and skeletal pain typically associated with fracture, other physical findings related to other conditions with associated increased risk for osteoporosis (see “Risk Factors”)

ETIOLOGY

•

Primary osteoporosis; multifactorial resulting from a combination of factors including nutrition, peak bone mass, genetics, level of physical activity, age of menopause (spontaneous vs. surgical), and estrogen status

•

Secondary osteoporosis: associated decrease in bone mass resulting from an identified cause, including endocrinopathies—hypogonadism, hyperthyroidism, hyperparathyroidism, Cushing's syndrome, hyperprolactinemia, acromegaly, diabetes mellitus, gastrointestinal disease, malabsorption, primary biliary cirrhosis, gastrectomy, malnutrition (including anorexia nervosa)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Malignancy (multiple myeloma, lymphoma, leukemia, metastatic carcinoma)

•

Primary hyperparathyroidism

•

Osteomalacia

•

Paget's disease

•

Osteogenesis imperfecta: types I, III, and IV (see also “Epidemiology and Demographics” and “Etiology”)

WORKUP

•

History and physical examination (20% of women with type I osteoporosis have associated secondary cause), with appropriate evaluation for identified risk factors and secondary causes

•

Diagnosis of osteoporosis made by bone mineral density (BMD) determination (BMD should ideally evaluate the hip, spine, and wrist): 1.

Dual-energy x-ray absorptiometry (DEXA)

2.

Single-energy x-ray

3.

Peripheral dual-energy x-ray

4.

Single-photon absorptiometry

5.

Dual-photon absorptiometry

6.

Quantitative CT scan

7.

Radiographic absorptiometry

LABORATORY TESTS

•

Biochemical profile to evaluate renal and hepatic function, primary hyperparathyroidism, and malnutrition

•

CBC for nutritional status and myeloma

•

TSH to rule out the presence of hyperthyroidism

•

Consideration of 24-hr urine collection for calcium (excess skeletal loss, vitamin D malabsorption/deficiency), creatinine, sodium, and free cortisol (to detect occult Cushing's disease); no need to measure calcitropic hormones (PTH, calcitriol, calcitonin) unless specifically indicated

•

Biochemical markers of bone remodeling; may be useful to predict rate of bone loss and/or follow therapy response; specific biochemical markers followed (e.g., 3-mo interval) to document normalization as a response to therapy 1.

High turnover osteoporosis: high levels of resorption markers (lysyl pyridinoline [LP], deoxy lysyl pyridinoline [DPD], n-telopeptide of collagen cross-links [NTX], C-telopeptide of collagen crosslinks [PICP]) and formation markers (osteocalcin [OCN], bone-specific alkaline phosphatase [BSAP], carboxy-terminal extension peptide of type I procollagen [PICP]); accelerated bone loss responding best to antiresorptive therapy

2.

Low-normal turnover osteoporosis: normal or low levels of the markers of resorption and formation (see “high turnover osteoporosis” above); no accelerated bone loss; responds best to drugs that enhance bone formation

IMAGING STUDIES

•

BMD determination (see “Workup”) should be performed on all women with determined risk factors and/or associated secondary causes; accepted screening criteria are currently being investigated. 1.

Normal: BMD 800 mg/day, vitamin D 400 to 800 U/day), physical activity, fracture prevention strategies

ACUTE GENERAL Rx

•

Vitamin D supplement: 400 U/day

•

Calcium supplement: 1000 to 1500 mg/day

•

Estrogen (conjugated equine estrogen or equivalent): 0.3 to 0.625 mg/day

•

Progestin: continuous (e.g., 2.5 mg medroxyprogesterone acetate/day or equivalent) or cyclic (e.g., 10 mg medroxyprogesterone acetate days 16 to 25 each month or equivalent) coadministered in nonhysterectomized women

•

Ibandronate (Boniva) 150 mg once monthly, swallow whole with 8 oz water on empty stomach, with no oral intake for at least 60 min. Do not lie down for 60 min after dose

•

Alendronate (10 mg/day) or risedronate (5 mg/day) on awakening with 8 oz water on empty stomach with no oral intake for at least 30 min

•

Alendronate (Fosamax): 70 mg once weekly on awakening, with 8 oz water on empty stomach, with no oral intake for at least 30 min. Use 70 mg dose for treatment of postmenopausal osteoporosis and a 35-mg tablet for the prevention of osteoporosis in postmenopausal women

•

Synthetic salmon calcitonin (Miacalcin): 100 U/day SC or 200 U/day intranasally

•

Raloxifene (Evista): 60 mg qd

•

Risedronate (Actonel): 35 mg once weekly on awakening with 8 oz water or empty stomach with no oral intake for at least 30 min. Do not lie down for 30 min after dose

•

Teriparatide (Forteo) is a recombinant human parathyroid hormone used for postmenopausal women with osteoporosis who are at high risk for fracture. It is also used in men with primary or hypogonadal osteoporosis who are at high risk of fracture. It is administered via injection 20 mcg qd SQ into thigh or abdominal wall. Use for >2 yr not recommended

•

Other FDA-approved drugs (without osteoporosis indication) used to treat osteoporosis: 1.

Calcitriol

2.

Etidronate

3.

Thiazide

•

Combination estrogen/alendronate or estrogen-progestin/alendronate may be considered in individualized patients on HRT with identified osteoporosis

•

BMD baseline obtained before onset of therapy and at 1 yr; decrease of 2% or greater results in dosage adjustment or medication change

•

Baseline biochemical markers of remodeling baseline considered; identified high turnover osteoporosis patients rescreened at 3 mo to document marker return to normal

CHRONIC Rx

•

Lifelong disorder requiring lifelong attention to behavior modification issues (nutrition, physical activity, fracture prevention strategies) and compliance with pharmacologic intervention

•

Continuing need to eliminate high-risk factors where possible and to diagnose and optimally manage secondary causes of osteoporosis

DISPOSITION

Goal for diagnosis and treatment: identification of women at risk, initiation of preventive measures for all women lifelong, institution of treatment modalities that will result in a decrease in fracture risk, and reduction of morbidity, mortality, and unnecessary institutionalization, thereby improving quality of independent life and productivity. REFERRAL

•

To reproductive endocrinologist, endocrinologist, gynecologist, or rheumatologist if unfamiliar with diagnosis and management of osteoporosis

•

If multidisciplinary management is required, to other specialties depending on presence of acute fracture and/or secondary associated disorders

EVIDENCE

In patients taking corticosteroids, calcium and vitamin D therapy are effective at preventing bone loss. In postmenopausal women, calcium and vitamin D appear to reduce the risk of hip fractures and other nonvertebral fractures after 18 months; the effect of either treatment alone is less clear. Calcium supplementation alone has a small positive effect on bone mineral density (BMD) in postmenopausal women. It probably also reduces the incidence of vertebral fractures.[[1]] Vitamin D with or without calcium supplementation appeared to decrease vertebral fractures in one metaanalysis and may also decrease nonvertebral fractures. No conclusions can be drawn about the relative effects of standard vitamin D and hydroxylated vitamin D.[[2]] However, another review of 14 randomized controlled trials (RCTs), has concluded that there is still uncertainty about the efficacy of treatment with vitamin D or its analogs in the prevention of fractures in elderly men and in women with involutional or postmenopausal osteoporosis.[[3]] Two further RCTs examining the effects of vitamin D3 alone vs. placebo have produced conflicting results.[[4]] Hormone replacement therapy (HRT) improves BMD and probably reduces the incidence of fracture in postmenopausal women. However, the overall health risks from HRT in this population appear to exceed the possible benefits. HRT has been shown to have a consistent, favorable, and large effect on BMD at all sites, with a nonsignificant trend toward a reduced incidence of vertebral and nonvertebral fractures.[[5]] Two recent large RCTs have concluded that the risks of HRT for indications such as the prevention of osteoporosis outweigh the benefits.[[6]] Risedronate substantially reduces the risk of both vertebral and nonvertebral fracture after the menopause.[[7]] Evidence suggests that alendronate increases BMD in men with osteoporosis. Calcitriol can reduce the rate of new vertebral deformity at 1 year in postmenopausal women. Two small RCTs included in a systematic review found a decrease in development of new vertebral deformity with women taking calcitriol vs. control.[[3]]

The evidence concerning exercise as a means of decreasing the rate of fractures due to falls is not clear. Two systematic reviews have studied the effect of exercise on fall reduction and subsequent fracture. They have produced conflicting results that have been difficult to analyze due to the differences in methods used and types of exercise studied.[[8]] The use of hip protectors may be associated with a reduction of hip fractures in the frail and elderly but the evidence is inconsistent. One systematic review analyzing only the results from cluster randomized studies indicates that, for those living in institutional care, the incidence of hip fracture can be reduced by the provision of hip protectors. There may however, be difficulties due to discomfort and practicality of use.[[9]] However, three RCTs found no significant difference in hip fracture occurrence in the groups using hip protectors vs. control, and one RCT only found a decrease in hip fracture rate of borderline significance in the hip protector group. [117] [118] A multifactorial interventional approach including nursing home staff education, exercise, walking aid provision, environmental manipulation, drug regime reviews, and the use of hip protectors significantly decreases the rate of hip fractures.

Evidence-Based References 1. Shea B et al: The Osteoporosis Methodology Group, and the Osteoporosis Research Advisory Group. Calcium supplementation on bone loss in postmenopausal women. 2. Papadimitropoulos E, et al: The Osteoporosis Methodology Group and the Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Endocr Rev 2002; 23:560.Reviewed in: 11:1450, 2004. 3. Gillespie WJ, et al: Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis, Reviewed. Cochrane Library, 3, Chichester, UK, John Wiley, 2004. 4. Trivedi DP, Doll R, Khaw KT: Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003; 326:469.11:1450, 2004. 5. Wells G, et al: The Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group: Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev 2002; 23:529. 6. Writing Group for the Women's Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.11:1450, 2004. 7. Cranney A, et al: Risedronate for the prevention and treatment of postmenopausal osteoporosis. Cochrane Database Syst Rev 2003; 4: 8. Gillespie LD, et al: Interventions for preventing falls in elderly people. Cochrane Database Syst Rev 2003; 4: 9. Parker MJ, Gillespie LD, Gillespie WJ: Hip protectors for preventing hip fractures in the elderly.

Cochrane Database Syst Rev 2004; 3: 10. van Schoor NM, et al: Prevention of hip fractures by external hip protectors: a randomised controlled trial. JAMA 2003; 289:1957.11:1450, 2004. 11. Meyer G, et al: Effect on hip fractures of increased use of hip protectors in nursing homes: cluster randomised controlled trial. BMJ 2003; 326:76.11:1450.

SUGGESTED READINGS Bone HG, et al: Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004; 350:12. Raisz LG: Screening for osteoporosis. N Engl J Med 2005; 353:164. Rosen CJ: Postmenopausal osteoporosis. N Engl J Med 2005; 353:595.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Otitis Externa GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JANE V. EASON, M.D.

BASIC INFORMATION DEFINITION

Otitis externa is a term encompassing a variety of conditions causing inflammation and/or infection of the external auditory canal (and/or auricle and tympanic membrane). There are six subgroups of otitis externa: •

Acute localized otitis externa (furunculosis)

•

Acute diffuse bacterial otitis externa (swimmer's ear)

•

Chronic otitis externa

•

Eczematous otitis externa

•

Fungal otitis externa (otomycosis)

•

Invasive or necrotizing (malignant) otitis externa ( Fig. 1-184 .)

FIGURE 1-184 Malignant external otitis. Severe infection of the ear has occurred after months of chronic inflammation of the pinna. (From Habif TP: Clinical dermatology: a color guide to diagnosis and therapy, ed 3, St Louis, 1996, Mosby.)

SYNONYMS

See “Definition.”

ICD-9CM CODES

38.10 Otitis externa EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.) •

Among the most common disorders

•

Affects 3% to 10% of patients seeking otologic care

PREVALENCE (IN U.S.) •

Diffuse otitis externa (swimmer's ear) is most often seen in swimmers and in hot, humid climates, conditions that lead to water retention in the ear canal.

•

Necrotizing otitis externa is more common in elderly, diabetics, immunocompromised patients.

PREDOMINANT SEX: None PREDOMINANT AGE: •

Occurs at all ages

•

Necrotizing otitis externa: typically occurs in elderly: mean age >65 yr

PHYSICAL FINDINGS & CLINICAL PRESENTATION

The two most common symptoms are otalgia, ranging from pruritus to severe pain exacerbated by motion (e.g., chewing), and otorrhea. Patients may also experience aural fullness and hearing loss secondary to swelling with occlusion of the canal. More intense symptoms may occur with bacterial otitis externa, with or without fever, and lymphadenopathy (anterior to tragus). There are also findings unique to the various forms of the infection: •

•

•

•

•

Acute localized otitis externa (furunculosis): 1.

Occurs from infected hair follicles, usually in the outer third of the ear canal, forming pustules and furuncles

2.

Furuncles are superficial and pointing or deep and diffuse

Impetigo: 1.

In contrast to furunculosis, this is a superficial spreading infection of the ear canal that may also involve the concha and the auricle

2.

Begins as a small blister that ruptures, releasing straw-colored fluid that dries as a golden crust

Erysipelas: 1.

Caused by group A streptococcus

2.

May involve the concha and canal

3.

May involve the dermis and deeper tissues

4.

Area of cellulitis, often with severe pain

5.

Fever chills, malaise

6.

Regional adenopathy

Eczematous otitis externa: 1.

Stems from a variety of dermatologic problems that can involve the external auditory canal

2.

Severe itching, erythema, scaling, crusting, and fissuring possible

Acute diffuse otitis externa (swimmer's ear):

•

•

•

1.

Begins with itching and a feeling of pressure and fullness in the ear that becomes increasingly tender and painful

2.

Mild erythema and edema of the external auditory canal, which may cause narrowing and occlusion of the canal, leading to hearing loss

3.

Minimal serous secretions, which may become profuse and purulent

4.

Tympanic membrane may appear dull and infected

5.

Usually absence of systemic symptoms such as fever, chills

Otomycosis: 1.

Chronic superficial infection of the ear canal and tympanic membrane

2.

In primary fungal infection, major symptom is intense itching

3.

In secondary infection (fungal infection superimposed on bacterial infection), major symptom is pain

4.

Fungal growth of variety of colors

Chronic otitis externa: 1.

Dry and atrophic canal

2.

Typically, lack of cerumen

3.

Itching, often severe, and mild discomfort rather than pain

4.

Occasionally, mucopurulent discharge

5.

With time, thickening of the walls of the canal, causing narrowing of the lumen

Necrotizing otitis externa (also known as malignant otitis externa). Typically seen in older patients with diabetes or in patients who are immunocompromised.

ETIOLOGY

1.

Redness, swelling, and tenderness of the ear canal

2.

Classic finding of granulation tissue on the floor of the canal and the bone-cartilage junction

3.

Small ulceration of necrotic soft tissue at bone-cartilage junction

4.

Most common complaints: pain (often severe) and otorrhea

5.

Lessening of purulent drainage as infection advances

6.

Facial nerve palsy often the first and only cranial nerve defect

7.

Possible involvement of other cranial nerves

•

Acute localized otitis externa: Staphylococcus aureus

•

Impetigo: 1.

S. aureus

2.

Streptococcus pyogenes

•

Erysipelas: S. pyogenes

•

Eczematous otitis externa:

•

•

1.

Seborrheic dermatitis

2.

Atopic dermatitis

3.

Psoriasis

4.

Neurodermatitis

5.

Lupus erythematosus

Acute diffuse otitis externa: 1.

Swimming

2.

Hot, humid climates

3.

Tightly fitting hearing aids

4.

Use of ear plugs

5.

Pseudomonas aeruginosa

6.

S. aureus

Otomycosis: 1.

Prolonged use of topical antibiotics and steroid preparations

2.

Aspergillus (80% to 90%)

3.

Candida

•

Chronic otitis externa: persistent low-grade infection and inflammation

•

Necrotizing otitis externa (NOE): 1.

Complication of persistent otitis externa

2.

Extends through Santorini's fissures, small apertures at the bone-cartilage junction of the canal, into the mastoid and along the base of the skull

3.

P. aeruginosa

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Acute otitis media

•

Bullous myringitis

•

Mastoiditis

•

Foreign bodies

•

Neoplasms

WORKUP

Thorough history and physical examination LABORATORY TESTS

•

Cultures from the canal are usually not necessary unless the patient is refractory to treatment.

•

Leukocyte count normal or mildly elevated.

•

ESR is often quite elevated in malignant otitis externa.

IMAGING STUDIES

•

CT scan is the best technique for defining bone involvement and extent of disease in malignant otitis externa.

•

MRI is slightly more sensitive in evaluation of soft tissue changes.

•

Gallium scans are more specific than bone scans in diagnosing NOE.

•

Follow-up scans are helpful in determining efficacy of treatment.

NOTE: Expert opinion supports history and physical examination as the best means of diagnosis. Persistent pain that is constant and severe should raise the question of NOE (particularly in elderly, diabetics, and immunocompromised).

TREATMENT NONPHARMACOLOGIC THERAPY

•

Cleansing and debridement of the ear canal with cotton swabs and hydrogen peroxide or other antiseptic solution allows for a more thorough examination of the ear.

•

If the canal lumen is edematous and too narrow to allow adequate cleansing, a cotton wick or gauze strip inserted into the canal serves as a conduit for topical medications to be drawn into the canal. Usually remove wick after 2 days.

•

Local heat is useful in treating deep furunculosis.

•

Incision and drainage is indicated in treatment of superficial pointing furunculosis.

ACUTE GENERAL Rx

Topical medications:

•

An acidifying agent, such as 2% acetic acid, inhibits growth of bacteria and fungi

•

Topical antibiotics (in the form of otic or ophthalmic solutions) or antifungals, often in combination with an acidifying agent and a steroid preparation

•

The following are some of the available preparations: 1.

a.

with polymyxin-B-hydrocortisone (Corticosporin)

b.

with hydrocortisone-thonzonium (Coly-Mycin S)

2.

Polymyxin-B-hydrocortisone (Otobiotic)

3.

Quinolone otic solutions:

4.

5.

•

Neomycin otic solutions and suspensions:

a.

Ofloxacin 0.3% solution (Floxin Otic)

b.

Ciprofloxacin 0.3% with hydrocortisone (Cipro HC)

Quinolone ophthalmic solutions: a.

Ofloxacin 0.3% (Ocuflox)

b.

Ciprofloxacin 0.3% (Ciloxan)

Aminoglycoside ophthalmic solutions: a.

Gentamicin sulfate 0.3% (Garamycin)

b.

Tobramycin sulfate 0.3% (Tobrex)

c.

Tobramycin 0.3% and dexamethasone 0.1% (TobraDex)

6.

Chloramphenicol 0.5% otic solution or 0.25% ophthalmic solution (Chloromycetin)

7.

Gentian violet (methylrosaniline chloride 1%, 2%)

8.

Antifungals: a.

Amphotericin B 3% (Fungizone lotion)

b.

Clotrimazole 1% solution (Lotrimin)

c.

Tolnaftate 1% (Tinactin)

Topical preparations should be applied qid (bid for quinolones, antifungals), generally for 3 days after cessation of symptoms (average 10 to 14 days total)

Systemic antibiotics: •

Reserved for severe cases, most often infections with P. aeruginosa or S. aureus

•

Treatment usually for 10 days with ciprofloxacin 750 mg q12h or ofloxacin 400 mg q12h, or with antistaphylococcal agent (e.g., dicloxacillin or cephalexin 500 mg q6h)

Treatment for NOE: •

Requires prolonged therapy up to 3 mo. Whether to use oral parenteral therapy is based on clinical judgment

•

Oral quinolones, ciprofloxacin 750 mg q12h or ofloxacin 400 mg q12h may be appropriate initial therapy or used to shorten the course of IV therapy

•

Intravenous antipseudomonals with or without aminoglycosides are also appropriate

•

Local debridement

Pain control:

•

May require NSAIDs or opioids

•

Topical corticosteroids to reduce swelling and inflammation

CHRONIC Rx

•

Patients prone to recurrent infections should try to identify and avoid precipitants to infection.

•

Swimmers should try tight-fitting ear plugs or tight-fitting bathing caps, and remove all excess water from the ears after swimming.

•

Treat underlying systemic diseases and dermatologic conditions that predispose to infection.

DISPOSITION

Inadequate treatment of otitis externa may lead to NOE and mastoiditis. REFERRAL

To an otolaryngologist: •

NOE

•

Treatment failure

•

Severe pain

PEARLS & CONSIDERATIONS Otitis externa varies in severity from a mild irritation of the external acoustic canal (swimmer's ear) that resolves spontaneously by simply removing the offending agent (stay out of fresh water or wear ear plugs) to a life-threatening infection with the risk of intracranial extension, gram-negative bacterial meningitis, and severe neurologic impairment with multiple cranial neuropathy. Don't miss severe malignant otitis externa in patients who are diabetic or immunocompromised.

EVIDENCE

Topical methylprednisolone-neomycin drops are an effective treatment of acute and chronic diffuse otitis externa.[[1]] Treatment with drops containing acetic acid alone results in a significantly lower cure rate and higher recurrence of symptoms of acute otitis media compared with treatment with corticosteroid and acetic acid or steroid and antibiotic drops.[[2]] In the treatment of acute diffuse otitis externa, no clinical benefit is derived from the addition of an oral antibiotic to a regimen of topical triamcinolone-neomycin-gramicidin ointment.[[3]] Evidence has not found topical quinolone preparations to be superior to other topical antiinfectives in the treatment of acute otitis externa. [125] [126] In the treatment of moderate to severe acute or chronic diffuse otitis externa, topical treatment with triamcinolone-neomycin undecenoate is associated with a higher resolution rate than hydrocortisoneneomycin sulfate-polymyxin B treatment.[[6]] Limited evidence suggests that topical preparations of neomycin-dexamethasone-acetic acid may be associated with an improved clinical outcome compared with agents not containing acetic acid. [128] [129]

Evidence-Based References 1. Cannon SJ, Grunwaldt E: Treatment of otitis externa with a topical steroid-antibiotic combination. Eye Ear Nose Throat Mon 1967; 46:1296-1302.Reviewed by Clin Evid 11:677, 2004. 2. van Balen FA, et al: Clinical efficacy of three common treatments in acute otitis externa in primary care: randomised controlled trial. BMJ 2003; 327:1201. 3. Yelland MJ: The efficacy of co-trimoxazole in the treatment of otitis externa in general practice. Med J Aust 1999; 158:697-699.Reviewed in: Clin Evid 11:677, 2004. 4. Pistorius B, et al: Prospective, randomized, comparative trial of ciprofloxacin otic drops, with or without hydrocortisone, vs polymyxin B-neomycin-hydrocortisone otic suspension in the treatment of acute diffuse otitis externa. Infect Dis Clin Pract 1999; 8:387.Reviewed in: Clin Evid 11:677, 2004. 5. Jones RN, Milazzo J, Seidlin M: Ofloxacin otic solution for treatment of otitis externa in children and adults. Arch Otolaryngol Head Neck Surg 1997; 123:1193.Reviewed in: Clin Evid 11:677, 2004. 6. Worgan D: Treatment of otitis externa. Report of a clinical trial. Practitioner 1969; 202:817820.Reviewed in: Clin Evid 11:677, 2004. 7. Smith RB, Moodie J: A general practice study to compare the efficacy and tolerability of a spray (“Otomize”) versus a standard drop formulation (“Sofradex”) in the treatment of patients with otitis externa. Curr Med Res Opin 1990; 12:12.Reviewed in: Clin Evid 11:677, 2004. 8. Smith RB, Moodie J: Comparative efficacy and tolerability of two antibacterial/anti-inflammatory formulations (‘Otomize’ spray and ‘Otosporin’ drops) in the treatment of otitis externa in general practice. Curr Res Med Opin 1990; 11:661.Reviewed in: Clin Evid 11:677, 2004.

SUGGESTED READINGS

Block SL: Otitis externa: providing relief while avoiding complications. J Fam Pract 2005; 54(8):669. Cantrell HF, et al: Declining susceptibility to neomycin and polymyxin B of pathogens recovered in otitis externa clinical trials. South Med J 2004; 97(5):465. Hajioff D: Otitis externa. Clin Evid 2004;755. McCoy SI, Zell ER, Besser RE: Antimicrobial prescribing for otitis externa in children. Pediatr Infect Dis J 2004; 23(2):181. Rutka J: Acute otitis externa: treatment perspectives. Ear Nose Throat J 2004; 83(9 Suppl 4):20.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Otitis Media GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JANE V. EASON, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

Otitis media is the presence of fluid in the middle ear accompanied by signs and symptoms of infection. SYNONYMS

Acute suppurative otitis media Purulent otitis media

ICD-9CM CODES

382.9

Acute or chronic otitis media

382.10 381.00 Otitis media with effusion EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Affects patients of all ages, but is largely a disease of infants and young children

•

Occurs once in about 75% of all children

•

Occurs three or more times in one third of all children by 3 yr of age

•

The diagnosis of acute otitis media increased from 9.9 million in 1975 to 25.5 million in 1990

•

From 1975 to 1990, office visits for acute otitis media increased threefold for children 0.1 µg/ml), ranging from 8% to 34%. About 50% of PNSSP isolates are penicillin-intermediate (MIC0.1 to 2.0 µg/ml)

Viral pathogens: 1.

Respiratory syncytial virus

2.

Rhinovirus

3.

Adenovirus

4.

Influenza

Others: 1.

Mycoplasma pneumoniae

2.

Chlamydia trachomatis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Otitis externa

•

Referred pain

•

1.

Mouth

2.

Nasopharynx

3.

Tonsils

4.

Other parts of the upper respiratory tract

Section II describes the differential diagnosis of earache

WORKUP

Thorough otoscopic examination; adequate visualization of the tympanic membrane requires removal of cerumen and debris.

•

•

Tympanometry 1.

Measures compliance of the tympanic membrane and middle ear pressure

2.

Detects the presence of fluid

Acoustic reflectometry 1.

Measures sound waves reflected from the middle ear

2.

Useful in infants >3 mo

3.

Increased reflected sound correlated with the presence of effusion

LABORATORY TESTS

•

Tympanocentesis 1.

Not necessary in most cases as the microbiology of middle ear effusions has been shown to be quite consistent

2.

May be indicated in: a.

Highly toxic patients

b.

Patients who fail to respond to treatment in 48 to 72 hr

c.

Immunocompromised patients

•

Cultures of the nasopharynx: sensitive but not specific

•

Blood counts: usually show a leukocytosis with polymorphonuclear elevation

•

Plain mastoid radiographs: generally not indicated; will reveal haziness in the periantral cells that may extend to entire mastoid

•

CT or MRI may be indicated if serious complications suspected (meningitis, brain abscess)

TREATMENT ACUTE GENERAL Rx

Hydration, avoidance of irritants (e.g., tobacco smoke), nasal systemic decongestants, cool mist humidifier Antimicrobials: NOTE: Most uncomplicated cases of acute otitis media resolve spontaneously, without complications. Studies have demonstrated limited therapeutic benefit from antibiotic therapy. However, when opting to employ antibiotic therapy:

•

Amoxicillin remains the drug of choice for first-line treatment of uncomplicated acute otitis media, despite increasing prevalence of drug-resistant S. pneumoniae.

•

Treatment failure is defined by lack of clinical improvement of signs or symptoms after 3 days of therapy.

•

With treatment failure, in the absence of an identified etiologic pathogen, therapy should be redirected to cover. 1.

Drug-resistant S. pneumoniae

2.

ß-lactamase–producing strains of H. influenzae and M. catarrhalis

•

Agents fulfilling these criteria include amoxicillin/clavulanate, second-generation cephalosporins (e.g., cefuroxime axetil, cefaclor); ceftriaxone (given IM). Cefaclor, cefixime, loracarbef and ceftibuten are active against H. influenzae and M. catarrhalis, but less active against pneumococci, especially drug resistant strains, than the agents listed previously.

•

TMP/SMX and macrolides have been used as first- and second-line agents, but pneumococcal resistance to these agents is rising (up to 25% resistance to TMP/SMX, and up to 10% resistance to erythromycin).

•

Cross-resistance between these drugs and the ß-lactams exist; therefore patients who are treatment failures on amoxicillin are more likely to have infections resistant to TMP/SMX and macrolides.

•

Newer fluoroquinolones (grepafloxacin, levofloxacin, moxifloxacin) have enhanced activity against pneumococci as compared with older agents (ciprofloxacin, ofloxacin).

•

Treatment should be modified according to cultures and sensitivities.

•

Generally treatment course is 10 to 14 days.

•

Follow up approximately 4 wk after discontinuation of therapy to verify resolution of all symptoms, return to normal otoscopic findings, and restoration of normal hearing.

NOTE: Effusions may persist for 2 to 6 wk or longer in many cases of adequately treated otitis media. SURGICAL Rx

•

No evidence to support the routine of myringotomy, but in severe cases it provides prompt pain relief and accelerates resolution of infection.

•

Purulent secretions retained in the middle ear lead to increased pressure that may lead to spread of infection to contiguous areas. Myringotomy to decompress the middle ear is necessary to avoid complications.

•

Complications include mastoiditis, facial nerve paralysis, labyrinthitis, meningitis, brain abscess.

•

Other procedures used for drainage of the middle ear include insertion of a ventilation tube and/or simple mastoidectomy.

CHRONIC Rx

•

Myringotomy and tympanostomy tube placement for persistent middle ear effusion unresponsive to medical therapy for =3 mo if bilateral or =6 mo if unilateral.

•

Adenoidectomy, with or without tonsillectomy, often advocated for treatment of recurrent otitis media, although indications for this procedure are controversial.

•

Chronic complications include tympanic membrane perforations, cholesteatoma, tympanosclerosis, ossicular necrosis, toxic or suppurative labyrinthitis, and intracranial suppuration.

DISPOSITION

Patients can be treated at home as outpatients with the rare exception of patients with evidence of local suppurative complications (e.g., meningitis, acute mastoiditis, brain abscess, cavernous sinus, or lateral vein

thrombosis). REFERRAL

•

To otorhinolaryngologist if: 1.

Medical treatment failure

2.

Diagnosis uncertain: adults with =1 episode of otitis media should be referred for ENT evaluation to rule out underlying process (e.g., malignancy)

3.

Any of the above mentioned acute and chronic complications

PEARLS & CONSIDERATIONS COMMENTS

Prevention: •

Multiple component conjugate vaccines hold promise for decreasing recurrent episodes of acute otitis media

•

Breast-feeding, bottle-feeding infants in an upright position

•

Avoidance of irritants (e.g., tobacco smoke)

EVIDENCE

Antibiotics appear to have a modest role in the management of acute otitis media. In acute otitis media in children, a short course of an appropriate antibiotic is modestly effective. [135] [136] [137] [138]

There is no evidence that the choice of a particular antibiotic influences the outcome, and extending antimicrobial coverage to include beta-lactamase-producing organisms did not significantly increase the rates of primary control or resolution of middle ear effusion.[[1]] However, in children younger than 2 years with acute otitis media, antibiotic therapy may not be effective. [[5]]

Immediate use of antibiotics vs. delayed use reduces the duration of earache, the number of disturbed nights, the number of days of crying, and the consumption of acetaminophen. However, it does not reduce the mean daily pain score, the number of episodes of pain each day, or the number of days of absence from school.[[6]] There is conflicting evidence about the effects of antibiotics in otitis media with effusion. A systematic review found that antibiotics vs. placebo or vs. no treatment significantly increased resolution of effusion at follow-up for up to 1 month.[[7]]

However, another systematic review failed to find a significant effect on cure rate of effusion with antibiotics vs. placebo.[[8]] In chronic otitis media with suppuration, oral antibiotics seem to be associated with resolution of otorrhea but are less effective than topical antibiotics. A systematic review of randomized trials of any method of management for patients with eardrum perforation and persistent otorrhea concluded that treatment with antibiotics or antiseptics accompanied by aural toilet was more effective in resolving otorrhea than no treatment or aural toilet alone.[[9]] However, the review concluded that long-term outcomes, such as prevention of recurrence, closure of tympanic perforation, and hearing improvement, need to be further evaluated.[[9]] Trials included in this review compared topical vs. systemic antibiotics and found that systemic treatment was less effective. [144] [145] There is some evidence supporting the effectiveness of tympanostomy tubes in the management of otitis media with effusion. The insertion of tympanostomy tubes in children with otitis media with effusion has been found to result in hearing improvement.[[12]] There is conflicting evidence about the efficacy of adenoidectomy in the treatment of otitis media with effusion. Adenoidectomy has been shown to give little additional benefit over tympanostomy tubes alone in terms of hearing gain.[[12]] However, a subsequent randomized controlled trial of adenotonsillectomy or adenoidectomy vs. neither procedure found that there was a statistically significant benefit in combining adenoidectomy with tympanostomy tubes in terms of reduced duration of otitis media with effusion.[[13]] Analgesia may be effective in reducing earache but not other outcomes. A randomized controlled trial in children with acute otitis media, receiving antibiotic treatment with cefaclor for 7 days, compared the effect of three times daily ibuprofen or paracetamol vs. placebo (for 48 hr). It found that paracetamol vs. placebo significantly reduced earache. No difference was found between paracetamol and ibuprofen, and none between ibuprofen or paracetamol and placebo for other outcomes.[[14]]

Evidence-Based References 1. Rosenfeld RM, et al: Clinical efficacy of antimicrobial drugs for acute otitis media: metaanalysis of 5400 children from thirty-three randomized trials. J Pediatr 1994; 124:355.Reviewed in: Clin Evid 11:314, 2004. 2. Marcy M, et al: Management of acute otitis media. Evidence Report/Technology Assessment No.15. AHRQ Publication No 01-E010, Rockville, MD, Agency for Healthcare Research and Quality, 2001. May. Reviewed in: Clin Evid 11:314, 2004. 3. Glasziou PP, et al: Antibiotics for acute otitis media in children. Reviewed. Cochrane Library, 2, Chichester, UK, John Wiley, 2004. 4. Kozyrskyj AL, et al: Short course antibiotics for acute otitis media. Reviewed. Cochrane Library, 2, Chichester, UK, John Wiley, 2004. 5. Damoiseaux RA, et al: Antibiotic treatment of acute otitis media in children under two years of age: evidence based?. Br J Gen Pract 1998; 48:1861.Reviewed in: Clin Evid 11:314, 2004. 6. Little P, et al: Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ 2001; 322:336.Reviewed in: Clin Evid 11:314, 2004. 7. Stool SE, et al: Otitis media with effusion in young children: clinical practice guideline number 12. AHPCR Publication 94-0622, Rockville, MD, Agency of Health Care Policy and Research, Public Health Service, United States Department of Health and Human Services, 1994. July. Reviewed in: Clin Evid 11:684, 2004. 8. Cantekin EI, McGuire TW: Antibiotics are not effective for otitis media with effusion: reanalysis of meta-analysis. Otorhinolaryngol Nova 1998; 8:214.Reviewed in: Clin Evid 11:684, 2004. 9. Acuin J, Smith A, Mackenzie I: Interventions for chronic suppurative otitis media. Reviewed. Cochrane Library, 2, Chichester, UK, John Wiley, 2004. 10. Browning G, et al: Controlled trial of medical treatment of active chronic otitis media. BMJ 1983; 287:1024.Reviewed in: Clin Evid 11:645, 2004. 11. Yuen P, et al: Ofloxacin eardrop treatment for active chronic suppurative otitis media: prospective randomized study. Am J Otol 1994; 15:670.Reviewed in: Clin Evid 11:645, 2004. 12. University of York. Centre for Reviews and Dissemination: The treatment of persistent glue ear in children. Effective Health Care 1992; 1(4):Reviewed in: Clin Evid 11:684, 2004. 13. Maw R, Bawden R: Spontaneous resolution of severe chronic glue ear in children and the effect of adenoidectomy, tonsillectomy, and insertion of ventilation tubes. BMJ 1993; 306:756.Reviewed in: Clin Evid 11:684, 2004. 14. Bertin L, et al: A randomized double blind multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children. Fundam Clin Pharmacol 1996; 10:387.Reviewed in: Clin Evid 11:314, 2004.

SUGGESTED READINGS American Academy of Pediatrics/American Academy of Family Physicians: Diagnosis and management of acute otitis media. Pediatrics 2004; 113(5):1451. Brook I, Gober AE: Antimicrobial resistance in the nasopharyngeal flora of children with acute otitis media and otitis media recurring after amoxicillin therapy. J Med Microbiol 2005; 54(Pt1):83.

Damoiseaux RA, et al: Long-term prognosis of acute otitis media in infancy: determinants of recurrent acute otitis media and persistent middle ear effusion. Fam Pract 2006; 23(1):40. Kenna MA: Otitis media and the new guidelines. J Otolaryngol 2005; 34(suppl 1):S24. Plasschaert AL, et al: Trends in doctor consultations, antibiotic prescription, and specialist referrals for otitis media in children: 1995–2003. Pediatrics 2006; 117(6):1879. Rovers MM, et al: Otitis media. Lancet 2004; 363(9407):465.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Otosclerosis (Otospongiosis) FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Otosclerosis is a conductive hearing loss secondary to fixation of the stapes resulting in gradual hearing loss. About 15% of cases affect only one ear.

ICD-9CM CODES

387.9 Otosclerosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Most common cause of hearing loss in young adults PEAK INCIDENCE: Middle age PREVALENCE (IN U.S.): 5 cases/1000 persons PREDOMINANT SEX: Male:female ratio of 2:1 PREDOMINANT AGE: Symptoms start between 15 and 30 yr, with slowly progressive hearing loss. GENETICS: One half of cases are dominantly inherited. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Tympanic membrane is normal in most cases (tested with tuning fork).

•

Bone conduction is greater than air conduction.

•

Weber test localizes to affected ear.

ETIOLOGY

•

A disease where vascular type of spongy bone is laid down

•

Unknown

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Hearing loss from any cause: cochlear otosclerosis, polyps, granulomas, tumors, osteogenesis imperfecta, chronic ear infections, trauma.

•

A clinical algorithm for evaluation of hearing loss is described in Section III.

•

Table 1-33 describes common types of conductive and sensorineural hearing loss.

TABLE 1-33 -- Common Types of Conductive and Sensorineural Hearing Loss Conductive Hearing Loss Sensorineural Hearing Loss Otitis media with effusion

Presbycusis (hearing loss with aging)

TM perforation

Ototoxicity

Tympanosclerosis

Meniere's disease

Retracted TM (eustachian tube dysfunction) Idiopathic loss Ossicular problems

Noise-induced loss

Otosclerosis

Perilymphatic flstula

Foreign body in ear canal

Hereditary (congenital) loss

Cerumen impaction

Multiple sclerosis

Tumor of the ear canal or middle ear

Diabetes

Cholesteatoma

Syphilis Acoustic neuroma

From Rakel RE (ed): Principles of family practice, ed 6, Philadelphia, 2002, WB Saunders. TM, Tympanic membrane. WORKUP

Audiometry LABORATORY TESTS

None, unless infection suspected IMAGING STUDIES

MRI or CT with specific cuts through inner ear ( Fig. 1-187 )

FIGURE 1-187 A patient with conductive hearing loss. By comparing the normal (A) and abnormal (B) sides on CT scan, the narrowing of the oval window can be clearly appreciated. This results in fixation of the stapes footplate and conductive hearing loss. (From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger & Allison's diagnostic radiology, ed 4, Philadelphia, 2001, Churchill Livingstone.)

TREATMENT NONPHARMACOLOGIC THERAPY

Hearing aid only of temporary use CHRONIC Rx

Progresses to deafness without surgical intervention DISPOSITION

Referral to ENT specialist REFERRAL

To ENT specialist for surgery if moderate hearing loss suspected

PEARLS & CONSIDERATIONS COMMENTS

A full ENT evaluation in a young or middle-aged person with hearing loss is mandatory unless cause is obvious (such as trauma or repeated infection). SUGGESTED READINGS

Chole RA, McKenna M: Pathophysiology of otosclerosis. Otol Neurotol 2001; 22(2):249.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ovarian Cancer GIL FARKASH, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Ovarian tumors can be benign, requiring operative intervention but not recurring or metastasizing; malignant, recurring, metastasizing, and having decreased survival; or borderline, having a small risk of recurrence or metastases but generally having a good prognosis. SYNONYMS

Epithelial ovarian cancer Germ cell tumor Sex cord stromal tumor Ovarian tumor of low malignant potential

ICD-9CM CODES

183.0 Malignant neoplasm of ovary EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 12.9 to 15.1 cases/100,000 persons; approximately 25,000 new cases annually PREVALENCE: Median age of 61 yr, peaks at age 75 to 79 yr (54/100,000) GENETICS: Familial susceptibility has been shown with the BRCA1 gene located on 17q12 to 21. This correlates with breast-ovarian cancer syndrome. RISK FACTORS: Low parity, delayed childbearing, use of talc on the perineum (unlikely), high-fat diet, fertility drugs (unlikely), Lynch II syndrome (nonpolyposis colon cancer, endometrial cancer, breast cancer, and ovarian cancer clusters in first- and second-degree relatives), breast-ovarian familial cancer syndrome, site-specific familial ovarian cancer (note: Use of oral contraceptives appears to have a protective effect.) PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

60% present with advanced disease

•

Abdominal fullness, early satiety, dyspepsia

•

Pelvic pain, back pain, constipation

•

Pelvic or abdominal mass

•

Lymphadenopathy (inguinal)

•

Sister Mary Joseph nodule (umbilical mass)

ETIOLOGY

•

Can be inherited as site-specific familial ovarian cancer (two or more first-degree relatives have ovarian cancer)

•

Breast-ovarian cancer syndrome (clusters of breast and ovarian cancer among first- and second-degree relatives)

•

Lynch syndrome

•

No family history and unknown etiology in the majority of ovarian cancer cases

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Primary peritoneal cancer mesothelioma

•

Benign ovarian tumor

•

Functional ovarian cyst

•

Endometriosis

•

Ovarian torsion

•

Pelvic kidney

•

Pedunculated uterine fibroid

•

Primary cancer from breast, GI tract, or other pelvic organ metastasized to the ovary

WORKUP

•

Definitive diagnosis made at laparotomy

•

Careful physical and history including family history

•

Exclusion of nongynecologic etiologies

•

Observation of small, cystic masses in premenopausal women for regression for 2 mo

LABORATORY TESTS

•

CBC

•

Chemistry profile

•

CA-125 or lysophosphatidic acid level

•

Consider: hCG, Inhibin, AFP, neuron-specific enolase (NSE), and LDH in patients at risk for germ cell tumors

IMAGING STUDIES

•

Ultrasound

•

Chest x-ray examination

•

Mammogram

•

CT scan to help evaluate extent of disease

•

Other studies (BE, MRI, IVP, etc.) as clinically indicated

TREATMENT NONPHARMACOLOGIC THERAPY

Virtually all cases of ovarian cancer involve surgical exploration. This includes: •

Abdominal cytology

•

Total abdominal hysterectomy and bilateral salpingo-oophorectomy (except in early stages where fertility is an issue)

•

Omentectomy

•

Diaphragm sampling

•

Selective lymphadenectomy (pelvis and paraaortic)

•

Primary cytoreduction with a goal of residual tumor diameter 220,000 hospital admissions in the U.S. each year.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Epigastric tenderness and guarding; pain usually developing suddenly, reaching peak intensity within 10 to 30 min, severe and lasting several hours without relief

•

Hypoactive bowel sounds (secondary to ileus)

•

Tachycardia, shock (secondary to decreased intravascular volume)

•

Confusion (secondary to metabolic disturbances)

•

Fever

•

Tachycardia, decreased breath sounds (atelectasis, pleural effusions, ARDS)

•

Jaundice (secondary to obstruction or compression of biliary tract)

•

Ascites (secondary to tear in pancreatic duct, leaking pseudocyst)

•

Palpable abdominal mass (pseudocyst, phlegmon, abscess, carcinoma)

•

Evidence of hypocalcemia (Chvostek's sign, Trousseau's sign)

•

Evidence of intraabdominal bleeding (hemorrhagic pancreatitis):

•

1.

Gray-bluish discoloration around the umbilicus (Cullen's sign)

2.

Bluish discoloration involving the flanks (Grey Turner's sign)

Tender subcutaneous nodules (caused by subcutaneous fat necrosis)

ETIOLOGY

•

In >90% of cases: biliary tract disease (calculi or sludge) or alcohol

•

Drugs (e.g., thiazides, furosemide, corticosteroids, tetracycline, estrogens, valproic acid, metronidazole, azathioprine, methyldopa, pentamidine, ethacrynic acid, procainamide, sulindac, nitrofurantoin, ACE inhibitors, danazol, cimetidine, piroxicam, gold, ranitidine, sulfasalazine, isoniazid, acetaminophen, cisplatin, opiates, erythromycin)

•

Abdominal trauma

•

Surgery

•

ERCP

•

Infections (predominantly viral infections)

•

Peptic ulcer (penetrating duodenal ulcer)

•

Pancreas divisum (congenital failure to fuse of dorsal or ventral pancreas)

•

Idiopathic

•

Pregnancy

•

Vascular (vasculitis, ischemic)

•

Hypolipoproteinemia (types I, IV, and V)

•

Hypercalcemia

•

Pancreatic carcinoma (primary or metastatic)

•

Renal failure

•

Hereditary pancreatitis

•

Occupational exposure to chemicals: methanol, cobalt, zinc, mercuric chloride, creosol, lead, organophosphates, chlorinated naphthalenes

•

Others: scorpion bite, obstruction at ampulla region (neoplasm, duodenal diverticula, Crohn's disease), hypotensive shock, autoimmune pancreatitis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

PUD

•

Acute cholangitis, biliary colic

•

High intestinal obstruction

•

Early acute appendicitis

•

Mesenteric vascular obstruction

•

DKA

•

Pneumonia (basilar)

•

Myocardial infarction (inferior wall)

•

Renal colic

•

Ruptured or dissecting aortic aneurysm

•

Mesenteric ischemia

LABORATORY TESTS

Pancreatic enzymes •

Amylase is increased, usually elevated in the initial 3 to 5 days of acute pancreatitis. Isoamylase determinations (separation of pancreatic cell isoenzyme components of amylase) are useful in excluding occasional cases of salivary hyperamylasemia. The use of isoamylase rather than total serum amylase reduces the risk of erroneously diagnosing pancreatitis and is preferred by some as initial biochemical test in patients suspected of having acute pancreatitis.

•

Urinary amylase determinations are useful to diagnose acute pancreatitis in patients with lipemic serum, to rule out elevated serum amylase secondary to macroamylasemia, and to diagnose acute pancreatitis in patients whose serum amylase is normal.

•

Serum lipase levels are elevated in acute pancreatitis; the elevation is less transient than serum amylase; concomitant evaluation of serum amylase and lipase increases diagnostic accuracy of acute pancreatitis. An elevated lipase/amylase ratio is suggestive of alcoholic pancreatitis.

•

Elevated serum trypsin levels are diagnostic of pancreatitis (in absence of renal failure); measurement is made by radioimmunoassay. Although not routinely available, the serum trypsin level is the most accurate laboratory indicator for pancreatitis.

•

Rapid measurement of urinary trypsinogen-2 (if available) is useful in the ER as a screening test for acute pancreatitis in patients with abdominal pain; a negative dipstick test for urinary trypsinogen-2 rules out acute pancreatitis with a high degree of probability, whereas a positive test indicates need for further evaluation.

Additional tests:

•

CBC: reveals leukocytosis; Hct may be initially increased secondary to hemoconcentration; decreased Hct may indicate hemorrhage or hemolysis.

•

BUN is increased secondary to dehydration.

•

Elevation of serum glucose in previously normal patient correlates with the degree of pancreatic malfunction and may be related to increased release of glycogen, catecholamines, and glucocorticoid release and decreased insulin release.

•

Liver profile: AST and LDH are increased secondary to tissue necrosis; bilirubin and alkaline phosphatase may be increased secondary to common bile duct obstruction. A threefold or greater rise in serum ALT concentrations is an excellent indicator (95% probability) of biliary pancreatitis.

•

Serum calcium is decreased secondary to saponification, precipitation, and decreased PTH response.

•

ABGs: Pao2 may be decreased secondary to ARDS, pleural effusion(s); pH may be decreased secondary to lactic acidosis, respiratory acidosis, and renal insufficiency.

•

Serum electrolytes: potassium may be increased secondary to acidosis or renal insufficiency, sodium may be increased secondary to dehydration.

IMAGING STUDIES

•

Abdominal plain film is useful initially to distinguish other conditions that may mimic pancreatitis (perforated viscus); it may reveal localized ileus (sentinel loop), pancreatic calcifications (chronic pancreatitis), blurring of left psoas shadow, dilation of transverse colon, calcified gallstones.

•

Chest x-ray may reveal elevation of one or both diaphragms, pleural effusions, basilar infiltrates, platelike atelectasis.

•

Abdominal ultrasonography is useful in detecting gallstones (sensitivity of 60% to 70% for detecting stones associated with pancreatitis). It is also useful for detecting pancreatic pseudocysts; its major limitation is the presence of distended bowel loops overlying the pancreas.

•

CT scan is superior to ultrasonography in identifying pancreatitis and defining its extent, and it also plays a role in diagnosing pseudocysts (they appear as a well-defined area surrounded by a high-density capsule); GI fistulation or infection of a pseudocyst can also be identified by the presence of gas within the pseudocyst. Sequential contrast enhanced CT is useful for detection of pancreatic necrosis ( Fig. 1-191 ). The severity of pancreatitis can also be graded by CT scan. (A = normal pancreas, B = enlarged pancreas [1 point], C = pancreatic and/or peripancreatic inflammation [2 points], D = single peripancreatic collection [3 points], E = at least 2 peripancreatic collections and/or retroperitoneal air [4 points]. Percentage of pancreatic necrosis 50% [6 points]. The CT severity index is calculated by adding grade points to points assigned for percentage of necrosis.)

•

Magnetic resonance cholangiopancreatography (MRCP) is also a useful diagnostic modality if a surgical procedure is not anticipated.

•

ERCP should not be performed during the acute stage of disease unless it is necessary to remove an impacted stone in the ampulla of Vater; patients with severe or worsening pancreatitis but without obstructive jaundice (biliary obstruction) do not benefit from early ERCP and papillotomy.

FIGURE 1-191 Acute necrotizing pancreatitis. Dynamic CT shows enlargement of the pancreas, a thin rim of contrast-enhancement (arrows) and lack of enhancement of the pancreatic parenchyma indicating almost complete gland necrosis (cursors 1 and 2 measure soft tissue density: 25 to 30 Hounsfield units). Small islands of normally enhancing parenchyma are seen (P) Patient died despite surgery. (From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger & Allison's diagnostic radiology, ed 4, Philadelphia, 2001, Churchill Livingstone.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Bowel rest with avoidance of PO liquids or solids during the acute illness

•

Avoidance of alcohol and any drugs associated with pancreatitis

ACUTE GENERAL

General measures:

•

Maintain adequate intravascular volume with vigorous IV hydration.

•

Patient should remain NPO until clinically improved, stable, and hungry. Enteral feedings are preferred over total parenteral nutrition (TPN). Parenteral nutrition may be necessary in patients who do not tolerate enteral feeding or in whom an adequate infusion rate cannot be reached within 2 to 4 days.

•

Nasogastric suction is useful only in severe pancreatitis to decompress the abdomen in patients with ileus.

•

Control pain: IV morphine or fentanyl

•

Correct metabolic abnormalities (e.g., replace calcium and magnesium as necessary).

Specific measures: •

•

•

Pancreatic or peripancreatic infection develops in 40% to 70% of patients with pancreatic necrosis. However, IV antibiotics should not be used prophylactically for all cases of pancreatitis; their use is justified if the patient has evidence of septicemia, pancreatic abscess, or pancreatitis secondary to biliary calculi. Their use should generally be limited to 5 to 7 days to prevent development of fungal superinfection. Appropriate empiric antibiotic therapy should cover: 1.

B. fragilis and other anaerobes (cefotetan, cefoxitin, metronidazole, or clindamycin plus aminoglycoside)

2.

Enterococcus (ampicillin)

Surgical therapy has a limited role in acute pancreatitis; it is indicated in the following: 1.

Gallstone-induced pancreatitis: cholecystectomy when acute pancreatitis subsides

2.

Perforated peptic ulcer

3.

Excision or drainage of necrotic or infected foci. Necrosectomy (debridement) with placement of wide-bore drains for continuous postoperative irrigation is the preferred surgical procedure. Surgery is not indicated for patients with sterile necrosis unless there is clinical deterioration despite intensive medical care

Identification and treatment of complications: 1.

Pseudocyst: round or spheroid collection of fluid, tissue, pancreatic enzymes, and blood. a.

Diagnosed by CT scan or sonography

b.

Treatment: CT scan or ultrasound-guided percutaneous drainage (with a pigtail catheter left in place for continuous drainage) can be used, but the recurrence rate is high; the conservative approach is to reevaluate the pseudocyst (with CT scan or sonography) after 6 to 7 wk and surgically drain it if the pseudocyst has not decreased in size. Generally pseudocysts 5 cm require surgical intervention after the wall has matured.

2.

Phlegmon: represents pancreatic edema. It can be diagnosed by CT scan or sonography. Treatment is supportive measures, because it usually resolves spontaneously.

3.

Pancreatic abscess: diagnosed by CT scan (presence of bubbles in the retroperitoneum); Gram staining and cultures of fluid obtained from guided percutaneous aspiration (GPA) usually identify bacterial organism. Therapy is surgical (or catheter) drainage and IV antibiotics (imipenemcilastin [Primaxin] is the drug of choice).

4.

Pancreatic ascites: usually caused by leaking of pseudocyst or tear in pancreatic duct. Paracentesis reveals very high amylase and lipase levels in the pancreatic fluid; ERCP may demonstrate the lesion. Treatment is surgical correction if exudative ascites from severe pancreatitis does not resolve spontaneously.

5.

GI bleeding: caused by alcoholic gastritis, bleeding varices, stress ulceration, or DIC.

6.

Renal failure: caused by hypovolemia resulting in oliguria or anuria, cortical or tubular necrosis (shock, DIC), or thrombosis of renal artery or vein.

DISPOSITION

7.

Hypoxia: caused by ARDS, pleural effusion, or atelectasis.

DISPOSITION

Prognosis varies with the severity of pancreatitis; overall mortality in acute pancreatitis is 5% to 10%; poor prognostic signs according to the Ranson criteria are as follows: •

Age >55 yr

•

Fluid sequestration >6000 ml

•

Laboratory abnormalities on admission: WBC >16,000, blood glucose >200 ml/dl, serum LDH >350 IU/L, AST >250 IU/L

•

Laboratory abnormalities during the initial 48 hr: decreased Hct >10% with hydration or Hct 5 mg/dl, serum calcium boys).

•

Infestation of the eyelashes is most frequently seen in children and may indicate sexual abuse.

•

The chance of acquiring pubic lice from one sexual exposure with an infested partner is >90% (most contagious STD known).

•

Body lice is most common in conditions of poor hygiene.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pruritus with excoriation may be caused by hypersensitivity reaction, inflammation from saliva, and fecal material from the lice.

•

Nits can be identified by examining hair shafts.

•

The presence of nits on clothes is indicative of body lice.

•

Lymphadenopathy may be present (cervical adenopathy with head lice, inguinal lymphadenopathy with pubic lice).

•

Head lice is most frequently found in the back of the head and neck, behind the ears.

•

Scratching can result in pustules and crusting.

•

Pubic lice may affect the hair around the anus.

ETIOLOGY

Lice are transmitted by close personal contact or use of contaminated objects (e.g., combs, clothing, bed linen, hats).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Seborrheic dermatitis

•

Scabies

•

Eczema

•

Other: pilar casts, trichonodosis (knotted hair), monilethrix

WORKUP

Diagnosis is made by seeing the lice or their nits. Combing hair with a fine-toothed comb is recommended because visual inspection of the hair and scalp may miss more than 50% of infestations. LABORATORY TESTS

Wood's light examination is useful to screen a large number of children: live nits fluoresce, empty nits have a gray fluorescence, nits with unborn louse reveal white fluorescence.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Patients with body lice should discard infested clothes and improve their hygiene.

•

Combing out nits is a widely recommended but unproven adjunctive therapy.

•

Personal items such as combs and brushes should be soaked in hot water for 15 to 30 min.

•

Close contacts and household members should also be examined for the presence of lice.

ACUTE GENERAL

The following products are available for treatment of lice: •

Permethrin: available over the counter (1% permethrin [Nix]) or by prescription (5% permethrin [Elimite]); should be applied to the hair and scalp and rinsed out after 10 min. A repeat application is generally not necessary in patients with head lice. It can be applied to clean, dry hair and left on overnight (8 to 14 hours) under a shower cap.

•

Lindane 1% (Kwell), pyrethrin S (Rid): available as shampoos or lotions; they are applied to the affected area and washed off in 5 min; treatment should be repeated in 7 to 10 days to destroy hatching nits. Resistance to this medication is increasing. Lindane is potentially neurotoxic and should be avoided in infants and children weighing 38°C, immunosuppressed state, history of trauma, subacute onset, oral anticoagulant therapy, presence of myocarditis, large pericardial effusion, or tamponade.

SUGGESTED READINGS Lange RA, Hillis LD: Acute pericarditis. N Engl J Med 2005; 351:2195-2202. Roy C, et al: Does this patient with pericardial effusion have cardiac tamponade?. JAMA 2007; 297:1810. Tingle LE, et al: Acute pericarditis. Am Fam Physician 2007; 76:1509-1514.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Peripheral Arterial Disease PRANAV M. PATEL, M.D.

BASIC INFORMATION DEFINITION

Peripheral arterial disease (PAD) refers to stenotic, occlusive, and aneurysmal diseases of the aorta and its branch arteries, exclusive of the coronary arteries. This chapter deals specifically with the arteries of the lower extremities. SYNONYMS

Peripheral vascular disease (PVD), arteriosclerosis obliterans, atherosclerotic occlusive disease, atherosclerosis of the extremities, peripheral arterial stenosis, vaso-occlusive disease of the legs, chronic critical limb ischemia

ICD-9CM CODES

443.9 Peripheral vascular disease EPIDEMIOLOGY & DEMOGRAPHICS

•

The likelihood of developing PAD increases after age 40 yr. As a result it is an increasingly prevalent problem given the aging populations in most Western countries.

•

The 1999-2000 National Health and Nutrition Examination Survey (NHANES) found the incidence of PAD to be approximately 14.5% in patients aged 70 yr or older.

•

Other studies have shown a prevalence of up to 29% in patients aged 50-69 yr with a history of diabetes and smoking.

•

PAD is a common manifestation of atherosclerosis and its prevalence increases with age and the presence of cardiovascular risk factors.

•

Cigarette smoking and diabetes mellitus are the strongest risk factors.

•

Greater than 80% of patients with PAD are current or former smokers.

•

PAD affects men and women equally.

•

African Americans and Hispanics with diabetes have a higher prevalence of PAD than whites.

•

Cardiovascular disease is the major cause of death in patients with intermittent claudication.

•

Patients with newly diagnosed PAD are 6 times more likely to die within the next 10 years when compared with patients without PAD.

•

Risk factors associated with PAD are similar to coronary artery disease including tobacco use, diabetes, hyperlipidemia, hypertension, and advanced age.

•

Other potential risk factors include elevated levels of C-reactive protein, fibrinogen, homocysteine, apolipoprotein A, and plasma viscosity.

•

An inverse relationship has been suggested between PAD and alcohol consumption.

•

In 2006 American College of Cardiology/American Heart Association (ACC/AHA) suggested that the following individuals would be at risk from lower extremity PAD: Age 2.5 pmol/ml or metanephrine levels >1.4 pmol/ml indicate a pheochromocytoma with 100% specificity.

•

24-hr urine collection for metanephrines (100% sensitive) will also show increased metanephrines; the accuracy of the 24-hr urinary levels for metanephrines can be improved by indexing urinary metanephrine levels by urine creatinine levels.

•

The clonidine suppression test is useful for distinguishing between high levels of plasma norepinephrine caused by release from sympathetic nerves and those caused by release from a pheochromocytoma. A decrease 0.5 inch in diameter (90% to 95% accurate).

•

MRI: pheochromocytomas demonstrate a distinctive MRI appearance (100% sensitivity); MRI may become the diagnostic imaging modality of choice.

•

Scintigraphy with 131I-MIBG (100% sensitivity): this norepinephrine analog localizes in adrenergic tissue; it is particularly useful in locating extraadrenal pheochromocytomas.

•

6 [ 18F] Fluorodopamine positron emission tomography is reserved for cases in which clinical symptoms and signs suggest pheochromocytoma and results of biochemical tests are positive but conventional imaging studies cannot locate the tumor. An alternative approach is to use vena caval sampling for plasma catecholamines and metanephrines.

TREATMENT GENERAL Rx

Laparoscopic removal of the tumor (surgical resection for both benign and malignant disease): 1.

Preoperative stabilization with combination of phenoxybenzamine, ß-blocker, metyrosine, and liberal fluid and salt intake starting 10 to 14 days before surgery.

2.

Hypertensive crisis preoperatively and intraoperatively can be controlled with phentolamine (Regitine) 2 to 5 mg IV q1 to 2h prn or nitroprusside used in combination with ß-adrenergic blockers.

PEARLS & CONSIDERATIONS COMMENTS

•

Obtaining a detailed family history is important because 10% of pheochromocytomas are familial.

•

Screening for pheochromocytoma should be considered in patients with any of the following: 1.

Malignant hypertension

2.

Poor response to antihypertensive therapy

3.

Paradoxical hypertensive response

4.

Hypertension during induction of anesthesia, parturition, surgery, or thyrotropin-releasing hormone testing

5.

Hypertension associated with imipramine or desipramine

6.

Neurofibromatosis (increased incidence of pheochromocytoma)

•

All patients with pheochromocytoma should be screened for MEN-II and von Hippel-Lindau disease with pentagastrin test, serum PTH, ophthalmoscopy, MRI of the brain, CT scan of the kidneys and pancreas, and ultrasonography of the testes.

•

In patients with pheochromocytoma, routine analysis for mutations of RET, VHL, SDHD, and SDHB is indicated to identify pheochromocytoma-associated syndromes.

AUTHOR: FRED F. FERRI, M.D. Phobias

BASIC INFORMATION

DEFINITION

Phobic anxiety disorders have at their core an extreme anxiety that is elicited by a specific object or situation that is usually perceived as more threatening than it really is and that often leads to avoidance behavior. The provoking stimuli may be social or performance situations (social phobia) or any other stimulus (specific phobia of objects, e.g., animals, natural environments, blood, or situational). Additionally, a person may experience intense anxiety about being in a place or situation from which they will not be able to escape in the event of a panic attack (agoraphobia in conjunction with or independent of panic disorder). SYNONYMS

Simple phobia (obsolete name for specific phobia) Phobias named according to the inducing stimulus, for example, arachnophobia (fear of spiders), claustrophobia (fear of tight spaces) Social anxiety disorde

ICD-9CM CODES

F40.2 Specific phobia (DSM-IV: 300.29) F40.1 Social phobia (DSM-IV: 300.23) Agoraphobia (DSM-IV: 300.21 [with panic disorder], 300.22 [without panic disorder]) EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: Specific phobias: often lifelong condition, but phobias with onset in childhood (e.g., animal phobias) tend to remit spontaneously. PREVALENCE (IN U.S.): •

Specific phobias affect 5% to 10% of the general population.

•

Social phobias affect about 13%.

•

Agoraphobias without panic disorder affect 3% to 7% of the general population.

PREDOMINANT SEX AND AGE: •

Females with specific phobias outnumber males, though rates vary according to the phobia.

•

More women are affected with social phobia; however, men are more likely to seek treatment.

•

Agoraphobia also affects more women than men.

•

Childhood onset for most specific phobias.

•

Situational phobias have two peaks—the first in childhood and the second in the mid-20s.

•

Fears are generally stable.

•

Roots of social phobia may be in childhood, with described shyness or social inhibition, but onset usually in the midteens or into late adulthood; disorder is generally lifelong.

GENETICS: Both specific phobias and social phobias are more common in first-degree relatives than the general population. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Specific phobias: frequently occur with other anxiety disorders, particularly panic and agoraphobias.

•

When approaching the phobic object the patient experiences extreme anxiety often accompanied by autonomic symptoms such as tachycardia, tremor, and diaphoresis. In addition, depersonalization may occur. In blood phobias, however, these symptoms are often followed by a parasympathetic response consisting of hypotension and in some instances vasovagal syncope.

•

Social phobias are distinguished from specific phobias in that what is feared is humiliation or embarrassment rather than the thing itself.

ETIOLOGY

Unknown

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Body dysmorphic disorder (BDD): similar to social phobia but in BDD the fear arises from the patient's belief that they are misshapen in some way.

•

Panic attacks (with or without agoraphobia): anxiety symptoms seen in specific phobia may resemble panic attacks, but the stimulus in specific phobias or social phobias is clear, whereas panic attacks are unexpected.

•

Generalized anxiety disorder: may be difficult to distinguish from social phobia, but in social phobia the cognitive focus is fear of embarrassment or humiliation, whereas in generalized anxiety disorder the focus is more internal on the subjective sensations of discomfort.

•

Avoidant personality disorder is often comorbid with social phobia.

•

Psychotic disorders: fear of being in public arises from delusions.

WORKUP

•

History: usually diagnostic. Should elicit information about other medical disorders, medications, any history of physical or emotional abuse and substance abuse.

•

Social phobia is a chronic condition. Individuals with social phobia often underachieve, drop out of school, avoid seeking work as a result of anxiety about interviews, refrain from dating and remain with family of origin, and are less likely to marry.

•

Physical examination: to confirm absence of cardiovascular abnormalities (e.g., a chronic sinus arrhythmia).

LABORATORY TESTS

No specific laboratory tests are indicated. IMAGING STUDIES

No specific imaging studies are recommended.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Cognitive-behavioral therapy (CBT) and other psychotherapeutic approaches found to be effective in controlled trials.

•

Behavioral treatment involves relaxation training, usually paired with visualization and progressive desensitization.

•

Success rates are higher when the phobia is not complicated by other anxiety disorders.

•

Social phobia is more problematic to treat because the psychological difficulties are more pervasive, but cognitive-behavioral therapy and other psychotherapies are quite effective.

ACUTE GENERAL Rx

•

Benzodiazepines provide rapid relief of anxiety associated with exposure to fearful stimuli.

•

Alprazolam or lorazepam: both administered sublingually to increase rate of absorption.

•

Beta-blockers (e.g., propanolol) have been used to decrease autonomic hyperarousal and tremor associated with performance situations (e.g., before a public speech).

CHRONIC Rx

•

If the phobic stimulus is rarely encountered, benzodiazepines as needed may be appropriate long-term treatment.

•

Selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine and sertraline, are effective in reducing symptoms and improving function for persons with social phobia.

COMPLEMENTARY & ALTERNATIVE MEDICINE

There is no definitive evidence for complementary and alternative medicine in treatment of phobic disorders. Several studies of supplements (e.g., valerian, St. John's wort, passiflora) have been done without statistically significant outcomes. DISPOSITION

Usually present for life without treatment. Treatment may effectively reduce symptoms but not eliminate the fear. REFERRAL

Recommended to confirm diagnosis and to evaluate for psychotherapy.

PEARLS & CONSIDERATIONS Persons with social phobia usually have low self-esteem and fear of evaluation from others; they avoid or are fearful of any situation in which others may assess or evaluate them directly or indirectly. Concurrent anxiety disorders are common. Patients with social phobias may have comorbid substance abuse issues.

EVIDENCE

SSRIs There is evidence that SSRIs are effective in the management of social phobia A systematic review identified 36 randomized controlled trials (RCTs) that compared antidepressants with placebo in the treatment of social phobia. The review found that in 26 of the studies short-term treatment with antidepressant therapy of all classes produced significant response compared with placebo.[[1]] The review found that the response was significantly greater with SSRIs than other classes of antidepressant.[[1]] Two subsequent RCTs compared paroxetine with placebo over 12 weeks in adults with social phobia. Both studies found that paroxetine significantly improved patient response over the period of treatment. [143] [144]

Another RCT found that sertraline produced significantly greater improvements in clinical outcome, over a 20-week period, compared to placebo in adults with generalized social phobia.[[4]] One RCT compared fluvoxamine with placebo over an 8-week period in children diagnosed with social phobia, separation anxiety disorder, or generalized anxiety disorder. The study found that fluvaxamine was superior to placebo in reducing anxiety symptoms with significant benefit at the end of the treatment.[[5]] Cognitive-Behavioral Therapy (CBT) There is evidence that CBT is of benefit in the management of social phobia. An RCT compared phenelzine (a monoamine oxidase inhibitor [MAOI]) or cognitive-behavioral group therapy with placebo/attention placebo procedure over a 12-week period in adults with social phobia. At 12 weeks both CBT and phenelzine were equally effective in significantly improving patient responses compared to placebo.[[6]] Exposure Therapy There is evidence that exposure therapy is effective in the treatment of social phobia. An RCT involving 375 adults suffering from social phobia compared sertraline with placebo with or without exposure therapy for 24 weeks. At the end of the trial all patients receiving active treatment showed an improved response compared to placebo, with the greatest response being seen in those patients receiving sertraline alone. Patients were followed up for a further 28 weeks at which point those patients receiving exposure therapy showed continued improvement whereas there was some deterioration in those patients receiving sertraline. The study suggests that better long-term outcome may be achieved with exposure therapy.[[7]]

Evidence-Based References 1. Stein DJ, et al: Pharmacotherapy for social anxiety disorder. Cochrane Database Syst Rev 2000; 4:

2. Baldwin D, et al: Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Br J Psychiatry 1999; 175:120.Reviewed in: Evidence Based Mental Health 3:41, 2000. 3. Stein MB, et al: Paroxetine treatment of generalised social phobia (social anxiety disorder): a randomized controlled trial. JAMA 1998; 280:708.Reviewed in: Evidence Based Mental Health 2:53, 1999. 4. Van Ameringen MA, et al: Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Am J Psychiatry 2001; 158:275.Reviewed in: Evidence Based Mental Health 4:91, 2001. 5. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group: Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med 2001; 344:1279.Reviewed in: Evidence Based Mental Health 4:116, 2001. 6. Heimberg RG, et al: Cognitive behavioural group therapy vs phenelzine therapy for social phobia: 12 week outcome. Arch Gen Psychiatry 1998; 55:1131.Reviewed in: Evidence Based Mental Health 2:80, 1999. 7. Haug TT, et al: Exposure therapy and sertraline in social phobia: 1-year follow up of a randomised control trial. Br J Psychiatry 2003; 182:312.Reviewed in: Evidence Based Mental Health 6:90, 2003.

SUGGESTED READINGS Anxiety Disorders Association of America: http://www.adaa.org Kripke C: Is pharmacotherapy useful in social phobia?. Am Fam Physician 2005; 71(9):1700. Schneir FR: Clinical practice: social anxiety disorder. N Engl J Med 2006; 355(10):1029.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pilonidal Disease MITCHELL D. FELDMAN, M.D., M.PHIL., AMANDA A. WULFSTAT, M.D.

BASIC INFORMATION DEFINITION

From Latin: pilus = hair and nidus = nest. A pilonidal sinus is a short tract that extends from the skin surface, is most commonly found in the intergluteal fold sacrococcygeal region, additionally described in the interdigital area, umbilicus, chest wall, and scalp. It most likely represents a distended hair follicle. An acute pilonidal abscess, which consists of pus and a wall of edematous fat, results from rupture of an infected follicle into fat. A chronic pilonidal abscess results when an infected follicle ruptures directly into surrounding tissues; the wall of a chronic pilonidal abscess consists of fibrous tissue. A pilonidal cyst develops from a chronic abscess of long duration as a thin and flat lining of epithelium grows into the cavity from the skin surface. SYNONYMS

Jeep disease

ICD-9CM CODES

685.1 Pilonidal cyst EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 26 cases/100,000 person PREDOMINANT SEX: Male > female (2.2:1) AVERAGE AGE OF PRESENTATION: 21 y RISK FACTORS:

•

Male sex

•

Caucasian race

•

Family predisposition

•

Obesity

•

Sedentary lifestyle

•

Occupation requiring prolonged sitting

•

Local hirsutism

•

Poor hygiene

•

Increased sweat activity

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

May manifest as asymptomatic pits or pores in the natal cleft

•

Tenderness after physical activity or prolonged sitting

•

Acute pilonidal abscess in 20% of patients with pilonidal disease

•

Presents as a hot, tender, fluctuant swelling just lateral to the midline over the sacrum that may exude pus through the midline pit

•

Chronic pilonidal abscess in 80% of patients with pilonidal disease

•

Acute suppuration, tenderness, swelling, and heat

•

Infrequently, systemic reaction: occasionally fever, leukocytosis, and malaise

ETIOLOGY

•

Currently, thought to be acquired rather than congenital.

•

Drilling of hair shed from the perineum or the head into sebaceous or hair follicles in the natal cleft.

•

Drilling is facilitated by the friction of the natal cleft.

•

Subsequent infection by skin organisms leads to pilonidal abscess.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Perianal abscess arising from the posterior midline crypt

•

Hidradenitis suppurativa

•

Carbuncle

•

Furuncle

•

Osteomyelitis

•

Anal fistula

•

Coccygeal sinus

WORKUP

•

Diagnosis is based on history and physical examination.

•

Midline pits present behind the anus overlying the sacrum and coccyx.

•

Broken hairs are often seen extruding from the midline pits.

•

Insert probe in pilonidal sinus in path away from the anus.

•

Complicated anal fistula may be angulating posteriorly before passing into a retrorectal abscess, but thorough examination of the anal cavity usually discloses point of origin.

LABORATORY TESTS

CBC IMAGING STUDIES

CT scan in advanced recurrent cases

TREATMENT NONPHARMACOLOGIC THERAPY

Prevention of exacerbations: 1.

Local hygiene

2.

Avoidance of prolonged sitting position

3.

Weight reduction

ACUTE GENERAL Rx

•

Procedure of choice for first-episode acute abscess: simple incision and drainage in an outpatient setting

•

Cure rate of 76% after 18 mo

•

Antibiotics: generally not indicated unless the patient has a medical condition such as rheumatic heart disease or is immunosuppressed

CHRONIC Rx

Elective treatment of pilonidal disease:

1.

2.

3.

4.

Minimal surgery a.

Remove hair from midline pits and shave buttocks.

b.

May use a fine wire brush with local anesthesia to clear the pits and any lateral openings of granulation tissue and hair.

c.

Keep area clean.

Fistulotomy and curettage a.

Used when minimal surgery does not control episodes of suppuration

b.

Pass probe to outline the pilonidal sinus and open tract surgically

c.

Curette granulation tissue at the base of the sinus and excise edges of the skin

d.

Keep open granulating wound meticulously clean and allow to heal

e.

If complete healing does not take place, use a skin graft or advancement flap to close the defect

Marsupialization a.

This is the treatment of choice for chronic pilonidal disease.

b.

Wide excision of the pilonidal area is performed, including all affected skin and subcutaneous tissues down to the presacral fascia.

c.

Wound is left open, allowed to marsupialize, or closed as a primary procedure.

d.

Give antibiotics for 24 hr (particularly those directed against Staphylococcus and Bacteroides spp).

Other procedures a.

Excision and closure

b.

Excision and skin grafting

c.

Bascom procedure (follicle removal & lateral drainage)

d.

Flaps: Z-plasty, V-Y advancement flap, rhomboid flap, gluteus maximus myocutaneous flap

DISPOSITION

•

Recurrence rate for excision (most definitive procedure): 1% to 6%

•

Incidence of squamous cell carcinoma in a chronic, recurrent pilonidal sinus is rare 200 ng/ml are diagnostic, with levels of 100 to 200 ng/ml being equivocal.

•

Basal PRL levels between 20 and 100 suggest a microprolactinoma, as well as other conditions such as drug ingestion.

•

Basal level 80% of tumors with the ratio of the alpha subunit to thyrotropin 60 mm Hg

•

IV hydration, correction of dehydration

•

Assisted ventilation in patients with significant respiratory failure

ACUTE GENERAL Rx

•

Initial antibiotic therapy should be based on clinical, radiographic, and laboratory evaluation.

•

Macrolides (azithromycin or clarithromycin) or levofloxacin is recommended for empirical out-patient treatment of community-acquired pneumonia; cefotaxime or a beta-lactam/beta-lactamase inhibitor can be added in patients with more severe presentation who insist on out-patient therapy. Duration of treatment ranges from 7 to 14 days.

•

In the hospital setting, patients admitted to the general ward can be treated empirically with a second- or third-generation cephalosporin (ceftriaxone, ceftizoxime, cefotaxime, or cefuroxime) plus a macrolide (azithromycin or clarithromycin) or doxycycline. An antipseudomonal quinolone (levofloxacin or moxifloxacin) may be substituted in place of the macrolide or doxycycline.

•

Empiric therapy in ICU patients: IV beta-lactam (ceftriaxone, cefotaxime, ampicillin-sulbactam) plus an IV quinolone (levofloxacin, moxifloxacin) or IV azithromycin.

•

In hospitalized patients at risk for P. aeruginosa infection, empirical treatment should consist of an antipseudomonal beta-lactam (cefepime or piperacillin-tazobactam) plus an aminoglycoside plus an antipseudomonal quinolone or macrolide.

•

In patients with suspected MRSA, use vancomycin or linezolid.

CHRONIC Rx

Parapneumonic effusion-empyema can be managed with chest tube placement for drainage. Instillation of fibrinolytic agents (streptokinase, urokinase) via the chest tube may be necessary in resistant cases. DISPOSITION

•

Most patients respond well to antibiotic therapy.

•

Indications for hospital admission are: 1.

Hypoxemia (oxygen saturation 1:64 a.

May be detectable with bedside testing

b.

Appear between days 5 and 10 of the illness (so may be demonstrable when patient is first examined) and disappear within about 1 mo

Complement fixation testing or other immunoassays specific for mycoplasm antigens of paired sera (fourfold rise) in patients with pneumonia and a compatible history: 1.

Considered diagnostic in the appropriate clinical setting

•

•

Culture of the organism from specimens 1.

Only truly specific test for infection

2.

Technically difficult and done reliably by few laboratories

3.

May require weeks to get results

Sputum 1.

Often no sputum produced for laboratory testing

2.

When present, gram-stained specimens show PMNs without organisms

•

Infection occasionally complicated by pancreatitis or glomerulitis

•

Disseminated intravascular coagulation is a rare complication

•

Electrocardiographic evidence of pericarditis or myocarditis may be present

IMAGING STUDIES

•

Predilection for lower lobe involvement (upper lobes involved in less than a fourth), with radiographic abnormalities frequently out of proportion to those on physical examination ( Fig. 1-205 )

•

Small pleural effusions in about 30% of patients

•

Large effusions: rare

•

Infiltrates: patchy, unilateral, and with a segmental distribution, although multilobar involvement may be seen

•

Evidence of hilar adenopathy on chest films in 20% to 25%

•

Rare cases reported: 1.

Associated lung abscess

2.

Residual pneumatoceles

3.

Lobar collapse

4.

Hyperlucent lung syndrome

FIGURE 1-205 Localized airspace opacification secondary to Mycoplasma pneumoniae. (From Specht N [ed]: Practical guide to diagnostic imaging, St Louis, 1998, Mosby.)

TREATMENT ACUTE GENERAL Rx

•

Therapy (10 to 14 days) with erythromycin (500 mg qid), azithromycin (500 mg initially, then 250 mg daily for 4 days), or clarithromycin (500 mg bid) is preferred to tetracycline, especially in young children or women of childbearing age. Respiratory fluoroquinolones such as levaquin or moxifloxacin are alternative agents for treatment but should not be used in young children.

•

Therapy shortens the duration and severity of symptoms and may hasten radiographic clearing, but the disease is self-limiting.

CHRONIC Rx

•

Effective antimicrobial therapy does not eliminate the organism from the respiratory secretions, which may be positive for weeks.

•

Serum antibody response does not necessarily provide lifelong immunity.

•

Chronic symptoms do not occur, although clinical relapses may occur 7 to 10 days following the initial response and may be associated with new areas of infiltration.

DISPOSITION

•

Clinical improvement is almost universal within 10 days.

•

Infiltrates generally clear within 5 to 8 wk.

•

Rare deaths are likely attributable to underlying medical diseases.

•

Person-to-person spread can be minimized by avoiding open coughing, especially in enclosed areas.

REFERRAL

•

Not responding to treatment

•

Severe infection

•

Severe extrapulmonary manifestations

•

Multilobe involvement accompanied by respiratory embarrassment (very rare)

PEARLS & CONSIDERATIONS COMMENTS

X-ray resolution complete by 8 wk in about 90% of patients.

EVIDENCE

Much of the data on treatment of atypical pneumonia have been taken from studies on patients with community-acquired pneumonia, which include a large number of patients with atypical pneumonia.[[1]] Oral antibiotic therapy results in a 90% rate of clinical cure or improvement in outpatients with communityacquired pneumonia.[[2]] Little evidence exists suggesting superior clinical efficacy of one oral antibiotic over another. Oral azithromycin may be more effective than other macrolides, penicillins, and cephalosporins in the treatment of community-acquired pneumonia, but further study is required in this area to confirm this finding. Betalactam agents are ineffective against M. pneumoniae. [174] [176] In hospitalized and nonhospitalized patients with community-acquired pneumonia, clinical outcome at 5 to 7 days is significantly better when treated with levofloxacin (oral or intravenous) compared with intravenous ceftriaxone or oral cefuroxime axetil.[[4]]

Monotherapy with levofloxacin is as effective as combination therapy with intravenous azithromycin plus ceftriaxone in patients hospitalized with community-acquired pneumonia.[[5]]

Evidence-Based References 1. Loeb M: Community acquired pneumonia, 10. London: BMJ Publishing Group; 2003:1724. 2. Pomilla PV, Brown RB: Outpatient treatment of community-acquired pneumonia in adults. Arch Intern Med 1994; 154:1793.Reviewed in: Clin Evid 10:1724, 2003. 3. Contopoulos-Ioannidis DG, et al: Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. J Antimicrob Chemother 2001; 48:691. 4. File TM, et al: A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimocrob Agents Chemother 1997; 41:1965.Reviewed in: Clin Evid 10:1724, 2003. 5. Frank E, et al: A multicenter, open-label, randomized comparison of levofloxacin and azithromycin plus ceftriaxone in hospitalized adults with moderate to severe community-acquired pneumonia. Clin Ther 2002; 24:1292.Reviewed in: Clin Evid 10:1724, 2003.

SUGGESTED READINGS La Scola B, et al: Mycoplasma pneumoniae: a rarely diagnosed agent in ventilator-acquired pneumonia. J Hosp Infect 2005; 59(1):74. Meloni F, et al: Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations. J Chemother 2004; 16(1):70. Michelow IC, et al: Diagnostic utility and clinical significance of naso- and oropharyngeal samples used in a PCR assay to diagnose Mycoplasma pneumoniae infection in children with community-acquired pneumonia. J Clin Microbiol 2004; 42(7):3339. Waites KG, Talkington DF: Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev 2004; 17(4):697.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pneumonia, Pneumocystis jirovecii (carinii) GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

Pneumocystis jirovecii pneumonia is a serious respiratory infection caused by the fungal or protozoal organism P. jirovecii (formerly known as P. carinii). SYNONYMS

PCP PJ

ICD-9CM CODES

136.3 Pneumocystis jirovecii (P. carinii) pneumonia EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Seen primarily in the setting of acquired immunodeficiency syndrome (AIDS)

•

Approximately 11 cases/100 patient-years among HIV-infected patients with CD4 lymphocyte counts 80% of cases).

•

The presence of any three of the following ten items allows the diagnosis of polyarteritis nodosa with a sensitivity of 82% and a specificity of 86%: 1.

Weight loss >4 kg

2.

Livedo reticularis

3.

Testicular pain or tenderness

4.

Myalgias, weakness, or leg tenderness

5.

Neuropathy

6.

Diastolic blood pressure >90 mm Hg

7.

Elevated BUN or creatinine

8.

Positive test for hepatitis B virus

9.

Arteriography revealing small or large aneurysms and focal constrictions between dilated segments

10. Biopsy of small or medium-size artery containing WBC LABORATORY TESTS

•

Elevated BUN or creatinine, positive test for hepatitis B virus or hepatitis C

•

Elevated ESR and C-reactive protein, anemia, elevated platelets, eosinophilia, proteinuria, hematuria

•

Biopsy of small or medium-size artery of symptomatic sites (muscle, nerve) is >90% specific. Biopsy of the gastrocnemius muscle and sural nerve are commonly performed

•

Assays for ANA and RF are negative; however, low, nonspecific titers may be detected

IMAGING STUDIES

Arteriography can be done in patients with negative biopsies or if there are no symptomatic sites. Visceral angiography will reveal aneurysmal dilation of the renal, mesenteric, or hepatic arteries.

TREATMENT NONPHARMACOLOGIC THERAPY

Low-sodium diet in hypertensive patients ACUTE GENERAL Rx

Prednisone 1 to 2 mg/kg/day; cyclophosphamide in refractory cases CHRONIC Rx

Monitoring for infections and potential complications such as thrombosis, infarction, or organ necrosis DISPOSITION

The 5-yr survival is 80%. Poor prognostic signs are severe renal or GI involvement. REFERRAL

Surgical referral for biopsy

EVIDENCE

Treatment with prednisone plus plasma exchange was compared with prednisone, plasma exchange, and cyclophosphamide in patients with polyarteritis nodosa and Churg-Strauss angiitis in a small randomized controlled trial. The two groups had comparable survival but the patients who had received cyclophosphamide had fewer relapses.[[1]] Because polyarteritis nodosa is such a rare disease, few definitive studies have been performed that compare treatment options. Therefore, in the absence of such evidence, clinical experience and longitudinal studies will provide the basis for treatment.

Evidence-Based Reference 1. Guillevin L, et al: Long-term follow-up after treatment of polyarteritis nodosa and Churg-Strauss angiitis with comparison of steroids, plasma exchange and cyclophosphamide to steroids and plasma exchange: a prospective randomized trial of 71 patients. The Cooperative Study Group for Polyarteritis Nodosa. J Rheumatol 1991; 18:567.

SUGGESTED READINGS Stone JH: Polyarteritis nodosa. JAMA 2002; 288:1632.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Polycystic Kidney Disease PURVA AGARWAL, M.D.

BASIC INFORMATION DEFINITION

Polycystic kidney disease refers to a systemic hereditary disorder characterized by the formation of cysts in the cortex and medulla of both kidneys (Figs. 1-208 and 1-209 [21] [22]).

FIGURE 1-208 Tomogram of autosomal dominant polycystic kidney disease. Kidney cysts. (From Stein JH [ed]: Internal medicine, ed 5, St Louis, 1998, Mosby.)

FIGURE 1-209 Markedly enlarged polycystic kidneys from a patient with ADPKD in comparison to a normal kidney in the middle. (From Johnson RJ, Feehally J: Comprehensive clinical nephrology, ed 2, St Louis, 2000, Mosby.)

SYNONYMS

Autosomal dominant polycystic kidney disease (ADPKD)

ICD-9CM CODES

753.1

Polycystic kidney, unspecified type

753.13 Polycystic kidney, autosomal dominant EPIDEMIOLOGY & DEMOGRAPHICS

•

Occurs in between 1:400 and 1:1000 people

•

Incidence: 6000 new cases per year

•

Approximately 500,000 people with ADPKD in the U.S.

•

Found in all ages

•

Accounts for 10% of end-stage renal disease

•

Associated with liver cysts (50% to 70%), pancreatic cysts (10%), splenic cysts (5%), and CNS arachnoid cysts (5%), and cerebral aneurysms (20%)

•

Increased incidence of diverticular disease and mitral valve prolapse

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Usually presents in the third to fourth decade of life

•

Pain (abdominal, flank, or back)

•

Palpable flank mass

•

Hypertension

•

Headache

•

Nocturia

•

Hematuria

•

Nephrolithiasis (20%)

•

Urinary tract infection

ETIOLOGY

•

Approximately 90% of cases are inherited as an autosomal dominant trait.

•

Spontaneous mutations occur in 10% of cases.

•

The abnormal gene in the majority of cases has been located to the short arm of chromosome 16. In the minority of cases the defect is located on chromosome 4.

•

All cysts develop from preexisting renal tubules segments and only a small portion of the nephrons (1%) undergoes cystic formation.

DIAGNOSIS A person is considered to have polycystic kidney disease if three or more cysts are noted in both kidneys and there is a positive family member with ADPKD. DIFFERENTIAL DIAGNOSIS

•

Simple cysts

•

Autosomal recessive polycystic kidney disease in children

•

Tuberous sclerosis

•

von Hippel Lindau syndrome

•

Acquired cystic kidney disease

WORKUP

The workup to establish the diagnosis of ADPKD includes a detailed family history and either an ultrasound or a CT scan of the abdomen to visualize bilateral renal cysts. •

Complications of ADPKD should be excluded and they are: End-stage renal failure Infected cysts and urinary tract infections Pyelonephritis Nephrolithiasis Electrolyte abnormalities Cerebral aneurysm rupture Intractable pain from enlarging cysts Hypertension

LABORATORY TESTS

•

Hemoglobin and hematocrit is elevated because of increased secretion of erythropoietin from functioning renal cysts. This also explains the relatively mild severity of anemia found in patients with ADPKD and severe renal insufficiency.

•

Electrolyte abnormalities commonly seen in any patients with renal insufficiency may be present.

•

BUN and creatinine can be elevated.

•

Urinalysis can show microscopic hematuria, WBC casts in pyelonephritis, or proteinuria (seldom >1 g/24 hr).

•

Increased erythropoietin level.

•

Patients with a strong positive family history of ADPKD and no cysts detected by imaging studies can undergo genetic linkage analysis.

IMAGING STUDIES

•

Abdominal renal ultrasound is the easiest and more cost-efficient test for renal cysts. Renal ultrasound can detect cysts from 1 to 1.5 cm.

•

Abdominal CT scan is more sensitive than ultrasound and can detect cysts as small as 0.5 cm.

•

Both studies can detect associated hepatic, splenic, and pancreatic cysts.

•

MRI is more sensitive than ultrasound and may help in distinguishing renal cell carcinomas from simple cysts.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Associated nephrolithiasis can be treated in a similar manner with either IV or PO hydration. If stones remain lodged, lithotripsy or percutaneous nephrostolithotomy can also be done.

•

Hypertension treatment is initiated with salt restriction, weight loss, and daily exercise.

•

Avoidance of physical contact sports is advised.

ACUTE GENERAL Rx

•

Kidney infections should be treated with antibiotics known to penetrate the cyst (e.g., trimethoprimsulfamethoxazole 1 tablet PO bid or ciprofloxacin 250 mg PO bid).

•

Angiotensin-converting enzyme inhibitors (e.g., captopril 25 mg bid or tid, lisinopril 10 mg PO qd, fosinopril 10 mg PO qd, or enalapril 10 mg qd) are effective in the treatment of hypertension associated with ADPKD.

•

Calcium channel blockers (e.g., nifedipine 30 to 90 mg PO qd, amlodipine 5 to 10 mg PO qd, or felodipine 5 to 10 mg PO qd) can be used with or without ACE inhibitors in the treatment of hypertension.

•

Alpha-blockers and diuretics can be added as adjunctive therapy for hypertension.

•

Blood pressure 1 g of urinary protein per 24 hr, the target blood pressure is 2 mm in diameter.

•

A positive family history of ADPKD is found in approximately 60% of the cases. Renal ultrasound performed on patient's parents reveals ADPKD in about 30% of the cases.

•

Up to 25% of patients may not have cysts present before the age of 30.

COMMENTS

Routine screening patients with ADPKD for cerebral aneurysms is not recommended unless there is a positive family history of cerebral aneurysms.

EVIDENCE

For low-protein diet in chronic renal failure: It appears that reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by about 40% as compared with higher or unrestricted protein intake. The optimum level of protein intake cannot be confirmed from available studies.[[1]] For use of angiotensin-converting enzyme inhibitors: Enalapril slows the rate of progression to end-stage renal failure in patients with chronic renal failure without diabetes, but these studies did not provide specific data regarding autosomal-dominant polycystic kidney disease. For method of continuous ambulatory peritoneal dialysis (CAPD): double-bag system should be the preferred exchange system in CAPD. Significantly fewer patients suffered peritonitis, and number of patient months on CAPD per episode of peritonitis was consistently greater with double bag system compared with standard system.[[2]]

Evidence-Based References 1. Fouque D, et al: Low protein diets for chronic renal failure in non-diabetic adults (Cochrane review). Reviewed. Cochrane Library 3, Oxford, Update Software, 2001. 2. Daly C, et al: Double bag or Y set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end stage renal disease (Cochrane review). Reviewed. Cochrane Library 3, Oxford, Update Software, 2001.

SUGGESTED READINGS Chapman AB: Autosomal dominant polycystic kidney disease: time for a change?. J Am Soc Nephrol 2007; 18(5):1399. Pei Y: Diagnostic approach in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2006; 1(5):1108. Torres VE, Harris PC, Pirson Y: Autosomal dominant polycystic kidney disease. Lancet 2007; 369(9569):1287.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Polycystic Ovary Syndrome FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Polycystic ovary syndrome (PCOS) in its complete form associates polycystic ovaries, amenorrhea, hirsutism, and obesity. SYNONYMS

Stein-Leventhal syndrome PCO

ICD-9CM CODES

256.4 Polycystic ovary syndrome EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 3% of adolescent and adult women. •

Symptoms usually begin around the time of menarche, and the diagnosis is often made during adolescence or young adulthood.

•

Increased risk of endometrial and ovarian cancers.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Oligomenorrhea or amenorrhea

•

Dysfunctional uterine bleeding

•

Infertility

•

Hirsutism

•

Acne

•

Obesity (40% only)

•

Insulin resistance (type 2 diabetes mellitus)

ETIOLOGY & PATHOGENESIS

Elevated serum LH concentrations and an increased serum LH:FSH ratio result either from an increased GnRH

hypothalamic secretion or less likely from a primary pituitary abnormality. This results in dysregulation of androgen secretion and increased intraovarian androgen, the effect of which in the ovary is follicular atresia, maturation arrest, polycystic ovaries, and anovulation. Hyperinsulinemia is a contributing factor to ovarian hyperandrogenism, independent of LH excess. A role for insulin growth factor (IGF) receptors has been postulated for the association of PCOS and diabetes.

DIAGNOSIS Clinical: •

PCOS is the most common cause of chronic anovulation with estrogen present. A positive progesterone withdrawal test establishes the presence of estrogen. Medroxyprogesterone (Provera) 10 mg qd is administered for 5 days and bleeding occurs if estrogen is present.

•

The presence of oligomenorrhea, hirsutism, obesity, and documentation of polycystic ovaries establishes the diagnosis.

DIFFERENTIAL DIAGNOSIS

Causes of amenorrhea: •

Primary (unusual in PCOS)

Genetic disorder (Turner's syndrome) Anatomic abnormality (e.g., imperforate hymen)

•

Secondary

Pregnancy Functional (cause unknown, anorexia nervosa, stress, excessive exercise, hyperthyroidism, less commonly hypothyroidism, adrenal dysfunction, pituitary dysfunction, severe systemic illness, drugs such as oral contraceptives, estrogens, or dopamine agonists) Abnormalities of the genital tract (uterine tumor, endometrial scarring, ovarian tumor) LABORATORY TESTS

Fasting blood glucose to rule out diabetes Elevated LH/FSH ratio >2.5 Prolactin level elevation in 25% Elevated androgens (testosterone, DHEA-S) IMAGING STUDIES

Pelvic ultrasound (or CT scan) reveals the presence of twofold to fivefold ovarian enlargement with a thickened tunica albuginea, thecal hyperplasia, and 20 or more subcapsular follicles from 1 to 15 mm in diameter ( Fig. 1-

210 ).

FIGURE 1-210 Sagittal section of a polycystic ovary illustrating large number of follicular cysts and thickened stroma. (From Mishell DR: Comprehensive gynecology, ed 3, St Louis, 1997, Mosby.)

TREATMENT The goal is to interrupt the self-perpetuating abnormal hormone cycle: •

Reduction of ovarian androgen secretion by laparoscopic ovarian wedge resection

•

Reduction of ovarian androgen secretion by using oral contraceptives or LHRH analogs

•

Weight reduction for all obese women with PCOS

•

FSH stimulation with clomiphene HMG, or pulsatile LHRH

•

Urofollitropin (pure FSH) administration

•

Glitazones (e.g., rosiglitazone, pioglitazone) may improve ovulation and hirsutism in the polycystic ovary syndrome

Choice of treatment:

•

The management of hirsutism without risking pregnancy includes oral contraceptives, glucocorticoids, LHRH analogs, or spironolactone (an antiandrogen)

•

Pregnancy can be achieved with clomiphene (alone or with glucocorticoids, hCG, or bromocriptine), HMG, urofollitropin, pulsatile LHRH, or ovarian wedge resection.

(Metformin may induce ovulation.)

EVIDENCE

Oral contraceptives containing desogestrel or norgestrel significantly improve acne and hirsutism.[[1]] Spironolactone, 100 mg for 6 mo, results in significant, subjective improvement in hair growth and decrease in hair scores, compared with placebo.[[2]]

Evidence-Based References 1. Shaw JC: Antiandrogen and hormonal treatment of acne. Dermatol Clin 1996; 14:803. 2. Farquhar C, et al: Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev 2003; 4:(Cochrane Review).

SUGGESTED READINGS Ehrmann DA: Polycystic ovary syndrome. N Engl J Med 2005; 352:1223.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Polycythemia Vera FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

xsPolycythemia vera is a chronic myeloproliferative disorder characterized mainly by erythrocytosis (increase in RBC mass). SYNONYMS

Primary polycythemia, vaquez disease

ICD-9CM CODES

238.4 Polycythemia vera EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE/PREVALENCE: 0.5 cases/100,000 persons; mean age at onset is 60 yr; men are more affected than women. PHYSICAL FINDINGS & CLINICAL PRESENTATION

The patient generally comes to medical attention because of symptoms associated with increased blood volume and viscosity or impaired platelet function: •

Impaired cerebral circulation resulting in headache, vertigo, blurred vision, dizziness, TIA, CVA

•

Fatigue, poor exercise tolerance

•

Pruritus, particularly following bathing (caused by overproduction of histamine)

•

Bleeding: epistaxis, UGI bleeding (increased incidence of PUD)

•

Abdominal discomfort secondary to splenomegaly; hepatomegaly may be present

•

Hyperuricemia may result in nephrolithiasis and gouty arthritis

The physical examination may reveal: Facial plethora, congestion of oral mucosa, ruddy complexion

Enlargement and tortuosity of retinal veins Splenomegaly (found in >75% of patients)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

SMOKING: •

Polycythemia is secondary to increased carboxyhemoglobin, resulting in left shift in the Hgb dissociation curve.

•

Laboratory evaluation shows increased Hct, RBC mass, erythropoietin level, and carboxyhemoglobin.

•

Splenomegaly is not present on physical examination.

HYPOXEMIA (SECONDARY POLYCYTHEMIA): Living for prolonged periods at high altitudes, pulmonary fibrosis, congenital cardiac lesions with right-to-left shunts •

Laboratory evaluation shows decreased arterial oxygen saturation and elevated erythropoietin level.

•

Splenomegaly is not present on physical examination.

ERYTHROPOIETIN-PRODUCING STATES: Renal cell carcinoma, hepatoma, cerebral hemangioma, uterine fibroids, polycystic kidneys •

The erythropoietin level is elevated in these patients; the arterial oxygen saturation is normal.

•

Splenomegaly may be present with metastatic neoplasms.

STRESS POLYCYTHEMIA (GAISBCK'S SYNDROME, RELATIVE POLYCYTHEMIA): •

Laboratory evaluation demonstrates normal RBC mass, arterial oxygen saturation, and erythropoietin level; plasma volume is decreased.

•

Splenomegaly is not present on physical examination.

HEMOGLOBINOPATHIES ASSOCIATED WITH HIGH OXYGEN AFFINITY: An abnormal oxyhemoglobindissociation curve (P50) is present. WORKUP

Recent developments in molecular biology have identified a single, acquired point mutation in the Janus kinase 2 (JAK2) gene in the majority of patients with polycythemia vera and other pH-negative myeloproliferative disorders. The JAK2 mutation is found in .95% of patients with polycythemia vera and can be used for diagnostic purposes. Testing for the JAK2 V617F mutation with PCR assay is now available. In patients with high hematocrit (.52% in men or .48% in women) and in the absence of coexisting secondary erythrocytosis, the presence of the JAK2 mutation is sufficient for the diagnosis of polycythemia vera The diagnosis of polycythemia vera, using standards from the classic Polycythemia Vera Study Group, generally requires the following three major criteria or the first two major criteria plus two minor criteria:

•

•

Major criteria 1.

Increased RBC mass (>36 ml/kg in men, >32 ml/kg in women)

2.

Normal arterial oxygen saturation (>92%)

3.

Splenomegaly

Minor criteria 1.

Thrombocytosis (>400,000/mm3)

2.

Leukocytosis (>12,000/mm3)

3.

Elevated leukocyte alkaline phosphatase (>100)

4.

Elevated serum vitamin B12 (>900 pg/ml) or vitamin B12 binding protein (>2200 pg/ml)

Serum erythropoietin level is the best initial test for the diagnosis of polycythemia vera. A low serum erythropoietin level is highly suggestive of polycythemia vera. A normal level does not exclude the diagnosis. If the erythropoietin level is elevated, obtain abdominal and pelvic CT to rule out renal cercal carcinoma and other causes of polycythemia. In patients with elevated erythropoietin level, evaluate for secondary erythrocytosis: •

Measure RBC mass by isotope dilution using 51Cr-labeled autologous RBCs (expensive test); a high value eliminates stress polycythemia.

•

Measure arterial saturation; a normal value eliminates polycythemia secondary to smoking.

•

The diagnosis of hemoglobinopathy with high affinity is ruled out by a normal oxyhemoglobin dissociation curve.

•

A diagnostic algorithm for polycythemia is described in Section III.

LABORATORY TESTS

•

Elevated RBC count (>6 million/mm3), elevated Hgb (>18 g/dl in men, >16 g/dl in women), elevated Hct (>54% in men, >49% in women)

•

Increased WBC (often with basophilia); thrombocytosis in the majority of patients

•

Elevated leukocyte alkaline phosphatase, serum vitamin B12, and uric acid levels

•

Low serum erythropoietin level

•

Bone marrow aspiration revealing RBC hyperplasia and absent iron stores

TREATMENT NONPHARMACOLOGIC THERAPY

Phlebotomy to keep Hct 5 g in a 24-hr urine collection, oliguria (4 lb/wk) even in the absence of edema

•

Auscultation of pulmonary rales

•

Right upper quadrant pain (HELLP syndrome or subcapsular liver hematoma)

•

Hyperreflexia or clonus

•

Vaginal bleeding (placental abruption)

•

Acute or chronic fetal compromise manifested by intrauterine growth restriction or fetal tachycardia with late decelerations, respectively

•

Wide range of symptoms attributable to multiorgan system dysfunction, involving hepatic, hematologic, renal, pulmonary, and CNS

•

Possibility of severe disease despite “normal” blood pressure readings, so a high index of suspicion must be maintained in high-risk situations

ETIOLOGY

•

Exact etiology or toxic substance is unknown

•

Theories 1.

Imbalance between thromboxane A2 (vasoconstrictor and platelet aggregator) and prostacyclin (vasodilator)

2.

Abnormal trophoblastic invasion of spiral arteries

3.

Increased sensitivity to angiotensin II by the muscular walls of the arteries

4.

Excess circulating soluble fms-like tyrosine kinase 1 (SFlT-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Acute fatty liver of pregnancy

•

Appendicitis

•

Diabetic ketoacidosis

•

Gallbladder disease

•

Gastroenteritis

•

Glomerulonephritis

•

Hemolytic-uremic syndrome

•

Hepatic encephalopathy

•

Hyperemesis gravidarum

•

Idiopathic thrombocytopenia

•

Thrombotic thrombocytopenic purpura

•

Nephrolithiasis

•

Pyelonephritis

•

PUD

WORKUP

•

SLE

•

Viral hepatitis

WORKUP

•

Two blood pressure measurements in lateral recumbent position 6 hr apart, with an absolute pressure >140/90 mm Hg or an increase of 30 mm Hg systolic or 15 mm Hg diastolic from baseline, an increase in the mean arterial pressure (MAP) of 20 mm Hg, or an absolute MAP >105 mm Hg

•

Evaluation for proteinuria as defined by >0.1 g/L on urine dipstick or >300 mg protein on a 24-hr urine collection

•

Evaluation of fetal status for evidence of intrauterine growth restriction, oligohydramnios, alteration in umbilical or uterine artery Doppler flow, or acute compromise, such as abruption

•

Because of the insidious nature of the disease with potential for multiple organ involvement, complete evaluation for preeclampsia in any pregnant patient presenting with CNS derangement or GI complaints after 20 wk of gestation

•

Evaluation for associated conditions such as disseminated intravascular coagulation, hepatic dysfunction, or subcapsular hematoma

LABORATORY TESTS

•

High-risk patients: baseline assessment of renal function (24-hr urine collection for protein and creatinine clearance), platelets, BUN, creatinine, LFTs, and uric acid should be obtained at the first prenatal visit.

•

CBC (Hgb, HCT, platelets) may show signs of volume contraction or HELLP syndrome.

•

LFTs (AST, ALT, LDH) are useful in evaluation for HELLP syndrome or to exclude important differentials.

•

Hyperuricemia or increased creatinine may indicate decreasing renal function.

•

PT, PTT, and fibrinogen should be checked to rule out disseminated intravascular coagulation.

•

Peripheral smear may demonstrate microangiopathic hemolytic anemia.

•

Complement levels can be used to differentiate from an acute exacerbation of a collagen-vascular disease.

•

Increased levels of SFlT-1 and reduced levels of PlGF predict subsequent development of preeclampsia.

IMAGING STUDIES

•

CT scan of head if atypical presentation of eclampsia, possibility of intracerebral bleed, or prolonged postictal state

•

Sonogram of fetus to evaluate for IUGR, amniotic fluid, placenta

•

Sonogram of maternal liver if suspect subcapsular hematoma

TREATMENT NONPHARMACOLOGIC THERAPY

Bed rest in left lateral decubitus position ACUTE GENERAL Rx

Delivery is the treatment of choice and the only cure for the disease. This must be taken in the context of the gestational age of the fetus, severity of the preeclampsia, and the likelihood of a successful induction and

reliability of patient. •

Administer magnesium sulfate 6 g IV loading dose, with 2 to 3 g maintenance or phenytoin at 10 to 15 mg/kg loading dose, then 200 mg IV q8h starting 12 hr after loading dose.

•

Hydralazine 10 mg IV, labetalol hydrochloride 20 to 40 mg IV, nifedipine 20 mg SL can be used for acute blood pressure control.

•

Continuous fetal monitoring is needed.

•

Epidural is anesthesia of choice for pain management in labor or C-section.

•

All patients undergoing induction of labor should receive antiseizure medications regardless of severity of disease.

CHRONIC Rx

•

Mild preeclampsia 37 wk with favorable cervix or at 40 wk regardless of cervical status.

•

Severe preeclampsia: delivery in the presence of maternal or fetal compromise, labor, or >34 wk; at 28 to 34 wk consider steroids with close monitoring, and at 50 cm3, 38% in glands 10 yr. Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 yr is small, but the reductions in the risks of metastasis and local tumor progression are substantial. Postoperative complications of radical prostatectomy include urinary incontinence (10%-20% depending on degree of neurovascular bundle and urethral preservation, patient age, and correct mucosal apposition) and erectile dysfunction (percentage exceeds 50% and varies with patient age, preoperative erectile dysfunction, stage of tumor at time of surgery, and preservation of neurovascular bundle). Lower complication rates occur in hospitals that perform a large number of prostatectomies. Fewer men will have postsurgical erectile dysfunction after unilateral or bilateral nerve-sparing surgery.

2.

Radiation therapy (external beam irradiation or brachytherapy with implantation of radioactive pellets [iodine-125 or palladium-103 seeds] into the prostate gland) represents an alternative in patients with localized prostate cancer, especially poor surgical candidates or patients with a high-grade malignancy. The efficacy of brachytherapy is comparable to external radiation. In patients receiving external beam radiation, a total dose of 79.2 Gy (high dose) as compared with a total dose of 70.2 Gy (conventional dose) has been reported to lower the risk of recurrence without increased risk of morbidity and mortality. Patients with localized prostate cancer and high risk for extraprostatic disease and disease recurrence (e.g., Gleason score =7 with multiple positive biopsy cores and clinical stage T1b-T2b) may benefit (increased overall survival) with the addition of 6 mo of androgen suppression therapy to radiation therapy.

3.

Watchful waiting is reasonable in patients who are too old or too ill to survive longer than 10 yr. If the cancer progresses to the point where it becomes symptomatic, palliation can be attempted with several methods. Conservative management is also reasonable for patients with Gleason 2 to 4 cancer because these patients do not have a shortened life expectancy, and treatment is associated with long-term side effects.

•

Patients with advanced disease and projected life expectancy 2.0 µg/ml during the year before the diagnosis of cancer may have a relatively high risk of death from prostate cancer despite undergoing radical prostatectomy.

•

Extraprostatic disease is detected at radical prostatectomy in 38% to 52% of patients and is associated with a risk of disease recurrence, progression, and death. In these patients, adjuvant radiotherapy results in significantly reduced risk of PSA relapse and disease recurrence; however, the improvements in metastases-free survival and overall survival are not statistically significant.

EVIDENCE

Any benefits of radical prostatectomy need to be balanced with potential harms A systematic review including two randomized controlled trials (RCTs) comparing radical prostatectomy with watchful waiting in men with localized disease was unable to show any difference in death rates from any cause. However, the larger trial found a significant reduction in death rates at 6 years due to prostate cancer with surgery vs. watchful waiting. Twenty to seventy percent reported sexual dysfunction and 15% to 50% reported urinary difficulties after radical prostatectomy.[[1]] More evidence should result from the completion of the U.S. Prostatectomy Intervention Versus Observation Trial (PIVOT), which started in 1994 and is scheduled for 12 to 15 years. One RCT comparing radical prostatectomy vs. external beam radiation for men with either localized or locally advanced disease found that radical prostatectomy significantly increased prostate cancer specific survival rates vs. external beam radiation after 5 years.[[1]]

Another RCT comparing radical prostatectomy vs. external beam radiation therapy in men with clinically localized prostate cancer found that prostatectomy was associated with a lower risk of metastatic disease.[[2]] The outcome of watchful waiting varies widely according to the stage at presentation and the degree of differentiation of the tumor Two large prospective clinical cohort studies found that watchful waiting was associated with a 15-year disease-specific survival rate of 80% in men with clinically localized disease. This ranged from 95% for welldifferentiated tumors to 30% for poorly differentiated tumors. [304] [305] Androgen deprivation therapy is effective in prolonging survival among men with prostate cancer outside the capsule A systematic review found that early androgen deprivation improved overall 5-year survival compared with deferred treatment in patients with locally advanced prostate cancer who were receiving external beam radiation therapy.[[5]] An RCT compared immediate androgen deprivation vs. delayed androgen deprivation in men with nodepositive disease following radical prostatectomy. There was a significant improvement in survival and a reduction in recurrence in the immediate-treatment group.[[6]] An RCT compared immediate androgen deprivation (at time of diagnosis) vs. delayed androgen deprivation (at time of disease progression) in men with stage C or D prostate cancer. Disease-related mortality was significantly reduced in patients with stage C disease receiving immediate treatment, and the risk of major complications was also reduced. [[7]] Inconclusive evidence from systematic reviews suggests that combined androgen blockade (androgen deprivation plus nonsteroidal antiandrogen) improves survival in patients with metastatic prostate cancer compared with androgen deprivation alone.[[8]] An RCT found no significant difference between orchiectomy, radiotherapy, and both treatments in combination for overall survival or need for further treatment of local disease progression in patients with locally advanced prostate cancer.[[9]] The evidence for different forms of androgen deprivation for metastatic prostate cancer has produced similar overall survival rates A systematic review compared different forms of androgen deprivation (diethylstilbestrol, orchiectomy, and GnRH agonists) in men with metastatic prostate cancer. There were no significant differences between the therapies in terms of overall progression-free survival, time to progression, or overall survival. [[10]] Patients with symptomatic metastatic prostate cancer (androgen independent) may benefit from chemotherapy RCTs have shown that some men have reduced pain and prolonged palliation with chemotherapy, but there is no evidence of improved survival.[[8]]

Evidence-Based References 1. Harris RP et al: Screening for prostate cancer. Systematic Evidence Review no. 16. Rockville, MD, 2001, Agency for Healthcare Research and Quality. Reviewed in: Clin Evid 13:1128, 2005. 2. Paulson DFthe Uro-Oncology Research Group, et al: Radical surgery versus radiotherapy for adenocarcinoma of the prostate. J Urol 1982; 128:502-504.Reviewed in: Clin Evid 11:1169-1185, 2004.

3. Albertsen PC, et al: Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 1998; 280:975-980.Reviewed in: Clin Evid 11:1169-1185, 2004. 4. Lu-Yao GL, Yao S: Population-based study of long-term survival in patients with clinically localized prostate cancer. Lancet 1997; 349:906-910.Reviewed in: Clin Evid 11:1169-1185, 2004. 5. Agency for Health Care Policy and Research: Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostatic cancer: summary. Rockville, MD: Agency for Health Care Policy and Research, 1999. Reviewed in: Clin Evid 11:1169-1185, 2004.

6. Messing EM, et al: Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999; 341:1781-1789.Reviewed in: Clin Evid 11:1169-1185, 2004. 7. Medical Research Council Prostate Cancer Working Party Investigators Group: Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial. Br J Urol 1997; 79:235-246.Reviewed in: Clin Evid 11:1169-1185, 2004. 8. Michaelson MD, Smith MR, Talcott JA: Prostate cancer (metastatic). Reviewed. Clin Evid, 11. London: BMJ Publishing Group; 2004:1158-1168. 9. Fellows GJ, et al: Treatment of advanced localised prostatic cancer by orchiectomy, radiotherapy, or combined treatment. Br J Urol 1992; 70:304-309.Reviewed in: Clin Evid 11:1169-1185, 2004. 10. Seidenfeld J, et al: Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000; 132:566-577.Reviewed in: Clin Evid 11:1158-1168, 2004.

SUGGESTED READINGS Bill-Axelson A, et al: Radical prostatectomy versus watchful waiting for early prostate cancer. N Engl J Med 2005; 352:1977-1984. Freenspan S, et al: Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer. Ann Intern Med 2007; 146:416. Hoffman RM, et al: Health outcomes in older men with localized prostate cancer: results from the prostate cancer outcomes study. Am J Med 2006; 119:418. Petrylak DP, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced prostate cancer. N Engl J Med 2005; 351:1513-1520. Routh JC, Leibovich BC: Adenocarcinoma of the prostate: epidemiological trends, screening, diagnosis, and surgical management of localized disease. Mayo Clin Proc 2005; 80(b):899-907. Sanda MG, et al: Quality of life and satisfaction with outcome among prostate cancer survivors. N Engl J

Med 2008; 358:1250-1261. Sharifi N, et al: Androgen deprivation therapy for prostate cancer. JAMA 2005; 294:238-244. Tannock IF, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2005; 351:1502-1512. Thompson IM, et al: Adjuvant radiotherapy for pathologically advanced prostate cancer. JAMA 2006; 296:2329. Walczak J, Carducci M: Prostate cancer: a practical approach to current management of recurrent disease. Mayo Clin Proc 2007; 82(2):243. Walsh PC, et al: Localized prostate cancer. N Engl J Med 2007; 357:26. Wilt TS, et al: Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med 2008; 148:435-448.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Prostatic Hyperplasia, Benign FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Benign prostatic hyperplasia is the benign growth of the prostate, generally originating in the periureteral and transition zones, with subsequent obstructive and irritative voiding symptoms. SYNONYMS

BPH Prostatic hypertroph

ICD-9CM CODES

600 Benign prostatic hyperplasia EPIDEMIOLOGY & DEMOGRAPHICS

•

80% of men have evidence of benign prostatic hypertrophy by age 80 yr.

•

Medical and surgical intervention for problems caused by BPH is required in >20% of males by age 75 yr.

•

Transurethral resection of the prostate (TURP) is the tenth most common operative procedure (>400,000/yr in U.S.).

•

10% to 30% of men with BPH have occult prostate cancer.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Digital rectal examination (DRE) reveals enlargement of the prostate.

•

Focal enlargement may be indicative of malignancy.

•

There is poor correlation between size of prostate and symptoms (BPH may be asymptomatic if it does not encroach on the urethral lumen).

•

Most patients with BPH complain of difficulty in initiating urination (hesitancy), decrease in caliber and force of stream, incomplete emptying of bladder often resulting in double voiding (need to urinate again a few minutes after voiding), postvoid “dribbling,” and nocturia.

ETIOLOGY

Multifactorial; a functioning testicle is necessary for development of BPH (as evidenced by the absence in

males who were castrated before puberty).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Prostatitis

•

Prostate cancer

•

Strictures (urethral)

•

Medication interfering with the muscle fibers in the prostate and also with bladder function

WORKUP

Symptom assessment (use of American Urological Association [AUA] Symptom Index for BPH [ Table 1-37 ]), laboratory tests, and imaging studies

TABLE 1-37 -- International Prostate Symptom Score (I-PSS) SCORE

Symptom

Less Not Than 1 At Time All in 5

Less More Than Than Half About Half the Half the the Time Time Time

Almost Total Always Score

Incomplete emptying:Over the past month, how often have you had a sensation of not emptying your bladder completely after you finished urinating?

0

1

2

3

4

5

Frequency: Over the past month, how often have you had to urinate again 70% of patients with proper treatment.

DISPOSITION

With appropriate therapy, symptoms improve or stabilize in >70% of patients with BPH. REFERRAL

Urology referral for patients with severe or intolerable symptoms and for any patient suspected of having prostate cancer (10% to 30% of men with BPH).

PEARLS & CONSIDERATIONS COMMENTS

•

Emerging technologies for treating BPH include lasers, coils, stents, thermal therapy, and hyperthermia. Laser prostatectomy appears promising; however, long-term effectiveness has not yet been demonstrated.

•

The increase in the use of pharmacologic management has resulted in more than 30% reduction in the total number of transurethral resections of the prostate.

EVIDENCE

Alpha blockers are effective in the management of BPH and may be more effective than 5-a-reductase inhibitors (finasteride) Three systematic reviews of randomized controlled trials (RCTs) found that alpha blockers are more effective than placebo in relieving symptoms of BPH. [324] [325] [326]

One of the reviews noted there was comparable efficacy among the alpha blockers on the basis of three trials, which included tamsulosin vs. alfuzosin, alfuzosin vs. prazosin, and tamsulosin vs. terazosin.[[2]] Two RCTs compared finasteride with an alpha blocker and with both treatments combined. The trials found that the alpha blocker was associated with a greater reduction in symptoms than finasteride and that addition of finasteride to alpha-blocking therapy conferred no additional benefit. Neither trial selected patients on the basis of prostate size. [327] [328] There is evidence for the efficacy of 5-a-reductase inhibitors (finasteride and dutasteride) in the management of BPH, and they may be most useful for men with large prostates. A systematic review found that finasteride was significantly more effective than placebo at reducing symptom scores.[[3]] A nonsystematic review also found that treatment with finasteride was significantly more effective than placebo at reducing symptom scores and that the benefit over placebo was greatest in men with larger prostates (40 g or more).[[6]] Another nonsystematic review (a meta-analysis) found that finasteride vs. placebo reduced the 2-year risk of acute urinary retention and of progression to prostatectomy.[[7]] A large RCT compared finasteride with placebo in men with symptomatic BPH. After 4 years, finasteride vs. placebo significantly reduced symptoms, the risk of acute urinary retention (AUR), or the need for prostatectomy. The risk reduction was greatest in men with a higher baseline level of prostate-specific antigen (reflecting larger prostates). Further follow-up at 6 years found the decrease in the incidence of AUR- or BPH-related surgery was sustained in those that had continued on finasteride. [331] [332] A good-quality RCT with mean follow-up of 4.5 years, in men with moderate to severe symptoms and an average prostate volume of 31 ml, found the risk of overall clinical progression was significantly reduced by both doxazosin alone (39% risk reduction) and finasteride alone (34% risk reduction), and that combination therapy (doxazosin and finasteride together) produced a significantly better risk reduction (66%) than either drug used alone. The particular risks of acute retention and the need for invasive therapy were significantly reduced by combination therapy and finasteride alone, but not by doxazosin alone.[[10]] Daily dutasteride (a dual inhibitor of the 5-a-reductase isoenzymes types 1 and 2) was compared with placebo in men with benign prostatic hyperplasia. At 24 months, treatment with dutasteride was associated with a significant reduction in serum dihydrotestosterone, prostate volume, and symptoms, and a significant increase in maximum urinary flow rates. The risk of acute urinary retention and the need for surgical intervention was also reduced compared with placebo.[[11]] There is limited evidence that TURP is more effective than watchful waiting for improving symptoms and reducing complications. There is no evidence for any significant difference in outcome between TURP and TUIP. TURP is more effective than transurethral needle ablation (TUNA) but is associated with more adverse effects. TURP has been found to be associated with more symptomatic improvement and lower rates of treatment failure than watchful waiting. [335] [336] There is little clear evidence that TURP is more effective than laser therapy or electrical vaporization.[[14]]

A systematic review found no significant difference between TURP and TUIP in terms of symptom scores at 1 year. The review found little good evidence for longer-term results. [[15]] TURP was found to be associated with more symptomatic improvement than TUNA. However, TURP was also associated with increased incidence of retrograde ejaculation and bleeding.[[16]] Transurethral microwave therapy (TUMT) is more effective than sham treatment or terazosin for the treatment of BPH. Three RCTs comparing TUMT with sham treatment found that TUMT improved symptoms more than sham treatment. [340] [341] [342] Transurethral microwave therapy (TUMT) has been shown to produce significantly more symptomatic improvement than terazosin at both 6 and 18 months. [343] [344] Symptoms of BPH may be effectively treated with saw palmetto. A systematic review found that saw palmetto provides mild to moderate improvement in urinary symptoms and flow measures compared with placebo and has efficacy comparable with that of finasteride.[[22]] Symptoms and flow measures have been improved in BPH with the use of beta-sitosterols. A systematic review assessing the use of nonglucosidic beta-sitosterols for the treatment of mild to moderate BPH showed that urinary symptoms and flow measures were improved, although the long-term effectiveness and safety of beta-sitosterols are not known.[[23]] Pygeum africanum may be a useful treatment option for men with lower urinary symptoms consistent with BPH. A systematic review showed that compared with placebo, Pygeum africanum provided a moderately large improvement in overall symptoms, although the trials were small in size, of short duration, and different methods of reporting outcomes were used.[[24]]

Evidence-Based References 1. Wilt TJ, MacDonald R, Rutks I: Tamsulosin for benign prostatic hyperplasia. Cochrane Database Syst Rev 2002; 4: 2. Djavan B, Marberger M: A meta-analysis on theefficacy and tolerability of alpha-1 adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol 1999; 36:1.Reviewed in Clin Evid 11:1119, 2004. 3. Clifford GM, Farmer RD: Medical therapy for benign prostatic hyperplasia: a review of the literature. Eur Urol 2000; 38:2.Reviewed in: Clin Evid 11:1119, 2004. 4. Lepor H, Williford WO, Barry MJ: The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996; 335:533.Reviewed in: Clin Evid 11:1119, 2004. 5. Debruyne FMJ, et al: Sustained-release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. Eur Urol 1998; 34:169.Reviewed in: Clin Evid 11:1119, 2004.

6. Boyle P, Gould AL, Roehrborn CG: Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48:398.Reviewed in: Clin Evid 11:1119, 2004. 7. Andersen JT, et al: Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia. Urology 1997; 49:839.Reviewed in: Clin Evid 11:1119, 2004. 8. McConnell J, et al: The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med 1998; 338:557.Reviewed in: Clin Evid 11:1119, 2004. 9. Roehrborn CG, et al: Proscar Long-Term Efficacy and Safety Study Group. Sustained decrease in incidence of acute urinary retention and surgery with finasteride for 6 years in men with benign prostatic hyperplasia. J Urol 2004; 171:1194. 10. McConnell JD, et al: Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The longterm effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349:2387.Reviewed in: Bandolier, Knowledge Library. 11. Roehrborn CP, et al: Efficacy and safety of a dual inhibitor of 5 alpha reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60:434. 12. Wasson JH, et al: A comparison of transurethral surgery (TURP) with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med 1995; 332:75.Reviewed in: Clin Evid 11:1119, 2004. 13. Donovan JL, et al: A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: the ClasP study. J Urol 2000; 164:65.Reviewed in: Clin Evid 11:1119, 2004. 14. Webber R: Benign prostatic hyperplasia. Clin Evid 2004; 11:1119. 15. Yang Q, et al: Transurethral incision compared with transurethral resection of the prostate for bladder outlet obstruction: a systematic review and meta-analysis of randomized controlled trials. J Urol 2001; 165:1526.Reviewed in: Clin Evid 11:1119, 2004. 16. Bruskewitz R, et al: A prospective, randomized 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia. J Urol 1998; 159:1588.Reviewed in: Clin Evid 11:1119, 2004. 17. Roehrborn CG, et al: Microwave thermotherapy for benign prostatic hyperplasia with the Dornier Urowave: results of a randomized, double blind, multicenter, sham-controlled trial. Urology 1998; 51:19.Reviewed in: Clin Evid 11:1119, 2004. 18. Larson T, et al: A high-efficiency microwave thermoablation system for the treatment of benign prostatic hyperplasia: results of a randomized, sham-controlled, prospective, double-blind, multicenter clinical trial. Urology 1998; 51:731.Reviewed in: Clin Evid 11:1119, 2004. 19. de la Rosette J, et al: Transurethral microwave thermotherapy (TUMT) in benign prostatic hyperplasia: placebo versus TUMT. Urology 1994; 44:58.Reviewed in: Clin Evid 11:1119, 2004. 20. Djavan B, et al: Prospective randomized comparison of high energy transurethral microwave thermotherapy versus alpha blocker treatment of patients with benign prostatic hyperplasia. J Urol 1999; 161:139.Reviewed in: Clin Evid 11:1119, 2004. 21. Djavan B, et al: Targeted transurethral microwave thermotherapy versus alpha-blockade in benign

prostatic hyperplasia: outcomes at 18 months. Urology 2001; 57:66.Reviewed in: Clin Evid 11:1119, 2004. 22. Wilt T, Ishani A, MacDonald R: Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev 2002; 3: 23. Wilt T, et al: Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev 1999; 3: 24. Wilt T, et al: Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev 1998; 1:

SUGGESTED READINGS AUA Practice Guidelines Committee: AUA guideline on management of benign prostatic hyperplasia. J Urol 2003; 170: Bent S, et al: Saw palmetto for benign prostatic hyperplasia. N Engl J Med 2006; 354:557. Lepor H: Insights into the natural history and treatment of benign prostatic hyperplasia. J Urol 2006; 175:815.

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Prostatitis MARIA A. CORIGLIANO, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Prostatitis refers to inflammation of the prostate gland. There are four major categories:

•

Acute bacterial prostatitis (type I)

•

Chronic bacterial prostatitis (type II)

•

Chronic prostatitis/pelvic pain syndrome (CP/CPPS) (type III): subdivided in type IIIA (inflammatory) and IIIB (noninflammatory)

•

Asymptomatic inflammatory prostatitis (type IV)

ICD-9CM CODES

601.0

Prostatitis (acute)

601.1

Prostatitis (chronic)

099.54 Prostatitis (chlamydial) EPIDEMIOLOGY & DEMOGRAPHICS

•

50% of men experience symptoms of prostatitis in their lifetime.

•

Acute bacterial prostatitis is uncommon.

•

The prevalence of chronic bacterial prostatitis is 5% to 10%.

•

Chronic prostatitis/pelvic pain syndrome (CP/CPPS) is the most common of the clinically defined prostatitis syndromes, with the prevalence of the syndrome ranging from 9% to 12% among men.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

ACUTE BACTERIAL PROSTATITIS:

•

Sudden or rapidly progressive onset of: 1.

Dysuria

2.

Frequency

3.

Urgency

4.

Nocturia

5.

Perineal pain that may radiate to the back, the rectum, or the penis

•

Hematuria or a purulent urethral discharge may occur.

•

Occasionally urinary retention complicates the course.

•

Fever, chills, and signs of sepsis can also be part of the clinical picture.

•

On rectal examination the prostate is typically tender.

CHRONIC BACTERIAL PROSTATITIS: •

Characterized by positive culture of expressed prostatic secretions. May cause symptoms such as suprapubic, low back, or perineal pain, mild urgency, frequency, and dysuria with urination, and may be associated with recurrent urinary tract infections.

•

May be asymptomatic when the infection is confined to the prostate.

•

May present as an increase in severity of baseline symptoms of benign prostatic hypertrophy.

•

When cystitis is also present, urinary frequency, urgency, and burning may be reported.

•

Hematuria may be a presenting complaint.

•

In elderly men, new onset of urinary incontinence may be noted.

CHRONIC PROSTATITIS/CHRONIC PAIN SYNDROME: •

Presents similarly with pain in the pelvic region lasting more than 3 mo. Symptoms also can include pain in the suprapubic region, low back, penis, testes, or scrotum.

•

The symptoms can be of variable severity and may include lower urinary tract symptoms, sexual dysfunction, and reduced quality of life.

ETIOLOGY

ACUTE BACTERIAL PROSTATITIS: •

Acute usually gram-negative infection of the prostate gland. 1.

Generally associated with cystitis

2.

Resulting from the ascent of bacteria in the urethra

•

Occasionally the route of infection is hematogenous or a lymphatogenous spread of rectal bacteria.

•

The condition is seen in young or middle-aged men.

CHRONIC BACTERIAL PROSTATITIS: •

Often asymptomatic.

•

Exacerbation of symptoms of benign prostatic hypertrophy caused by the same mechanism as in acute bacterial prostatitis.

CHRONIC PROSTATITIS/CHRONIC PAIN SYNDROME:

•

Type IIIA: refers to symptoms of prostatic inflammation associated with the presence of WBCs in prostatic secretions with no identifiable bacterial organism.

•

Chlamydia infection may be etiologically implicated in some cases.

•

Type IIIB: refers to symptoms of prostatic inflammation with no or few WBCs in the prostatic secretion.

•

Its cause is unknown. Spasm in the bladder neck or urethra may be responsible for the symptoms.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Benign prostatic hypertrophy with lower urinary tract symptoms

•

Prostate cancer

•

Also see differential diagnosis of hematuria

WORKUP

•

•

Rectal examination: 1.

Tender prostate most suggestive of acute bacterial prostatitis.

2.

Enlarged prostate common in chronic bacterial prostatitis.

3.

Normal prostate is consistent with chronic bacterial prostatitis and chronic prostatitis/chronic pain syndrome.

Expression of prostatic secretions (EPS) by prostate massage is contraindicated in acute bacterial prostatitis but is appropriate in the other three situations.

LABORATORY TESTS

•

Urinalysis.

•

Urine culture and sensitivity.

•

Bacterial localization studies can be performed but are cumbersome and impractical in most clinical settings.

•

Cell count and culture of expressed prostatic secretions.

•

The yield of a urine culture may be increased if the specimen is obtained after a prostatic massage.

•

PSA is not used to diagnose prostatitis and is not recommended unless a nodule is present on digital examination. A rapid rise over baseline should raise the possibility of prostatitis even in the absence of symptoms. In such cases, a follow-up PSA after treatment of prostatitis is appropriate.

•

CBC and blood cultures if fever, chills, or signs of sepsis exist.

•

If hematuria is present, a workup to rule out a urologic malignancy should be considered if the hematuria does not clear after treatment of prostatitis.

TREATMENT ACUTE BACTERIAL PROSTATITI

Culture-guided antibiotic therapy for 4 wk (beginning with a few days of intravenous antibiotics if the infection is serious or if the patient is bacteremic)

CHRONIC BACTERIAL PROSTATITIS

•

Trimethoprim-sulfamethoxazole is first line choice for 4 wk if the organism is sensitive.

•

Second line choice for treatment failure or organisms resistant to TMP-SMX is with a quinolone.

•

Patient with refractory infection or with multiple relapses may be offered long-term suppressive therapy.

CHRONIC PROSTATITIS/CHRONIC PAIN SYNDROME

•

No specific treatment. A brief course of NSAIDs may be tried until urine localization cultures are completed.

•

Antibiotics are not effective and should be avoided in patients who are afebrile and have normal urinalysis results.

•

A trial of treatment with an alpha-adrenergic blocker (terazosin, doxazosin, or tamsulosin) may be considered, but recent trials failed to show a significant reduction in symptoms.

•

Contributing factors (e.g., stress, neuromuscular factors) should be addressed.

•

Any underlying bladder pathology should be ruled out by cystoscopy and treated if identified.

AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Pruritus Ani

BASIC INFORMATION DEFINITION

Pruritus ani refers to an intense chronic itching of the anus and perianal skin.

ICD-9CM CODES

698.0 Pruritus ani EPIDEMIOLOGY & DEMOGRAPHICS

•

Any age can be affected.

•

Occurs in 1% to 5% of the population.

•

Male to female predominance of 4:1.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Anal itching

•

Anal fissures

•

Hemorrhoids

•

Excoriations

•

Pinworms

•

Fecal incontinence

ETIOLOGY

ANORECTAL DISEASES AND FECAL CONTAMINATION: •

Diarrhea

•

Anal incontinence

•

Hemorrhoids

•

Fissures

•

Fistulae

•

Rectal prolapse

•

Malignancy: Bowen's disease, epidermoid cancer, perianal Paget's disease

INFECTIONS: •

Fungal: candidiasis, dermatophytes

•

Parasitic: pinworms, scabies

•

Bacterial: Staphylococcus aureus, erythrasma

•

Lymphogranuloma venereum

•

Granuloma inguinale

•

Chancroid

•

Molluscum contagiosa

•

Trichomoniasis

•

Venereal: herpes, gonococcal syphilis, human papillomavirus

LOCAL IRRITANTS: •

Moisture, obesity, excessive perspiration

•

Soaps, hygiene products

•

Toilet paper: perfumed, dyed

•

Underwear: irritating fabrics, detergents

•

Anal creams, suppositories

•

Dietary: coffee, beer, acidic foods

•

Drugs: mineral oil, ascorbic acid, hydrocortisone sodium succinate, quinine, colchicine

DERMATOLOGIC DISEASES: •

Psoriasis

•

Atopic dermatitis

•

Seborrheic dermatitis

Section II also describes the various causes of pruritus ani.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Allergies

•

Anxiety

•

Dermatologic conditions

•

Infections

•

Parasites

•

Diabetes mellitus

•

Chronic liver disease

•

Neoplasia

•

Proctalgia fugax

WORKUP

•

Detailed history regarding bowel habits, hygiene, use of perfumed products, and medical history

•

Inspection of perianal area

•

Possible biopsy to exclude neoplasia

•

Microscopic inspection of scrapings

•

Colposcopy of perineum

LABORATORY TESTS

•

Chemistry profile

•

Urinalysis

•

Cultures

•

Stool for ova and parasites

•

Tape test

•

Glucose tolerance test, if necessary

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoidance of tight, nonporous clothing and underclothing

•

Discontinuation or curtailment of coffee, beer, citrus fruits, tomatoes, chocolate, and tea

•

Cleansing of anal area after bowel movements with a premoistened pad or tissue and avoidance of perfumes and dyes present in toilet paper and soaps

•

Avoidance of excessive perspiration

•

Aggressive management of fecal leakage or incontinence to avoid soiling of perianal skin

ACUTE GENERAL Rx

•

Minimization of frequent loose stools with antidiarrheals and fiber agents if appropriate

•

Use of a 1% hydrocortisone cream sparingly bid during the acute phase of pruritus ani but not for >2 wk to avoid atrophy

•

Treatment of predisposing factors, such as parasites, diabetes, liver disease, hemorrhoids, and other infections

CHRONIC Rx

•

Possible complications: excoriation and secondary bacterial infection; must be treated aggressively

•

Long-standing, intractable pruritus ani: good response to intracutaneous injections of methylene blue and other agents, steroid injection

DISPOSITION

•

Usually good results with total resolution of symptoms

•

In some, persistent and recurrent symptoms

REFERRAL

To colorectal specialist if conservative measures fail SUGGESTED READINGS Heard S: Puritus ani. Aust Fam Physician 2004; 33(7):511.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pruritus Vulvae MARIA A. CORIGLIANO, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Pruritus vulvae refers to intense itching of the female external genitalia. SYNONYMS

Vulvodynia

ICD-9CM CODES

698.1 Pruritus of genital organs EPIDEMIOLOGY & DEMOGRAPHICS

•

A female disorder that can affect women at any age

•

Young girls: infection is usually causative

•

Postmenopausal women: frequently affected because of hypoestrogenic state

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Constant intense itching or burning of the vulva ETIOLOGY

•

About 50% are caused by monilial infection or trichomoniasis.

•

Other infectious causes are herpes simplex, condylomata acuminata, and molluscum contagiosum.

•

Other causes: 1.

Infestations with scabies, pediculosis pubis, and pinworms

2.

Dermatoses such as hypertrophic dystrophy, lichen sclerosus, lichen planus, and psoriasis

3.

Neoplasms such as Bowen's disease, Paget's disease, and squamous cell carcinoma

4.

Allergic or chemical dermatitis caused by dyes in clothing or toilet paper, detergents, contraceptive gels, vaginal medications, douches, or soaps

5.

Vulvar or vaginal atrophy

•

Severe pruritus is probably caused by degeneration and inflammation of terminal nerve fibers.

•

Most intense itching occurs with hyperplastic lesions.

•

Children (75%) nonspecific pruritus, lichen sclerosus, bacterial infections, yeast infection, and pinworm infestation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Vulvitis

•

Vaginitis

•

Lichen sclerosus

•

Squamous cell hyperplasia

•

Pinworms

•

Vulvar cancer

•

Syringoma of the vulva

WORKUP

•

Inspection of vulva, vagina, and perianal area looking for infection, fissures, ulcerations, induration, or thick plaques

•

Must rule out trichomoniasis, candidiasis, bacterial vaginosis, allergy, vitamin deficiencies, diabetes

LABORATORY TESTS

•

Wet prep of saline and KOH of vaginal discharge

•

Tape test to look for pinworms

•

Vaginal cultures

•

Biopsy when needed

TREATMENT NONPHARMACOLOGIC THERAPY

•

Keep vulva clean and dry.

•

Wear white cotton panties.

•

Avoid perfumes and body creams over vulvar area because they can cause irritation.

•

Reduce stress.

•

Apply wet dressings with aluminum acetate (Burow's) solution frequently.

•

Avoid coffee and caffeine-containing beverages, chocolate, tomatoes.

•

Sitz baths may be helpful.

ACUTE GENERAL Rx

Need to treat underlying problem: •

Yeast infection: any of the vaginal creams or Diflucan 150-mg one-time dose

•

Trichomoniasis or Gardnerella vaginalis: Flagyl 500 mg or 375 mg PO bid for 7 days

•

Urinary tract infection: treatment of specific organism

•

Estrogen replacement therapy if atrophy is the cause of pruritus

•

Pinworms: mebendazole (Vermox) 100 mg one tablet at diagnosis and repeated in 1 to 2 wk; also treat other members in family >2 yr of age

•

Squamous cell hyperplasia: local application of corticosteroids 1.

One of the high- or medium–potency corticosteroids (0.025% or 0.01% fluocinolone acetonide or 0.01% triamcinolone acetonide) can be used to relieve itching.

2.

Rub into vulva bid or tid for 4 to 6 wk.

3.

Once itching is controlled, fluorinated steroid can be discontinued and patient can be switched to hydrocortisone preparation.

•

Lichen sclerosus: topical 2% testosterone in petrolatum massaged into the vulvar tissue bid or tid; Temovate (clobetasol propionate gel 0.05%) cream tid × 5 days is very effective

•

Treatment with immune response modifiers

CHRONIC Rx

•

If not relieved by topical measures: intradermal injection of triamcinolone (10 mg/ml diluted 2:1 saline) 0.1 ml of the suspension injected at 1-cm intervals and tissue gently massaged

•

If symptoms still uncontrollable: SC injection of absolute alcohol 0.1 ml at 1-cm intervals

DISPOSITION

Usually controlled with conservative measures and topical steroids REFERRAL

To a gynecologist for further workup if conservative measures do not give relief SUGGESTED READINGS Boardman LA, et al: Recurrent vulvar itching. Obstet Gynecol 2005; 105(6):1451. Welch B, et al: Vulval itch. Aust Fam Physcian 2004; 33(7):505.

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Pseudogout LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Pseudogout is one of the clinical patterns associated with a crystal-induced synovitis resulting from the deposition of calcium pyrophosphate dehydrate (CPPD) crystals in joint hyaline and fibrocartilage. The cartilage deposition is termed chondrocalcinosis. SYNONYMS

Calcium pyrophosphate dehydrate crystal deposition disease (CPDD) Chondrocalcinosis Pyrophosphate arthropath

ICD-9CM CODES

275.4 Chondrocalcinosis EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: •

Uncertain

•

Probably similar to gout (3/1000 persons)

•

Chondrocalcinosis is present in >20% of all people at age 80 yr, but most are asymptomatic

PREDOMINANT SEX: Female:male ratio of approximately 1.5:1 PREDOMINANT AGE: 60 to 70 yr at onset PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms are similar to those of gouty arthritis with acute attacks and chronic arthritis

•

Knee joint is most commonly affected

•

Swelling, stiffness, and increased heat in affected joint

ETIOLOGY

•

Unknown

•

Often associated with various medical conditions, including hyperparathyroidism and amyloidosis

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Gouty arthritis

•

Rheumatoid arthritis

•

Osteoarthritis

•

Neuropathic joint

Section II describes the differential diagnosis of acute monoarticular and oligoarticular arthritis and crystalinduced arthritides. An algorithm for evaluation of arthralgia is described in Section III, “Arthralgia Limited to One or Few Joints.” WORKUP

•

Variable clinical presentation

•

Diagnosis dependent on the identification of CPPD crystals

•

The American Rheumatism Association revised diagnostic criteria for CPPD crystal deposition disease (pseudogout) are often used: 1.

Criteria I.

Demonstration of CPPD crystals (obtained by biopsy, necroscopy, or aspirated synovial fluid) by definitive means (e.g., characteristic “fingerprint” by x-ray diffraction powder pattern or by chemical analysis)

II.

(a) Identification of monoclinic and/or triclinic crystals showing either no or only a weakly positive birefringence by compensated polarized light microscopy (b) Presence of typical calcifications in roentgenograms

III. (a) Acute arthritis, especially of knees or other large joints, with or without concomitant hyperuricemia (b) Chronic arthritis, especially of knees, hips, wrists, carpus, elbow, shoulder, and metacarpophalangeal joints, especially if accompanied by acute exacerbations; the following features are helpful in differentiating chronic arthritis from osteoarthritis: 1.

Uncommon site—for example, wrist, MCP, elbow, shoulder

2.

Appearance of lesion radiologically—for example, radiocarpal or patellofemoral joint space narrowing, especially if isolated (patella “wrapped around” the femur)

3.

Subchondral cyst formation

4.

Severity of degeneration—progressive, with subchondral bony collapse (microfractures), and fragmentation, with formation of intraarticular radiodense bodies

5.

Osteophyte formation—variable and inconstant

6.

Tendon calcifications, especially Achilles, triceps, obturators

Definite—Criteria I or II (a) plus (b) must be fulfilled.

2.

Categories

Definite—Criteria I or II (a) plus (b) must be fulfilled. Probable—Criteria II(a) or II(b) must be fulfilled. Possible—Criteria III(a) or (b) should alert the clinician to the possibility of underlying CPPD deposition. LABORATORY TESTS

Crystal analysis of the synovial fluid aspirate to reveal rhomboid calcium pyrophosphate crystals IMAGING STUDIES

Plain radiographs to reveal the following: •

Stippled calcification in bands running parallel to the subchondral bone margins

•

Crystal deposition in menisci, synovium, and ligament tissue; triangular wrist cartilage and symphysis pubis are often affected

TREATMENT NONPHARMACOLOGIC THERAPY

General measures such as heat, rest, and elevation as needed ACUTE GENERAL Rx

•

NSAIDs (as for gout)

•

Colchicine

•

Aspiration/steroid injection

DISPOSITION

Structural joint damage may occasionally occur, requiring arthroplasty in rare cases. REFERRAL

For orthopedic consultation for destructive joint changes

PEARLS & CONSIDERATIONS COMMENTS

As with gout, acute attacks may be triggered by various surgical or medical events. SUGGESTED READINGS Liote F, Ea HK: Recent developments in crystal-induced inflammation pathogenesis and management. Curr

Rheumatol Rep 2007; 9(3):243. McGonagle D, et al: Successful treatment of resistant pseudogout with anakinra. Arthritis Rheum 2008; 58:631. Mader B: Calcium pyrophosphate dihydrate deposition disease of the wrist. Clin Rheumatol 2004; 23(1):95. Rosenthal AK: Crystal arthropathies and other unpopular rheumatic diseases. Curr Opin Rheumatol 2004; 16(3):262. Wise CM: Crystal-associated arthritis in the elderly. Rheum Dis Clin North Am 2007; 33(1):33.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pseudomembranous Colitis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Pseudomembranous colitis is the occurrence of diarrhea and bowel inflammation associated with antibiotic use. SYNONYMS

Antibiotic-induced colitis

ICD-9CM CODES

008.45 Clostridium difficile, pseudomembranous colitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Cephalosporins are the most frequent offending agent in pseudomembranous colitis because of their high rates of use.

•

The antibiotic with the highest incidence is clindamycin (10% incidence of pseudomembranous colitis with its use).

•

Clostridium difficile is responsible for approximately 3 million cases of diarrhea and colitis in the U.S. every year.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Abdominal tenderness (generalized or lower abdominal)

•

Fever

•

In patients with prolonged diarrhea, poor skin turgor, dry mucous membranes, and other signs of dehydration may be present

ETIOLOGY

Risk factors for C. difficile (the major identifiable agent of antibiotic-induced diarrhea and colitis):

•

Administration of antibiotics: can occur with any antibiotic, but occurs most frequently with clindamycin, ampicillin, and cephalosporins

•

Prolonged hospitalization

•

Advanced age

•

Abdominal surgery

•

Hospitalized, tube-fed patients are at risk for C. difficile–associated diarrhea. Clinicians should consider testing for C. difficile in tube-fed patients with diarrhea unrelated to the feeding solution

DIAGNOSIS The clinical signs of pseudomembranous colitis generally include diarrhea, fever, and abdominal cramps following use of antibiotics. DIFFERENTIAL DIAGNOSIS

•

GI bacterial infections (e.g., Salmonella, Shigella, Campylobacter, Yersinia)

•

Enteric parasites (e.g., Cryptosporidium, Entamoeba histolytica)

•

IBD

•

Celiac sprue

•

Irritable bowel syndrome

•

Ischemic colitis

•

Antibiotic intolerance

WORKUP

•

All patients with diarrhea accompanied by current or recent antibiotic use should be tested for C. difficile (see “Laboratory Tests”).

•

Sigmoidoscopy (without cleansing enema) may be necessary when the clinical and laboratory diagnosis is inconclusive and the diarrhea persists.

•

In antibiotic-induced pseudomembranous colitis, the sigmoidoscopy often reveals raised white-yellow exudative plaques adherent to the colonic mucosa ( Fig. 1-217 ).

FIGURE 1-217 Pseudomembranous plaques seen with colonoscopy in a patient with C. difficile–associated PMC. (From Gorbach SL: Infectious diseases, ed 2, Philadelphia, 1998, WB Saunders.)

LABORATORY TESTS

•

C. difficile toxin can be detected by cytotoxin tissue-culture assay (gold standard for identifying C. difficile toxin in stool specimen). This test is difficult to perform and results are not available for 24-48 hr. A more useful test enzyme-linked immunoabsorbent assay (ELISA) for C. difficile toxins A and B. The latter is used most widely in the clinical setting. It has a sensitivity of 85% and a specificity of 100%.

•

Fecal leukocytes (assessed by microscopy or lactoferrin assay) are generally present in stool samples.

•

CBC usually reveals leukocytosis. A sudden increase in WBC to >30,000/mm3 may be indicative of fulminant colitis.

IMAGING STUDIES

Abdominal film (flat plate and upright) is useful in patients presenting with abdominal pain or evidence of

obstruction on physical examination.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Discontinue offending antibiotic

•

Fluid hydration and correct electrolyte abnormalities

ACUTE GENERAL Rx

•

Metronidazole 500 mg PO qid for 10 to 14 days.

•

Vancomycin 125 mg PO qid for 10 to 14 days in cases resistant to metronidazole. However, vancomycin may be considered as first-line therapy in hospitalized patients who are seriously ill.

•

Cholestyramine 4 g PO qid for 10 days in addition to metronidazole to control severe diarrhea (avoid use with vancomycin).

•

When parenteral therapy is necessary (e.g., patient with paralytic ileus), IV metronidazole 500 mg qid can be used. It can also be supplemented with vancomycin 500 mg via NG tube with intermittant clamping or retention enema.

CHRONIC Rx

Judicious future use of antibiotics to prevent recurrences (e.g., avoid prolonged antibiotic therapy) DISPOSITION

Most patients recover completely with appropriate therapy. Fever resolves within 48 hr and diarrhea within 4 to 5 days. Overall mortality is 1% to 2.5% but exceeds 10% in untreated patients. REFERRAL

Hospital admission and IV hydration in severe cases

PEARLS & CONSIDERATIONS COMMENTS

Possible complications of pseudomembranous colitis include dehydration, bowel perforation, toxic megacolon, electrolyte imbalance, and reactive arthritis. SUGGESTED READINGS Bartlett JG: Antibiotic-associated diarrhea. N Engl J Med 2002; 346:334. Hurley BW, Nguyen CC: The spectrum of pseudomembranous enterocolitis and antibiotic-associated diarrhea. Arch Intern Med 2002; 162:2177. Schroeder MS: Clostridium difficile-associated diarrhea. Am Fam Physician 2005; 71:921.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Psittacosis GLENN G. FORT, M.D., M.P.H., MICHELE HALPERN, M.D., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Psittacosis is a systemic infection caused by Chlamydophila psittaci (formerly known as Chlamydia psittaci). SYNONYMS

Ornithosis Parrot pneumoni

ICD-9CM CODES

073.9 Psittacosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

21 cases reported in 2005

•

True incidence possibly higher because infections may be subclinical

•

Highest incidence among pet owners and people working in contact with birds

PEAK INCIDENCE: 30 to 60 yr of age PREVALENCE (IN U.S.): •

Low among humans

•

Organism carried in 5% to 8% of birds

PREDOMINANT SEX: Equal sex distributio PREDOMINANT AGE: More common in adults PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Incubation period of 5 to 15 days

•

Subclinical infection

•

Onset abrupt or insidious

•

Most common symptoms: 1.

Fever

2.

Myalgias

3.

Chills

4.

Cough

•

Most common clinical syndrome: atypical pneumonia with fever, headache, dry cough, and a chest x-ray more dramatically abnormal than the physical examination

•

Ranges from mild disease to respiratory failure and death, although this is extremely unusual

•

Other clinical presentations:

•

•

•

1.

Mononucleosis-like syndrome

2.

Typhoidal form

Most frequent physical findings: 1.

Fever

2.

Pharyngeal erythema

3.

Rales

4.

Hepatomegaly

Less common findings: 1.

Somnolence

2.

Confusion

3.

Relative bradycardia

4.

Pleural rub

5.

Adenopathy

6.

Splenomegaly

7.

Horder's spots (pink blanching maculopapular rash)

Besides the lungs, other specific end-organ involvement:

ETIOLOGY

1.

Pericarditis

2.

Myocarditis

3.

Endocarditis

4.

Hepatitis

5.

Joints

6.

Kidneys (glomerulonephritis)

7.

CNS

•

Chlamydophila (formerly Chlamydia) psittaci is an obligate intracellular bacterium.

•

Infection is usually spread by the respiratory route from infected birds.

•

There is a history of exposure to birds in 85% of patients.

•

Strains from turkeys and psittacine birds are most virulent for humans.

•

Cows, goats, and sheep are occasionally implicated.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Legionella

•

Mycoplasma

•

Chlamydophila pneumoniae (TWAR)

•

Viral respiratory infections

•

Typhoid fever

•

Viral hepatitis

•

Aseptic meningitis

•

Mononucleosis

WORKUP

•

CBC, renal and liver function tests

•

Chlamydophila serology

•

Chest x-ray examination

•

Special immunostaining of respiratory secretions

LABORATORY TESTS

•

WBC count is normal or slightly elevated.

•

Mild liver function abnormalities are common (50%).

•

Blood cultures are almost always negative.

•

Studies on respiratory secretions:

•

1.

Direct immunofluorescent antibody (DFA) of respiratory secretions with monoclonal antibodies to chlamydial antigens

2.

Chlamydophila LPS (lipopolysaccharide) antigen by enzyme immunoassay (EIA)

3.

Polymerase chain reaction (PCR)

Serologic studies: 1.

Complement-fixing antibodies

2.

Microimmunofluorescence

3.

Possible false-negative results and cross-reaction with other chlamydial species with both techniques

IMAGING STUDIES

•

Chest x-ray examination is abnormal in 50% to 90% with a variety of patterns.

•

Pleural effusions are common.

TREATMENT NONPHARMACOLOGIC THERAPY

Oxygen supplementation as needed ACUTE GENERAL Rx

•

Tetracycline (500 mg PO qid) or

•

Doxycycline (100 mg PO bid) or

•

Erythromycin (500 mg PO qid): less effective

CHRONIC Rx

In the rare cases of endocarditis, combination of heart valve replacement and prolonged antibiotic course may be the treatment of choice. DISPOSITION

•

Mortality low (0.7%)

•

Poor prognostic factors:

•

1.

Advanced age

2.

Leukopenia

3.

Severe hypoxemia

4.

Renal failure

5.

Confusion

6.

Multilobe pulmonary involvement

Possible reinfection

REFERRAL

•

•

To infectious disease expert: 1.

Complicated atypical pneumonia or other end-organ involvement

2.

Suspicion of an outbreak

To pulmonologist for diagnostic bronchoscopy

PEARLS & CONSIDERATIONS COMMENTS

•

Hospitalized patients do not require specific isolation precautions.

•

Any confirmed or suspected case of psittacosis should be reported to public health authorities.

•

Recent evidence indicates that C. psittaci may be associated with induction of a rare form of lymphoma found in the ocular adnexa; case reports have described regression of ocular lymphoma with antibiotic treatment for C. psittaci.

SUGGESTED READINGS Cunha BA: The atypical pneumonias: clinical diagnosis and importance. Clin Microbiol Infect 2006; 3:12. Ferreri AJ, et al: Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol 2005; 23(22):5067. Ferreri AJ, et al: Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004; 96(8):586. Smith KA, et al: Compendium of measures to control Chlamydophila psittaci (formerly Chlamydia psittaci) infection among humans (psittacosis) and pet birds, 2005. J Am Vet Med Assoc 2005; 226(4):532. Vargas RL, et al: Is there an association between ocular adnexal lymphoma and infection with Chlamydia psittaci? The University of Rochester experience. Leuk Res 2006; 30(5):547.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Psoriasis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Psoriasis is a chronic skin disorder characterized by excessive proliferation of keratinocytes, resulting in the formation of thickened scaly plaques, itching, and inflammatory changes of the epidermis and dermis. The various forms of psoriasis include guttate, pustular, and arthritis variants.

ICD-9CM CODES

696.0 Psoriasis, arthritis, arthropathic 696.1 Psoriasis, any type except arthropathic EPIDEMIOLOGY & DEMOGRAPHICS

•

Psoriasis affects 1% to 3% of the world's population. Most patients have limited psoriasis involving 5 days

Physical examination •

If associated with a mood disorder, delusions/hallucinations are usually consistent with mood (e.g., auditory hallucinations in a depressed patient may tell the patient what a terrible person he is).

•

Altered, disorganized thought pattern, which is usually reflected in disorganized speech (including word salad, thought blocking, rhyming, clang).

•

Lack insight into problems.

•

Behavior is odd or unpredictable; patient may clearly be responding to internal stimuli.

•

Signs of Parkinson's disease, dementia.

ETIOLOGY

•

Pathophysiologically, an interaction among: 1.

Dopaminergic overactivity (particularly in the mesolimbic, nigrostriatal, and mesocortical systems)

2.

Environmental, social/childhood factors

3.

Genetic predisposition

•

Underlying mental disorder: schizophrenia, major depression, brief psychotic disorder, delusional disorder, schizoaffective disorder, schizophreniform disorder, shared psychotic disorder

•

Underlying personality disorder: borderline, paranoid, schizoid, schizotypal

•

Underlying medical condition: HIV/AIDS, Parkinson's, Huntington's, leprosy, malaria, sarcoidosis, SLE, prion disease, hypoglycemia, postpartum state, cerebrovascular event, temporal lobe epilepsy, brain neoplasm

•

Medications: systemic steroids, anticonvulsants, anti-parkinsonian medications, some chemotherapy, scopolamine

•

Underlying dementia: Alzheimer's, Lewy body dementia

•

Illicit drugs (usually with chronic use; can be with intoxication or withdrawal): LSD, PCP, cocaine, GHB (withdrawal), alcohol, amphetamines, marijuana

•

Traumatic brain injury

•

ICU stay: hypoxia, decreased cardiac output, infection, medications, sleep deprivation, alteration of diurnal cycle, sensory deprivation/overload, pain

•

Emotional stress

DIAGNOSIS WORKUP

Any workup would be to better assess etiology and would depend on the clinical situation. LABORATORY TESTS

Consider checking chemistry panel (calcium), complete blood count, liver function tests, cortisol, HIV, RPR, TSH, toxicology screen, LP. IMAGING STUDIES

Consider CXR (sarcoid), EEG, head CT/MRI.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Cognitive behavioral therapy.

•

Social/behavioral skills training.

•

Training for self-management of disease.

•

Aforementioned strategies favored over psychoanalytic techniques given the relative inability for abstract thought and lack of insight in psychotic patients.

•

Family intervention, including education and strategies to reduce emotional expression.

•

Counseling for substance abuse.

ACUTE GENERAL Rx

•

Antipsychotics; low doses should control first episode. Use with caution in elderly patients because adverse effects limit effectiveness.

•

Benzodiazepines if agitation is severe.

•

Discontinue offending medication if present.

CHRONIC Rx

Antipsychotics, second-generation antipsychotics may reduce incidence of tardive dyskinesia, but may increase incidence of metabolic disorders compared to first-generation antipsychotics. DISPOSITION

Prognosis varies according to etiology of psychosis. In general, the more severe and longer the psychotic episode, the worse the prognosis. REFERRAL

Patient should be admitted for acute stabilization if actively psychotic to prevent harm to self and others, as well as to ensure administration of medications.

PEARLS & CONSIDERATIONS

•

Delusions and/or hallucinations are hallmarks of psychosis.

•

Rule out medical or drug causes of psychosis.

•

Antipsychotics are the mainstay of acute and chronic treatment.

•

Consider alternatives to antipsychotics in elderly patients.

SUGGESTED READINGS Byrne P: Managing the acute psychotic episode. BMJ 2007; 334(7595):686. Petersen L, et al: A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005; 17(7517):331.602 Schneider LS, et al: Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med 2006; 355(15):1525. Wang PS, et al: Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005; 353(22):2335.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

NIRALI BORA, M.D.

BASIC INFORMATION DEFINITION

Pubertal delay refers to delayed development and maturation of the reproductive system. The diagnostic criterion is a delay of more than 2 to 3 standard deviations from the mean age of pubertal onset. See Figure 3238 in Section III.

ICD-9CM CODES

259.0 Delay in sexual development and puberty, not elsewhere classified EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 2.5% of healthy adolescents have a diagnosis of pubertal delay using the statistical diagnostic criteri GENETICS: Constitutional delay of puberty often runs in families. Pubertal delay occurs with some congenital syndromes, such as Prader-Willi syndrome and Noonan syndrome, and in patients with enzyme defects in sex steroid synthesis, as well as others. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Puberty is clinically delayed for girls if there is no evidence of breast development by 13 yr of age, absence of menarche by age 16 yr, or absence of menarche within 5 yr of pubertal onset. Puberty is clinically delayed for boys if there is no evidence of testicular enlargement by 14 yr of age, or >5 yr between start and completion of growth of genitalia. ETIOLOGY

Puberty begins with increased pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, increased pituitary responsiveness to GnRH, secretion of gonadotropins, gonadal maturation, and increasing production of sex steroids. Increased concentration of sex steroids induces the development of secondary sexual characteristics, acceleration of growth, and fertility. Numerous causes can lead to pubertal delay including chronic disease, normal variation, abnormal chromosomes, or other factors.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Normal or low serum gonadotropins •

Constitutional delay

•

Hypothalamic dysfunction Malnutrition or eating disorder Strenuous exercise Chronic illness Severe obesity Central nervous system tumors

•

Hypopituitarism Panhypopituitarism Isolated gonadotropin deficiency Kallman syndrome (associated with anosmia) Growth hormone deficiency

•

Hypothyroidism

•

Hyperprolactinemia Pituitary adenoma Drug-associated (cannabis, cocaine)

Increased serum gonadotropins •

Turner syndrome (gonadal dysgenesis)

•

Klinefelter syndrome

•

Bilateral gonadal failure Primary testicular failure Anorchia Premature ovarian failure Resistant ovary syndrome Irradiation, cytotoxic therapy Trauma Infections (e.g., mumps, orchitis)

Other conditions •

Anatomic abnormalities

•

Prader-Willi syndrome

•

Noonan syndrome

•

Androgen resistance

•

Steroidogenic enzyme defects

WORKUP

•

Given the extensive differential diagnosis for pubertal delay, a systematic and focused approach is necessary. A careful history, including family history and social history, can identify eating and exercise habits, chronic illnesses, and parental history of pubertal delay.

•

Growth measurement should include height and weight, a growth chart to assess rate of growth, and calculation of the sex-adjusted midparental height that represents the statistically most probable adult height for the child. For boys add 2.5 inches (or 6.5 cm) from the mean of the parents' heights. For girls, subtract 2.5 inches (or 6.5 cm) from the mean of the parents' height. Physical exam can reveal signs of sexual maturation, stigmata of congenital syndromes, nutritional status. Include neurologic exam (visual fields, ophthalmologic), thyroid, chest, heart, abdomen, Tanner staging.

LABORATORY TESTS

•

Serum gonadotropin levels (LH/FSH) distinguish disorders of congenital or acquired gonadal failure from other causes. By bone age 10 to 12 yr gonadal failure produces elevated levels of serum gonadotropins. If levels are low or normal constitutional delay is the most frequent diagnosis.

•

Chromosomal analysis if there is a suspicion of gonadal dysgenesis or Klinefelter syndrome.

•

Screening studies include CBC, erythrocyte sedimentation rate, serum prolactin, serum TSH.

•

Endocrinologist may do further studies including: GH testing, GnRH stimulation testing, hCG stimulation with testosterone levels.

IMAGING STUDIES

Consider bone age (left hand and wrist film), which is delayed in constitutional delay and GnRH deficiency; CT or MRI of head to evaluate for tumors of pituitary or hypothalamus and absence of olfactory bulb and tract, which occurs in Kallman syndrome (absence of GnRH); and pelvic ultrasound.

TREATMENT

•

Treat underlying cause if it is identified.

•

Constitutional delay can be managed with reassurance that the delay will have no effect on final adult height or development. Short-term hormonal therapy can be used to hasten puberty if the delay is causing severe psychosocial difficulties. Monthly testosterone injections are used for boys who have begun pubertal development while oral oxandrolone is used for boys who have not yet begun puberty. Potential side effects include premature epiphyseal closure and hepatic peliosis. Treatment is discontinued when endogenous hormone production has begun.

•

Gonadotropin deficiency or hypogonadism requires lifelong sex steroid replacement.

•

Psychosocial evaluation, support, and treatment as needed.

REFERRAL

Pediatric endocrinology

PEARLS & CONSIDERATIONS COMMENTS

•

Constitutional delay is the most common cause of pubertal delay and is often associated with a positive family history in parents and/or siblings, but other causes, such as Turner syndrome and systemic disorders, should be excluded.

•

No studies reliably distinguish constitutional delay from gonadotropin deficiency.

PATIENT/FAMILY EDUCATION

•

The Magic Foundation, a support group for patients and their families (http://www.magicfoundation.org )

•

The American Academy of Family Physicians (http://www.aafp.org

•

American Academy of Pediatrics (http://www.aap.org

)

)

Evidence-Based References Blondell et al.. Blondell RD, Foster MB, Kamlesh CD: Disorders of puberty, Am Fam Physician. Available at http://www.aafp.org/afp/990700ap/209.html . Accessed online July 2, 2007. Master-Hunter and Heiman, 2006. Master-Hunter T, Heiman D: Amenorrhea: evaluation and treatment. Am Fam Physician 2006; 73:1376-1382. Rosen and Foster, 2001. Rosen D, Foster C: Delayed puberty. Pediatr Rev 2001; 27:9. Sedlmeyer and Palmort, 2002. Sedlmeyer IL, Palmort MR: Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab 2002; 87:1613-1620.

SUGGESTED READINGS Rosen D, Foster C: Delayed puberty. Pediatr Rev 2001; 27:9.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pulmonary Edema FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Cardiogenic pulmonary edema is a life-threatening condition caused by severe left ventricular decompensation. SYNONYMS

Cardiogenic pulmonary edema

ICD-9CM CODES

428.1 Acute pulmonary edema with heart disease PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Dyspnea with rapid, shallow breathing

•

Diaphoresis, perioral and peripheral cyanosis

•

Pink, frothy sputum

•

Moist, bilateral pulmonary rales

•

Increased pulmonary second sound, S3 gallop (in association with tachycardia)

•

Bulging neck veins

ETIOLOGY

Increased pulmonary capillary pressure secondary to: •

Acute myocardial infarction

•

Exacerbation of CHF

•

Valvular regurgitation (e.g., mitral regurgitation)

•

Ventricular septal defect

•

Severe myocardial ischemia

•

Mitral stenosis

•

Other: cardiac tamponade, endocarditis, myocarditis, arrhythmias, cardiomyopathy, hypertensive crisis

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Noncardiogenic pulmonary edema

•

Pulmonary embolism

•

Exacerbation of asthma

•

Exacerbation of COPD

•

Sarcoidosis

•

Pulmonary fibrosis

•

Viral pneumonitis and other pulmonary infections

LABORATORY TESTS

•

ABGs: respiratory and metabolic acidosis, decreased Pao2, increased Pco2, low pH. (NOTE: The patient may initially show respiratory alkalosis secondary to hyperventilation in attempts to maintain Pao2.)

•

Measurement of plasma BNP (elevated).

IMAGING STUDIES

•

•

•

Chest x-ray examination: 1.

Pulmonary congestion with Kerley B lines; fluffy perihilar infiltrates in the early stages; bilateral interstitial alveolar infiltrates

2.

Pleural effusions

Echocardiogram: 1.

Useful to evaluate valvular abnormalities, diastolic vs. systolic dysfunction

2.

Can aid in differentiation of cardiogenic vs. noncardiogenic pulmonary edema

3.

Can also estimate pulmonary capillary wedge pressure and rule out presence of myxoma or atrial thrombus

Right heart catheterization (selected patients): cardiac pressures and cardiogenic pulmonary edema reveal increased PADP and PCWP =25 mm Hg

TREATMENT ACUTE GENERAL Rx

All the following steps can be performed concomitantly:

•

100% oxygen by face mask. Both CPAP and BiPAP systems can improve oxygenation and lower carbon dioxide tensions. Check ABGs; if marked hypoxemia or severe respiratory acidosis, intubate the patient and place on a ventilator. Positive end-expiratory pressure (PEEP) increases functional capacity and improves oxygenation.

•

Furosemide: 1 mg/kg IV bolus (typically 40 to 100 mg) to rapidly establish diuresis and decrease venous return through its venodilator action; may double the dose in 30 min if no effect.

•

Vasodilator therapy: 1.

2.

Nitrates: particularly useful if the patient has concomitant chest pain. a.

Nitroglycerin: 150 to 600 µg SL or nitroglycerin spray (Nitrolingual) may be given immediately on arrival and repeated multiple times if the patient remains symptomatic and blood pressure remains stable.

b.

2% nitroglycerin ointment: 1 to 3 inches out of the tube applied continuously; absorption may be erratic.

c.

IV nitroglycerin: 100 mg in 500 ml of D5W solution; start at 6 µg/min (2 ml/hr).

Nitroprusside: useful for afterload reduction in hypertensive patients with decreased cardiac index (CI). a.

Increases the CI and decreases left ventricular filling pressure.

b.

Vasodilator and diuretic therapy should be tailored to achieve PCWP =18 mm Hg, RAP =8 mm Hg, systolic blood pressure >90 mm Hg, SVR >1200 dynes/sec/cm-5. The use of nitroprusside in patients with acute MI is controversial because it may intensify ischemia by decreasing the blood flow to the ischemic left ventricular myocardium.

3.

Nesiritide (Natrecor): dosage is 2 mcg/kg IV bolus, then 0.01 mcg/kg/min. Use of nesiritide should be reserved for patients who present to the hospital with acutely decompensated heart failure and dyspnea at rest, in whom standard combination therapy with diuretics and nitroglycerin has been inadequate. It should not be substituted for diuretics, used for intermittent outpatient infusion, or used repetitively.

4.

Morphine: 2 to 4 mg IV/SC/IM, may repeat q15 min prn. It decreases venous return, anxiety, and systemic vascular resistance (naloxone should be available at bedside to reverse the effects of morphine if respiratory depression occurs). Morphine may induce hypotension in volume-depleted patients.

5.

Afterload reduction with ACE inhibitors. Captopril 25 mg PO tablet can be used for SL administration (placing a drop or two of water on the tablet and placing it under the tongue helps dissolve it), onset of action is 25 mm Hg at rest or greater than 30 mm Hg with exercise. Sustained elevation in PAP due to increased pulmonary venous pressure, hypoxic pulmonary vasoconstriction, or increased flow is often referred to as secondary pulmonary hypertension. SYNONYMS

Primary pulmonary hypertension (PPH) Secondary pulmonary hypertensio

ICD-9CM CODES

416.0 Primary pulmonary hypertension 416.8 Secondary pulmonary hypertension EPIDEMIOLOGY & DEMOGRAPHICS

•

Primary pulmonary hypertension (PPH) is rare, occurring in 1 to 2 cases per 1 million people per year, with an overall prevalence estimated at 1300 per million.

•

PPH is more common in women than men (1.7:1), usually presenting in the third to fourth decade of life.

•

Secondary pulmonary hypertension is more common than PPH.

•

Secondary pulmonary hypertension is the common pathophysiologic mechanism leading to cor pulmonale in patients with underlying pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD], pulmonary embolism).

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Primary pulmonary hypertension:

•

PPH is insidious and may go undetected for years.

•

Exertional dyspnea is the most common presenting symptom (60%).

•

Fatigue and weakness.

•

Syncope, classically exertion related or after a warm shower with peripheral vasodilation.

•

Chest pain.

•

Hoarse voice due to compression of recurrent laryngeal nerve by an enlarged pulmonary artery (Ortner's syndrome).

•

Loud P2 component of the second heart sound and paradoxical splitting of second heart sound.

•

Right-sided S4.

•

Jugular venous distension.

•

Abdominal distention/ascites.

•

Prominent parasternal (right ventricular [RV]) impulse.

•

Holosystolic tricuspid regurgitation murmur heard best along the left fourth parasternal line that increases in intensity with inspiration.

•

Peripheral edema.

Secondary pulmonary hypertension:

•

Similar to PPH, but caused by an underlying cause (e.g., left-sided congestive heart failure, mitral stenosis, COPD).

ETIOLOGY

•

The etiology of PPH is unknown. Most cases are sporadic, but there is a 6% to 12% familial incidence.

•

PPH is associated with several known risk factors: portal hypertension and liver cirrhosis, appetitesuppressant drugs (fenfluramine), and HIV disease.

•

Several genetic abnormalities have been associated with the familial form of PPH, many of which are mutations in the genes that code for members of the TGF-ß family of receptors (BMPR-II, ALK-1) on chromosome 2q33.

•

Familial PPH is an autosomal dominant disease with variable penetrance, affecting only about 10% to 20% of carriers.

•

Several factors play a role in the pathogenesis of PPH, including a genetic predisposition, endothelial cell dysfunction, abnormalities in vasomotor control, thrombotic obliteration of the vascular lumen, and vascular remodeling through cell proliferation and matrix production.

•

New WHO classification of pulmonary hypertension (based on common clinical features): Pulmonary arterial hypertension Primary: familial and sporadic Related to: collagen vascular diseases, congenital systemic to pulmonary shunts, HIV, portal hypertension, drugs and toxins

Pulmonary venous hypertension

Left-sided atrial, ventricular, or valvular heart disease Fibrosing mediastinitis, adenopathy, and tumors

Pulmonary veno-occlusive disease PH associated with disorders of the respiratory system or hypoxemia COPD, interstitial lung disease, sleep disordered breathing, alveolar hypoventilation syndromes, chronic exposure to high altitude, neonatal lung disease, alveolar capillary dysplasia PH due to chronic thrombotic and or embolic disease

Pulmonary embolus (thrombus, tumor, parasites, foreign material) Miscellaneous: schistosomiasis, sarcoidosis, other

DIAGNOSIS

•

PH is a hemodynamic diagnosis involving the detection of elevated pressure in the pulmonary arteries, and characterization of this abnormality to determine its etiology.

•

Right-sided heart catheterization must be performed in all patients suspected of having PH to establish the diagnosis and document pulmonary hemodynamics.

•

Primary pulmonary hypertension is a diagnosis of exclusion.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis is as listed under “Etiology.” WORKUP

•

Screening for the presence of PH using Doppler echocardiography is warranted in individuals with a known predisposing genetic mutation or first-degree relative with idiopathic PPH, scleroderma, congenital heart disease with left-to-right shunt, or portal hypertension undergoing evaluation for orthotopic liver transplantation.

•

The workup of a patient suspected of having PPH includes a detailed evaluation of the heart and lungs. Blood tests, chest x-ray, pulmonary function tests, CT scan of the chest, radionuclide studies of the heart and lungs, echocardiogram, electrocardiograms, pulmonary angiogram, and right- and left-sided heart catheterization are all required to exclude secondary causes of pulmonary hypertension.

•

Once the diagnosis has been made, functional assessment should be done to determine disease prognosis and potential therapeutic options.

•

Determining the degree of functional impairment, as assessed by the WHO classification system and the 6-minute-walk test (6MWT), is a useful way to monitor disease progression and assess response to treatment.

LABORATORY TESTS

•

CBC is usually normal in PPH, but may show secondary polycythemia.

•

ABGs show low PO2 and oxygen saturation.

•

Pulmonary function tests (PFTs) are done to exclude obstructive or restrictive lung disease.

•

Overnight oximetry and sleep study to rule out sleep apnea/hypopnea.

•

ECG may show evidence of both right atrial enlargement (tall P wave >2.5 mV in leads II, III, aVF) and right ventricular enlargement (right axis deviation > 100 and R wave > S wave in lead V1).

•

Other blood tests: ANA titer to screen for underlying connective tissue disease, HIV serology, liver function tests, and antiphospholipid antibodies.

•

Assessment of exercise capacity is a key part of the evaluation of PH. The 6MWT is most commonly used. It has been shown to determine prognosis and identify those patients who require treatment, and allows noninvasive monitoring of response to treatment.

IMAGING STUDIES

•

Chest x-ray shows enlargement of the main and hilar pulmonary arteries with rapid tapering of the distal vessels, described as peripheral oligemia ( Fig. 1-219 ). Right ventricular enlargement may be evident on lateral films.

•

Lung perfusion scan (V/Q scan) is the test of choice in excluding chronic pulmonary embolism.

•

Transthoracic Doppler echocardiogram including M-mode, 2D mode, pulse, continuous, and color Doppler assesses ventricular function, excludes significant valvular pathology, and visualizes abnormal shunting of blood between heart chambers if present. It also provides an estimate of the pulmonary artery systolic pressure that has been shown to correlate well (0.57 to 0.93) with pressures measured by right-sided heart catheterization.

•

Pulmonary angiogram is done in patients with inconclusive V/Q scans.

•

Cardiac catheterization is performed to directly measure PAPs, assess pulmonary vasodilator response, and detect any shunting of blood.

TREATMENT

FIGURE 1-219 Progressive pulmonary arterial hypertension. This patient initially presented with a relatively normal chest radiograph (A). However, several years later (B) there is increasing heart size and marked dilation of the main pulmonary artery (MPA) and right pulmonary artery (RPA). Rapid tapering of the arteries as they proceed peripherally is suggestive of pulmonary hypertension and is sometimes referred to as pruning. (From Mettler FA [ed]: Primary care radiology, Philadelphia, 2000, WB Saunders.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Oxygen therapy to improve alveolar oxygen flow in both primary and secondary pulmonary hypertension.

•

Avoidance of vigorous exercise and pregnancy.

ACUTE GENERAL Rx

•

•

PPH 1.

Diuretics (e.g., furosemide 40 to 80 mg qd) improve dyspnea and peripheral edema.

2.

Digoxin 0.25 mg qd has been used in patients with PPH, although no benefit has been demonstrated unless patients have atrial fibrillation or left ventricular dysfunction.

3.

Right-sided heart catheterization to establish diagnosis and evaluation for treatment with vasodilators.

4.

Short-acting vasodilators to test for vasodilator response including: IV adenosine, epoprostenol, or inhaled nitric oxide.

Secondary pulmonary hypertension treatment is aimed at the underlying cause.

CHRONIC Rx

•

Vasodilator trials showing at least 10 mm Hg drop in mean PAP and mean PAP =40, while maintaining cardiac output, may benefit from treatment with calcium channel blockers (diltiazem, amlodipine, or nifedipine). Verapamil is not recommended due to its negative inotropic effects. All patients should be reassessed in 6 to 8 wk to demonstrate continued benefit from calcium channel blocker.

•

Nonresponders are eligible for selective pulmonary vasodilators.

•

Warfarin therapy with goal INR 1.5 to 2.0 is recommended for all patients with PPH and although not proven may be indicated in secondary PH.

•

Prostanoids (epoprostenol, treprostinil, and iloprost) act as potent vasodilators of pulmonary arteries, and inhibitors of platelet aggregation. Epoprostenol: IV formulation with very short half-life. Requires long-term IV access with associated risks of infection and thrombosis. Rapid tachyphylaxis, thus, dose escalation is seen. Common side effects include jaw pain, abdominal cramping, and diarrhea. Limited evidence exists for use in secondary PH patients. Treprostinil: IV and SQ formulation with longer half-life. Main disadvantage is pain at SQ pump site (no long-term evidence for IV formulation). Iloprost: aerosolized formulation with short half-life requiring 6 to 8 treatments/day.

•

Endothelin receptor antagonists: (bosentan, ambrisentan, and sitaxsentan).

Bosentan (nonselective endothelin A and B receptor blocker): only oral pulmonary vasodilator, requires monthly liver function tests (LFT), often response delay by weeks. Thus, it is not an ideal starting therapy for WHO class IV patients. Sitaxsentan and ambrisentan (selective endothelin A receptor blockers): both with limited longterm evidence. •

Phosphodiesterase inhibitors: (sildenafil and tadalafil).

•

Combination therapies: limited evidence at this point.

•

Lung transplantation and heart-lung transplantation are other options in patients with end-stage class IV disease. Atrial septostomy may be performed as a bridge to transplant. The defect can be closed at the time of transplantation.

•

Atrial septostomy is recommended for individuals with a room air SaO2 >90% who suffer from severe rightsided heart failure (with refractory ascites) despite maximal diuretic therapy, or who have signs of impaired systemic blood flow (such as syncope) due to reduced left heart filling.

•

Lung transplant recipients with PPH had survival rates of 73% at 1 yr, 55% at 3 yr, and 45% at 5 yr.

DISPOSITION

•

The 6MWT is predictive of survival in patients with idiopathic PPH. Desaturation >10% during the test increases mortality risk 2.9 times over a median follow-up of 26 mo.

•

The actual 6-minute-walk distance on chronic epoprostenol treatment is more predictive of survival than the change in 6-minute-walk distance before and after treatment.

•

WHO class II and III patients with PPH have a mean survival of 3.5 yr.

•

WHO class IV patients have a mean survival of 6 mo.

REFERRAL

If the diagnosis of PPH is suspected, a consultation with a pulmonary specialist is recommended. Secondary causes of pulmonary hypertension may require disease specific consultations.

PEARLS & CONSIDERATIONS

•

The exertional dyspnea of PH is typically described by patients as being relentlessly progressive over several months to a year, often out of proportion to, or in the absence of, underlying heart or lung disease.

•

Chest x-ray may reveal evidence of interstitial fluid within the lungs in cases of secondary pulmonary hypertension. PPH is not associated with infiltrates on chest x-ray.

COMMENTS

•

Right ventricular systolic pressure (RVSP) as estimated by echocardiography is not a very good indicator of the presence of PH because RVSP increases with age and body mass index (BMI). Athletically conditioned men also have a higher resting RVSP. Thus, these measurements can be misleading.

•

Abrupt development of pulmonary edema during acute vasodilator testing suggests pulmonary venoocclusive disease or pulmonary capillary hemangiomatosis and is a contraindication to chronic vasodilator treatment.

EVIDENCE

Medical Therapy Many of the therapies used in the treatment of pulmonary hypertension considered important and effective are not supported by randomized controlled trials (RCTs). The evidence for the use of calcium channel antagonists is mainly derived from expert opinion. Recommendations include the following. Calcium Channel Antagonists In the absence of right-sided heart failure, patients who demonstrate a favorable acute response to vasodilator should be considered candidates for a trial of therapy with an oral calcium channel antagonist.[[1]] In patients with PAH, calcium channel antagonists should not be used empirically in the absence of demonstrated acute vasoreactivity.[[1]] Epoprostenol: A recently updated systematic review identified nine RCTs involving 1175 participants that evaluated the use of prostacyclin/prostacyclin analogues in the treatment of pulmonary hypertension. These studies showed a consistent, significant improvement in exercise capacity, cardiopulmonary hemodynamics, and New York Heart Association (NYHA) function with epoprostenol, compared with placebo. The review concluded that the use of prostacyclin, in addition to conventional therapy, can result in some short-term benefit in exercise capacity and cardiopulmonary hemodynamics. In addition, subgroup analysis suggested that such benefits were greater in those patients with primary pulmonary hypertension.[[2]] Treprostinil: A recently updated systematic review identified nine RCTs involving 1175 participants that evaluated the use of prostacyclin or prostacyclin analogues in the treatment of pulmonary hypertension. Cardiopulmonary hemodynamics and symptom scores favored the treprostinil group and there was a significant improvement in exercise capacity reported in the larger study. However, treatment with treprostinil was associated with a number of withdrawals due to adverse effects.[[2]] Iloprost: A recently updated systematic review identified nine RCTs involving 1175 participants that evaluated the use of prostacyclin or prostacyclin analogues in the treatment of pulmonary hypertension. Use of inhaled iloprost was associated with a significant increase in exercise capacity, and improved hemodynamic and symptom scores compared with placebo.[[2]] Sildenafil: There is a lack of clinical trials evaluating the role of sildenafil in the long-term management of PH. Early reports from clinical studies show promising results and, as such, the use of sildenafil is supported by expert opinion. In patients with PAH who have failed or are not candidates for other available therapy, treatment with sildenafil should be considered.[[1]] Bosentan: A systematic review identified three RCTs, involving 423 patients that compared short-term (12 to 16 weeks) use of endothelin antagonists (bosentan or sitaxsentan) vs. placebo in the management of pulmonary hypertension. The review found that the use of endothelin antagonists improved exercise capacity, Borg dyspnea scores, and cardiopulmonary hemodynamic values compared with placebo. The reviewers concluded that, in the short term, endothelin antagonists may benefit patients with pulmonary hypertension.[[3]] Anticoagulation The evidence for the use of anticoagulants is mainly derived from expert opinion. Patients with idiopathic

pulmonary hypertension (IPAH) should receive anticoagulation with warfarin; for patients with PAH associated with other underlying processes, anticoagulation should be considered.[[1]] Surgical Treatment Recommendations are based, in part, upon expert opinion from clinicians with experience in the surgical management of pulmonary hypertension. Recommendations for lung transplant/heart-lung transplant (LT/HLT) include: •

Patients with pulmonary hypertension with NYHA functional class III/IV symptoms should be referred to a transplant center for evaluation and listing for LT or HLT.[[4]]

•

Listed patients whose prognosis remains poor despite medical therapy should undergo LT or HLT.[[4]]

•

In patients undergoing transplantation, the procedure of choice is bilateral LT.[[4]]

•

In adults with simple congenital heart lesions, bilateral LT with repair of the cardiac defect is the procedure of choice.[[4]]

•

In adults with complex congenital defects, HLT is the procedure of choice.[[4]]

Supplemental Oxygen Therapy Recommendation regarding the use of oxygen in patients with pulmonary hypertension are supported by expert opinion. In patients with PAH, supplemental oxygen should be used as necessary to maintain oxygen saturations >90% at all times.[[1]]

Evidence-Based References 1. Badesch DBAmerican College of Chest Physicians, et al: Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126(suppl 1):35S-62S.

2. Paramothyan NS, et al: Prostacyclin for pulmonary hypertension in adults. Cochrane Database Syst Rev 2005; 2: 3. Liu C, Chen J: Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst Rev 2004; 4: 4. Doyle RLAmerican College of Chest Physicians, et al: Surgical treatments/interventions for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126(suppl 1):63S71S.

SUGGESTED READINGS Barst RJ, et al: Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43:40S. Lee SH, Rubin LJ: Current treatment strategies for pulmonary arterial hypertension. J Intern Med 2005; 258(3):199. McLaughlin VV, et al: Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126(suppl 1):S78. Rubin LJ, Badesch DB: Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med 2005; 143:282.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pyelonephritis GLENN G. FORT, M.D., M.P.H., JOSEPH J. LIEBER, M.D., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Pyelonephritis is an infection, usually bacterial in origin, of the upper urinary tract. SYNONYMS

Acute pyelonephritis Pyonephrosis Renal carbuncle Lobar nephronia Acute bacterial nephriti

ICD-9CM CODES

590.81 Pyelonephritis 599.0

Urinary tract infection

595.9

Cystitis

EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Extremely commo PREDOMINANT SEX: Femal PREDOMINANT AGE: •

Sexually active years in women

•

Usually >50 yr of age in men

GENETICS:

Congenital Infection: Congenital urologic structural disorders may predispose to infections at an early age. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Fever, rigors, chills

•

Flank pain

•

Dysuria

•

Polyuria

•

Hematuria

•

Toxic feeling and appearance

•

Nausea and vomiting

•

Headache

•

Diarrhea

•

Physical examination notable 1.

Costovertebral angle tenderness

2.

Exquisite flank pain

ETIOLOGY

•

Gram-negative bacilli such as E. coli and Klebsiella spp. in more than 95% of cases

•

Other, more unusual gram-negative organisms, especially if instrumentation of the urinary system has occurred

•

Resistant gram-negative organisms or even fungi in hospitalized patients with indwelling catheters

•

Gram-positive organisms such as enterococci

•

Staphylococcus aureus: presence in urine indicates hematogenous origin

•

Viruses: rarely, but these are usually limited to the lower tract

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Nephrolithiasis

•

Appendicitis

•

Ovarian cyst torsion or rupture

•

Acute glomerulonephritis

•

PID

•

Endometritis

•

Other causes of acute abdomen

•

Perinephric abscess

•

Hydronephrosis

WORKUP

•

No workup usually indicated in sexually active women

•

Poorly responding infections, especially with azotemia and frank bacteremia 1.

Renal sonogram or CT scan to assess for underlying urologic pathology such as hydronephrosis

•

Urologic imaging studies in all young men and boys

•

Prostate assessment in older men

LABORATORY TESTS

•

CBC with differential

•

Renal panel

•

Blood cultures

•

Gram stain of urine, urinalysis and urine cultures

•

Urgent renal sonography if obstruction or closed space infection suspected

•

CT scans may better define the extent of collections of pus

•

Helical CT scans excellent to detect calculi

TREATMENT ACUTE GENERAL Rx

•

Hospitalization for: 1.

Toxic patients

2.

Complicated infections

3.

Diabetes

4.

Suspected bacteremia

•

Keep patients well hydrated.

•

IV fluids are indicated for those unable to take adequate amounts of liquids.

•

Give antipyretics such as acetaminophen when necessary.

•

Antibiotic therapy should be initiated after cultures are obtained and guided by the results of culture and sensitivity testing.

1.

Oral TMP-SMX DS (bid for 10 days) or ciprofloxacin (500 mg orally bid for 10 days): adequate for stable patients who can tolerate oral medications with sensitive pathogens

2.

TMP-SMX or ciprofloxacin IV for more toxic patients

3.

Ceftazidime 1 g IV q6 to 8h

4.

Aminoglycosides such as gentamicin (2 mg/kg IV load followed by 1 mg/kg IV q8h adjusted for renal function) added but nephrotoxic especially in diabetics with azotemia

5.

Vancomycin 1 g IV q12h or linezlid to cover gram-positive cocci such as enterococci or staphylococci

6.

Ampicillin 1 to 2 g IV q4 to 6h to cover enterococci with an aminoglycoside for synergy

7.

Oral ampicillin or amoxicillin: no longer adequate for therapy of gram-negative infections because of resistance

•

Prompt drainage with nephrostomy tube placement for obstruction.

•

Surgical drainage of large collections of pus to control infection.

•

Diabetic patients, as well as those with indwelling catheters, are especially prone to complicated infections and abscess formation.

CHRONIC Rx

•

Repair underlying structural problems, especially when renal function is compromised. 1.

Reflux

2.

Obstruction

3.

Nephrolithiasis should be considered

•

Patients with diabetes mellitus and indwelling urinary catheters are at particular risk of severe and complicated infections.

•

When possible, remove catheters.

DISPOSITION

Most patients with uncomplicated pyelonephritis are now treated as outpatients or in short hospitalizations. Indications to admit a patient with pyelonephritis include: pregnancy, suspected urinary obstruction, suspected renal abscess or perinephric abscess, bacterial sepsis, diabetic or other immunocompromised patients, recurrent or refractory pyelonephritis, or infection with an unusual or antibiotic resistant microorganism. REFERRAL

•

To a surgeon for correction of underlying urologic problems (e.g., reflux and hydronephrosis)

•

To a pediatrician for detection of reflux to avoid recurrent UTI and loss of renal function

•

To an internist for aggressive metabolic and urologic evaluation for patients with nephrolithiasis

PEARLS & CONSIDERATIONS Pyelonephritis is a systemic illness and may be a source of bacteremia and sepsis, especially if accompanied by urinary obstruction. Workup for abscess, obstruction, papillary necrosis, and other local complications of pyelonephritis should be initiated if the patient is septic, fails to respond to antibiotic therapy after 72 hr of treatment, or if infection is accompanied by worsening renal function.

EVIDENCE

In children with acute pyelonephritis: Oral cefixime for 14 days, or short courses of intravenous (IV) therapy (ceftriaxone) followed by oral therapy, are as effective as longer duration IV therapy regimens.[[1]] Aminoglycosides are just as effective given as a single daily dose as given three times daily.[[1]] In adults with acute pyelonephritis: Evidence suggests that oral levofloxacin, ciprofloxacin, and lomefloxacin are equally effective in treating acute, uncomplicated pyelonephritis.[[2]] A single dose of IV tobramycin does not enhance the efficacy of a 10-day course of oral ciprofloxacin in hospitalized women with acute, uncomplicated pyelonephritis.[[3]] Existing evidence does not allow for a comparison of efficacies of intravenous antibiotic regimens.[[4]] In pregnant patients: Antibiotic treatment of asymptomatic bacteriuria is effective in reducing the risk of pyelonephritis in pregnancy and preterm delivery, but the optimal duration of antibiotic treatment has yet to be established. [407] [408]

There is insufficient evidence to recommend any specific treatment regimen for symptomatic urinary tract infections during pregnancy.[[7]]

Evidence-Based References 1. Bloomfield P, Hodson EM, Craig JC: Antibiotics for acute pyelonephritis in children. Reviewed. Cochrane Library 2, Chichester, UK, John Wiley, 2004. 2. Richard GA, et al: Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology 1998; 52:51-55.Reviewed in: Clin Evid 11:2527, 2004. 3. Le Conte P, et al: Acute pyelonephritis. Randomized multicentre double-blind study comparing ciprofloxacin with combined ciprofloxacin and tobramycin. Presse Med 2001; 30:11.Reviewed in: Clin Evid 11:2527, 2004. 4. Wechsler A: Pyelonephritis in non-pregnant women. Reviewed. Clin Evid, 11. London: BMJ Publishing Group; 2004:2527. 5. Smaill F: Antibiotics for asymptomatic bacteriuria in pregnancy. Reviewed. Cochrane Library 2, Chichester, UK, John Wiley, 2004. 6. Villar J, et al: Duration of treatment for asymptomatic bacteriuria during pregnancy. Reviewed. Cochrane Library 2, Chichester, UK, John Wiley, 2004.

7. Vazquez JC, Villar J: Treatments for symptomatic urinary tract infections during pregnancy. Reviewed. Cochrane Library 2, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Bloomfield P, Hodson EM, Craig JC: Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev 2005; 1:CD003772 Hill JB, et al: Acute pyelonephritis in pregnancy. Obstet Gynecol 2005; 105(1):18. Pitukkijronnakorn S, Chittacharoen A, Herabutya Y: Maternal and perinatal outcomes in pregnancy with acute pyelonephritis. Int J Gynaecol Obstet 2005; 89(3):286. Scholes D, et al: Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med 2005; 142(1):20. Taskinen S, Ronnholm K: Post-pyelonephritic renal scars are not associated with vesicoureteral reflux in children. J Urol 2005; 173(4):1345.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Pyogenic Granuloma

BASIC INFORMATION DEFINITION Pyogenic granuloma is a benign vascular lesion of the skin and mucus membranes. They are a result of capillary proliferation generally secondary to trauma. SYNONYMS Granuloma pyogenicum Tumor of pregnancy Eruptive hemangioma Lobular capillary hemangioma Granulation tissue-type hemangiom

ICD-9CM CODES

686.1 Pyogenic granuloma EPIDEMIOLOGY & DEMOGRAPHICS

•

Common in children and young adults.

•

Equally prevalent in males and females and show no racial or familial predisposition.

•

Caused by trauma or surgery.

•

Gingival lesions occur more frequently during pregnancy.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Small (1:200 to phase I antigen is diagnostic

IMAGING STUDIES

•

Chest x-ray examination is abnormal, showing segmental lobe consolidation

•

Pleural effusions (35%)

TREATMENT NONPHARMACOLOGIC THERAPY Oxygen as needed in patients with pneumonia ACUTE GENERAL Rx

•

Acute Q fever can be treated with doxycycline (100 mg bid) for 14 to 21 days or

•

Erythromycin (500 mg qid) for 14 days or

•

Ofloxacin 200 mg PO q8h for 14 to 21 days

•

Hydroxychloroquine plus doxycycline for endocarditis associated with Q fever

•

Fluoroquinolones are recommended for suspected meningoencephalitis

CHRONIC Rx

•

Chronic Q fever is treated with a combination of two antibiotics, doxycycline 100 mg bid and rifampin 300 mg qd or

•

Doxycycline 100 mg bid and Ofloxacin 200 mg po q8h or

•

Doxycycline 100 mg bid and hydroxychloroquine 200 mg PO tid

•

Duration of treatment: 2 to 3 yr

DISPOSITION

•

Patients with acute Q fever respond well with antibiotics, with rare deaths reported.

•

Mortality rate in chronic Q fever endocarditis is high (24%). Most patients will need valve replacement surgery.

REFERRAL Referral to an infectious disease expert is recommended in any cases of suspected acute or chronic Q fever.

PEARLS & CONSIDERATIONS COMMENTS

•

No vaccines are available.

•

Infected patients do not require specific isolation precautions.

•

Q fever derived its name in 1935 from Derrick, who was suspicious of a new disease during a series of acute febrile illnesses in abattoir workers of Queensland, Australia, justifying the name of Q fever (for query).

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

SUGGESTED READINGS Healy B, et al: The value of follow-up after acute Q fever infection. J Infect 2006; 52(4):e109. McQuiston JH, et al: National surveillance and the epidemiology of human Q-fever in the United States, 19782004. Am J Trop Med Hyg 2006; 75(1): Milazzo A, et al: Q fever vaccine uptake in South Australian meat processors prior to the introduction of the National Q Fever Management Program. Commun Dis Intell 2005; 29(4):400. Oren I, et al: An outbreak of Q fever in an urban area in Israel. Eur J Clin Microbiol Infect Dis 2005; 24(5):338. Raoult D, Marrie T, Mege J: Natural history and pathophysiology of Q fever. Lancet Infect Dis 2005; 5(4):219. Rolain JM, Raoult D: Molecular detection of Coxiella burnetii in blood and sera during Q fever. QJM 2005; 98(8):615. Wagner-Wiening C, et al: Serological diagnosis and follow-up of asymptomatic and acute Q fever infections. Int J Med Microbiol 2006; 40:294.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

R Rabies GLENN G. FORT, M.D., DENNIS J. MIKOLICH, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Rabies is a fatal illness caused by the rabies virus and transmitted to humans by the bite of an infected animal. SYNONYMS

Hydrophobia

ICD-9CM CODES

071 Rabies EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Approximately 2 cases/yr PREDOMINANT SEX: Men (70% of cases) PREDOMINANT AGE: 55 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

Incubation period of 10 to 90 days 1.

Shorter with bites of the face

2.

Longer if extremities involved

Prodrome 1.

Fever

2.

Headache

3.

Malaise

4.

Pain or anesthesia at exposure site

5.

Sore throat

6.

GI symptoms

7.

Psychiatric symptoms

Acute neurologic period, with objective evidence of CNS involvement 1.

Extreme hyperactivity and bizarre behavior alternating with periods of relative calm

2.

Hallucinations, disorientation

3.

Seizures

4.

Paralysis

5.

Fear, pain, and spasm of the pharynx and larynx caused by drinking

6.

Coma, death

ETIOLOGY

•

Rabies virus

•

Cases in U.S. are associated with: 1.

Bats

2.

Raccoons

3.

Foxes

4.

Skunks

•

In 8 of the 32 cases occurring in the U.S. since 1980, there was a history of exposure to bats without a clinically evident bite or scratch.

•

Imported cases are usually associated with dogs.

•

Unusual acquisition: 1.

Via organ transplantation

2.

Via aerosol transmission in laboratory workers and spelunkers

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Delirium tremens

•

Tetanus

•

Hysteria

•

Psychiatric disorders

•

Other viral encephalitides

•

Guillain-Barré syndrome

•

Poliomyelitis

WORKUP

•

•

Rabies antibody 1.

Serum

2.

CSF

Viral isolation 1.

Saliva

2.

CSF

3.

Serum

•

Rabies fluorescent antibody: skin biopsy from the hair-covered area of the neck

•

Characteristic eosinophilic inclusions (Negri bodies) in infected neurons

TREATMENT NONPHARMACOLOGIC THERAPY

•

Isolation of the patient to prevent transmission to others

•

Supportive therapy

ACUTE GENERAL Rx

•

No known beneficial therapy. A recent report describes a 15-year-old girl who survived rabies and had been treated with a combination of ketamine, midazolam, ribavirin, and amamtadine. This therapy is worth trying despite the fact this is a single case report.

•

Emphasis is placed on prophylaxis of potentially exposed individuals following an exposure:

•

•

1.

Thorough wound cleansing and irrigation of the wound as soon as possible

2.

Active and passive immunization most effective when used within 72 hr of exposure

Vaccinations: 1.

Human diploid cell vaccine (HDCV) or rhesus monkey diploid cell vaccine (RVA), 1 ml IM (deltoid) on days 0, 3, 7, 14, and 28

2.

Human rabies hyperimmune globulin (RIG) 20 IU/kg, to persons not previously vaccinated. If anatomically feasible, the full dose should be infiltrated into the wound; any remaining volume should be given IM at a site separate from vaccine administration

Preexposure prophylaxis using HDCV or RVA (1 ml IM days 0, 7, and 21 or 28) in individuals at high risk for acquisition: 1.

Veterinarians

2.

Laboratory workers working with rabies virus

3.

Spelunkers

4.

Visitors to endemic areas

DISPOSITION

Virtually always fatal REFERRAL

•

To infectious disease consultant

•

To local health authorities

PEARLS & CONSIDERATIONS COMMENTS

•

•

Most cases in the U.S. are caused by: 1.

Bat bites, often after minimal contact and inapparent exposure to infected bat saliva

2.

Dog bites occurring outside the U.S.

Rare cases can be transmitted by mucous membrane contact of aerosolized virus (caves, laboratory acquired cases).

EVIDENCE

Studies conducted in the U.S. by the CDC have documented that a regimen of one dose of RIG and five doses of HDCV over a 28-day period was safe and induced an excellent antibody response in all recipients.[[1]] Rabies vaccines induce an active immune response with neutralizing antibodies. This antibody response requires 7 to 10 days to develop and usually persists for 2 years or longer.[[2]] RIG provides a rapid, passive, short-lived immunity (half-life of approximately 21 days).[[1]]

Evidence-Based References 1. CDC: Human rabies prevention—United States, 1999: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999; 48(RR-1): 2. Dreesen DW, et al: Two-year comparative trial on the immunogenicity and adverse effects of purified chick embryo cell rabies vaccine for pre-exposure immunization. Vaccine 1989; 7:397.

SUGGESTED READINGS Hemachudha T, Wilde H: Survival after treatment of rabies. N Engl J Med 2005; 353(10):1068. Rupprecht CE, Gibbons RV: Prophylaxis against rabies. N Engl J Med 2004; 351:2626. Srinivasan A, et al: Transmission of rabies virus from an organ donor to four transplant recipients. N Engl J Med 2005; 352:1103.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Radiation Exposure FRED F. FERRI, M.D, TOM J. WACHTEL, M.D

BASIC INFORMATION DEFINITION

Exposure to ionizing radiation has the potential for radiation injury. Radionuclides present a danger to humans through the particles emitted during radioactive decay. These particles can damage cellular structures and may result in mutation, cancer, or cell death. Radiation injury can occur from external irradiation, external contamination with radioactive materials, and internal contamination by inhalation, ingestion, or transdermal absorption with incorporation of radiologic materials into the body's cells and tissues. These three types of exposure can occur in combination and can be associated with thermal burns and traumatic injuries. PRINCIPLES OF RADIOACTIVITY, ADDITIONAL DEFINITIONS: Particles of radiation •

Photons: massless particles that travel at the speed of light and produce electromagnetic radiation. Their wavelength determines their energy; the longer the wavelength the lower the energy. In order of increasing energy, they are called ultraviolet, visible light, infrared, microwave, gamma, and x-rays. X-rays consist of a spectrum of wavelengths whereas gamma rays have a fixed wavelength specific to the radioactive material that produces them. X-rays and gamma rays are highly penetrating.

•

Beta particles are electrons. They may be emitted during decay of a radionuclide (atom) that disintegrates. Positrons (positively charged electrons) may also be produced during radioactive decay. Beta particles are less penetrating than x-rays and gamma rays, but can still pass through several centimeters of human tissue. Nonetheless, their main toxic effect is through inhalation.

•

Alpha particles are helium nuclei (2 protons and 2 neutrons) stripped of their electrons. They are stopped by clothing; therefore, they need to be “incorporated” to cause health problems.

•

Neutrons are released during nuclear fission, not during natural radionuclide decay. They can cause a stable atom to become radioactive by collision (e.g., during nuclear fallout).

•

Cosmic rays are streams of electrons, protons, and alpha particles that come from outer space. Most of their energy is dissipated by the earth's atmosphere.

•

Ionizing radiation describes any radiation with sufficient energy to break up an atom or molecule with which it collides. This is the mechanism of radiation toxicity.

•

Nonionizing radiation has insufficient energy to break up atoms; nonetheless sufficient energy in the form of heat may be produced to cause localized tissue damage.

•

Radioactive decay: process of transformation of unstable nuclei into more stable ones via the emissions of various particles. Decay is described by half-life, which is a characteristic of every radioisotope.

•

Radiation units of measure:

1.

Roentgen: amount of radiation to which an object is exposed.

2.

Rad (radiation absorbed dose) and Gray (Gy, the same concept in the international system): amount of radiation absorbed by tissue (1 Gy = 100 Rad).

3.

Rem (roentgen equivalent man) and Sievert (Sv, the same concept in the International System): a measure that standardizes the amount of cellular damage produced by different types of radiation. One Rem (or 0.01 Sv) is the dose of radiation that produces damage equivalent to one Rad of x-ray.

IRRADIATION, CONTAMINATION, AND INCORPORATION: •

Irradiation: exposure to ionizing radiation

•

Contamination: an object or person covered with a radioactive substance

•

Incorporation: exposure to a radionuclide by inhalation, ingestion, intravenous infusion, or percutaneously

STOCHASTIC EFFECTS OF IONIZING RADIATION: Any dose of ionizing radiation can alter DNA, causing mutations or carcinogenic changes that may take years to be expressed. There is no dose threshold, and the effect is cumulative. The stochastic effects of radiation are mostly a concern with small but prolonged exposure to radiation. DETERMINISTIC EFFECTS OF IONIZING RADIATION: The dose of radiation is sufficient to kill cells; the higher the dose, the greater the number of killed cells and the greater the impact on an organ system. The deterministic effects of radiation are the consequence of a large whole-body exposure. SYNONYMS

Acute radiation syndrome Radiation sickness

ICD-9CM CODE

990 Radiation exposure PHYSICAL FINDINGS & CLINICAL PRESENTATION

ACUTE RADIATION SYNDROME: Follows a large whole-body exposure of 2 Sv or more (500 times the average annual exposure) or greater than 1 Gy delivered at a relatively high dose rate. The mean lethal dose of radiation required to kill 50% of humans at 60 days (LD 50/60) of whole body radiation is between 3.25 and 4 Gy in persons managed without supportive care and 6 to 7 Gy when antibiotics and transfusion support are provided. Sequence of events: four stages:

•

Stage 1 (prodromal phase): usually occurs in the first 48 hr but may develop up to 6 days after exposure.

•

Stage 2 (latent phase): short period characterized by improvement of symptoms, as the person appears to have recovered. Unfortunately this effect is transient, lasting for several days to a month.

•

Stage 3 (manifest illness phase): third to fifth week following exposure. This stage is characterized by intense immunosuppression and is the most difficult to manage. If the person survives this stage, recovery is likely. Signs and symptoms consist of abdominal pain, diarrhea, hair loss, bleeding, infection. During this stage, several subsyndromes may coexist, overlap, or occur in sequence.

•

1.

Cerebrovascular syndrome: fever, hypotension, ataxia, apathy, lethargy, and seizures. These symptoms may be observed in those receiving more than 20 to 30 Gy of radiation. The prodromal phase is characterized by disorientation, confusion, and prostration. The physical exam may show papilledema, ataxia, decreased or absent DTRs, and corneal reflexes.

2.

Cutaneous syndrome: due from thermal or radiation burns and characterized by loss of epidermis, local edema, and increased risk for a compartmental syndrome.

3.

GI syndrome: radiation induces loss of intestinal crypts and breakdown of mucosal barrier. These changes result in abdominal pain, anorexia, nausea, vomiting, diarrhea, and dehydration, and predispose patients to superinfection and sepsis.

4.

Hematopoietic syndrome: lymphopenia is common and occurs before the onset of other cytopenias; pancytopenia with bleeding diathesis and sepsis often follow. A predictable decline in lymphocytes occurs after irradiation. A potentially lethal exposure is characterized by a 50% decline in absolute lymphocyte count within the first 24 hr after exposure, followed by a further, more severe decline within 48 hr. The onset of cytopenias varies, depending on the dose and dose rate. Granulocyte counts may transiently increase before decreasing in patients with exposure to less than 5 Gy. This transient increase before decline is known as an “abortive rise” and may indicate a survivable exposure.

Stage 4: recovery, lasting weeks to months.

DIAGNOSIS DOSE ESTIMATION AND PROGNOSIS: Because radiation is often mixed and because body parts may be exposed to different amounts of radiation, the dose received is difficult to estimate in the field. Therefore, it is usually the acute radiation syndrome itself that allows prognosis. At a dose received under 3 Sv a lymphocyte count >1200/mm3 at 48 hr confers a favorable prognosis; if the count is3 Gy, treatment with CSFs should be rapidly initiated (e.g., G-CSF or filgrastim, 5 mcg/kg of body weight per day). CSF may be withdrawn when the absolute neutrophil count reaches a level greater than 1.0 × 10 9 after recovery from the nadir.

10. Consider stem-cell transplantation in people with exposure dose of 7 to 10 Gy who do not have significant burns or other major organ toxicity and who have an appropriate donor. 11. Provide counseling: 75% of individuals exposed to nuclear weapon denotations exhibit some form of psychologic symptoms, ranging from insomnia to difficulty concentrating and social withdrawal.

PEARLS & CONSIDERATIONS COMMENTS

Individual biodosimetry is essential for predicting the clinical severity, treatment, and survivability of exposed individuals. The three most useful elements for calculating the exposure dose are time to onset of vomiting, lymphocyte depletion kinetics, and the presence of chromosome dicentrics. A radiation casualty management software program (biologic assessment tool) is available at the Armed Forces' Radiobiology Research Institute web-site (www.afrri.usuhs.mil ).

Monitoring of lymphocyte count requires obtaining a CBC with leukocyte differential immediately after exposure, three times/day for next 3 days, then twice/day for the following 6 days. CBC with differential should then be obtained weekly until a nadir in neutrophil count is defined. The chromosome-aberration cytogenetic bioassay should be obtained from a qualified radiation cytogenetic biodosimetry laboratory. SUGGESTED READINGS Rella J: Radiation. In: Goldfrank LR, et al ed. Toxicologic emergencies, ed 7. New York: McGraw-Hill; 2002. Turai I, et al: Medical response to radiation incidents and radionuclear threats. BMJ 2004; 4:247. Waselenko JK, et al: Medical management of the acute radiation syndrome. Ann Intern Med 2004; 140:1037.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ramsay Hunt Syndrome GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

Ramsay Hunt syndrome is a localized herpes zoster infection involving the seventh nerve and geniculate ganglia, resulting in hearing loss, vertigo, and facial nerve palsy. SYNONYMS

Herpes zoster oticus Geniculate herpes Herpetic geniculate ganglionitis

ICD-9CM CODES

053.11 Ramsay Hunt syndrome EPIDEMIOLOGY & DEMOGRAPHICS

PREDOMINANT SEX: Equal sex distribution PREDOMINANT AGE: •

Increasingly common with advancing age

•

Rare in childhood

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

Characteristic vesicles: 1.

On pinna

2.

In external auditory canal

3.

In distribution of the facial nerve and, occasionally, adjacent cranial nerves

Facial paralysis on the involved side

ETIOLOGY

Reactivation of dormant infection with varicella-zoster virus following primary varicella

DIAGNOSIS

•

Usually made by recognition of the clinical features detailed previously

•

Viral culture and/or microscopic examination of specimens taken from active vesicles

DIFFERENTIAL DIAGNOSIS

•

Herpes simplex

•

External otitis

•

Impetigo

•

Enteroviral infection

•

Bell's palsy of other etiologies

•

Acoustic neuroma (before appearance of skin lesions)

•

The differential diagnosis of headache and facial pain is described in Section II

WORKUP

If the diagnosis is in doubt, confirmation of varicella-zoster virus infection should be sought. LABORATORY TESTS

•

Viral culture of specimens of vesicular fluid and scrapings of the vesicle base

•

Tzanck preparation, which may reveal multinucleated giant cells

•

Direct immunofluorescent staining of scrapings

IMAGING STUDIES

MRI may demonstrate enhancement of the facial and vestibulocochlear nerves before appearance of vesicles.

TREATMENT ACUTE GENERAL Rx

•

Prednisone (40 mg PO for 2 days; 30 mg for 7 days; followed by tapering course) is recommended by some authors.

•

Acyclovir (800 mg PO 5 times qd for 10 days), famciclovir (500 mg tid for 7 days), or valacyclovir (1 g every 8 hr for 7 days) may hasten healing.

•

Analgesics should be used as indicated.

CHRONIC Rx

•

Amitriptyline is effective in some cases of postherpetic pain.

•

Other agents for postherpetic pain include gabapentin (Neurontin) and pregabalin (Lyrica).

•

Narcotic analgesics may occasionally be necessary.

DISPOSITION

Recurrences are unusual. REFERRAL

To otolaryngologist: patients with persistent facial paralysis for potential surgical decompression of the facial nerve

PEARLS & CONSIDERATIONS COMMENTS

Immunodeficiency states, particularly infection with the human immunodeficiency virus (HIV), should be considered in: •

Younger patients

•

Severe cases

•

Patients with a history of specific risk behavior

SUGGESTED READINGS Diaz GA, Rakita RM, Koelle DM: A case of Ramsay Hunt-like syndrome caused by herpes simplex virus type 2. Clin Infect Dis 2005; 40(10):1545. Kinishi M, et al: Acyclovir improves recovery rate of facial nerve palsy in Ramsay Hunt syndrome. Auris Nasus Larynx 2001; 28(3):223. Verm AM, Scott IU, Davis JL: Necrotizing herpetic retinopathy associated with Ramsay Hunt syndrome. Arch Ophthalmol 2002; 120(7):989.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Raynaud's Phenomenon PRANAV M. PATEL, M.D.

BASIC INFORMATION DEFINITION

Raynaud's phenomenon (RP) is a vasospastic disorder that produces an exaggerated response to cold temperatures and/or emotional stress resulting in transient digital ischemia. It is manifested as a triphasic discoloration of the fingers and toes (a result of pallor, cyanosis, and rubor). SYNONYMS

Primary Raynaud's phenomenon or Raynaud's disease Secondary Raynaud's phenomenon

ICD-9CM CODES

443.0 Raynaud's syndrome, Raynaud's disease, Raynaud's phenomenon (secondary) 785.4 If gangrene present EPIDEMIOLOGY & DEMOGRAPHICS

•

RP is classified clinically into primary or secondary forms and affects approximately 3% of the general population.

•

Primary RP usually occurs between the ages of 15 and 25 yr. It is more likely to effect women than men, and appears to be more common in colder climates.

•

Secondary RP tends to begin after 35 to 40 yr of age.

•

Secondary RP occurs in more than 90% of patients with scleroderma, and in about 30% of patients with systemic lupus erythematosus and with Sjögren's syndrome.

•

There is also some suggestion that secondary RP may be associated withdrugs (nicotine, caffeine, ergotamine, vinyl chloride) or trauma to the hands from vibrating tools such as jack hammers.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The classic manifestation is the triphasic color response to cold exposure, which may or may not be accompanied by pain ( Fig. 1-221 ): 1.

Pallor of the digit resulting from vasospasm.

2.

Blue discoloration (cyanosis) secondary to desaturated venous blood.

3.

Red (rubor) with or without pain and paresthesia when vasospasm resolves and blood returns to the digit.

•

Initial pallor is typically necessary for the diagnosis to be made.

•

The triphasic color changes can sometimes be induced in the office by placing the hand in an ice bath.

•

Color changes are well delineated, symmetric, and usually bilateral involving the fingers and toes. The index, middle, and ring fingers are commonly involved.

•

Fingertips are most often involved, but feet, ears, and nose can be affected.

•

Duration of attacks can range from seconds to hours.

•

Chronic skin changes resulting from repeated attacks may include skin thickening and brittle nails. Ulcerations and, rarely, gangrene may occur.

•

Physical exam should also include examination for symptoms associated with autoimmune disease, such as fever, rash, arthritis, dry eyes, dry mouth, myalgias, or cardiopulmonary abnormalities.

FIGURE 1-221 Raynaud's phenomenon. Sharply demarcated cyanosis of the fingers with proximal venular congestion (livedo reticularis) is seen. (From Klippel J, Dieppe P, Ferri F [eds]: Primary care rheumatology, London, 1999, Mosby.)

ETIOLOGY

•

Primary RP can also be called idiopathic Raynaud's phenomenon, primary Raynaud's syndrome, or Raynaud's disease. It occurs in the absence of any associated disease.

•

With primary RP, the possibility that another first-degree family member is affected is reported as approximately 25%.

•

Secondary RP is associated with an underlying pathologic condition or disease and may include the following: 1.

CREST syndrome (calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia)

2.

Scleroderma

3.

Mixed connective tissue disease, polymyositis, and dermatomyositis

4.

Systemic lupus erythematosus

5.

Rheumatoid arthritis

6.

Thromboangiitis obliterans (Buerger's disease)

7.

Drug induced (beta-blockers, ergotamine, methysergide, vinblastine, bleomycin, oral contraceptives, nicotine, caffeine, vinyl chloride)

8.

Hematological disorders (polycythemia, cryoglobulinemia, cold agglutinins, paraproteinemia)

9.

Carpal tunnel syndrome

10. Use of tools that vibrate 11. Endocrine disorders (hypothyroidism, carcinoid syndrome)

DIAGNOSIS The suggested criteria for primary RP are: •

Symmetric attacks.

•

Absence of tissue necrosis, ulceration, or gangrene.

•

Absence of a secondary cause on the basis of a patient's history and general physical examination.

•

Normal nail-fold capillaries.

•

Negative test for antinuclear antibody.

•

Normal erythrocyte sedimentation rate (ESR).

Secondary RP is suggested by the following findings: •

Onset of symptoms after the age of 30 years.

•

Episodes that are painful, asymmetric, or associated with ischemic skin lesions.

•

Clinical features suggestive of a connective-tissue disease.

•

Specific autoantibody tests and ESR are elevated.

•

Evidence of microvascular disease on microscopy of nail-fold capillaries.

DIFFERENTIAL DIAGNOSIS

•

Neurogenic thoracic outlet syndrome or carpal tunnel syndrome

•

Frostbite or cold weather injury

•

Medication reaction (ergotamine, chemotherapeutic agents)

•

Atherosclerosis, thromboembolic disease

•

Buerger's disease, embolic disease

•

Acrocyanosis

•

Livedo reticularis

•

Injury from repetitive motion

WORKUP

•

Once the diagnosis of RP is established, differentiating primary from secondary is helpful in treatment and prognosis.

•

Patients who are younger when their symptoms occur; have a normal history and physical examination and normal nail-fold capillaries; and have no history of digital ischemic lesions can be considered as having primary RP. These patients can be monitored clinically without any further testing.

•

If a secondary cause of RP is suspected, appropriate lab testing is recommended (see “Laboratory Testing”). Secondary RP will reveal abnormal nail-fold microscopy.

LABORATORY TESTS

•

Complete blood count, serum electrolytes, blood urea nitrogen (BUN), creatinine, ESR, antinuclear antibodies (ANA), VDRL antibody test, rheumatoid factor (RF), and urinalysis should be included in the initial evaluation.

•

If the history, physical examination, and initial laboratory tests suggest a possible secondary cause, specific serologic testing (e.g., anticentromere antibodies, anti-Scl 70, cryoglobulins, complement testing, and protein electrophoresis) may be indicated.

•

Noninvasive vascular testing includes finger systolic blood pressures, segmental blood pressure measurements, cold recovery time (measure vasoconstrictor and vasodilator responses of finger to cold), finger tip thermography, and laser Doppler with thermal challenge (measure relative change in skin blood flow with ambient warming).

IMAGING STUDIES

•

The diagnosis of RP should not be made on the basis of laboratory tests and imaging studies should not replace a good history and physical exam.

•

Duplex ultrasound can image the palmar arch and digital arteries for patency.

•

Magnetic resonance angiography (MRA) is useful imaging larger arteries.

•

Contrast angiography is the gold standard for arterial imaging.

•

Nail-fold capillary microscopy can differentiate primary from secondary RP.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoid drugs that may precipitate RP (see “Etiology”).

•

Avoid cold exposure. Use warm gloves, hats, and garments during the winter months or before going into cold environments (e.g., air-conditioned rooms). Sudden shifts in temperature are more likely to precipitate RP.

•

Avoid stressful situations, and use relaxation techniques in preventing RP attacks.

ACUTE GENERAL Rx

•

Typically, patients with RP respond well to nonpharmacologic measures.

•

Medications are indicated in the treatment of RP if there are signs of critical ischemia or if the quality of life of the patient is affected to the degree that activities of normal living are no longer possible, and preventative techniques do not work.

CHRONIC Rx

•

Calcium channel blockers are the most effective treatment for RP.

•

Calcium channel blockers differ in their peripheral vasodilator properties. Nifedipine, amlodipine, felodipine, nisoldipine, and isradipine appear more effective than diltiazem and verapamil in the treatment of RP.

•

Nifedipine is most often prescribed at a dose of 10 to 20 mg 30 min before going outside. If symptoms occur with long duration, nifedipine XL 30 to 180 mg PO qd is effective.

•

Patients who do not tolerate or fail to respond to calcium channel blocker therapy can try other vasodilator drugs alone or in combination. Options include nitroglycerin, nitroprusside, hydralazine, papaverine, minoxidil, niacin, and topical nitrates.

•

Agents that indirectly cause vasodilation (selective serotonin reuptake inhibitors, ACE inhibitors, phosphodiesterase inhibitors) may be useful, but there is no convincing evidence that they are better than calcium channel blockers alone.

•

Sympatholytic agents (reserpine, guanethidine) may be helpful for acute treatment, but their effect tends to decrease with time, and they often have intolerable side effects.

•

Alpha receptor blockers such as prazosin or doxazosin counteract the actions of norepinephrine, which will constrict blood vessels.

•

The prostaglandins, including inhaled iloprost, intravenous epoprostenol, and alprostadil, may be promising in severe RP. However, additional experience and controlled studies are needed to substantiate this claim.

•

Phosphodiesterase inhibitors (such as cilostazol [Pletal], pentoxifylline [Trental], and sildenafil [Viagra], and angiotensin II receptor antagonists (such as losartan [Cozaar]) have also been used with some limited success.

•

Anticoagulation with aspirin and heparin can be considered during the acute phase of an ischemic event. Aspirin (81 mg/day) therapy can be considered in all patients with secondary RP with a history of ischemic ulcers or thrombotic events; however, caution should be exercised because aspirin can theoretically worsen vasospasm via inhibition of prostacyclin. Long-term anticoagulation with heparin or warfarin is not recommended unless there is evidence of a hypercoagulable disorder.

•

Bypass surgery can be performed for severe RP associated with reconstructible arterial occlusive disease.

•

Sympathectomy is available for unreconstructable occlusive disease or pure vasospastic disease refractory to medical treatment.

DISPOSITION

The prognosis of patients with RP depends on the etiology.

•

Primary RP is fairly benign, usually remaining stable and controlled with nonpharmacologic medical treatment.

•

Patients with secondary RP, specifically those with scleroderma, CREST syndrome, and thromboangiitis obliterans, may develop severe ischemic digits with ulceration, gangrene, and autoamputation.

REFERRAL

•

Rheumatology consult is indicated if secondary collagen vascular disease is diagnosed.

•

Vascular surgery consult is indicated if ulcers, gangrene, or threatened digit loss is noted.

PEARLS & CONSIDERATIONS

•

Most patients with RP can be managed by a primary care provider.

•

It is important to differentiate primary from secondary forms. Secondary forms may become manifest as far out as 10 yr from the diagnosis of RP. It is important to take immediate action during an attack and patients' are encouraged to: 1.

Keep warm

2.

Not smoke

3.

Avoid aggravating medications

4.

Control stress

5.

Exercise

6.

Follow up with a physician

EVIDENCE

A meta-analysis of calcium channel blockers in systemic sclerosis concluded that there is moderate evidence for the efficacy of nifedipine in reducing the frequency and severity of attacks of Raynaud's in this group.[[1]] Other medical therapies have been shown to be beneficial in some trials, but the evidence so far is limited: A crossover randomized controlled trial (RCT) comparing prazosin 1 mg twice daily vs. placebo in 24 people (14 with the primary disease) found that prazosin significantly reduced the mean number and duration of attacks vs. placebo but not the severity of attacks.[[2]] Topical nitrates have been shown to reduce severity and frequency of attacks but side effects are not unusual.[[3]] The synthetic prostacyclin analog iloprost was found to reduce the frequency and severity of Raynaud's attacks significantly and also to prevent and heal digital ulcers.[[4]] There is evidence for the successful use of surgical sympathectomy to reduce symptoms and avoid amputation. [16] [17] [18]

Evidence-Based References 1. Thompson AE, et al: Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis. Arthritis Rheum 2001; 44:1841. 2. Wollersheim H, et al: Double-blind, placebo-controlled study of prazosin in Raynaud's phenomenon. Clin Pharmacol Ther 1986; 40:219.Reviewed in: Clin Evid 11:1603, 2004. 3. Teh LS, et al: Sustained-release transdermal glyceral trinitrate patches as treatment for primary and secondary Raynaud's phenomenon. Br J Rheumatol 1995; 34:636. 4. Pope J, et al: Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis. Reviewed. Cochrane Library 2, Chichester, UK, John Wiley, 2004. 5. McCall TE, et al: The use of digital artery sympathectomy as a salvage procedure for severe ischaemia of Raynaud's disease and phenomenon. J Hand Surg [Am] 1999; 24:173. 6. Tomaino MM, et al: Surgery for ischemic pain and Raynaud's phenomenon in scleroderma: description of treatment protocol and evaluation of results. Microsurgery 2001; 21:75. 7. Tham S, et al: Limited microsurgical arteriolysis for complications of digital vasospasm. J Hand Surg [Br] 1997; 22:359.

SUGGESTED READINGS Cook JP, et al: Mechanisms of Raynaud's disease. Vasc Med 2005; 10:297-307. Thompson AE, Pope JE: Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. Rheumatology 2005; 44:145.(Oxford) Wigley FM: Raynaud's phenomenon. N Engl J Med 2002; 347:1001-1008.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Raynaud's Phenomenon JORGE WILLAFUERTE, M.D.

BASIC INFORMATION DEFINITION

Reflex sympathetic dystrophy (RSD) or complex regional pain syndrome (CRPS) type 1 is a pain disorder characterized by constant and intense limb pain associated with vasomotor and sudomotor abnormalities that occurs without a definable nerve lesion. RSD or CRPS type 1 should be distinguished from CRPS type 2, which refers to pain disorders where a definable nerve lesion exists. SYNONYMS

CRPS type 1 Causalgia (or CRPS type 2) Shoulder-hand syndrome Sudeck's atrophy Posttraumatic pain syndrome

ICD-9CM CODES

337.20 Dystrophy sympathetic (posttraumatic) (reflex) EPIDEMIOLOGY & DEMOGRAPHICS

•

First described by Mitchell et al during the American Civil War.

•

The incidence and prevalence is not known.

•

Usually initiated by trauma, mostly after orthopedic procedures, especially those on the extremities

•

Can occur in adults or children.

•

Often associated with psychiatric and emotional lability, anxiety, and depression.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

RSD is divided into three stages:

•

•

•

Acute stage (occurring within hours to days after the injury) 1.

Burning or aching pain occurring over the injured extremity

2.

Hyperalgesia (exquisitely sensitive to touch)

3.

Edema

4.

Dysthermia

5.

Increased hair and nail growth

Dystrophic stage (3 to 6 mo after the injury) 1.

Burning pain radiating both distal and proximally from the site of injury

2.

Brawny edema

3.

Hyperhidrosis

4.

Hypothermia and cyanosis

5.

Muscle tremors and spasms

6.

Increased muscle tone and reflexes

Atrophic stage (6 mo after injury) 1.

Spread of pain proximally

2.

Cold, pale cyanotic skin

3.

Trophic skin changes with subcutaneous atrophy

4.

Fixed joints

5.

Contractures

ETIOLOGY

•

The cause is unknown. It is thought to represent dysfunction of the sympathetic nervous system.

•

Any injury can precipitate RSD including: 1.

Crush blunt trauma, burns, frostbite

2.

Surgery

3.

Parkinson's disease

4.

Cerebrovascular accident

5.

Myocardial infarction

6.

Osteoarthritis, cervical and lumbar disk disease

7.

Carpal tunnel and tarsal tunnel syndrome

8.

Diabetes

9.

Hyperthyroidism

10. Isoniazid therapy

DIAGNOSIS The diagnosis is primarily clinical, based on the patient's history and physical presentation. DIFFERENTIAL DIAGNOSIS

The differential diagnosis includes all the causes mentioned under “Etiology.” WORKUP

•

No workup is needed because there are no specific diagnostic tests establishing the diagnosis.

•

Electrophysiologic testing is useful to identify patients with type 2 CRPS.

LABORATORY TESTS

Blood tests are not specific. IMAGING STUDIES

•

No imaging studies are diagnostic. Three-phase bone imaging may be helpful.

•

Autonomic testing, although not commonly done, has been proposed.

•

1.

Measuring resting sweat output

2.

Measuring resting skin temperature

3.

Quantitative sudomotor axon reflex test

X-ray studies of the affected limb may show osteoporosis from disuse.

TREATMENT Treatment is aimed at relieving the pain and improving disuse atrophy with physical therapy. NONPHARMACOLOGIC THERAPY

•

Physical therapy

•

Transcutaneous nerve stimulation

ACUTE GENERAL Rx

•

The following has been tried for neuropathic pain relief: 1.

Amitriptyline 10 mg to 150 mg qd

2.

Phenytoin 300 mg qd

3.

Carbamazepine 100 mg bid

4.

Calcium channel blockers, nifedipine extended release 30 to 60 mg qd

5.

Prednisone 60 to 80 mg qd × 2 wk and then tapered over 1 to 2 wk to a maintenance dose of 5 mg qd for 2 to 3 mo

6.

Vitamin C 500 mg daily for 50 days after wrist fracture can decrease the occurrence of CRPS

7.

Gabapentin 300 mg daily up to 3 times a day

•

Regional nerve block that provides a perioperative sympathectomy may be advantageous for patients with a history of CRPS who require orthopedic surgery.

•

Because CRPS type 2 is the result of a definable nerve lesion, using a surgical technique that minimizes the risk of nerve damage is important.

CHRONIC Rx

•

Stellate ganglion and lumbar sympathetic blocks can be tried

•

Intravenous alpha-adrenergic blockade with phentolamine may predict response to subsequent sympatholytic treatment.

•

Surgical sympathectomy.

DISPOSITION

Spontaneous remission can occur after several weeks to months. REFERRAL

RSD is a very difficult diagnosis to make and referral to either rheumatology, neurology, orthopedic, or psychiatry is recommended.

PEARLS & CONSIDERATIONS COMMENTS

•

RSD is a common clinical entity without clear definition, pathophysiologic features, or treatment.

•

Pain is the most disabling symptom for most patients and is usually out of proportion to the extent of the injury.

SUGGESTED READINGS Baron R: Reflex sympathetic dystrophy and causalgia. Suppl Clin Neurophysiol 2004; 57:24. Dowd GSE, et al: Complex regional pain syndrome with special emphasis on the knee. J Bone Joint Surg 2007; 89-B(3):285-290. Low AK, et al: Pediatric complex regional pain syndrome. J Pediatr Orthop 2007; 27(b):567-572. Reuben SS, Buvanendran A: Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques. J Bone Joint Surg [Am] 2007; 89(b):1343-1358.

Teasdall RD, et al: Complex regional pain syndrome (reflex sympathetic dystrophy). Clin Sports Med 2004; 23(1):145.

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Reiter's Syndrome (Reactive Arthritis) GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., DEBORAH L. SHAPIRO, M.D.

BASIC INFORMATION DEFINITION

Reiter's syndrome is one of the seronegative spondyloarthropathies, so called because serum rheumatoid factor is not present in these forms of inflammatory arthritis. There is an international consensus that the term reactive arthritis should replace the name Reiter's syndrome to describe this constellation of signs and symptoms. Unfortunately, the original name is still associated with the syndrome. Reiter's syndrome is an asymmetric polyarthritis that affects mainly the lower extremities and is associated with one or more of the following: •

Urethritis

•

Cervicitis

•

Dysentery

•

Inflammatory eye disease

•

Mucocutaneous lesions

SYNONYMS

Reiter's disease Reactive arthritis Seronegative spondyloarthropathy

ICD-9CM CODES

099.3 Reiter's syndrome EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 0.0035% annually of men 250,000/yr receive dialysis treatment for ESRD.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Skin pallor, ecchymoses

•

Edema

•

Hypertension

•

Emotional lability and depression

•

The clinical presentation varies with the degree of renal failure and its underlying etiology. Common symptoms are generalized fatigue, nausea, anorexia, pruritus, insomnia, taste disturbances

ETIOLOGY

•

Diabetes (37%), hypertension (30%), chronic glomerulonephritis (12%)

•

Polycystic kidney disease

•

Tubular interstitial nephritis (e.g., drug hypersensitivity, analgesic nephropathy), obstructive nephropathies (e.g., nephrolithiasis, prostatic disease)

•

Vascular diseases (renal artery stenosis, hypertensive nephrosclerosis)

DIAGNOSIS

•

CRF is primarily distinguished from ARF by the duration (progression over several months).

•

Sonographic evaluation of the kidneys reveals smaller kidneys with increased echogenicity in CRF.

WORKUP

•

Laboratory evaluation and imaging studies should be aimed at identifying reversible causes of acute decrements in GFR (e.g., volume depletion, urinary tract obstruction, CHF) superimposed on chronic renal disease

•

Kidney biopsy: generally not performed in patients with small kidneys or with advanced disease

•

The glomerular filtration rate is the best overall indicator of kidney function. It can be estimated using prediction equations that take into account the serum creatinine level and some or all of specific variables (body size, age, sex, race). GFR calculators are available on the National Kidney Foundation website (http://www.kidney.org/kls/professionals/gfr_calculator.cfm )

LABORATORY TESTS

•

Elevated BUN, creatinine, creatinine clearance.

•

Urinalysis: may reveal proteinuria, RBC casts.

•

Serum chemistry: elevated BUN and creatinine, hyperkalemia, hyperuricemia, hypocalcemia, hyperphosphatemia, hyperglycemia, decreased bicarbonate.

•

Measure urinary protein excretion. The finding of a ratio of protein to creatinine of >1000 mg/g suggests the presence of glomerular disease.

•

Special studies: serum and urine immunoelectrophoresis (in suspected multiple myeloma), ANA (in suspected SLE).

•

Cystatin C is a cysteine proteinase inhibitor produced by all nucleated cells, freely filtered at the glomerulus but not secreted by tubular cells. Given these characteristics, it may be superior to creatinine concentration both in kidney disease and as a marker of acute kidney injury. It is a better index of kidney function in elderly patients and a better predictor of outcomes than creatinine. The association of cystatin C is stronger than the association of measured GFR with all-cause and CVD mortality in patients with advanced chronic kidney disease.

IMAGING STUDIES

Ultrasound of kidneys to measure kidney size and to rule out obstruction

TREATMENT

NONPHARMACOLOGIC THERAPY

•

Provide adequate nutrition and calories (147 to 168 kJ/kg/day in energy intake, chiefly from carbohydrate and polyunsaturated fats). Referral to a dietician for nutritional therapy for patients with GFR 5.5 in RTA type I, 85%) have periodic leg movements in sleep (PLMS), which also may disrupt sleep. SYNONYMS

Restless limb syndrome Growing pains Night kicking Night walker syndrome

ICD-9CM CODES

333.99 Restless legs syndrome EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 8% to 12% depending on population and severity of symptoms DEMOGRAPHICS: Age 2 and up (youngest case: 8 wk of age)

•

Age 3 cm

N2

Ipsilateral, contralateral, or bilateral node 6 cm

M0

No distant metastasis

M1

Distant metastasis

Stage I

T1a or 2aN0M0

Stage II T1b,2b,3a N0M0 Stage III T3b,4a N0M0 or any T except 4bN1M 0

Stage IV T4b any N any M or any T N2,3M0 or any T, any N1M1 WORKUP

•

Fine-needle aspiration. The sensitivity, specificity, and accuracy of parotid gland aspirates is approximately 92%, 100%, and 98%, respectively

•

Imaging by CT scan or MRI

•

Open biopsy (rarely indicated)

TREATMENT Malignant tumors: •

Surgery is the mainstay of treatment; gland resection and neck dissection if lymph nodes are involved.

•

A lateral lobectomy with preservation of facial nerve should be considered for tumors confined to the superficial lobe of the parotid gland. Gross tumor should not be left in situ, but if the facial nerve is able to be preserved by “peeling” tumor off the nerve, it should be attempted, followed by radiation therapy for microscopic disease.

•

Postoperative radiation is indicated for high-grade malignancies demonstrating extraglandular disease, perineural invasion, direct invasion of surrounding tissues, or regional metastases.

•

Chemotherapy.

Benign tumors: surgery for tumor resection PROGNOSIS OF MALIGNANT TUMORS

Five-year survival rates:

•

Mucoepidermoid carcinoma: 75% to 95%

•

Adenoid cystic carcinoma: 40% to 80%

•

Adenocarcinoma: 20% to 75%

•

Malignant mixed tumor: 35% to 75%

•

Squamous cell carcinoma: 25% to 60%

PEARLS & CONSIDERATIONS COMMENTS

Salivary gland neoplasms most often present as slow-growing, well-circumscribed masses. Pain, rapid growth, nerve weakness, fixation to skin or underlying muscle, and paresthesias usually are indicative of malignancy. SUGGESTED READINGS Stewart CJ, et al: Fine needle aspiration cytology of salivary gland: a review of 341 cases. Diagn Cytopathol 2000; 22:139.

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Salmonellosis GLENN G. FORT, M.D., M.P.H., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Salmonellosis is an infection caused by one of several serotypes of Salmonella. SYNONYMS

Typhoid fever Paratyphoid fever Enteric fever

ICD-9CM CODES

003.0 Salmonellosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Estimated 1 million cases/yr of nontyphoidal salmonellosis

•

Approximately 500 cases of Salmonella typhi infection reported each year

•

Largest outbreak: 200,000 persons who ingested contaminated milk

PEAK INCIDENCE: Summer and fall PREDOMINANT AGE: •

< 20 yr old

•

> 70 yr old

•

Highest rates of infection in infants, especially neonates

GENETICS: Neonatal Infection: Highly susceptible to infection with nontyphoidal Salmonella

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

•

Infections 1.

Localized to GI tract (gastroenteritis)

2.

Systemic (typhoid fever)

3.

Localized outside of GI tract

Gastroenteritis 1.

Incubation period: 12 to 48 hr

2.

Nausea, vomiting

3.

Diarrhea, abdominal cramps

4.

Fever

5.

Bacteremia: Occurs mostly in the immunocompromised host or those with underlying conditions, including HIV infection

6.

Self-limited illness lasting 3 or 4 days

7.

Colonization of GI tract persistent for months, especially in those treated with antibiotics

Typhoid fever 1.

Incubation period of few days to several weeks

2.

Prolonged fever, often with a stepwise-increasing temperature pattern

3.

Myalgias

4.

Headache, cough, sore throat

5.

Malaise, anorexia

6.

Abdominal pain

7.

Hepatosplenomegaly

8.

Diarrhea or constipation early in the course of illness

9.

Rose spots (faint, maculopapular, blanching lesions) sometimes seen on chest or abdomen

Untreated disease 1.

Fever lasting 1 to 2 mo

2.

Main complication: GI bleeding caused by perforation from ulceration of Peyer's patches in the ileum ( Fig. 1-237 )

3.

Rare complications:

4. •

a.

Mental status changes

b.

Shock

Relapse rate of approximately 10%

Infections outside GI tract

1.

Can occur in virtually any location

2.

Usually occur in patients with underlying diseases

3.

Endocarditis, endovascular infections are caused by seeding of atherosclerotic plaques or aneurysms

4.

Hepatic or splenic abscesses in patients with underlying disease in these organs

5.

Urinary tract infections in patients with renal TB or schistosomiasis

6.

Salmonellae are a frequent cause of gram-negative meningitis in neonates

7.

Osteomyelitis in children with hemoglobinopathies (particularly sickle cell disease)

FIGURE 1-237 Salmonella typhi invade M cells through membrane ruffling and EGF receptor-dependent pathways. Macrophages originating from Peyer's patch take up S. typhi in close association with M cells. S. typhi replicate in Peyer's patches and then enter the lymphatic system, leading to bacteremia. Replication in Peyer's patches causes hypertrophy followed by necrosis, which can cause intestinal perforation. (From Stein JH [ed]: Internal medicine, ed 5, St Louis, 1998, Mosby.)

ETIOLOGY

•

More than 2000 serotypes of Salmonella exist, but only a few cause disease in humans.

•

Some found only in humans are the cause of enteric fever.

•

1.

S. typhi

2.

S. paratyphi

Some responsible for gastroenteritis and frequently isolated from raw meat and poultry and uncooked or undercooked eggs. 1.

S. typhimurium

2.

S. enteritidis

•

S. cholerae-suis is a prototype organism that causes extraintestinal nontyphoidal disease.

•

Transmission generally via ingestion of contaminated food or drink.

•

Outbreaks of gastroenteritis related to contaminated poultry, meat, and dairy products.

•

Typhoid fever is a systemic illness caused by serotypes exclusive to humans. 1.

Acquisition by ingestion of food or water contaminated by other humans

2.

Most cases in the U.S. are: a.

Acquired during foreign travel

b.

Acquired by ingestion of food prepared by chronic carriers, many of whom have acquired the organism outside of the U.S.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

•

Other causes of prolonged fever: 1.

Malaria

2.

TB

3.

Brucellosis

4.

Amebic liver abscess

Other causes of gastroenteritis:

WORKUP

1.

Bacterial: Shigella, Yersinia, Campylobacter spp.

2.

Viral: Norwalk virus, rotavirus

3.

Parasitic: Entamoeba histolytica, Giardia lamblia

4.

Toxic: enterotoxigenic E. coli, Clostridium difficile

•

Typhoid fever 1.

Cultures of blood, stool, urine; repeat if initially negative.

2.

Blood cultures are more likely to be positive early in the course of illness.

3.

Stool and urine cultures are more commonly positive in the second and third week of illness.

4.

Highest yield with bone marrow biopsy cultures: 90% positive

5.

Serology using Widal's test is helpful in retrospect, showing a fourfold increase in convalescent titers.

•

Gastroenteritis: stool cultures

•

Extraintestinal localized infection: 1.

Blood cultures

2.

Cultures from the site of infection

LABORATORY TESTS

•

Neutropenia is common

•

Transaminitis is possible

•

Culture to grow organism: blood, body fluids, biopsy specimens

IMAGING STUDIES

•

Radiographs of bone may be suggestive of osteomyelitis (particularly in patients with sickle cell disease and bone infarctions).

•

CT scan or sonogram of abdomen: 1.

May reveal hepatic or splenic abscesses or pleural involvement

2.

May reveal aortic aneurysm

TREATMENT NONPHARMACOLOGIC THERAPY

Adequate hydration and electrolyte replacement in persons with diarrhea ACUTE GENERAL Rx

•

•

Typhoid fever: 1.

Ciprofloxacin 500 mg PO bid or 400 mg IV bid for 14 days

2.

Ceftriaxone 2 g IV qd for 14 days

3.

If sensitive, may switch therapy to TMP/SMX 1 to 2 DS tabs PO bid or amoxicillin 2 g PO q8h to complete 14 days

4.

Dexamethasone 3 mg IV initially, followed by 1 mg IV q6h for eight doses for patients with shock or mental status changes

Gastroenteritis: 1.

Usually not indicated for gastroenteritis alone because this illness usually self-limited

2.

May prolong the carrier state

3.

Prophylactic treatment for patients who are at high risk of developing complications from bacteremia

4. •

a.

Neonates

b.

Patients with hemoglobinopathies

c.

Patients with atherosclerosis

d.

Patients with aneurysms

e.

Patients with prosthetic devices

f.

Immunocompromised patients

Treatment can be oral or parenteral, with the same regimens used for typhoid, but only for 48 to 72 hr

Intravascular infections require 6 wk of parenteral therapy.

CHRONIC Rx

•

Carrier states are possible in those with typhoid fever.

•

More common in persons > 60 yr of age and in persons with gallstones.

•

Usual site of colonization is the gallbladder.

•

Treatment should be considered for those with persistently positive stool cultures and for food handlers.

•

Suggested regimens for eradication of carrier state: 1.

Ciprofloxacin 500 mg PO bid for 4 wk

2.

SMX/TMP 1 to 2 DS tabs PO bid for 6 wk (if susceptible)

3.

Amoxicillin 2 g PO q8h for 6 wk (if susceptible)

•

Cholecystectomy may be required in carriers with gallstones who fail medical therapy but this is rarely indicated for non-typhoidal salmonellosis currently.

•

Prolonged course of oral therapy or lifetime suppression for patients with AIDS who have chronic infection

DISPOSITION

•

•

Typhoid fever 1.

Treated patients usually respond to therapy; small percentage of chronic carriers.

2.

Untreated patients may have serious complications.

Gastroenteritis 1.

Usually self-limited

2.

May be recurrent or persistent in AIDS patients

REFERRAL

•

If gastroenteritis is persistent or recurrent

•

If there is evidence of extraintestinal infection, typhoid fever, or chronic carriers

PEARLS & CONSIDERATIONS COMMENTS

•

Quinolones should not be used in children or pregnant women.

•

Infections should be reported to local health departments.

•

Recent outbreaks in the U.S. have been traced back to raw tomatoes, peanut butter, and frozen pot pies.

EVIDENCE

Antibiotic therapy has not been shown to have any positive clinical effect in healthy children and adults with mild diarrhea caused by Salmonella spp.[[1]] Oral rehydration fluids are as effective as intravenous rehydration fluids in children with mild or moderate dehydration caused by gastroenteritis. [3] [4] Oral rehydration fluid has been shown to be associated with significant reductions in the duration of diarrhea and with increased weight gain at discharge compared with intravenous rehydration fluid, in a randomized controlled trial conducted in a developing country.[[4]]

Evidence-Based Referenceces 1. Sirinavin S, Garner P: Antibiotics for treating salmonella gut infections. Cochrane Database Syst Rev 1999; 1: 2. Gavin N, Merrick N, Davidson B: Efficacy of glucose-based oral rehydration therapy. Pediatrics 1996; 98:45.Reviewed in: Clin Evid 10:86, 2003. 3. Singh M, et al: Controlled trial of oral versus intravenous rehydration in the management of acute gastroenteritis. Indian J Med Res 1982; 75:691.Reviewed in: Clin Evid 9:367, 2003. 4. Sharifi J, et al: Oral versus intravenous rehydration therapy in severe gastroenteritis. Arch Dis Child 1985; 60:856.Reviewed in: Clin Evid 9:367, 2003.

SUGGESTED READINGS CDC: Salmonellosis associated with pet turtles—Wisconsin and Wyoming, 2004. MMWR Morb Mortal Wkly Rep 2005; 54(9):223. Delaloye J, et al: Nosocomial nontyphoidal salmonellosis after antineoplastic chemotherapy reactivation of asymptomatic colonization?. Eur J Clin Microbiol Infect Dis 2004; 23(10):751. Wells EV, et al: Reptile-associated salmonellosis in pre-school aged children in Michigan, January 2001-June 2003. Clin Infect Dis 2004; 39(5):687.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Sarcoidosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Sarcoidosis is a chronic systemic granulomatous disease characterized histologically by the presence of nonspecific, noncaseating granulomas. SYNONYMS

Boeck's sarcoid

ICD-9CM CODES

135.0 Sarcoidosis EPIDEMIOLOGY & DEMOGRAPHICS

Incidence (IN U.S.) 10.9/100,000 whites, 35.5/100,000 blacks •

Presents most commonly in the winter and early spring

PREDOMINANT SEX: Increased incidence in females PREDOMINANT AGE: 20 to 40 yr old PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Clinical manifestations often vary with the stage of the disease and degree of organ involvement; patients may be asymptomatic, but a chest x-ray may demonstrate findings consistent with sarcoidosis (see “Imaging Studies”). Nearly 50% of patients with sarcoidosis are diagnosed by incidental findings on chest x-ray.

•

Frequent manifestations: 1.

Pulmonary manifestations: dry, nonproductive cough, dyspnea, chest discomfort

2.

Constitutional symptoms: fatigue, weight loss, anorexia, malaise

3.

Visual disturbances: blurred vision, ocular discomfort, conjunctivitis, iritis, uveitis

4.

Dermatologic manifestations: erythema nodosum, macules, papules, subcutaneous nodules, hyperpigmentation, lupus pernio

5.

Myocardial disturbances: arrhythmias, cardiomyopathy

6.

Splenomegaly, hepatomegaly

7.

Rheumatologic manifestations: arthralgias have been reported in up to 40% of patients

8.

Neurologic and other manifestations: cranial nerve palsies, diabetes insipidus, meningeal involvement, parotid enlargement, hypothalamic and pituitary lesions, peripheral adenopathy

ETIOLOGY

Unknown. Multiple lines of evidence suggest that sarcoidosis may result from the interaction of multiple genes with environmental exposures or infection.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

TB

•

Lymphoma

•

Hodgkin's disease

•

Metastases

•

Pneumoconioses

•

Enlarged pulmonary arteries

•

Infectious mononucleosis

•

Lymphangitic carcinomatosis

•

Idiopathic hemosiderosis

•

Alveolar cell carcinoma

•

Pulmonary eosinophilia

•

Hypersensitivity pneumonitis

•

Fibrosing alveolitis

•

Collagen disorders

•

Parasitic infection

Section II describes the differential diagnosis of granulomatous lung disease and a classification of granulomatous disorders.

WORKUP

•

Workup is aimed at excluding critical organ involvement, determining extent and severity of disease, and excluding other disease. A complete neurologic and ophthalmologic exam is mandatory. A complete occupational and environmental exposure history is recommended.

•

Initial lab evaluation should include CBC, serum chemistries (ALT, AST, lytes, BUN, creatinine, serum calcium), urinalysis, and tuberculin test.

•

Chest x-ray and ECG should also be obtained in all patients with sarcoidosis.

•

Pulmonary function testing; spirometry, diffusion capacity of carbon monoxide-single breath.

•

Biopsy should be done on accessible tissues suspected of sarcoid involvement (conjunctiva, skin, lymph nodes); bronchoscopy with transbronchial biopsy is the procedure of choice in patients without any readily accessible site.

LABORATORY TESTS

Laboratory abnormalities: •

Hypergammaglobulinemia, anemia, leukopenia

•

LFT abnormalities

•

Hypercalcemia, hypercalciuria (secondary to increased GI absorption, abnormal vitamin D metabolism, and increased calcitriol production by sarcoid granuloma)

•

Cutaneous anergy to Trichophyton, Candida, mumps, and tuberculin

•

Angiotensin-converting enzyme (ACE): elevated in approximately 60% of patients with sarcoidosis; nonspecific and generally not useful in following the course of the disease

IMAGING STUDIES

•

Chest x-ray ( Fig. 1-238 ): adenopathy of the hilar and paratracheal nodes is a frequent finding; parenchymal changes may also be present, depending on the stage of the disease (stage 0, normal x-ray; stage I, bilateral hilar adenopathy; stage II, stage I plus pulmonary infiltrate; stage III, pulmonary infiltrate without adenopathy); stage IV, advanced fibrosis with evidence of honey-combing, hilar retraction, bullae, cysts, and emphysema.

•

PFTs (spirometry and diffusing capacity of the lung for carbon dioxide): may be normal or may reveal a restrictive pattern and/or obstructive pattern.

•

Gallium-67 scan: will localize in areas of granulomatous infiltrates; however, it is not specific. The “panda” sign (localization in the lacrimal and salivary glands, giving a “panda” appearance to the face) is suggestive of sarcoidosis.

FIGURE 1-238 Sarcoid. Marked lymphadenopathy (dotted lines) is seen in the region of both hila in the right paratracheal region (A). The transverse contrast-enhanced CT scan of the upper chest (B) clearly shows the ascending and descending aorta (Ao) as well as the pulmonary artery (PA) and superior vena cava. The right and left mainstem bronchus area is also seen. The arrows indicate the extensive lymphadenopathy. LB, Left bronchus; RB, right bronchus. (From Mettler FA [ed]: Primary care radiology, Philadelphia, 2000, WB Saunders.)

TREATMENT GENERAL Rx

•

Corticosteroids ( Table 1-43 ) remain the mainstay of therapy when treatment is required (e.g., prednisone 40 mg qd for 8 to 12 wk with gradual tapering of the dose to 10 mg qod over 8 to 12 mo); corticosteroids should be considered in patients with severe symptoms (e.g., dyspnea, chest pain), hypercalcemia, ocular, CNS, or cardiac involvement, and progressive pulmonary disease. Patients with interstitial lung disease benefit from oral steroid therapy for 6 to 24 mo.

•

Patients with progressive disease refractory to corticosteroids may be treated with methotrexate 7.5 to 15 mg once/week or azathioprine.

•

Hydroxychloroquine is effective for chronic disfiguring skin lesions.

•

NSAIDs are useful for musculoskeletal symptoms and erythema nodosum.

•

Pulmonary rehabilitation in patients with significant respiratory insufficiency.

TABLE 1-43 -- Indications for Use of Corticosteroids in Sarcoidosis Disorder Treatment Iridocyclitis

Corticosteroid eyedrops Local subjunctival deposit of cortisone

Posterior uveitis

Oral prednisone

Pulmonary involvement

Steroids rarely recommended for stage I; usually employed if infiltrate remains static or worsens over 3-mo period or the patient is symptomatic

Disorder

Treatment

Upper airway obstruction

Rare indication for intravenous steroids

Lupus pernio

Oral prednisone shrinks the disfiguring lesions

Hypercalcemia

Responds well to corticosteroids

Cardiac involvement

Corticosteroids usually recommended if patient has arrhythmias or conduction disturbances

CNS involvement

Response is best in patients with acute symptoms

Lacrimal/salivary gland involvement

Corticosteroids recommended for disordered function, not gland swelling

Bone cysts

Corticosteroids recommended if symptomatic

From Andreoli TE (ed): Cecil essentials of medicine, ed 5, Philadelphia, 2001, WBSaunders. CNS, Central nervous system

DISPOSITION

•

The majority of patients with sarcoidosis have spontaneous remission within 2 yr and do not require treatment. Their course can be followed by periodic clinical evaluation, chest x-ray, and PFTs.

•

Blacks have increased rates of pulmonary involvement, a worse long-term prognosis, and more frequent relapses.

•

Adverse prognostic factors in sarcoidosis include age of onset > 40 yr, cardiac involvement, neurosarcoidosis, progressive pulmonary fibrosis, chronic hypercalcemia, chronic uveitis, involvement of nasal mucosa, nephrocalcinosis, and presence of cystic bone lesions and lupus pernio.

REFERRAL

Ophthalmologic examination is indicated in all patients with suspected sarcoidosis, because ocular findings (iridocyclitis, uveitis, conjunctivitis, and keratopathy) are found in > 25% of documented cases.

PEARLS & CONSIDERATIONS COMMENTS

Approximately 15% to 20% of patients with lung involvement advance to irreversible lung impairment (bronchiectasis, cavitation, progressive fibrosis, pneumothorax, and respiratory failure). Death from pulmonary failure occurs in 5% to 7% of patients with sarcoidosis.

EVIDENCE

Oral corticosteroids improve chest x-ray findings over 6 to 24 months, and they improve global scores (a combination of symptoms, chest x-ray changes, and lung function) in patients with stages II and III pulmonary sarcoidosis, but not in patients with stage I disease. A systematic review ease. A systematic review found little evidence of an improvement in lung function, and there were insufficient data on the effects of corticosteroids on long-term disease progression.[[1]]

Evidence-Based Referencece 1. Paramothayan NS, Jones PW: Corticosteroids for pulmonary sarcoidosis (Cochrane Review), 1, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Judson MA: The management of sarcoidosis by the primary care physician. Am J Med 2007; 120:403. Fannuzzi MC, et al: Sarcoidosis. N Engl J Med 2007; 357:2153-2165.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Scabies VASANTHI ARUMUGAM, M.D., GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Scabies is a contagious disease caused by the mite Sarcoptes scabiei.

ICD-9CM CODES

133.0 Scabies EPIDEMIOLOGY & DEMOGRAPHICS

•

Scabies is generally acquired by sleeping with or in the bedding of infested individuals.

•

It is generally associated with poor living conditions and is also common in hospitals and nursing homes.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Primary lesions are caused when the female mite burrows within the stratum corneum, laying eggs within the tract she leaves behind; burrows (linear or serpiginous tracts) end with a minute papule or vesicle.

•

Primary lesions are most commonly found in the web spaces of the hands, wrists, buttocks, scrotum, penis, breasts, axillae, and knees.

•

Secondary lesions result from scratching or infection.

•

Intense pruritus, especially nocturnal, is common; it is caused by an acquired sensitivity to the mite or fecal pellets and is usually noted 1 to 4 wk after the primary infestation.

•

Examination of the skin may reveal burrows, tiny vesicles, excoriations, inflammatory papules.

•

Widespread and crusted lesions (Norwegian or crusted scabies) may be seen in elderly and immunocompromised patients.

ETIOLOGY

Human scabies is caused by the mite S. scabiei, var. hominis ( Fig. 1-239 ).

FIGURE 1-239 Scabies organism in a wet mount preparation. (From Mandell GL: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, ed 5, New York, 2000, Churchill Livingstone.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Pediculosis

•

Atopic dermatitis

•

Flea bites

•

Seborrheic dermatitis

•

Dermatitis herpetiformis

•

Contact dermatitis

•

Nummular eczema

•

Syphilis

•

Other insect infestation

WORKUP

Diagnosis is made on the clinical presentation and on the demonstration of mites, eggs, or mite feces. LABORATORY TESTS

•

Microscopic demonstration of the organism, feces, or eggs: a drop of mineral oil may be placed over the suspected lesion before removal; the scrapings are transferred directly to a glass slide; a drop of potassium hydroxide is added and a cover slip is applied.

•

Skin biopsy is rarely necessary to make the diagnosis.

TREATMENT NONPHARMACOLOGIC THERAPY

Clothing, underwear, and towels used in the 48 hr before treatment must be laundered. ACUTE GENERAL Rx

•

Following a warm bath or shower, Lindane (Kwell, Scabene) lotion should be applied to all skin surfaces below the neck (can be applied to the face if area is infested); it should be washed off 8 to 12 hr after application. Repeat application 1 wk later is usually sufficient to eradicate infestation.

•

Pruritus generally abates 24 to 48 hr after treatment, but it can last up to 2 wk; oral antihistamines are effective in decreasing postscabietic pruritus.

•

Topical corticosteroid creams may hasten the resolution of secondary eczematous dermatitis.

•

If the patient is a resident of an extended care facility, it is important to educate the patients, staff, family, and frequent visitors about scabies and the need to have full cooperation in treatment. Scabicide should be applied to all patients, staff, and frequent visitors, whether symptomatic or not; symptomatic family members of staff and visitors should also receive treatment.

•

Permethrin 5% cream (Elimite) is also effective with usually one treatment; it should be massaged into the skin from head to soles of feet; remove 8-14 hr later by washing. If living mites are present after 14 days, treat again.

•

A single dose (150 to 200 mg/kg in 6-mg tablets) of ivermectin, an antihelminthic agent, is as effective as topical lindane for the treatment of scabies. It is the best treatment for generalized crusted scabies.

DISPOSITION

Refractory cases usually are seen with immunocompromised hosts or patients with underlying skin diseases.

PEARLS & CONSIDERATIONS COMMENTS

•

Lindane is potentially neurotoxic and should not be used for infants and pregnant women (permethrin is safe and effective in these situations).

•

Sexual partners should be notified and treated.

EVIDENCE

A systematic review concludes that, on balance, permethrin should be used as the treatment of choice. However, this recommendation is based on information from small trials, together with professional opinion and traditional reviews.[[1]] All the commonly used treatments are effective, and in general, there is little evidence to suggest that any one is superior. [12] [13]

Evidence-Based Referenceces 1. Walker GJA, Johnstone PW: Interventions for treating scabies. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 2. Walker G, Johnstone P: Scabies, 10. London: BMJ Publishing Group; 2003:1910.

AUTHOR: FRED F. FERRI, M.D. Scarlet Fever

BASIC INFORMATION DEFINITION

Scarlet fever is a rash involving skin and tongue and complicating a streptococcal group A pharyngitis. SYNONYMS

Scarlatina SF

ICD-9CM CODES

034.1 Scarlet fever EPIDEMIOLOGY & DEMOGRAPHICS

•

Same as streptococcal pharyngitis; namely, children aged 5 to 15 yr. May also complicate impetigo.

•

Most common in cooler climates during the late fall, winter, and early spring.

•

Most cases follow tonsillitis or pharyngitis; however, it has also been reported following wounds (“surgical scarlet fever”), burns, and pelvic or puerperal infections.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Diffuse erythema, beginning on face and spreading to neck, back, chest, rest of trunk, and extremities. Most intense on inner aspects of arms and thighs.

•

Erythema blanches, but nonblanching petechiae may be present or produced by a tourniquet.

•

Strawberry or raspberry tongue.

•

Rash lasts about 1 wk and then desquamates.

•

Febrile illness with headache, malaise, anorexia, and pharyngitis begins after a 2- to 4-day incubation period.

•

Scarlatinal rash begins 1 or 2 days after the onset of pharyngitis ( Fig. 1-240 ).

FIGURE 1-240 Scarlet fever. Evolution of signs and symptoms. (From Habif TP: Clinical dermatology: a color guide to diagnosis and therapy, ed 3, St Louis, 1996, Mosby.)

ETIOLOGY

Caused by group A beta-hemolytic Streptococcus infection, which produces one of three erythrogenic toxins (note: Some streptococcal species have the ability to cause both scarlet fever and rheumatic fever).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Viral exanthems (covered in Section II)

•

Kawasaki disease

•

Toxic shock syndrome

•

Drug rashes

See differential diagnosis of “Pharyngitis” in Section I. WORKUP

•

Identification of group A Streptococcus by throat culture

•

SLO antibody titers

TREATMENT

•

Penicillin 250 mg po qid for 10 days or erythromycin 250 mg po qid for 10 days in penicillin-allergic patients. A clinical response can be expected in 24 to 48 hr.

•

Benzathine penicillin 1 to 2 million U IM once; may be used for a patient who cannot swallow pills.

COMPLICATIONS (RARE)

•

Peritonsillar abscess

•

Mastoiditis

•

Otitis media

•

Pneumonia

•

Sepsis and distant foci of infection

•

Acute rheumatic fever

•

Inability to swallow liquids or upper airway obstruction requires hospitalization.

Note: Failure to respond to penicillin should raise doubt about the diagnosis because Streptococcus may be carried in the pharynx without causing infection.

PEARLS & CONSIDERATIONS COMMENTS

Patients with antibodies against the toxin are spared the rash but still develop other symptoms of the infection (e.g., sore throat). AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Schistosomiasis

BASIC INFORMATION DEFINITION

Schistosomiasis is caused by infection with parasite blood flukes known as schistosomes. SYNONYMS

Bilharziasis Urinary schistosomiasis Hepatosplenic schistosomiasis Swimmers itch Katayama fever

ICD-9CM CODES

120.9 Schistosomiasis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: •

More than 200 million people worldwide and more than 200,000 deaths annually. In U.S., estimated to exceed 400,000 persons.

•

Geographic distribution of schistosomiasis is confined to an area between 36° north and 34° south latitude, where fresh water temperatures average 25 to 30° C.

PREVALENCE: The greatest cercarial exposure usually occurs in boys aged 5 to 10 yr DISTRIBUTION:

•

S. mansoni in tropical and subtropical areas of sub-Saharan Africa, the Middle East, South America, and the Caribbean

•

S. haematobium in North Africa, sub-Saharan Africa, the Middle East, and India

•

S. japonicum in Asia, particularly in China, the Philippines, Thailand, and Indonesia

•

S. intercalatum in central and west Africa

•

S. mekongi in Cambodia

ETIOLOGY & PATHOGENESIS

•

Human infections are caused by S. mansoni, S. haematobium, S. japonicum, S. mekongi, and S. intercalatum.

•

Acquisition of disease via contact with fresh water containing infectious free-living cercarial larvae.

•

In U.S., most cases are acquired during foreign travel.

•

Human disease is primarily associated with the host's granulomatous response to eggs retained in the tissue.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

ACUTE SYMPTOMS: •

Swimmers itch

•

Katayama fever

CHRONIC SYMPTOMS: •

•

•

Intestinal schistosomiasis 1.

Abdominal pain

2.

Bloody diarrhea

3.

Iron deficiency anemia

4.

Intestinal polyp

5.

Bowel ulcer and strictures

Hepatic schistosomiasis 1.

Hepatomegaly

2.

Splenomegaly

3.

Portal hypertension

4.

Esophageal varices

Urinary schistosomiasis 1.

Hematuria

2.

Dysuria

3.

Urinary frequency

4.

Fibrosis of bladder and ureters

5.

Squamous cell ca of bladder

6.

Proteinuria

7.

Nephrotic syndrome

COMPLICATIONS: •

•

Neurologic complication 1.

Granuloma of spinal cord or brain

2.

Transverse myelitis

3.

Epilepsy or focal neurologic deficit

Pulmonary complication 1.

Granulomatous pulmonary endarteritis

2.

Pulmonary hypertension

3.

Cor pulmonale

•

Other complications include tubal obstruction and infertility

•

Recurrent bacteremia and recurrent UTI

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Amebiasis

•

Bacillary dysentery

•

Bowel polyp

•

Prostatic disease

•

Genitourinary tract cancer

•

Bacterial infections of the urinary tract

WORKUP

•

Microscopy in urine or stool

•

Tissue biopsy

•

Serology

•

CBC

•

LFT

•

US of abdomen

•

CT scan of abdomen

LABORATORY TESTS

•

CBC shows eosinophilia, anemia, thrombocytopenia

•

LFT with mild increase in alkaline phosphatase and GGT

•

Microscopy: stool and urine

•

Serology: ELISA for detecting both schistosomal antibodies and antigen

•

Rectal biopsy or bladder mucosal biopsy

IMAGING STUDIES

•

X-ray of abdomen shows “fetal head” calcification.

•

Sonography also documents a thickened bladder wall, hydronephrosis and hydroureter, and bladder polyps or calcification. It also demonstrates the thickened fibrosed portal tracts.

•

Esophagoscopy documents esophageal varices.

•

Liver biopsy may also demonstrate granuloma and clay pipestem fibrosis.

TREATMENT

•

Praziquantel 40 mg/kg of body weight orally in one or two doses

•

Oxamniquine 15 mg/kg orally once or 20 mg/kg orally daily for 3 days for recalcitrant infections

•

Metrifonate 7.5 to 10 mg/kg of body weight given orally in three doses at 2-wk intervals

DISPOSITION

Treated patients usually respond to therapy. Definitive cure has occurred only when there is total

disappearance of viable eggs from the excreta for a total of 6 mo after treatment. REFERRAL

•

To an infectious disease specialist knowledgeable in parasitology and geographic medicine for treatment and follow-up

•

To a gastroenterologist for sclerotherapy of bleeding esophageal varices, if needed in advanced hepatosplenic schistosomiasis

•

To a urologist for management and follow-up of urinary complications of S. haematobium infection of the genitor-urinary tract

PEARLS & CONSIDERATIONS COMMENTS

Prevention: •

•

•

Chemotherapy 1.

Mass

2.

Targeted population

Snail control 1.

Mollusciciding

2.

Environmental modification

3.

Biologic control

Reduction of water contact and contamination 1.

Provision of domestic water supplies

2.

Provision for sanitary disposal of excreta

•

Vaccination

•

Improved living standards

SUGGESTED READINGS Steinmann P, et al: Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 2006; 6(7):411. Swai B, et al: Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania. BMC Infect Dis 2006; 6:134. Vennervald BJ, et al: Morbidity in schistosomiasis: an update. Curr Opin Infect Dis 2004; 17(5):439.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Schizophrenia MICHAEL K. ONG, M.D., PH.D.

BASIC INFORMATION DEFINITION

Schizophrenia is a disorder that causes significant distortions in thinking, perception, speech, and behavior. Characteristics include psychosis, apathy and social withdrawal, and cognitive impairment, which result in significant social impairment. SYNONYMS

Dementia praecox

ICD-9CM CODES

295.9 Schizophrenia EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 0.5%, incidence 0.2 per 1000. Lifetime prevalence risk is 0.4%. PEAK INCIDENCE: Ages 16 to 30 PREDOMINANT SEX: Males have a more severe illness with earlier onset; however, distribution is probably equal. PREDOMINANT AGE:

•

Age at onset of psychotic symptoms is in the early 20s for males and late 20s for females.

•

Age of onset of the negative symptoms is usually earlier (midteenage years).

GENETICS:

•

Accounts for 70% of risk, remaining 30% is biologic or psychosocial.

•

First-degree relatives of schizophrenics have 10 times greater chance of becoming schizophrenic than the general population.

•

Discordant rates among identical twins are higher than expected with simple inheritance pattern.

•

Associations with several chromosomes have been described, but none have been replicated.

•

Evidence exists that triplet nucleotide repeat expansion (such as seen with Huntington's disease) may play a role in inheritance of the disease.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Best defined as a dementing illness beginning in early life and progressing slowly throughout the lifetime.

•

Initial “negative” symptoms of adolescence—cognitive decline, social withdrawal and awkwardness, loss of motivation and pleasure, and loss of emotional expressiveness—begin after a period of normal development.

•

In early adulthood, positive symptoms of psychosis and thought disturbance occur; psychotic symptoms then wax and wane throughout life; treatment ameliorates positive symptoms but generally does little for negative ones.

•

It is also accompanied by cognitive impairment, including problems in attention and concentration, psychomotor speed, learning and memory, and executive functions (e.g., abstract thinking, problem solving).

•

Social and occupational dysfunction can be profound.

ETIOLOGY

•

Basic distinction of whether this is a degenerative or a developmental condition is not settled.

•

Frequent findings include enlargement of ventricular system and loss of brain volume and cortical gray matter.

•

Major hypothesis: generation of the mesocortical pathways produce the hypofrontality and negative symptoms, along with a compensatory hyperactivation of the mesolimbic pathways, which produce the positive symptoms of psychosis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Schizophrenia is diagnosed when an individual has experienced at least 1 month of hallucinations, delusions, thought disorder, catatonia, or negative symptoms (avolition, anhedonia, social isolation, affective flattening).

•

Any medical condition, medicine, or substance of abuse that can affect brain homeostasis and cause psychosis: distinguished from schizophrenia by their relatively brief course and the alteration in mental status that could suggest an underlying delirium.

•

Other neurologic conditions (e.g., Huntington's) that have psychosis as the initial presentation.

•

Other psychiatric disorders: source of greatest confusion.

•

Mood disorders with psychosis: indistinguishable from schizophrenia cross-sectionally, but have a longitudinal course that includes full recovery.

•

Delusional disorder: has nonbizarre delusions and lacks the thought disturbance, hallucinations, and negative symptoms of schizophrenia.

•

Autism in the adult: has an early age at onset and lacks significant hallucinations or delusions.

WORKUP

•

History and physical examination to aid in determining if psychosis is secondary or primary

•

Neurologic examination to uncover soft neurologic signs (clumsy, cortical thumb, loss of fine motor movements) common in schizophrenia

LABORATORY TESTS

•

No laboratory tests are specific for schizophrenia.

•

Laboratory examinations (chemistry profile, blood count, sedimentation rate, toxicology screen, and urinalysis) are geared toward excluding a primary medical condition.

IMAGING STUDIES

•

CT scan or MRI of brain during initial workup; repeated if the course of the illness varies from expected

•

Sometimes EEG to reveal slowing when psychosis is secondary to an encephalopathy

•

Chest x-ray examination during initial workup to rule out a primary medical condition

TREATMENT NONPHARMACOLOGIC THERAPY

•

Significant social support is required by most schizophrenic patients; available support services are grossly inadequate, and schizophrenia patients constitute nearly one third of all homeless individuals. They usually require help with basic social, occupational, and interactive skills.

•

For schizophrenic patients who continue to live with their families, family stress can precipitate relapse and rehospitalization; family interventions can reduce morbidity.

•

Cognitive behavioral therapy can reduce severity of both psychotic and negative symptoms.

•

Illness management training for patients can increase medication adherence and reduce distress due to symptoms.

•

Integrated treatment of assertive community treatment, family involvement programs, and social skills training reduces severity of both psychotic and negative symptoms, reduces comorbid substance misuse, reduces hospital days, increases adherence to treatment, and increases satisfaction with treatment.

ACUTE GENERAL Rx

•

Acute psychosis is usually adequately controlled by antipsychotic agents.

•

Mainstay of therapy is the second-generation antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and clozapine). Traditional neuroleptic (e.g., haloperidol, perphenazine, fluphenazine, chlorpromazine) use is decreasing in part because of their propensity to cause a parkinsonian state and eventual tardive dyskinesia (rate of tardive dyskinesia 15% to 30%). Antiparkinsonian drugs (benztropine, amantadine) are used to ameliorate the parkinsonism. Risperidone has been shown to be superior to haloperidol in preventing acute psychotic relapse.

•

Sedatives (benzodiazepines, and to a lesser degree, barbiturates) can be used transiently if there is an agitated state.

CHRONIC Rx

•

Relapse prevention is a major goal of treatment. Noncompliance is common and leads to high relapse rates. Antipsychotic agents usually must be continued at the same doses that controlled psychosis. For noncompliant patients, depot preparations that are given biweekly or monthly can be used.

•

Most patients frequently switch between antipsychotics; fewer patients discontinue olanzapine compared to other second-generation antipsychotics for all causes, lack of efficacy, or by patient choice.

•

Neurocognitive improvement associated with antipsychotic treatment in patients with schizophrenia is small and does not differ between first-generation and second-generation antipsychotics.

•

Antiparkinsonian agents may also need to be continued chronically.

•

Tardive dyskinesia (choreoathetoid movements of the muscles of tongue, face, and occasionally other muscle groups) can occur in as many as 30% of patients with long-term use of the neuroleptics.

•

The negative symptoms of schizophrenia can resemble depression. In addition, depressive disorders may occur in schizophrenic patients. Antidepressant treatment of the negative symptoms is usually without effect. However, antidepressants can improve the symptoms of a discrete comorbid depressive episode.

•

Mood stabilizers, such as lithium, valproate, or carbamazepine, are of little use unless there is a comorbid impulse control disorder.

•

Substance abuse is a major problem in more than one third of schizophrenics. Unfortunately, these patients do poorly in traditional substance abuse treatment programs. Specialized “dual diagnosis” programs with highly structured aftercare are required.

•

Specific antipsychotics have been associated with weight gain (olanzapine and clozapine) and QT prolongation. Hyperlipidemia and diabetes mellitus are associated with second-generation antipsychotics, and hyperprolactinemia is associated with first-generation antipsychotics. Clozapine is associated with agranulocytosis.

DISPOSITION

•

The positive symptoms of as many as 20% to 30% of schizophrenic patients do not respond to available treatments. A much higher fraction relapse as a result of poor compliance.

•

The negative symptoms are responsible for the 50% to 70% of cases in which deterioration in occupational and social function continues.

•

Approximately 10% of patients will complete suicide.

•

Course of illness most strongly predicted by level of social development attained at onset of psychosis.

REFERRAL

•

If hospitalization is required

•

If patient is noncompliant

•

If patient is resistant to treatment

PEARLS & CONSIDERATIONS

•

Rule out delirium due to medical condition, medicine, or substance abuse before diagnosing psychotic behavior as schizophrenia.

•

All antipsychotics have high discontinuation rates in chronic schizophrenia treatment. Olanzapine and clozapine may be more effective than other antipsychotics for chronic treatment but have significant side effects.

•

Significant social support is required by most patients with schizophrenia, and nonpharmacologic therapy should be used in conjunction with pharmacotherapy.

EVIDENCE

Typical antipsychotic drugs Typical antipsychotic drugs, such as chlorpromazine and haloperidol, are effective in the management of schizophrenia, although they have high rates of adverse effects, which may limit their acceptability. [17] [18]

Atypical antipsychotic drugs Atypical antipsychotic drugs, such as clozapine, olanzapine, and risperidone, are in general at least as effective as the typical agents and tend to have fewer extrapyramidal side effects, which may improve acceptability.[[3]] Cognitive behavioral therapy (CBT) CBT plus standard care has significant beneficial effects on discharge from hospital, as well on improvement in mental state at 13 to 26 weeks compared with standard care alone; the effects on mental state are not apparent by 52 weeks. [[4]] Family therapy Multiple session family interventions are effective in reducing relapse rates at 12 months compared with

single session, psychoeducational intervention and usual care practices.[[5]] Social skills training Social skills training reduces relapse rates at 24 months, but not at 12 months, compared with standard or psychoeducational care.[[6]]

Evidence-Based Referenceces 1. Adams CE, et al: Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev 2007; 2: 2. Joy CB, Adams CE, Lawrie SM: Haloperidol versus placebo for schizophrenia. Cochrane Database Syst Rev 2001; 2: 3. Leucht S, et al: Relapse prevention in schizophrenia with new generation antipsychotics: a systematic review, and exploratory meta-analysis of randomized, controlled trials. Am J Psychiatry 2003; 160:1209-1222.Reviewed in: Evid Based Ment Health 7, 2004. 4. Jones C, et al: Cognitive behaviour therapy for schizophrenia. Cochrane Database Syst Rev 2004; 4: 5. Pilling S, et al: Psychological treatments in schizophrenia: I. Meta-analysis of family interventions and cognitive behaviour therapy. Psychol Med 2002; 32:763.Reviewed in: Clin Evid 12:1500, 2004. 6. Pilling S, et al: Psychological treatments in schizophrenia: II. Meta-analysis of randomised controlled trials of social skills training and cognitive remediation. Psychol Med 2002; 32:783.Reviewed in: Clin Evid 12:1500, 2004.

SUGGESTED READINGS Lieberman JA, et al: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209. Mueser KT, McGurk SR: Schizophrenia. Lancet 2004; 363:2063. Petersen L, et al: A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005; 331:602. Picchioni MM, Murray RM: Schizophrenia. BMJ 2007; 335:91.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Scleritis MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

Scleritis is inflammation of the sclera. SYNONYMS

Anterior scleritis Diffuse nodular, necrotizing scleritis Scleromalacia perforans Scleral melt syndrome

ICD-9CM CODES

379.0 Scleritis and episcleritis EPIDEMIOLOGY & DEMOGRAPHICS

PEAK INCIDENCE: Increases with increasing age INCIDENCE (IN U.S.): Busy ophthalmologist may see 1 or 2 cases a year PREVALENCE (IN U.S.): Relatively rare PREDOMINANT SEX: 61% women PREDOMINANT AGE: 52 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Deep, boring eye pain

•

Photophobia

•

Tearing

•

Conjunctival injection ( Fig. 1-241 )

•

Thinning of the sclera

•

44% of patients have associated medical conditions: 7% infections, 37% rheumatic disease. Most common infection is Herpes zoster. Most common rheumatic problem is rheumatoid arthritis. 4% have systemic vasculitis. Most patients with systemic disease are diagnosed before development of scleritis

FIGURE 1-241 In diffuse anterior scleritis, widespread injection of the conjunctival and deep episcleral vessels occurs. (From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY

•

Inflammatory

•

Allergic

•

Toxic

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Most common causes are rheumatoid arthritis and other collagen-vascular disease.

•

Occasionally, there are allergic, infectious, or traumatic causes.

•

Conjunctivitis, iritis, and episcleritis should be considered in the differential diagnosis.

WORKUP

•

Fluorescein angiography

•

Eye examination

•

Visual field examination

•

Workup for autoimmune disease

•

Workup for vasculitis

•

Collagen vascular workup

LABORATORY TESTS

•

RF, ANA, ESR may be useful

•

For underlying etiology

IMAGING STUDIES

Usually not necessary; CT scan of orbit may be useful in selected patients for collagen vascular disease or vasculitis

TREATMENT NONPHARMACOLOGIC THERAPY

•

Bandage lenses

•

Surgery if thinning of the sclera is severe to prevent eye rupture

ACUTE GENERAL Rx

Immunotherapy (with steroids and Imuran, etc.): •

Steroids (topical, periocular, and systemic)

•

Cycloplegic drops

•

NSAIDs (topical and systemic); systemic more effective than topical

•

Other immunosuppressive drugs

CHRONIC Rx

•

Systemic steroids can be given for the underlying disease.

•

Local steroids may be helpful.

•

Control underlying disease.

DISPOSITION

Urgent referral to ophthalmologist

REFERRAL

If not referred to an ophthalmologist early, patients may develop uveitis and other complications.

PEARLS & CONSIDERATIONS COMMENTS

An ominous diagnosis because these patients often have other severe underlying debilitating disease processes. SUGGESTED READINGS Akpek EK, et al: Evaluation of patients with scleritis for systemic disease. Ophthalmology 2004; 111(3):501. Paresio CG, et al: Systemic disorders associated with episcleritis and scleritis. Curr Opin Ophthalmal 2001; 12(6):471. Sainz de la Maza M, et al: Ocular characteristics and disease associations in scleritis: associated peripheral keatopathy. Arch Ophth 2002; 120(1):15. Thorne JE, et al: Severe scleritis and urticarial lesions. Am J Ophthalmol 2002; 134(6):932.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Scleroderma (Progressive Systemic Sclerosis) FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Scleroderma is a connective tissue disorder characterized by thickening and fibrosis of the skin and variably severe involvement of diverse internal organs. SYNONYMS

Systemic sclerosis; morphea applies to localized scleroderma affecting only the skin. Scleredema is a disease of the skin distinct from scleroderma.

ICD-9CM CODES

710.1 (Morphea: 701.0) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 4 to 12 cases/million persons per year, but many mild cases go unrecognized PREDOMINANT SEX: Female:male ratio of 4:1 PREDOMINANT AGE: 30 to 50 yr DISTRIBUTION: Worldwide PHYSICAL FINDINGS & CLINICAL PRESENTATION

PHYSICAL FINDINGS: Skin

•

Begins on hands, then face; skin is shiny, taut, sometimes red with loss of creases and hair

•

Later skin tightening may limit movement

•

Pigmentary changes occur

•

Skin atrophy occurs in late stages

Musculoskeletal •

Symmetric inflammatory arthritis

•

Myopathy

GI involvement •

Esophageal dysmotility with heartburn, dysphagia, odynophagia

•

Delayed gastric emptying

•

Small bowel dysmotility with abdominal cramps and diarrhea

•

Colon dysmotility with constipation

•

Primary biliary cirrhosis (see “Cirrhosis, Primary Biliary” in Section I)

Pulmonary manifestations •

Pulmonary fibrosis with symptoms of dyspnea and nonproductive cough and fine inspiratory crackles on examination

•

Pulmonary hypertension

Cardiac involvement •

Myocardial fibrosis leading to congestive heart failure

Renal involvement •

Malignant hypertension

•

Rapidly progressive renal failure

Other organ involvement •

Hypothyroidism

•

Erectile dysfunction

•

Sjögren's syndrome

•

Entrapment neuropathies

CREST syndrome •

Calcinosis, Raynaud's syndrome, esophageal dysmotility, sclerodactyly, telangiectasias (in CREST scleroderma is limited to distal extremities)

CLINICAL PRESENTATION: •

Raynaud's phenomenon: initial complaint in 70% (note: The prevalence of Raynaud's is 5% to 10% of the general population; most do not progress to scleroderma)

•

Finger or hand swelling, sometimes associated with carpal tunnel syndrome

•

Arthralgias/arthritis

•

Internal organ involvement

ETIOLOGY

Etiology is unknown. Stimulatory autoantibodies against platelet-derived growth factor (PDGF) appear to be a specific hallmark of scleroderma. Their biologic activity on fibroblasts suggests that they have a causal role in the pathogenesis of the disease. In scleroderma, unifying features exist in spite of heterogenous patterns of organ involvement and disease progression:

•

Extracellular connective tissue activation

•

Frequent immunologic abnormalities

•

Inflammation

•

Vasoconstriction

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Dermatologic •

Mycosis fungoides

•

Amyloidosis

•

Porphyria cutanea tarda

•

Eosinophilic fasciitis

•

Reflex sympathetic dystrophy

Systemic

•

Idiopathic pulmonary fibrosis

•

Primary pulmonary hypertension

•

Primary biliary cirrhosis

•

Cardiomyopathies

•

GI dysmotility problems

•

SLE and overlap syndromes

WORKUP

Laboratory tests and imaging studies LABORATORY TESTS

•

Antinuclear antibodies (homogeneous, speckled, or nucleolar patterns)

•

Negative antibody to native DNA

•

Negative anti-Sm antibody

•

Anti-nRNP positive in 20%

•

Rheumatoid factor positive in 30%

•

Anticentromere antibodies in fewer than 10% with systemic illness and in 50% to 95% with limited scleroderma (i.e., good prognosis if positive)

•

Positive extractable nuclear antibody to SCL 70 in 30%

•

Routine biochemistry tests may indicate specific organ involvement (e.g., liver, kidney, muscle)

IMAGING AND OTHER STUDIES

Arthritis: joint x-rays

GI

•

Barium swallow

•

Cine esophagography

•

Endoscopy

•

Esophageal manometry

Pulmonary •

Chest x-ray

•

PFTs

•

Chest CT scan

•

Bronchoscopy with biopsy

•

Gallium lung scan

•

Bronchoalveolar lavage

Heart •

ECG

•

Ambulatory (Holter) ECG monitoring

•

Echocardiography

•

Cardiac catheterization

Kidney: renal biopsy Skin: skin biopsy

TREATMENT D-penicillamine; recombinant human relaxin; supportive therapies used. Raynaud's syndrome: •

Calcium channel blockers

•

Peripheral a1-adrenergic blockers

Arthralgias: NSAIDs Skin: moisturizing agents Esophageal reflux

•

H2-receptor blockers

•

Proton pump inhibitors

Pulmonary hypertension and fibrosis •

Oxygen

•

Lung transplant

•

Cyclophosphamide chemotherapy in symptomatic scleroderma-related interstitial lung disease

Renal involvement •

Angiotensin-converting enzyme inhibitors

•

Dialysis

•

Renal transplantation

REFERRAL

To rheumatologist SUGGESTED READINGS Baron SS, et al: SS et al: Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 2006; 354:2667. Pope JE, et al: A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 2001; 44(6):1351. Seibold JR, Koan JH, Simms R, et al: Recombinant human relaxin in the treatment of scleroderma. Ann Intern Med 2000; 132:871. Tashkin DP, et al: Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354:2655. Thompson AE, et al: Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis. Arthritis Rheum 2001; 44(8):1841.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Scoliosis LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Scoliosis is a lateral curvature of the spine in the upright position, usually 10 degrees or greater. Scoliosis may be classified as either structural (fixed, nonflexible) or nonstructural (flexible, correctable).

ICD-9CM CODES

737.30 Idiopathic scoliosis 737.39 Paralytic scoliosis 754.2

Congenital scoliosis

724.3

Sciatic scoliosis

737.43 Associated with neurofibromatosis EPIDEMIOLOGY & DEMOGRAPHICS (IDIOPATHIC FORM)

PREDOMINANT SEX: Females > males (7:1) PREVALENCE: 4 cases/1000 persons PREDOMINANT AGE:

•

Onset is variable.

•

Most curves are found in adolescents (age 11 yr and over).

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Record patient age (in years plus months) and height.

•

Perform neurologic examination to rule out neuromuscular disease.

•

Inspect the shoulders and iliac crests to determine if they are level.

•

Palpate the spinous processes to determine their alignment.

•

Have the patient bend forward symmetrically at the waist with the arms hanging free (Adams' position); observe from the back or front to detect abnormal spine rotation ( Fig. 1-242 ).

FIGURE 1-242 Structural changes in idiopathic scoliosis. A, As curvature increases, alterations in body configuration develop in both the primary and compensatory curve regions. B, Asymmetry of shoulder height, waistline, and the elbow-to-flank distance are common findings. C, Vertebral rotation and associated posterior displacement of the ribs on the convex side of the curve are responsible for the characteristic deformity of the chest wall in scoliosis patients. D, In the school screening examination for scoliosis, the patient bends forward at the waist. Rib asymmetry of even a small degree is obvious. (From Scoles PV: Spinal deformity in childhood and adolescence. In Behrman RE, Vaughn VC III [eds]: Nelson textbook of pediatrics, ed 5, Philadelphia, 1989, WB Saunders.)

ETIOLOGY

•

90% unknown, usually referred to as idiopathic (genetic)

•

Congenital spine deformity

•

Neuromuscular disease

•

Leg length inequality

•

Local inflammation or infection

•

Acute pain (disc disease)

•

Chronic degenerative disc disease with asymmetric disc narrowing

Curves of an idiopathic nature or those accompanying congenital deformity or neuromuscular disease are those associated with structural changes. The nonstructural types (leg length discrepancy, inflammation, or acute pain) disappear when the offending disorder is corrected.

DIAGNOSIS WORKUP

•

Curvatures associated with congenital spine abnormalities, neuromuscular disease, and the other less common forms of scoliosis can usually be identified by history or associated radiographic or physical findings.

•

Section III, “Scoliosis,” describes an approach to scoliosis screening.

IMAGING STUDIES

•

Diagnosis of idiopathic scoliosis is confirmed by a standing roentgenogram of the spine.

•

Severity of the curve is measured in degrees, usually by the Cobb method.

•

MRI is usually not indicated unless there is: (1) pain, (2) a neurologic deficit, or (3) a left thoracic curve (which is often associated with an underlying spinal disorder).

TREATMENT ACUTE GENERAL Rx

•

Treatment or correction of cause if curve is nonstructural

•

Early detection is key in treating genetic curve

•

Regular observation for curves < 20 degrees

•

Bracing for idiopathic curves of 20 to 40 degrees to prevent progression

•

Surgery for idiopathic curves > 40 to 50 degrees in immature patient

DISPOSITION

•

The larger the curve at detection, the greater the chance of progression.

•

Progression is more common in young children who are beginning their growth spurt.

•

Curves in females are more likely to progress.

•

Curves < 20 degrees will improve spontaneously more than 50% of the time.

•

Failure to diagnose and treat these curves may allow progressive deformity, pain, and cardiopulmonary compromise to develop.

•

Spinal deformities > 50 degrees in adults may progress and eventually become painful.

•

There is no difference in the rate of back pain in the general population and patients with adolescent idiopathic scoliosis.

REFERRAL

For orthopedic consultation if structural curve is present

PEARLS & CONSIDERATIONS COMMENTS

•

Congenital scoliosis has a high incidence of cardiac and urinary tract abnormalities.

•

Bracing is not intended to completely straighten the idiopathic curve. It may improve the curvature but is mainly used to stabilize and prevent progression.

SUGGESTED READINGS Davids JR, Chamberlin E, Blackhurst DW: Indications for magnetic resonance imaging in presumed adolescent idiopathic scoliosis. J Bone Joint Surg 2004; 86A:2187. Fernandes P, Weinstein SL: Natural history of early onset scoliosis. J Bone Joint Surg 2007; 89A(suppl 1):21. Gillingham BL, et al: Early onset idiopathic scoliosis. J Am Acad Orthop Surg 2006; 14:101.

Lenke LG, Dobbs MB: Management of juvenile idiopathic scoliosis. J Bone Joint Surg 2007; 89A(suppl 1):55. McCarthy JJ, et al: Scoliosis in the child with cerebral palsy. J Am Acad Orthop Surg 2006; 14:367. Richards BS, Vitale MG: Screening for idiopathic scoliosis in adolescents. J Bone Joint Surg 2008; 90A:195. Sanders JO, et al: Predicting scoliosis progression from skeletal maturity: a simplified classification during adolescence. J Bone Joint Surg Am 2008; 90:540. Ugwonali OF, et al: Effect of bracing on the quality of life of adolescents with idiopathic scoliosis. Spine J 2004; 4:254.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Seasonal Affective Disorder MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Recurrent depressive episodes during autumn and winter alternating with nondepressive episodes during spring and summer. Patients with the disorder have experienced two episodes of major depression in the last 2 yr that demonstrate temporal seasonal relationships and there have been no nonseasonal episodes over this time period. SYNONYMS

Seasonal depression Winter depression Wintertime blues

ICD-9CM CODES

296.30 Seasonal affective disorder EPIDEMIOLOGY & DEMOGRAPHICS

•

Climate, genetic vulnerability, and social-cultural factors all play a role. The risk of seasonal mood swings is clearly associated with northern latitudes. The prevalence of seasonal affective disorder (SAD) is estimated to be 0.5% to 1.5% in northern European populations, and 10% to 20% of these populations report milder, recurrent episodes consistent with subsyndromal SAD.

•

As with other depressive disorders, women are affected disproportionate to men.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The symptoms of SAD are similar to those of other depressive episodes, but tend to include those features associated with an atypical major depression, including low energy, irritability, weight gain, and overeating.

•

The average duration of symptoms is 5 mo, generally commencing in November.

ETIOLOGY

•

Explanations for SAD tend to focus on biologic models. The shorter photoperiod and decrease in sunlight exposure experienced by people living in temperate and higher latitudes during the winter is hypothesized to be the main trigger for SAD.

•

Several neurotransmitters have been implicated in SAD, including dopamine, serotonin, and norepinephrine. Current research is focused on the role of serotonin in the mediation of seasonal affective changes.

DIAGNOSIS Diagnostic workup similar to that for major depression but with focus on the seasonal nature of the symptoms. DIFFERENTIAL DIAGNOSIS

•

Depressive disorders

•

Bipolar affective disorder

•

Evaluate for substance use (especially alcohol)

•

Medical illness or medications that may contribute to depression (e.g., endocrine or neurologic disorders)

WORKUP

•

As with major depression, consider medical etiologies and rule out as indicated by the presenting signs and symptoms.

•

Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version (SIGH-SAD) used in research settings.

LABORATORY TESTS

As directed by presenting complaints IMAGING STUDIES

Generally not indicated

TREATMENT NONPHARMACOLOGIC THERAPY

•

Phototherapy is based on the principle that the presentation of artificial light at a similar strength to natural sunlight will prevent the biologic changes that mediate SAD during the winter.

•

There have been at least 20 randomized trials comparing light treatment with placebo in the treatment of SAD. Some of these trials have found a benefit; others have been unable to demonstrate a benefit over placebo.

•

Phototherapy for SAD tends to use 2500 to 10,000 lux delivered via a commercial light box or a portable head-mounted unit. Phototherapy is recommended to commence within 2 wk of the start of symptoms and to continue through the winter months. Patients are instructed to sit approximately 18 inches away from the light box for 30 min up to several hours once or twice per day for a minimum of 1 wk.

•

One study suggests that cognitive-behavioral therapy plus light therapy may improve short-term remission rates over light therapy alone.

ACUTE GENERAL Rx

None necessary unless patient is suicidal. CHRONIC Rx

There is some evidence from randomized trials to support the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of SAD. DISPOSITION

Psychiatric referral may be helpful to confirm diagnosis. Recommended for high-risk and suicidal patients. REFERRAL

For active suicidal ideation, psychosis, symptoms suggestive of bipolar disorder

PEARLS & CONSIDERATIONS Patients with SAD may present with a complaint of overeating, particularly food high in carbohydrates.

EVIDENCE

Light Therapy (Phototherapy) A small randomized controlled trial compared light-box treatment with dawn simulation in patients with winter depression. Improvement in symptoms was noted in both groups, but there was significantly greater improvement in the light-box group. The majority of patients in both treatment groups maintained improvement at 9-week follow-up.[[1]] SSRIs A randomized controlled trial compared fluoxetine with placebo over 5 weeks in patients with SAD. The rate of clinical response (> 50% reduction in depression score between baseline and study termination) was greater in the fluoxetine group.[[2]]

Evidence-Based Referenceces 1. Lingjaerde O, et al: Dawn simulation vs. lightbox treatment in winter depression: a comparative study. Acta Psychiatr Scand 1998; 98:73. 2. Lam RW, et al: Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Am J Psychiatry 1995; 152:1765.

SUGGESTED READINGS Glickman G, et al: Light therapy for seasonal affective disorder with blue narrow-band light-emitting diodes (LEDs). Biol Psychiatry 2006; 59(6):502. Lam RW, et al: The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Am J Psychiatry 2006; 163(5):805. Rohan KJ, et al: A randomized controlled trial of cognitive-behavioral therapy, light therapy, and their combination for seasonal affective disorder. J Consult Clin Psychol 2007; 75(3):489.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Seizures, Absence JOHN E. CROOM, M.D., PH.D., SUZETTE LAROCHE, M.D.

BASIC INFORMATION DEFINITION

Absence seizures are a common type of generalized onset seizure characterized by brief episodes of loss of awareness (typically 10 to 15 seconds) followed by abrupt return to full consciousness. They are associated with a classic EEG pattern of 3 Hz generalized spike and slow wave discharges. SYNONYMS

Petit mal seizures (obsolete) Childhood absence epilepsy

ICD-9CM CODES

345.0 Generalized nonconvulsive epilepsy EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 11 cases/100,000 persons from ages 3 to 10 yr, rare after age 14 yr PEAK INCIDENCE: 6 to 7 yr PREVALENCE (IN U.S.): Accounts for 2% to 15% of the cases of childhood epilepsy PREDOMINANT AGE: 4 to 8 yr but can persist into adulthood GENETICS: Clear genetic predisposition; undetermined mode of inheritance PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Findings are normal between seizures in children with typical absence epilepsy.

•

During the seizure, patients typically appear awake but have sudden behavioral arrest typically lasting less than 30 seconds followed by immediate resumption of activity.

•

There may be associated automatisms and therefore can be mistaken for complex partial seizures.

•

Tonic-clonic seizures can occur in approximately 40% of patients.

ETIOLOGY

•

Idiopathic with a presumed genetic cause

•

Absence seizures are most commonly seen in childhood absence epilepsy with onset between age 4 and 8 but can also be seen with other idiopathic generalized epilepsy syndromes such as juvenile absence epilepsy or juvenile myoclonic epilepsy where onset is later, generalized tonic-clonic seizures are more common, and seizures are less likely to spontaneously resolve with age.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Complex partial seizures

•

Daydreaming

•

Psychogenic unresponsiveness

WORKUP

•

EEG is the most powerful tool for identification of this seizure type.

•

In the vast majority of untreated individuals, vigorous hyperventilation for 3-5 min will provoke a typical absence seizure.

IMAGING STUDIES

None needed for typical presentation

TREATMENT NONPHARMACOLOGIC THERAPY

Avoid sleep deprivation and hyperventilation. ACUTE GENERAL Rx

Not indicated for individual typical seizures CHRONIC Rx

•

Drug of choice is ethosuximide or valproate.

•

Ethosuximide does not suppress tonic-clonic seizures. Thus, valproate is the drug of choice for patients with absence and tonic clonic seizures.

•

In patients with child-bearing potential, valproate should be used with caution due to the high risk of teratogenicity.

•

The initial dose of ethosuximide in children is 10 to 15 mg/kg/day with maintenance dose of 15 to 40 mg/kg/day divided into a bid or tid dosing schedule. Can result in gastrointestinal side-effects so may be best to take with meals.

•

Common pediatric doses for valproate are 15 to 60 mg/kg/day (bid-qid). Can result in hepatotoxity and blood dyscrasias.

•

Lamotrigine has been shown to be effective, but is not FDA approved for the treatment of absence seizures.

•

Because most patients will have spontaneous resolution of their seizures, one can consider withdrawing anticonvulsant therapy when the patient has been seizure-free for at least 2 yr and EEG is normal.

DISPOSITION

•

Favorable prognosis in typical childhood absence epilepsy without other seizure types

•

Excellent response to medication

•

Subsidence of seizures with advancing age in 70% to 90% of patients

REFERRAL

If uncertain about diagnosis or treatment

PEARLS & CONSIDERATIONS COMMENTS

•

Absence seizures may be mistakenly diagnosed as complex partial seizures based on clinical descriptions. The EEG is essential for making this distinction.

•

Administering other anticonvulsants (particularly carbamazepine or phenytoin) to patients with typical absence epilepsy may exacerbate seizures.

•

Patient education information can be obtained from the Epilepsy Foundation, 4351 Garden City Drive, Landover, MD 20785; phone: (800) 332-1000, web address: www.epilepsyfoundation.org .

EVIDENCE

A systematic review assessing the efficacy of valproate, ethosuximide, and lamotrigine in the treatment of absence seizures in children and adolescents found insufficient evidence to guide clinical practice due to the poor methodological quality of the included trials.[[1]] A more recent review found lamotrigine to be effective for newly diagnosed absence seizures in children.[[2]]

Evidence-Based Referenceces 1. Posner EB, Mohamed K, Marson AG: Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev 2003; 3: 2. French JA, et al: Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy. Neurology 2004; 62:1252.

SUGGESTED READINGS Bourgeois BF: Chronic management of seizures in the syndromes of idiopathic generalized epilepsy. Epilepsia 2003; 44(2):27. Mattson RH: Overview: idiopathic generalized epilepsies. Epilepsia 2003; 44(2):2. Panayiotopoulos CP: Treatment of typical absence seizures and related epileptic syndromes. Paediatr Drugs 2001; 3(5):379.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Seizures, Febrile JOHN E. CROOM, M.D., PH.D., SUZETTE LAROCHE, M.D.

BASIC INFORMATION DEFINITION

A febrile seizure is a seizure in infancy or childhood, usually occurring between 6 mo and 5 yr of age, associated with fever but without evidence of intracranial infection or defined cause. SYNONYMS

Benign febrile seizure Febrile convulsions

ICD-9CM CODES

780.3 Convulsions EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Not reported PREVALENCE (IN U.S.): 2% to 4% in children 65 yr of age account for 60% of all cases of severe sepsis

GENETICS: Familial Disposition: A great variety of congenital immunodeficiency states and other inherited disorders may predispose to septicemia. Neonatal Infection: Incidence is high in neonatal period. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Fever or hypothermia

•

Hypotension

•

Tachycardia

•

Tachypnea

•

Altered mental status

•

Bleeding diathesis

•

Skin rashes

•

Symptoms that reflect primary site of infection: urinary tract, GI tract, CNS, respiratory tract

ETIOLOGY

•

Disseminated infection with a great variety of bacteria: A.

B.

•

•

Gram-negative bacteria 1.

E. coli

2.

Klebsiella spp.

3.

Pseudomonas aeruginosa

4.

Proteus spp.

5.

Neisseria meningitidis

Gram-positive bacteria 1.

Staphylococcus aureus

2.

Streptococcus spp.

3.

Enterococcus spp.

Less common infections: 1.

Fungal

2.

Viral

3.

Rickettsial

4.

Parasitic

Activation of coagulation, inflammatory cytokines, complement, and kinin cascades with release of a variety of vasoactive endogenous mediators

•

Predisposing host factors: 1.

General medical condition

2.

Age

3.

Immunosuppressive therapy

4.

Recent surgery

5.

Granulocytopenia

6.

Hyposplenism

7.

Diabetes

8.

Instrumentation

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Cardiogenic shock

•

Acute pancreatitis

•

Pulmonary embolism

•

Systemic vasculitis

•

Toxic ingestion

•

Exposure-induced hypothermia

•

Fulminant hepatic failure

•

Collagen-vascular diseases

WORKUP

•

Evaluation should focus on identifying a specific pathogen and localizing the site of primary infection.

•

Hemodynamic, metabolic, coagulation disorders should be carefully characterized.

•

Intensive monitoring, including the use of central venous or Swan-Ganz catheters, may be necessary.

LABORATORY TESTS

•

Cultures of blood and examination and culture of sputum, urine, wound drainage, stool, CSF

•

CBC with differential, coagulation profile

•

Routine chemistries, LFTs

•

ABGs, lactic acid level; Procalcitonin might be useful as a general marker of infection/sepsis

•

Urinalysis

IMAGING STUDIES

•

Chest x-ray examination

•

Other radiographic and radioisotope procedures according to suspected site of primary infection

TREATMENT NONPHARMACOLOGIC THERAPY

•

Tissue oxygenation: mixed venous oxygen saturation maintained >70% if possible; early mechanical ventilation

•

Focal infection drained, if possible

ACUTE GENERAL Rx

•

•

Blood pressure support, rapid intravenous fluid resuscitation and vasopressors, if needed, with the goal of reestablishing a mean arterial blood pressure >65 mmHg; reduction in blood lactate and mixed venous oxygen saturation >70% within 6 hr of recognition of septic shock is associated with improved survival 1.

IV hydration; crystalloids are as effective as colloids as resuscitation fluids

2.

Therapy with pressors (e.g., dopamine, norepinephrine, vasopressin) if mean blood pressure of 70 to 75 mm Hg cannot be maintained by hydration alone

Correction of acidosis by improving the tissue perfusion, not by giving bicarbonate 1.

•

Mechanical ventilation

Antibiotics 1.

Directed at the most likely sources of infection

2.

Should generally provide broad coverage of gram-positive and gram-negative bacteria (or fungi if clinically indicated)

3.

Typical regimens: a.

For hospital-acquired sepsis (pending culture results): vancomycin plus cefepime, imipenem, aztreonam, quinolones, or an aminoglycoside. Monotherapy with appropriate agents appears to be as effective as combination therapy in immunocompetent hosts.

b.

For community-acquired infection in the absence of granulocytopenia: above or singledrug therapy with third-generation cephalosporin.

c.

For infection in the granulocytopenic host: above or dual gram-negative coverage (e.g., cephalosporin and aminoglycoside).

4.

Biological treatment Drotrecogin alfa (Xigris), a genetically engineered form of activated protein C, is approved for use in patients with severe sepsis with multiorgan dysfunction (or APACHE II score >24); when combined with conventional therapy, there may be a reduction in mortality.

5.

The role of corticosteroids in the acute management of septicemia has long been debated. Although most well-constructed clinical trials have demonstrated no benefit, recent data suggest that patients with relative adrenal insufficiency may benefit from low-dose therapy with hydrocortisone (50 mg IV q6h) and fludrocortisone (50 microgram daily PO) given together for 7 days. Recent data suggest that physiologic doses of corticosteroids with subsequent tapering may improve survival in some patients without proven adrenal insufficiency.

CHRONIC Rx

•

Adjust antibiotic therapy on the basis of culture results.

•

In general, continue therapy for a minimum of 2 wk.

DISPOSITION

All patients with suspected septicemia should be hospitalized and given access to intensive monitoring and nursing care. REFERRAL

•

To infectious diseases expert

•

To physician experienced in critical care

PEARLS & CONSIDERATIONS COMMENTS

Mortality rises quickly if antibiotic therapy is not instituted promptly and metabolic derangements are not treated aggressively.

EVIDENCE

A systematic review of 15 trials found corticosteroids did not change 28-day all-cause mortality or hospital mortality in patients with severe sepsis and septic shock. However, there was some evidence of reduction in intensive care unit mortality and an increase in the proportion of shock reversal by days 7 and 28.[[1]] A randomized controlled trial (RCT) compared low-dose corticosteroids (hydrocortisone and fludrocortisone) vs. placebo in patients with septic shock and relative adrenal insufficiency. There was a significantly lower risk of death over 28 days in the treatment group.[[2]] Early goal-directed therapy provides significant benefits in patients with septic shock. An RCT compared early goal-directed therapy (in which cardiac output was adjusted to balance oxygen delivery with oxygen demand) vs. standard therapy during the first 6 hr of ER admission in patients with septic shock. In-hospital mortality was significantly lower in the patients who received early goal-directed therapy, and during the period from 7 to 72 hr, these patients had more rapid hemodynamic and oxygenization improvement than standard care.[[3]]

Evidence-Based Referenceces 1. Annane D, et al: Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev 2004; 1: 2. Annane D, et al: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288:862. 3. Rivers E, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368.

SUGGESTED READINGS Calandra T, Cohen J: The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 2005; 33(7):1538.

Hackman DG, et al: Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet 2006; 367(9508):413. Johnson SB, et al: Gene expression profiles differentiate between sterile SIRS and early sepsis. Ann Surg 2007; 245(4):611. Uzzan B, et al: Procalcitonin as a diagnostic test for sepsis in critically ill patients and after surgery and trauma: a systemic review and meta-analysis. Crit Care Med 2006; 34(7):1996.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Serotonin Syndrome PURVA AGARWAL, M.D.

BASIC INFORMATION DEFINITION

Serotonin syndrome (SS) refers to a group of symptoms resulting from increased activity of serotonin (5hydroxytryptamine) in the central nervous system. Serotonin syndrome is a drug-induced disorder that is characterized by a change in mental status and alteration in neuromuscular activity and autonomic function. SYNONYMS

SS

ICD-9CM CODES

333.99 Syndrome serotonin EPIDEMIOLOGY & DEMOGRAPHICS

•

The incidence of serotonin syndrome is not known.

•

Serotonin syndrome is seen in all age groups, from neonates to elderly.

•

Serotonin syndrome commonly occurs in patients receiving two or more serotonergic drugs.

•

Concomitant use of a selective serotonin reuptake inhibitor (SSRI) with a monoamine oxidase inhibitor (MAOI) poses the greatest risk of developing SS.

•

Combination of SSRIs with other serotonergic drugs (e.g., tryptophan) or drugs with serotonin properties (e.g., lithium, meperidine) can also lead to SS.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Findings of clonus with hyperreflexia in the setting of recent (< 5 wk) use of serotonergic agents strongly suggests the diagnosis of serotonin syndrome.

•

Symptoms can manifest within minutes to hours after starting a new psychopharmacologic treatment or after administering a second serotonergic drug.

•

Clonus (inducible, spontaneous, and ocular) is the key finding in establishing a diagnosis of serotonin syndrome.

•

Other pertinent findings include: Confusion, agitation, hypomania Fever >38° C (100° F), tachycardia, and tachypnea Nausea, vomiting, abdominal pain, and diaphoresis Diarrhea, tremors, shivering, and seizures Hyperreflexia and muscle rigidity

ETIOLOGY

•

Hyperstimulation of the brainstem and spinal cord serotonin receptors because of blocking reuptake of serotonin and catecholamines leading to the neuromuscular and autonomic symptoms.

•

Psychopharmacologic drugs—in particular, fluoxetine and sertraline co-administered with MAOI (e.g., tranylcypromine and phenelzine)—have been cited in the literature as a common cause of SS.

DIAGNOSIS

•

The diagnosis of SS is made on clinical grounds. There are no specific laboratory tests for SS. A high index of suspicion along with a detailed medication history is the mainstay of diagnosis.

•

Diagnostic criteria: most accurate is Hunter Serotonin Toxicity Criteria (sensitivity 84%, specificity 97%).

•

To fulfill Hunter criteria a patient must have consumed a serotonergic drug and should have one of the following: 1.

Spontaneous clonus

2.

Inducible clonus plus agitation or diaphoresis

3.

Ocular clonus plus agitation or diaphoresis

4.

Tremor and hyperreflexia

5.

Temperature above 38° C (100° F) plus clonus or inducible clonus

DIFFERENTIAL DIAGNOSIS

•

Neuroleptic malignant syndrome (NMS), substance abuse (e.g., cocaine, amphetamines), thyroid storm, infection, alcohol and opioid withdrawal.

•

Classic features in differentiation of NMS vs. SS are that SS develops over 24 hr, involves neuromuscular hyperactivity, and begins to resolve within 24 hr with appropriate therapy, whereas NMS develops gradually over days to weeks, involves sluggish neuromuscular response, and resolves over an average period of 1 week to 10 days.

WORKUP

•

Because SS is a clinical diagnosis, there is no laboratory test that confirms the diagnosis and serum serotonin concentration does not correlate with clinical picture. Other causes are described in “Differential Diagnosis.” Thus, all patients should have blood tests and diagnostic imaging studies to rule out infectious, toxic, and metabolic etiologies.

•

Additional laboratory tests are performed to exclude complicating features of SS (e.g., renal failure secondary to rhabdomyolysis).

LABORATORY TESTS

•

CBC with differential to rule out sepsis

•

Electrolytes, BUN, and creatinine to rule out acidosis and renal failure

•

Blood and urine toxicology screen

•

Thyroid function tests

•

Creatine-phosphokinase (CPK) with isoenzymes

•

Urine and blood cultures

•

ECG because ventricular rhythm disturbance is a potentially fatal complication

IMAGING STUDIES

Imaging studies are not very specific in the diagnosis of SS and are only ordered to exclude other causes with similar clinical presentations as SS.

TREATMENT Once a diagnosis of SS is established, appropriate consultation with a medical toxicologist, clinical pharmacologist, and/or poison control center should be sought. Management includes: •

Discontinue use of all potential precipitating drugs

•

Provide supportive management

•

Control agitation

•

Administer serotonin antagonists

•

Control autonomic instability

•

Control hyperthermia

•

Reassess the need to resume the use of the serotonergic agent once the symptoms have resolved

NONPHARMACOLOGIC THERAPY

•

Discontinuation of the drug is the mainstay of therapy.

•

Treatment is supportive: maintaining oxygenation and blood pressure and monitoring respiratory status. Hypotensive patients may require both intravenous fluids and vasopressor therapy.

•

Patients who are severely hyperthermic with temperatures greater than 41° C (106° F) should be given intravenous sedation, paralyzed, and intubated. Cooling blankets can be used for patients with mildmoderate hyperthermia. There is no role of acetaminophen here.

•

Mechanical intubation is recommended for patients unable to protect their airways as a result of mental status changes or seizures.

ACUTE GENERAL Rx

•

•

Serotonin antagonists 1.

Cyproheptadine 4-mg tablet or 2 mg/5 ml syrup is given in 4- to 8-mg doses q1 to 4h (up to 32 mg for adults, 12 mg in children) until a therapeutic response is achieved.

2.

Atypical antipsychotic agents with serotonin antagonist properties (e.g., olanzapine 10 mg SL) have been tried with some success.

3.

Chlorpromazine 50 to 100 mg IM may be considered in severe cases.

Benzodiazepines 1.

Lorazepam 1 to 2 mg IV q30 min has been used effectively in treating agitation, muscle rigidity, myoclonus, and seizure complications.

2.

Diazepam is an alternative choice.

3.

Blood pressure management with short-acting agents such as esmolol and nitroprusside.

CHRONIC Rx

For patients not requiring hospital admission, cyproheptadine and lorazepam can be given in an oral dose on a prn basis with close follow-up. DISPOSITION

•

Serotonin syndrome is a potentially life-threatening condition if not recognized early.

•

Prompt diagnosis and withdrawal of the medication results in improvement of symptoms within 24 hr.

•

Seizures, rhabdomyolysis, hyperthermia, ventricular arrhythmia, respiratory arrest, and coma are all complicating features of SS.

REFERRAL

All cases of SS secondary to psychotropic medications should be referred to a psychiatrist. PREVENTION

Modify prescription practices by avoiding multidrug regimens.

PEARLS & CONSIDERATIONS The combined use of SSRIs and MAOIs is contraindicated.

COMMENTS

•

The use of SSRIs and other serotonergic agents is not an absolute contraindication; however, prompt withdrawal of the medication is recommended if any symptoms suggesting SS occur.

•

Serotonin syndrome is usually found in patients being treated for depression, bipolar disorders, obsessivecompulsive disorder, attention-deficit disorder, and Parkinson's disease.

SUGGESTED READINGS Boyer EW, Shannon M: The serotonin syndrome. N Engl J Med 2005; 352:1112-1120. Dunkley EJ, et al: The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003; 96:635.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Severe Acute Respiratory Syndrome FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Severe acute respiratory syndrome (SARS) is a respiratory illness caused by a coronavirus called SARSassociated coronavirus (SARS-CoV). CLINICAL CRITERIA: A.

Asymptomatic or mild respiratory illness

B.

Moderate respiratory illness

C.

1.

Temperature of >100.4° F (>38° C),[*] and

2.

One or more clinical findings of respiratory illness (e.g., cough, shortness of breath, difficulty breathing, or hypoxia)

Severe respiratory illness 1.

Temperature of >100.4° F (>38° C)[*], and

2.

One or more clinical findings of respiratory illness (e.g., cough, shortness of breath, difficulty breathing, or hypoxia), and a.

Radiographic evidence of pneumonia, or

b.

Respiratory distress syndrome, or

c.

Autopsy findings consistent with pneumonia or respiratory distress syndrome without an identifiable cause

EPIDEMIOLOGIC CRITERIA: •

Travel (including transit in an airport) within 10 days of onset of symptoms to an area with current or previously documented or suspected community transmission of SARS, or

•

Close contact[†] within 10 days of onset of symptoms with a person known or suspected to have SARS

•

The Chinese horseshoe bat, which is a healthy carrier of SARS, has been identified as the reservoir of the virus in nature. The spread of the virus was facilitated by people eating bats or using bat feces in traditional medicine for asthma, kidney ailments, and general malaise

Laboratory criteria

•

•

Confirmed 1.

Detection of antibody to SARS-associated coronavirus (SARS-CoV) in a serum sample, or

2.

Detection of SARS-CoV RNA by RT-PCR confirmed by a second PCR assay, by using a second aliquot of the specimen and a different set of PCR primers, or

3.

Isolation of SARS-CoV

Negative 1.

•

Absence of antibody to SARS-CoV in a convalescent-phase serum sample obtained >28 days after symptom onset[‡]

Undetermined 1.

Laboratory testing either not performed or incomplete

Case classification[§] •

Probable case: meets the clinical criteria for severe respiratory illness of unknown etiology and epidemiologic criteria for exposure; laboratory criteria confirmed or undetermined.

•

Suspect case: meets the clinical criteria for moderate respiratory illness of unknown etiology, and epidemiologic criteria for exposure; laboratory criteria confirmed or undetermined.

Exclusion criteria A case may be excluded as a suspect or probable SARS case if: •

An alternative diagnosis can fully explain the illness.[|]

•

The case has a convalescent-phase serum sample (i.e., obtained >28 days after symptom onset) that is negative for antibody to SARS-CoV.[‡]

•

The case was reported on the basis of contact with an index case that was subsequently excluded as a case of SARS, provided other possible epidemiologic exposure criteria are not present.

* A measured documented temperature of > 100.4° F (> 38° C) is preferred. However, clinical judgment should be used when evaluating patients for whom a measured temperature of > 100.4° F (> 38° C) has not been documented. Factors that might be considered include patient self-report of fever, use of antipyretics, presence of immunocompromising conditions or therapies, lack of access to health care, or inability to obtain a measured temperature. Reporting authorities should consider these factors when classifying patients who do not strictly meet the clinical criteria for this case definition. † Close contact is defined as having cared for or lived with a person known to have SARS or having a high likelihood of direct contact with respiratory secretions and/or body fluids of a patient known to have SARS. Examples of close contact include kissing or embracing, sharing eating or drinking utensils, close conversation (< 3 ft), physical examination, and any other direct physical contact between persons. Close contact does not include activities such as walking by a person or sitting across a waiting room or office for a brief period. ‡ The WHO has specified that the surveillance period for China should begin on November 1; the first recognized cases in Hong Kong, Singapore, and Hanoi (Vietnam) had onset in February 2003. The date for Toronto is linked to the occurrence of a laboratory confirmed case of SARS in a U.S. resident who had traveled to Toronto; the date for Taiwan is linked to CDC's issuance of travel recommendations. § The last date for illness onset is 10 days (i.e., one incubation period) after removal of a CDC travel alert. The case patient's travel should have occurred on or before the last date the travel alert was in place.Assays for the laboratory diagnosis of SARS-CoV infection include enzyme-linked immunosorbent assay, indirect fluorescent-antibody assay, and reverse transcription polymerase chain reaction (RT-PCR) assays of appropriately collected clinical specimens (Source: CDC. Guidelines for collection of specimens from potential cases of SARS. Available at http://www.cdc.gov/ncidod/sars/specimen_collection_sars2.htm

). Absence of SARS-CoV antibody from serum obtained < 28 days after illness

onset,‡ a negative PCR test, or a negative viral culture does not exclude SARS-CoV infection and is not considered a definitive laboratory result. In these instances, a convalescent serum sample obtained > 28 days after illness is needed to determine infection with SARS-CoV.‡ All SARS diagnostic assays are under evaluation.Asymptomatic SARS-CoV infection or clinical manifestations other than respiratory illness might be identified as more is learned about SARS-CoV infection.

| Factors that may be considered in assigning alternate diagnoses include the strength of the epidemiologic exposure criteria for SARS, the specificity of the diagnostic test, and the compatibility of the clinical presentation and course of illness for the alternative diagnosis. ‡ Does not apply to serum samples collected before July 11, 2003. Testing results from serum samples collected before July 11, 2003, and between 22 and 28 days after symptom onset are acceptable and will not require collection of an additional sample > 28 days after symptom onset.

SYNONYMS

SARS

ICD-9CM CODES Not available EPIDEMIOLOGY & DEMOGRAPHICS

•

The disease was first recognized in Asia in February 2003, and over the next several months spread to more than 2 dozen countries in North and South America, Europe, and Asia affecting more than 8000 patients and resulting in more than 750 deaths. In July 2003, cases were no longer being reported, and SARS outbreaks worldwide were considered contained.

•

Most reported cases of SARS in the United States were exposed through foreign travel to countries with community transmission of SARS, with only limited secondary spread to close contacts such as family members and health care workers.

•

Incubation period is 2 to 10 days.

•

Evidence of airborne transmission of the SARS virus and laboratory-acquired SARS has now been documented.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Early manifestations: fever, myalgias and headache. Fever is often high and associated with chills or rigors. Fever may be absent in elderly patients.

•

Dry nonproductive cough occurs within 2 to 4 days of onset of fever.

•

Diarrhea may occur in up to 25% of cases.

•

Dyspnea and hypoxemia follow the cough and may require intubation in nearly 20% of patients.

•

A biphasic course of illness may occur with initial improvement followed by subsequent deterioration in some patients.

ETIOLOGY

SARS-associated coronavirus

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Legionella pneumonia

•

Influenza A and B

•

Respiratory syncytial virus

•

Acute respiratory distress syndrome (ARDS)

WORKUP

•

Initial diagnostic testing for suspected SARS patients should include chest radiograph, pulse oximetry, blood cultures, sputum Gram's stain and culture, and testing for viral respiratory pathogens, notably influenza A and B and respiratory syncytial virus. A specimen for Legionella and pneumococcal urinary antigen testing should also be considered.

LABORATORY TESTS

When to test for SARS: •

In the absence of documented SARS transmission, diagnostic testing for SARS-associated coronavirus (SARS-CoV) should not be considered unless the clinician and health department have a high index of suspicion for SARS (e.g., a hospitalized pneumonia patient has a possible SARS exposure during travel and no other explanation for their pneumonia).

•

Respiratory specimens should be collected as soon as possible in the course of the illness. The likelihood of recovering most viruses diminishes markedly > 72 hours after symptom onset.

•

Three types of specimens may be collected for viral or bacterial isolation and PCR. These include (1) nasopharyngeal wash/aspirates, (2) nasopharyngeal swabs, or (3) oropharyngeal swabs. Nasopharyngeal aspirates are the specimen of choice for detection of respiratory viruses and are the preferred collection method among children aged < 2 yr.

•

Laboratory testing on initial evaluation should also include CBC with differential, platelet count, liver enzymes, LDH, and CPK. Common laboratory abnormalities in SARS include thrombocytopenia, lymphopenia, elevated LDH, and elevated CPK, ALT, AST.

IMAGING STUDIES

•

Chest x-ray: patchy focal infiltrates or consolidation with peripheral distribution.

•

Chest x-ray may be normal in up to 25% of patients.

•

Pleural effusions generally are not present.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Supportive care.

•

Nearly 25% of cases will require ventilator assistance.

•

Nutritional support.

ACUTE GENERAL Rx

•

There is no specific treatment currently available for SARS.

•

Broad-spectrum antibiotics (quinolone or macrolide) are generally started pending laboratory testing.

•

Use of corticosteroids (methylprednisolone 40 mg bid or doses up to 2 mg/kg/day) is controversial but may be beneficial in patients with significant hypoxemia and progressive pulmonary infiltrates.

•

In a preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was beneficial.

DISPOSITION

•

Case fatality rate is 3% to 12%.

•

Mortality rate is higher in elderly and immunocompromised patients and lower in pediatric age group.

REFERRAL

•

Infectious disease consultation and pulmonary consultation is recommended in all cases.

•

Notification of state Department of Health is mandatory.

PEARLS & CONSIDERATIONS COMMENTS

•

Persons who may have been exposed to SARS should be vigilant for fever (i.e., measure temperature twice daily) and respiratory symptoms over the 10 days after exposure. During this time, in the absence of both fever and respiratory symptoms, persons who may have been exposed to SARS patients need not limit their activities outside the home and should not be excluded from work, school, out-of-home child care, church, or other public areas.

•

Exposed persons should notify their health care provider immediately if fever or respiratory symptoms develop.

•

Symptomatic persons exposed to SARS should follow the following infection control precautions: 1.

If fever or respiratory symptoms develop, the person should limit interactions outside the home and not go to work, school, out-of-home child care, church, or other public areas. In addition, the person should use infection control precautions in the home to minimize the risk for transmission, and continue to measure temperature twice daily.

2.

If symptoms improve or resolve within 72 hr after first symptom onset, the person may be allowed, after consultation with local public health authorities, to return to work, school, out-ofhome child care, church, or other public areas, and infection control precautions can be discontinued.

3.

For persons who meet or progress to meet the case definition for suspected SARS (e.g., develop fever and respiratory symptoms), infection control precautions should be continued until 10 days after the resolution of fever, provided respiratory symptoms are absent or improving.

4.

If the illness does not progress to meet the case definition, but the individual has persistent fever or unresolving respiratory symptoms, infection control precautions should be continued for an additional 72 hr, at the end of which time a clinical evaluation should be performed. If the illness progresses to meet the case definition, infection control precautions should be continued as described earlier. If case definition criteria are not met, infection control precautions can be discontinued after consultation with local public health authorities and the evaluating clinician.

SUGGESTED READINGS

•

Persons who meet or progress to meet the case definition for suspected SARS (e.g., develop fever and respiratory symptoms) or whose illness does not meet the case definition, but who have persistent fever or unresolving respiratory symptoms over the 72 hr after onset of symptoms should be tested for SARS coronavirus infection.

SUGGESTED READINGS Lim PL, et al: Laboratory-acquired SARS. N Engl J Med 2004; 350:1740. Poutanen SM, et al: Identification of severe acute respiratory syndrome in Canada. N Engl J Med 2004; 348:20. Yu IT, et al: Evidence of airborne transmission of SARS virus. N Engl J Med 2004; 350:1731.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Sexual Dysfunction in Women ANNGENE A. GIUSTOZZI, M.D., M.P.H.

BASIC INFORMATION DEFINITION

Any disorder that interferes with female sexuality and causes marked distress to that person. Generally categorized into four types: 1.

Disorders of desire

2.

Disorders of arousal

3.

Orgasmic disorders

4.

Sexual pain disorders (includes dyspareunia, vaginismus, vulvodynia)

SYNONYMS

Female sexual dysfunction (FSD)

ICD-9CM CODES

302.70 Decreased libido 302.72 Disorders of arousal 302.73 Orgasmic disorders 625.x

Sexual pain disorders

EPIDEMIOLOGY & DEMOGRAPHICS

According to the National Health and Social Life Survey (1999), approximately 20% to 50% of women report some form of sexual dysfunction in their lifetime. One third of women report a decrease in sexual interest and one fourth report inability to achieve orgasm. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

History: Important to obtain the patient's definition of dysfunction including onset, duration, determination if dysfunction is situational vs. global, and if more than one dysfunction exists and the interrelationship of these dysfunctions Related medical and gynecologic conditions Psychosocial factors including sexual abuse, sexual orientation, depression/anxiety Current medications

•

Physical examination: external genitalia, vaginal vault, uterus/adenexa, rectovaginal, as well as other body systems (as indicated)

ETIOLOGY

•

Chronic medical conditions (diabetes, coronary vascular disease, arthritis, urinary incontinence)

•

Medication induced (e.g., antihypertensives, SSRIs)

•

Gynecologic conditions (cystitis, post-hysterectomy), gynecologic cancers, breast cancer (both femininity/self-image issues and/or postchemotherapy), postpregnancy, postmenopausal

•

Psychosocial (religion, taboos, identity conflicts, guilt, relationship problems, abuse/rape, life stressors)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Depression

•

Psychosocial stressors

•

Medical disease

LABORATORY TESTS

•

Cervical cultures and vaginal swabs for infectious disease, pap smear

•

Appropriate laboratory tests if comorbid or chronic disease is suspected

IMAGING STUDIES

Appropriate imaging studies if comorbid or chronic disease is suspected

TREATMENT NONPHARMACOLOGIC THERAPY

•

Education

•

Activities to enhance stimulation and eliminate routine

•

Distraction techniques

•

Noncoital behavior

•

Position changes (e.g., female astride)

•

Lubricants (non-petroleum based)

ACUTE GENERAL Rx

NSAIDs before intercourse for sexual pain disorders CHRONIC Rx

•

Treat underlying medical, gynecologic, or psychologic condition.

•

Reduce comorbidities.

•

Medication induced: decrease dose or change medication.

•

Postmenopausal women/hypoestrogenism: ERT +/- progesterone.

•

Testosterone therapy (controversial).

•

Sildenafil (controversial).

•

Behavioral therapy.

REFERRAL

•

Gynecologic referral for conditions that may be amenable to surgical therapy

•

Psychologic conditions (e.g., depression, abuse) that may benefit from counseling for psychotherapy

•

Social services referrals for active abuse issues

PEARLS & CONSIDERATIONS COMMENTS

Identify the earliest cause in the chain and treat first. PATIENT/FAMILY EDUCATION

When appropriate, involve patient's partner or significant other in treatment. SUGGESTED READINGS Basson R, et al: Report of the International Consensus Development Conference on Female Sexual Dysfunction: definitions and classifications. J Urology 2000; 163(b):888-893. Laumann EO, et al: Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281:537544. Phillips NA: Female sexual dysfunction: evaluation and treatment. Am Fam Physician 2000; 62(b):127-136.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Sheehan's Syndrome BETH J. WUTZ, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Sheehan's syndrome is a state of hypopituitarism resulting from an infarct of the pituitary secondary to postpartum hemorrhage or shock, causing partial or complete loss of the anterior pituitary hormones (i.e., ACTH, FSH, LH, GH, PRL, TSH) and their target organ functions.

ICD-9CM CODES

253.2 Sheehan's syndrome EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 1 case/10,000 deliveries (perhaps more rare in the U.S.) PREDOMINANT SEX: Affects only females RISK FACTORS:

•

Hypovolemic shock

•

Type I (insulin-dependent) diabetes mellitus (secondary to microvascular disease)

•

Sickle cell anemia (secondary to occlusion of the small vessels in the pituitary)

ONSET OF SYMPTOMS: Average delay of 5 to 7 yr between onset of symptoms and diagnosis of disease. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Failure of lactation

•

Infertility

•

Failure to resume menses after delivery

•

Failure to regrow shaved pubic or axillary hair

•

Skin depigmentation (including areola)

•

Rapid breast involution

•

Superinvolution of the uterus

•

Hypothyroidism

•

Adrenal cortical insufficiency

•

Diabetes insipidus (rare)

ETIOLOGY

•

Compromise of the blood supply to the low-pressure pituitary sinusoidal system may occur with postpartum hemorrhage or shock, resulting in pituitary infarct and/or necrosis.

•

It is hypothesized that locally released factors may mediate vascular spasm of the pituitary blood supply.

•

Severity of postpartum hemorrhage does not always correlate with the presence of Sheehan's syndrome.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Chronic infections

•

HIV

•

Sarcoidosis

•

Amyloidosis

•

Rheumatoid disease

•

Hemochromatosis

•

Metastatic carcinoma

•

Lymphocytic hypophysitis

WORKUP

•

Target gland deficiency should be investigated by measuring levels of ACTH, FSH, LH, TSH (which may be normal or low), and T4. Cortisol and estradiol (which may be low) should also be measured.

•

Provocative testing of pituitary hormone reserves (e.g., metyrapone test, insulin tolerance test, and cosyntropin test): normal, subnormal, or delayed responses may suggest the presence of islands of pituitary cells that no longer have the support of the hypothalamic-portal circulation.

•

Measurement of IGF-I to screen for GH deficiency: subnormal levels suggest decreased GH.

•

Impaired prolactin response to TRH or dopamine antagonist stimulation is frequently found.

•

During pregnancy, adjustments must be made in interpreting both hormone levels and responses to various stimuli because of normal physiologic changes.

IMAGING STUDIES

•

•

Study of choice: MRI of the pituitary 1.

Sella turcica partially or totally empty

2.

Rules out mass lesion

CT scan of the pituitary when MRI is unavailable or contraindicated

TREATMENT ACUTE GENERAL Rx

•

Acute form can be lethal, presenting with hypotension, tachycardia, failure to lactate, and hypoglycemia.

•

A high degree of suspicion is required with any woman who has undergone postpartum hemorrhage and shock.

•

Intravenous corticosteroids and fluid replacement should be given initially.

•

Diagnosis is confirmed with a full endocrinologic workup as noted previously.

•

Thyroid hormone is replaced as l-thyroxin in doses of 0.1 to 0.2 mg qd.

CHRONIC Rx

•

With late-onset disease (symptoms of general hypopituitarism, such as oligomenorrhea or amenorrhea, vaginal atrophic changes, and loss of libido): a full endocrinologic workup and replacement of the appropriate hormones are needed.

•

With symptoms of adrenal insufficiency: corticosteroids should be given. 1.

A maintenance dose of cortisone acetate or prednisone may be given.

2.

Because adrenal production of cortisol is not entirely dependent on ACTH, replacement of mineralocorticoids is rarely necessary.

3.

Stress doses of glucocorticoids should be administered during surgery or during labor and delivery.

DISPOSITION

Patients who receive early diagnosis and adequate hormonal replacement may expect favorable outcomes, including subsequent pregnancy. REFERRAL

Patients should have yearly examinations by endocrinologist. SUGGESTED READINGS Kovacs K: Sheehan's syndrome. Lancet 2003; 361(9356):520.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Shigellosis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Shigellosis is an inflammatory disease of the bowel caused by one of several species of Shigella. It is the most common cause of bacillary dysentery in the U.S. SYNONYMS

Bacillary dysentery

ICD-9CM CODES

004.9 Shigellosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Approximately 15,000 cases/yr PREDOMINANT SEX: Male homosexuals at increased risk PREDOMINANT AGE: Young children PEAK INCIDENCE: Summer GENETICS: Neonatal Infection: Rare but severe PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Possibly asymptomatic, but incubation period can range from 1 to 7 days with an average of 3 days

•

Mild illness that is usually self-limited, resolving in a few days

•

Fever

•

Watery diarrhea

•

Bloody diarrhea

•

Dysentery (abdominal cramps, tenesmus, and numerous, small-volume stools with blood, mucus, and pus)

•

Descending intestinal tract illness, reflecting infection of small bowel first and then the colon

•

Severe disease is more common in children and elderly and outside of U.S.

•

Complications of severe illness: 1.

Seizures

2.

Megacolon

3.

Intestinal perforation

4.

Death

•

Extraintestinal manifestations are rare

•

Bacteremia is more common in children; in adults it has been described in patients with AIDS, the elderly, and diabetics

•

Hemolytic-uremic syndrome (HUS): usually occurs as the initial illness seems to be resolving

•

Reactive arthritis, sometimes as part of Reiter's syndrome

ETIOLOGY

•

Shigella 1.

S. flexneri

2.

S. dysenteriae

3.

S. sonnei

4.

S. boydii

•

S. sonnei is the most commonly isolated species in the U.S., and it usually causes a mild watery diarrhea.

•

Direct person-to-person transmission is thought to be the most common route. Outbreaks among men who have sex with men have occurred because of direct or indirect oral-anal contact.

•

Contaminated food or water may transmit disease.

•

A recent outbreak occurred at a community wading pool frequented by toddlers.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

May mimic any bacterial or viral gastroenteritis

•

Dysentery also caused by Entamoeba histolytica

•

Bloody diarrhea may resemble disease caused by enterotoxigenic E. coli

LABORATORY TESTS

•

Total WBCs may be low, normal, or high. Leukemoid reactions can occur in children.

•

Stool should be cultured from fresh samples, because the yield is increased by processing the specimen soon after passage. The best yield is from the mucoid part of the stool.

•

Serology is available but rarely useful.

•

Polymerase chain reaction may be diagnostic.

•

Fecal leukocyte preparation may show WBCs.

IMAGING STUDIES

Abdominal radiographs may suggest megacolon or perforation in rare, severe cases.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Adequate hydration

•

Electrolyte replacement

ACUTE GENERAL Rx

Antibiotics: •

To shorten course of illness.

•

To limit transmission of illness.

•

For children: IV ceftriaxone (50 mg/kg/day) for severe disease. For oral therapy, can use SMX/TMP or ampicillin for 5 days for susceptible strains. Azithromycin can be used for 5 days when susceptibilities still not known or in areas of high resistance (12 mg/kg for the first day, then 6 mg/kg/day for 4 days).

•

For adults: Pending susceptibilities, ciprofloxacin 500 mg PO bid for 5 days should be used. If susceptible, can also use SMX/TMP one DS PO bid for 5 days. Azithromycin is a second alternative.

DISPOSITION

•

Most disease is self-limited.

•

Severe illness may be fatal.

REFERRAL

For severe illness or complications

PEARLS & CONSIDERATIONS COMMENTS

•

Shigella is one cause of “gay bowel syndrome.”

•

Illness is worsened by agents that decrease intestinal motility.

•

Food handlers, child-care providers, and health care workers should have a negative stool culture documented following treatment.

SUGGESTED READINGS Ashkenazi S: Shigella infections in children: new insights. Semin Pediatr Infect Dis 2004; 15(4):246. Ekdahl K, Andersson Y: The epidemiology of travel-associated shigellosis—regional risks, seasonality and serogroups. J Infect 2005; 51(3):222. Taylor DN, et al: Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge. Clin Infect Dis 2006; 42(9):1283.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Short Bowel Syndrome FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Short bowel syndrome is a malabsorption syndrome that results from extensive small intestinal resection. SYNONYMS

Short bowel

ICD-9CM CODES

579.3 (postsurgical malabsorption) EPIDEMIOLOGY & DEMOGRAPHICS

•

Parallels Crohn's disease (see “Crohn's Disease” in Section I), which is the most common cause of the syndrome in adults

•

In children, two thirds of short bowels are related to congenital abnormalities (intestinal atresia, gastroschisis, volvulus, aganglionosis) and one third are related to necrotizing enterocolitis

•

Prevalence: 10,000 to 20,000 cases are estimated to exist in the U.S.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Diarrhea and steatorrhea

•

Weight loss

•

Anemia related to iron or vitamin B12 absorption

•

Bleeding diathesis related to vitamin K malabsorption

•

Osteoporosis/osteomalacia related to vitamin D and calcium malabsorption

•

Hyponatremia, hypokalemia

•

Hypovolemia

•

Other macronutrient or micronutrient deficiency states

ETIOLOGY

•

Extensive bowel resection for treatment of the conditions mentioned previously (see “Epidemiology”).

•

Pathogenesis ( Fig. 1-244 ).

FIGURE 1-244 Specific areas of absorption of constituents of diet and secretions in the gastrointestinal tract. Macronutrients and micronutrients are predominantly absorbed in the proximal jejunum. Bile acids and vitamin B12 are only absorbed in the ileum. Electrolytes and water are absorbed in both the small and the large intestine. (From Feldman M, Scharschmidt BF, Sleisenger MH [eds]: Sleisenger and Fordtran's gastrointestinal and liver disease: pathophysiology, diagnosis, and management, ed 6, Philadelphia, 1998, WB Saunders.)

The human intestine is 3 to 8 m in length. Removal of up to one half of the small intestine produces no disruption in nutrient absorption, and most patients can maintain nutritional balance on oral feeding if they have more than 100 cm (3 ft) of jejunum. Similarly, 100 cm of intact jejunum can maintain a normal water, sodium, and potassium balance under normal circumstances. The presence of an intact colon can compensate for some small intestine loss. Site-specific functions: •

Calcium, magnesium, phosphorus, iron, and vitamins are absorbed in the duodenum and proximal jejunum.

•

Vitamin B12 and bile acids are absorbed in the ileum. The resection of more than 60 cm of ileum results in vitamin B 12 malabsorption. The loss of more than 100 cm results in fat malabsorption (from the loss of bile acids).

•

The loss of gastrointestinal endocrine hormones can affect intestinal motility.

•

Intestinal bacterial overgrowth may also occur, especially if the ileocecal valve is lost.

DIAGNOSIS Presence of macronutrient and/or micronutrient loss in a patient with a known history of bowel resection DIFFERENTIAL DIAGNOSIS

Because the history of significant bowel resection is typically known, there is no differential diagnosis. If that history is not known, all causes of weight loss, malabsorption, and diarrhea must be considered (see respective chapters).

TREATMENT Extensive small bowel resection with colectomy (< 100 cm of jejunum)

•

Rx: long-term parenteral nutrition (TPN). Some patients can switch to oral intake after 1 to 2 yr of TPN. In jejunostomy patients, excessive fluid loss can be reduced with H2 blockers, proton pump inhibitors, or octreotide. Micronutrients are supplemented.

Extensive small bowel resection with partial colectomy (usually patients with Crohn's disease) •

Rx: oral intake alone is possible in all patients with > 100 cm of jejunum. In addition to vitamin B12 deficiency, these patients often have diarrhea. Consider lactose malabsorption and bacterial overgrowth treated, respectively, with lactose restriction and antibiotics (tetracycline 250 mg tid or metronidazole 500 mg tid for 2 wk). Nonspecific antidiarrheal agents may also be indicated (e.g., Imodium or codeine). The patient must be monitored for micronutrient losses.

COMPLICATIONS

•

Oxalate kidney stones

•

Cholesterol gallstones

•

d-Lactic acidosis

PROGNOSIS

Directly dependent on the extent of the bowel resection and in the case of Crohn's disease by the underlying illness AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Sialadenitis

BASIC INFORMATION DEFINITION

Sialadenitis is an inflammation of the salivary glands.

ICD-9CM CODES

527.2 Sialadenitis EPIDEMIOLOGY & DEMOGRAPHICS

Parotid or submandibular glands are most frequently affected ( Fig. 1-245 ).

FIGURE 1-245 Sialogram of patient with chronic sialadenitis showing sausage link–like patterns and massive duct dilation. (From Blitzer CE, Lawson W, Reino A: Sialadenitis. In Johnson JT, Yu VL [eds]: Infectious diseases and antimicrobial therapy of the ears, nose, and throat, Philadelphia, 1997, WB Saunders.)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Pain and swelling of the affected salivary gland

•

Increased pain with meals

•

Erythema, tenderness at the duct opening

•

Purulent discharge from duct orifice

•

Induration and pitting of the skin with involvement of the masseteric and submandibular spatial planes in severe cases

ETIOLOGY

•

Ductal obstruction is generally secondary to a mucus plug caused by stasis of saliva with increased viscosity with subsequent stasis and infection.

•

Most frequent infecting organisms are Staphylococcus aureus, Pseudomonas, Enterobacter, Klebsiella, Enterococcus, Proteus, and Candida spp.

•

Sjögren's syndrome, trauma, radiation therapy, chemotherapy, dehydration, and chronic illness are predisposing factors.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Salivary gland neoplasm

•

Ductal stricture

•

Sialolithiasis

•

Decreased salivary secretion secondary to medications (e.g., amitriptyline, diphenhydramine, anticholinergics)

WORKUP

•

Generally not necessary

•

Ultrasound or CT scan in patients not responding to medical treatment (see “Imaging Studies”)

LABORATORY TESTS

•

Generally not indicated

•

CBC with differential to possibly reveal leukocytosis with left shift

IMAGING STUDIES

•

Ultrasound or CT scan may be needed in patients not responding to medical therapy.

•

Sialography should not be performed during the acute phase.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Massage of the gland: may express pus and relieve some of the pressure

•

Rehydration

•

Warm compresses

•

Oral cavity irrigations

ACUTE GENERAL Rx

•

Amoxicillin-clavulanate 500 to 875 mg or cefuroxime 250 to 500 mg bid should be given for 10 days. Clindamycin is an alternative choice in patients allergic to penicillin.

•

IV antibiotics (e.g., cefoxitin, nafcillin) can be given in severe cases.

DISPOSITION

Complete recovery unless the patient has underlying obstruction (e.g., ductal stricture, tumor, or stone) REFERRAL

•

To ENT for nonresolving cases despite appropriate antibiotic therapy

•

For salivary gland incision and drainage, which may be necessary in resistant cases

PEARLS & CONSIDERATIONS COMMENTS

Prevention of dehydration will decrease the risk of sialadenitis. AUTHOR: FRED F. FERRI, M.D. Sialolithiasis

BASIC INFORMATION DEFINITION

Sialolithiasis is the existence of hardened intraluminal deposits in the ductal system of a salivary gland. SYNONYMS

Salivary gland stone Salivary calculus

ICD-9CM CODES

527.5 Sialolithiasis EPIDEMIOLOGY & DEMOGRAPHICS

Affects patients mostly in their fifth to eighth decade and occurs most commonly in the submandibular gland (80%); only 14% are located in a parotid gland. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms: colicky postprandial pain and swelling of a salivary gland. Tends to have a remitting/relapsing course.

•

Signs: swelling and tenderness of a salivary gland. The stone may be felt by palpation of the floor of the mouth ( Fig. 1-246 ).

FIGURE 1-246 Patient with large calculus and obstruction of the left submandibular gland. (From Blitzer CE, Lawson W, Reino A: Sialadenitis. In Johnson JT, Yu VL [eds]: Infectious diseases and antimicrobial therapy of the ears, nose, and throat, Philadelphia, 1997, WB Saunders.)

ETIOLOGY

•

The cause is unknown. Contributing factors include saliva stagnation, sialadenitis (inflammation of a salivary gland), ductal inflammation or injury.

•

Salivary calculus composition is mainly calcium phosphate and carbonate, often combined with small proportions of magnesium, zinc, ammonium salts, and organic materials/debris.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Lymphadenitis

•

Salivary gland tumor

•

Salivary gland bacterial (Staphylococcus or Streptococcus), viral (mumps), or fungal infection (sialadenitis)

•

Noninfectious salivary gland inflammation (e.g., Sjögren's syndrome, sarcoidosis, lymphoma)

•

Salivary duct stricture

•

Dental abscess

IMAGING studies

•

Plain x-ray

•

Sialography

TREATMENT

•

Warm soaks to area

•

Antibiotics if associated bacterial sialadenitis is present

•

Bland diet—avoid citrus fruit and spices

•

Manual stone extraction sometimes associated with incisional enlargement of the ductal orifice

•

Surgical salivary gland removal for retained hilar calculi

REFERRAL

To otorhinolaryngologist AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Sick Sinus Syndrome

BASIC INFORMATION DEFINITION

Sick sinus syndrome is a group of cardiac rhythm disturbances characterized by abnormalities of the sinus node including (1) sinus bradycardia, (2) sinus arrest or exit block, (3) combinations of sinoatrial or

atrioventricular conduction defects, and (4) supraventricular tachyarrhythmias. These abnormalities may coexist in a single patient so that a patient may have episodes of bradycardia and episodes of tachycardia. SYNONYMS

Bradycardia-tachycardia syndrome

ICD-9CM CODES

427.81 Sick sinus syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

In children: associated with congenital heart disease

•

In adults: typically associated with ischemic heart disease but may occur in the presence of a normal heart

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Lightheadedness, dizziness, syncope, palpitation

•

Arterial embolization (e.g., stroke) associated with atrial fibrillation

•

Physical examination may be normal or reveal abnormalities (e.g., heart murmurs or gallop sounds) associated with the underlying heart disease

ETIOLOGY

•

Fibrosis or fatty infiltration involving the sinus node, atrioventricular node, the His bundle, or its branches

•

In addition, inflammatory or degenerative changes of the nerves and ganglia surrounding the sinus nodes and other sclerodegenerative changes may be found.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Bradycardia: atrioventricular block

•

Tachycardia: atrial fibrillation

•

Atrial flutter

•

Paroxysmal atrial tachycardia

•

Sinus tachycardia

•

Syncope (see “Syncope” in Section I)

WORKUP

•

ECG

•

Ambulatory cardiac rhythm monitoring

•

24-hour ambulatory ECG (Holter) ( Fig. 1-247 )

•

Event recorder

•

Electrophysiologic testing including sinus nodal recovery time and sino-atrial conduction time

FIGURE 1-247 Brady-tachy (sick sinus) syndrome. This rhythm strip shows a narrow-complex tachycardia (probably atrial flutter) followed by a sinus pause, an AV junctional escape beat (J), and then sinus rhythm. (From Goldberger AL: Clinical electrocardiography, ed 5, St Louis, 1994, Mosby.)

TREATMENT

•

Permanent pacemaker placement if symptoms are present

•

The drug treatment of the tachycardia (e.g., with digitalis or calcium channel blockers) may worsen or bring out the bradycardia and become the reason for pacemaker requirement

REFERRAL

To cardiologist Sickle Cell Disease

BASIC INFORMATION DEFINITION

Sickle cell disease is a hemoglobinopathy characterized by the production of hemoglobin S caused by substitution of the amino acid valine for glutamic acid in the sixth position of the -globin chain. When exposed to lower oxygen tension, RBCs assume a sickle shape resulting in stasis of RBCs in capillaries. Painful crises are caused by ischemic tissue injury resulting from obstruction of blood flow produced by sickled erythrocytes. SYNONYMS

Sickle cell anemia Hemoglobin S disease

ICD-9CM CODES

286.60 Sickle cell anemia EPIDEMIOLOGY & DEMOGRAPHICS

•

Sickle cell hemoglobin S is transmitted by an autosomal recessive gene. It is found mostly in blacks (1 in 400 black Americans).

•

Sickle cell trait occurs in nearly 10% of black Americans.

•

There is no predominant sex.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Physical examination is variable depending on the degree of anemia and presence of acute vasoocclusive syndromes or neurologic, cardiovascular, GU, and musculoskeletal complications.

•

There is no clinical laboratory finding that is pathognomonic of painful crisis of sickle cell disease. The diagnosis of a painful episode is made solely on the basis of the medical therapy and physical examination.

•

Bones are the most common site of pain. Dactylitis, or hand-foot syndrome (acute, painful swelling of the hands and feet), is the first manifestation of sickle cell disease in many infants. Irritability and refusal to walk are other common symptoms. After infancy, musculoskeletal pain can be symmetric, asymmetric, or migratory, and it may or may not be associated with swelling, low-grade fever, redness, or warmth.

•

In both children and adults, sickle vasoocclusive episodes are difficult to distinguish from osteomyelitis, septic arthritis, synovitis, rheumatic fever, or gout.

•

When abdominal or visceral pain is present, care should be taken to exclude sequestration syndromes (spleen, liver) or the possibility of an acute condition such as appendicitis, pancreatitis, cholecystitis, urinary tract infection, PID, or malignancy.

•

Pneumonia develops during the course of 20% of painful events and can present as chest and abdominal pain. In adults chest pain may be a result of vasoocclusion in the ribs and often precedes a pulmonary event. The lower back is also a frequent site of painful crisis in adults.

•

The “acute chest syndrome” manifests with chest pain, fever, wheezing, tachypnea, and cough. Chest xray reveals pulmonary infiltrates. Common causes include infection (mycoplasma, chlamydia, viruses), infarction, and fat embolism.

•

Musculoskeletal and skin abnormalities seen in sickle cell anemia include leg ulcers (particularly on the malleoli) and limb-girdle deformities caused by avascular necrosis of the femoral and humeral heads.

•

Endocrine abnormalities include delayed sexual maturation and late physical maturation, especially evident in boys.

•

Neurologic abnormalities on examination may include seizures and altered mental status.

•

Infections, particularly involving Salmonella, Mycoplasma, and Streptococcus, are relatively common.

•

Severe splenomegaly secondary to sequestration often occurs in children before splenic atrophy.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Thalassemia

•

Iron deficiency anemia, leukemia

•

The differential diagnosis of patients presenting with a painful crisis is discussed in “Physical Findings”

WORKUP

•

Screening of all newborns regardless of racial background is recommended. Screening can be performed with sodium metabisulfite reduction test (Sickledex test).

•

Hemoglobin electrophoresis will also confirm the diagnosis and is useful to identify hemoglobin variants such as fetal hemoglobin and hemoglobin A2.

LABORATORY TESTS

•

Anemia (resulting from chronic hemolysis), reticulocytosis, leukocytosis, and thrombocytosis are common.

•

Elevations of bilirubin and LDH are also common.

•

Peripheral blood smear may reveal sickle cells, target cells, poikilocytosis, and hypochromia ( Fig. 1-248 ).

•

Elevated BUN and creatinine may be present in patients with progressive renal insufficiency.

•

Urinalysis may reveal hematuria and proteinuria.

FIGURE 1-248 Photomicrograph of peripheral blood smear, sickle cells, typical of sickle cell anemia. (From Andreoli TE [ed]: Cecil essential of medicine, ed 4, Philadelphia, 1997, WB Saunders.)

IMAGING STUDIES

•

Chest x-ray is useful in patients presenting with “chest syndrome.” Cardiomegaly may be present on chest x-ray examination.

•

Bone scan is useful to rule out osteomyelitis (usually secondary to salmonella). MRI scan is also effective in diagnosing osteomyelitis.

•

CT scan or MRI of brain is often needed in patients presenting with neurologic complications such as TIA, CVA, seizures, or altered mental status.

•

Transcranial Doppler is a useful commodity to identify children with sickle cell anemia who are at risk for stroke.

•

Doppler echocardiography can be used to diagnose pulmonary hypertension.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Patients should be instructed to avoid conditions that may precipitate sickling crisis, such as hypoxia, infections, acidosis, and dehydration.

•

Maintain adequate hydration (PO or IV).

•

Correct hypoxia.

ACUTE GENERAL Rx

•

Aggressively diagnose and treat suspected infections (Salmonella osteomyelitis and pneumococcal infections occur more often in patients with sickle cell anemia because of splenic infarcts and atrophy). Combination therapy with a cephalosporin and erythromycin plus incentive spirometry and bronchodilators are useful in patients with acute chest syndrome.

•

Provide pain relief during the vasoocclusive crisis. Medications should be administered on a fixed time schedule with a dosing interval that does not extend beyond the duration of the desired pharmacologic effect. 1.

Meperidine is contraindicated in patients with renal dysfunction or CNS disease because its metabolite, normeperidine (which is excreted by the kidneys) can cause seizures.

2.

Narcotics (e.g., morphine 0.1 mg/kg IV q3 to 4h or 0.3 mg/kg PO q4h) should be given on a fixed schedule (not prn for pain), with rescue dosing for breakthrough pain as needed.

3.

Except when contraindications exist, concomitant use of NSAIDs should be standard treatment.

4.

Nurses should be instructed not to give narcotics if the patient is heavily sedated or respirations are depressed.

5.

When the patient shows signs of improvement, narcotic drugs should be tapered gradually to prevent withdrawal syndrome. It is advisable to observe the patient on oral pain relief medications for 12 to 24 hr before discharge from the hospital.

6.

Analgesic medications should be used in combination with psychologic, behavioral, and physical modalities in the management of sickle cell disease.

•

Aggressively diagnose and treat any potential complications (e.g., septic necrosis of the femoral head, priapism, bony infarcts, and acute “chest syndrome”).

•

Avoid “routine” transfusions but consider early transfusions for patients at high risk for complications. Indications for transfusion: aplastic crises, severe hemolytic crises (particularly during third trimester of pregnancy), acute chest syndrome, and high risk of stroke.

•

Hydroxyurea (500 to 750 mg/day) increases hemoglobin F levels and reduces the incidence of vasoocclusive complications. It is generally well tolerated. Side effects consist primarily of mild reversible neutropenia.

•

Replace folic acid (1 mg PO qd).

CHRONIC Rx

•

Guidelines for prompt management of fever, infections, pain, and specific complications should be reviewed.

•

Genetic counseling is recommended in all cases.

•

Avoid unnecessary transfusions. Exchange transfusions may be necessary for patients with acute neurologic signs, in aplastic crisis, or undergoing surgery.

•

Allogeneic stem cell transplantation can be curative in young patients with symptomatic sickle cell disease; however, the death rate from the procedure is nearly 10%, the marrow recipients are likely to be infertile, and there is an undefined risk of chemotherapy-induced malignancy.

•

Penicillin V 125 mg PO bid should be administered by age 2 mo and increased to 250 mg bid by age 3. Penicillin prophylaxis can be discontinued after age 5 except in children who have had splenectomy.

REFERRAL

•

Hospitalization is generally recommended for most crises and complications.

•

Psychosocial counseling and support structures should be developed.

PEARLS & CONSIDERATIONS COMMENTS

•

Pain in adults with sickle cell disease is the rule rather than the exception and needs to be treated appropriately.

•

Patients and their families should receive genetic counseling and should be made aware of the difference between sickle cell trait and sickle cell disease.

•

Regular immunizations and pneumococcal vaccination are recommended. The prophylactic administration of penicillin soon after birth and the timely administration of pneumococcal and H. influenzae type b vaccines have resulted in a significant decline in the incidence of these infections. The heptavalent conjugated pneumococcal vaccine (Prevan) should be administered from 2 mo of age. The 23-valent unconjugated pneumococcal vaccine is given from age 2 and can be boosted once 3 yr later. Influenza vaccination can be given after 6 mo of age.

•

Patients should be instructed on a well-balanced diet and appropriate folic acid supplementation.

•

The presence of dactylitis, Hb 7, or leukocytosis in the absence of infection during the first 2 yr of life, indicates a higher risk of severe sickle cell disease later in life.

•

Among patients with sickle cell disease, the acute chest syndrome is commonly precipitated by fat embolism and infection, especially community-acquired pneumonia. Among older patients and those with neurologic symptoms, the syndrome often progresses to respiratory failure.

•

Poloxamer 188, a nonionic surfactant with hemorrheologic and antithrombotic properties, has been reported to produce a significant but relatively small decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms. A more significant effect was observed in patients who received concomitant hydroxyurea.

•

Pulmonary hypertension is a complication of chronic hemolysis and is associated with a high risk of death. It can be detected by Doppler echocardiography in over 30% of adult patients with sickle cell disease. Cardiac catheterization will confirm the diagnosis. It is resistant to hydroxyurea therapy.

EVIDENCE

There is some evidence for the effectiveness of specific analgesics or analgesic regimens in relieving the pain of a sickle cell crisis. Oral controlled-release morphine has been shown to be as effective as intravenous morphine, after a loading dose of intravenous morphine, in children and adolescents.[[1]] There is some evidence for the effectiveness of parenteral ketorolac, but the trials are generally small, some show conflicting results, and overall the evidence is insufficient. [[2]] There is some evidence for the effectiveness of prophylactic penicillin in preventing pneumococcal infection

in children with sickle cell disease. Prophylactic penicillin significantly reduces the risk of pneumococcal infection, although the ideal age for safely withdrawing penicillin has not been established.[[3]] There is evidence for the effectiveness of conjugate pneumococcal vaccines in preventing pneumococcal infection in people with sickle cell disease. Conjugate pneumococcal vaccines are immunogenic and should be used in people with sickle cell disease.[[4]] There is evidence for the effectiveness of hydroxyurea in the management of sickle cell disease in those with severe disease. Hydroxyurea reduces the crisis rate, the use of transfusions, and the rate of life-threatening complications (in particular, the acute sickle chest syndrome). [[5]] Available data refer to severely affected adults with sickle cell disease; further studies are needed to elucidate the role of hydroxyurea in other groups of sickle cell patients. [[5]] There is some evidence for the use of blood transfusions for some indications in patients with sickle cell disease. Aggressive preoperative blood transfusion is no more effective than a more conservative regimen, and the more conservative regimen is associated with fewer transfusion-related adverse events.[[6]] However, further research is needed to identify the optimal regimen for different types of surgery and to address the question of whether preoperative transfusion is needed in all situations.[[6]] There is insufficient evidence to draw firm conclusions about the prophylactic use of blood transfusion for pregnant women with sickle cell disease. Comparison of routine blood transfusion with a policy of selective transfusion shows that selective transfusion reduces the number of transfusions required, but at the expense of more frequent crises.[[7]] There is evidence that long-term blood transfusion regimens prevent stroke in high-risk patients with sickle cell disease, but the benefits must be carefully weighed against the risks.[[8]]

Evidence-Based Referenceces 1. Jacobson SJ, et al: Randomised trial of oral morphine for painful episodes of sickle-cell disease in children. Lancet 1997; 350:1358.Reviewed in: Clin Evid 10:21, 2003. 2. Meremikwu MM: Sickle cell disease. Reviewed. Clin Evid, 10. London: BMJ Publishing Group; 2003:21. 3. Riddington C, Owusu-Ofori S: Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease. Cochrane Database Syst Rev 2002; 3: 4. Davies EG, et al: Pneumococcal vaccines for sickle cell disease. Cochrane Database Syst Rev 2004; 1: 5. Davies S, Olujohungbe A, Jones AP: Hydroxyurea for sickle cell disease. Cochrane Database Syst Rev 2002; 4: 6. Riddington C, Williamson L: Preoperative blood transfusions for sickle cell disease. Cochrane Database Syst Rev 2001; 3: 7. Mahomed K: Prophylactic versus selective blood transfusion for sickle cell anaemia during pregnancy. Cochrane Database Syst Rev 1996; 2: 8. Riddington C, Wang W: Blood transfusion for preventing stroke in people with sickle cell disease. Cochrane Database Syst Rev 2002; 1:

SUGGESTED READINGS Gladwin MT, et al: Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004; 350:886. Mehta S, et al: Opportunities to improve outcomes in sickle cell disease. Am Fam Physician 2006; 74:303. Orringer E, et al: Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease. JAMA 2001; 286:2099. Platt OS: Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 2008; 358:1362-1369. Smith WR, et al: Daily assessment of pain in adults with sickle cell disease. Ann Intern Med 2008; 148:94-101. Vichinski EP, et al: Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 2000; 342:1855. Wethers DL: Sickle cell disease in childhood. Am Fam Physician 2000; 62:1013.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Silicosis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JANE V. EASON, M.D.

BASIC INFORMATION DEFINITION

Silicosis is a lung disease attributable to the inhalation of silica (silicon dioxide) in crystalline form (quartz) or in cristobalite or tridymite forms. SYNONYMS

Pneumoconiosis caused by silica

ICD-9CM CODES

502 Silicosis, occupational 503 Pneumoconiosis caused by other inorganic dust EPIDEMIOLOGY & DEMOGRAPHICS

•

Occupational disease affecting men and women involved in gathering, milling, processing, or using silicacontaining rock or sand

•

An estimated 1 million Americans are exposed

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Dyspnea

•

Cough

•

Wheezing

•

Abnormal chest x-ray in an asymptomatic person

ETIOLOGY

•

Silica particles are ingested by alveolar macrophages, which in turn release oxidants causing cell injury and cell death, attract fibroblasts, and activate lymphocytes, increasing immunoglobulins in the alveolar space.

•

Hyperplasia of alveolar epithelial cells occurs.

•

Collagen accumulates in the interstitium.

•

Neutrophils also accumulate and secrete proteolytic enzymes, which leads to tissue destruction and emphysema.

•

Silica dust may be carcinogenic (not proven).

•

Exposure to silicosis predisposes to tuberculosis.

•

Some patients develop rheumatoid silicotic pulmonary nodules and may have arthritic symptoms of rheumatoid arthritis (Caplan's syndrome). Scleroderma has also been associated with silicosis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other pneumoconiosis, berylliosis, hard metal disease, asbestosis

•

Sarcoidosis

•

Tuberculosis

•

Interstitial lung disease

•

Hypersensitivity pneumonitis

•

Lung cancer

•

Langerhans' cell granulomatosis (histiocytosis X)

•

Granulomatous pulmonary vasculitis

WORKUP

•

History of occupational exposure

•

Chest x-ray ( Fig. 1-249 )

FIGURE 1-249 Simple silicosis. There are multiple small (2- to 4-mm) nodules distributed throughout the lungs, with an upper lobe predominance. (From McLoud TC: Thoracic radiology: the requisites, St Louis, 1998, Mosby.)

Chronic silicosis •

Characteristic finding: small, rounded lung parenchymal opacities

•

Hilar lymphadenopathy with “eggshell” calcifications

•

Pleural plaques (uncommon)

Accelerated silicosis (progressive massive fibrosis) •

Large parenchymal lesions resulting from coalesced small nodules

Acute silicosis •

Ground-glass appearance of the lung fields

•

Chest CT scan

•

Pulmonary function tests

Combination of obstructive and restrictive changes with or without reduction in diffusing capacity

•

Bronchoscopy with lung biopsy in uncertain cases

COURSE

CHRONIC SILICOSIS: •

May not progress with absence of further exposure

•

Accelerated silicosis: progressive respiratory failure and cor pulmonale

ACUTE SILICOSIS: Fatal course from respiratory failure over several months to a few years

TREATMENT

•

Prevention (industrial hygiene)

•

Treatment of associated tuberculosis if present

•

Supportive measures (oxygen, bronchodilators)

•

Lung transplant

AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Sinusitis

BASIC INFORMATION DEFINITION

Sinusitis is inflammation of the mucous membranes lining one or more of the paranasal sinuses. The various presentations are: •

Acute sinusitis: infection lasting < 30 days, with complete resolution of symptoms.

•

Subacute infection: lasts from 30 to 90 days, with complete resolution of symptoms.

•

Recurrent acute infection: episodes of acute infection lasting < 30 days, with resolution of symptoms, which recur at intervals at least 10 days apart.

•

Chronic sinusitis: inflammation lasting > 90 days, with persistent upper respiratory symptoms.

•

Acute bacterial sinusitis superimposed on chronic sinusitis: new symptoms that occur in patients with residual symptoms from prior infection(s). With treatment, the new symptoms resolve but the residual ones do not.

SYNONYMS

Rhinosinusitis: Sinusitis is almost always accompanied by inflammation of the nasal mucosa; thus it is now the preferred term.

ICD-9CM CODES

473.9 Sinusitis (accessory) (nasal) (hyperplastic) (nonpurulent) (purulent) (chronic) 461.9 Acute sinusitis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Seems to correlate with the incidence of upper respiratory tract infections PEAK INCIDENCE: Fall, winter, spring: September through March PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Patients often give a history of a recent upper respiratory illness with some improvement, then a relapse

•

Mucopurulent secretions in the nasal passage

•

1.

Purulent nasal and postnasal discharge lasting >7 to 10 days

2.

Facial tightness, pressure, or pain

3.

Nasal obstruction

4.

Headache

5.

Decreased sense of smell

6.

Purulent pharyngeal secretions, brought up with cough, often worse at night

Erythema, swelling, and tenderness over the infected sinus in a small proportion of patients 1.

Diagnosis cannot be excluded by the absence of such findings.

2.

These findings are not common, and do not correlate with number of positive sinus aspirates.

•

Intermittent low-grade fever in about half of adults with acute bacterial sinusitis

•

Toothache is a common complaint when the maxillary sinus is involved

•

Periorbital cellulitis and excessive tearing with ethmoid sinusitis 1.

•

•

•

Orbital extension of infection: chemosis, proptosis, impaired extraocular movements

Characteristics of acute sinusitis in children with upper respiratory tract infections: 1.

Persistence of symptoms

2.

Cough

3.

Bad breath

Symptoms of chronic sinusitis (may or may not be present) 1.

Nasal or postnasal discharge

2.

Fever

3.

Facial pain or pressure

4.

Headache

Nosocomial sinusitis is typically seen in patients with nasogastric tubes or nasotracheal intubation.

ETIOLOGY

•

Each of the four paranasal sinuses is connected to the nasal cavity by narrow tubes (ostia), 1- to 3-mm diameter; these drain directly into the nose through the turbinates. The sinuses are lined with a ciliated mucous membrane (mucoperiosteum).

•

Acute viral infection

•

1.

Infection with the common cold or influenza

2.

Mucosal edema and sinus inflammation

3.

Decreased drainage of thick secretions/obstruction of the sinus ostia

4.

Subsequent entrapment of bacteria a.

Multiplication of bacteria

b.

Secondary bacterial infection

Other predisposing factors 1.

Tumors

2.

Polyps

3.

Foreign bodies

4.

Congenital choanal atresia

5.

Other entities that cause obstruction of sinus drainage

6.

Allergies

7.

Asthma

•

Dental infections lead to maxillary sinusitis.

•

Viruses recovered alone or in combination with bacteria (in 16% of cases): 1.

Rhinovirus

2.

Coronavirus

3.

Adenovirus

4.

Parainfluenza virus

5.

Respiratory syncytial virus

•

The principal bacterial pathogens in sinusitis are Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis.

•

In the remainder of cases find Streptococcus pyogenes, Staphylococcus aureus, a-hemolytic streptococci, and mixed anaerobic infections (Peptostreptococcus, Fusobacterium, Bacteroides, Prevotella spp.).

•

Infection is polymicrobial in about one third of cases.

•

Anaerobic infections seen more often in cases of chronic sinusitis and in cases associated with dental infection; anaerobes are unlikely pathogens in sinusitis in children.

•

Fungal pathogens are isolated with increasing frequency in immunocompromised patients but remain uncommon pathogens in the paranasal sinuses. Fungal pathogens include: Phaeohyphomycoses, Aspergillus, Pseudallescheria, Sporothrix, and Zygomycetes spp.

•

Nosocomial infections: occur in patients with nasogastric tubes, nasotracheal intubation, cystic fibrosis, immunocompromised.

•

1.

S. aureus (including MRSA)

2.

Pseudomonas aeruginosa

3.

Klebsiella pneumoniae

4.

Enterobacter spp.

5.

Proteus mirabilis

Organisms typically isolated in chronic sinusitis:

1.

S. aureus

2.

S. pneumoniae

3.

H. influenzae

4.

P. aeruginosa

5.

Anaerobes

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Temporomandibular joint disease

•

Migraine headache

•

Cluster headache

•

Dental infection

•

Trigeminal neuralgia

WORKUP

•

In the normal healthy host the paranasal sinuses should be sterile. Although the contiguous structures are colonized with bacteria and likely contaminate the sinuses, the mucociliary lining functions to remove these bacteria.

•

Gold standard for diagnosis: recovery of bacteria in high density (=104 colony-forming units/ml) from a paranasal sinus, in the setting of a patient with history of upper respiratory infection and symptoms persisting 7 to 10 days. Sinus aspiration is the best method for obtaining cultures; however, it must be performed by an otorhinolaryngologist and is not practical for the primary care practitioner. Therefore most diagnoses are based on the clinical history and presentation, possibly supported by radiologic evaluations. 1.

2.

3.

Standard four-view sinus radiographs a.

Complete opacification and air-fluid levels are most specific findings (average 85% and 80%, respectively)

b.

Mucosal thickening has low specificity (40% to 50%)

c.

Absence of all three of the previous findings has estimated sensitivity of 90%

d.

Overall, standard radiographs are of limited use in diagnosis, although negative films are strong evidence against the diagnosis

CT scans: a.

Much more sensitive than plain radiographs in detecting acute changes and disease in the sinuses

b.

Recommended for patients requiring surgical intervention, including sinus aspiration; it is a useful adjunct to guide therapy

Transillumination: a.

Used for diagnosis of frontal and maxillary sinusitis

b.

Place transilluminator in the mouth or against cheek to assess maxillary sinuses, under medial aspect of the supraorbital ridge to assess frontal sinuses

c.

Absence of light transmission indicates that sinus is filled with fluid

d.

Dullness (decreased light transmission) is less helpful in diagnosing infection

4.

5.

Endoscopy: a.

Used to visualize secretions coming from the ostia of infected sinuses

b.

Culture collection via endoscopy often contaminated by nasal flora; not nearly as good as sinus puncture

Sinus puncture: a.

Gold standard for collecting sinus cultures

b.

Generally reserved for treatment failures, suspected intracranial extension, and nosocomial sinusitis

TREATMENT NONPHARMACOLOGIC THERAPY

To help promote sinus drainage: •

Air humidification with vaporizers (for steam) or humidifiers (for a cool mist)

•

Application of hot, wet towel over the face

•

Sipping hot beverages

•

Hydration

ACUTE GENERAL Rx

•

•

Sinus drainage: 1.

Nasal vasoconstrictors, such as phenylephrine nose drops, 0.25% or 0.5%

2.

Topical decongestants should not be used for more than a few days because of the risk of rebound congestion

3.

Systemic decongestants

4.

Nasal or systemic corticosteroids, such as nasal beclomethasone, short course oral prednisone

5.

Nasal irrigation, with hypertonic or normal saline (saline may act as a mild vasoconstrictor of nasal blood flow)

6.

Use of antihistamines has no proven benefit, and the drying effect on the mucous membranes may cause crusting, which blocks the ostia, thus interfering with sinus drainage

Analgesics, antipyretics

Antimicrobial therapy:

•

Most cases of acute sinusitis have a viral etiology and will resolve within 2 wk without antibiotics.

•

Current treatment recommendations favor symptomatic treatment for those with mild symptoms.

•

Antibiotics should be reserved for those with moderate to severe symptoms who meet the criteria for diagnosis of sinusitis.

•

Antibiotic therapy is usually empiric, targeting the common pathogens:

•

1.

First-line antibiotics include amoxicillin, erythromycin, TMP/SMX.

2.

Second-line antibiotics include the newer macrolides: clarithromycin, azithromycin, amoxicillin/clavulanate, cefuroxime axetil, cefprozil, cefaclor, loracarbef, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, metronidazole, others.

3.

For patients with uncomplicated acute sinusitis, the less expensive first-line agents appear to be as effective as the costlier second-line agents.

Hospitalization and IV antibiotics may be required for more severe infection and those with suspected intracranial complications. Broader-spectrum antibiotic coverage may be indicated in severe cases, to cover for MRSA, Pseudomonas, and fungal pathogens.

Duration of therapy generally 10 to 14 days, although some have success with much shorter regimens Surgery: •

•

Surgical drainage indicated 1.

If intracranial or orbital complications suspected

2.

Many cases of frontal and sphenoid sinusitis

3.

Chronic sinusitis recalcitrant to medical therapy

Surgical debridement imperative in the treatment of fungal sinusitis

Complications: •

Untreated, sinusitis may lead to a number of serious, life-threatening complications.

•

Intracranial complications include meningitis, brain abscess, epidural and subdural empyema.

•

Intracranial sequelae are more common with frontal and ethmoid infections.

•

Extracranial complications include orbital cellulitis, blindness, orbital abscess, osteomyelitis.

•

Extracranial sequelae are more commonly seen with ethmoid sinusitis.

CHRONIC Rx

•

Broad-spectrum antibiotics that cover both aerobes and anaerobes

•

Duration of therapy not clearly established: range 3 to 6 wk

•

Adjunctive therapy: one or more of the various options listed previously

•

Surgical intervention may be necessary in nonresponders

DISPOSITION

Appropriate diagnosis and treatment necessary to avoid the various sequelae that can occur without proper therapy REFERRAL

•

To infectious disease specialist if failure to respond to initial therapy

•

To otorhinolaryngologist for: 1.

Failure to respond to therapy

2.

Fungal infection suspected

3.

Intracranial or orbital complications suspected

PEARLS & CONSIDERATIONS

•

Recurrent sinusitis is usually related to anatomic defects, poor drainage, or immunocompromised states; such patients deserve a thorough workup by an ENT specialist and/or an infectious disease specialist.

•

Nosocomial sinusitis from obstruction by nasotracheal or nasogastric tubes is not uncommon and can be difficult to recognize in patients in the critical care units.

EVIDENCE

Antibiotics are effective in radiologically or bacteriologically confirmed sinusitis, although the benefits are modest. There is limited evidence that antibiotics (including amoxicillin, cephalosporins, and macrolides) for 7 to 10 days are effective in the treatment of radiologically or bacteriologically confirmed acute maxillary sinusitis. Nevertheless, the moderate benefits of antibiotic treatment should be weighed against the potential for adverse effects.[[1]] However, one randomized controlled trial of amoxicillin vs. placebo for 10 days did not find any difference between treatments in patients with clinically diagnosed sinusitis.[[2]] A systematic review of RCTs that compared antibiotics vs. placebo or standard therapy in children with rhinosinusitis found that antibiotics, including amoxicillin, trimethoprim-sulfamethoxazole, and erythromycin, for 10 days reduces the probability of persistent symptoms. Erythromycin may be associated with more clinical failures than amoxicillin and trimethoprim-sulfamethoxazole. Again, the benefits are modest and the risk of side effects should be borne in mind.[[3]] We are unable to cite evidence for other therapies that meets our criteria.

Evidence-Based Referenceces 1. Williams Jr JW, et al: Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev 2002; 3:Reviewed in: Clin Evid 11:710-717, 2004. 2. De Sutter AI, et al: Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A pragmatic randomized double-blind controlled trial in family practice. J Fam Pract 2002; 51:317.Reviewed in: Clin Evid 11:710, 2004. 3. Morris P, Leach A: Antibiotics for persistent nasal discharge (rhinosinusitis) in children (Cochrane Review). 2, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Brook I: Microbiology of acute and chronic maxillary sinusitis associated with an odontogenic origin. Laryngoscope 2005; 115(5):823. Gerencer RZ: Successful outpatient treatment of sinusitis exacerbations caused by community-acquired methicillin-resistant Staphylococcus aureus. Otolaryngol Head Neck Surg 2005; 132(6):828. Lindback M: Acute sinusitis: guide to selection of antibacterial therapy. Drugs 2004; 64(8):805. Llki A, Ulger N, Inanli S: Microbiology of sinusitis and the predictive value of throat culture for the aetiology of sinusitis. Clin Microbiol Infect 2005; 11(5):407. Oxford LE, McClay J: Complications of acute sinusitis in children. Otolaryngol Head Neck Surg 2005; 133(1):32. Stein M, Caplan ES: Nosocomial sinusitis: a unique subset of sinusitis. Curr Opin Infect Dis 2005; 18(2):147. Taxy JB: Paranasal funal sinusitis: contributions of histopathology to diagnosis: a report of 60 cases and literature review. Am J Surg Pathol 2006; 30(6):713.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Sjögren's Syndrome FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Sjögren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic and plasma cell infiltration and destruction of salivary and lacrimal glands with subsequent diminished lacrimal and salivary gland secretions.

•

Primary: dry mouth (xerostomia) and dry eyes (xerophthalmia) develop as isolated entities.

•

Secondary: associated with other disorders.

SYNONYMS

SS Sicca syndrome

ICD-9CM CODES

710.2 Sjögren's syndrome EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE/PREVALENCE: 1 case/2500 persons; secondary SS is just as common and can affect up to one third of SLE patients and nearly 20% of RA patients. PREDOMINANT SEX: Female > male PREDOMINANT AGE: Peak incidence is in the sixth decade. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Dry mouth with dry lips (cheilosis), erythema of tongue ( Fig. 1-250 ), and other mucosal surfaces, carious teeth

•

Dry eyes (conjunctival injection, decreased luster, and irregularity of the corneal light reflex)

•

Possible salivary gland enlargement and dysfunction with subsequent difficulty in chewing and swallowing food and in speaking without frequent water intake

•

Purpura (nonthrombocytopenic, hyperglobulinemic, vasculitic) may be present

•

Evidence of associated conditions (e.g., RA or other connective disease, lymphoma, hypothyroidism, COPD, trigeminal neuropathy, chronic liver disease, polymyopathy)

FIGURE 1-250 “Crocodile tongue” in a patient, with Sjögren's syndrome. (From Noble J: Primary care medicine, ed 3, St Louis, 2001, Mosby.)

ETIOLOGY

Autoimmune disorder

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Medication-related dryness (e.g., anticholinergics)

•

Age-related exocrine gland dysfunction

•

Mouth breathing

•

Anxiety

•

Other: sarcoidosis, primary salivary hypofunction, radiation injury, amyloidosis

WORKUP

Workup involves occular and oral examination and laboratory and radiographic testing to demonstrate the following criteria for diagnosis of primary and secondary Sjögren's syndrome: PRIMARY: •

•

•

Symptoms and objective signs of ocular dryness: 1.

Schirmer's test: 2 based on average of four assessable lobules)

Evidence of systemic autoimmune disorder: 1.

Elevated titer of rheumatoid factor >1:320

2.

Elevated titer of ANA >1:320

3.

Presence of anti-SS A (Ro) or anti-SS B (La) antibodies

SECONDARY: •

Characteristic signs and symptoms of SS (described in “Physical Findings”)

•

Clinical features sufficient to allow a diagnosis of RA, SLE, polymyositis, or scleroderma

LABORATORY TESTS

•

Positive ANA (> 60% of patients) with autoantibodies anti-SS A and anti-SS B may be present.

•

Additional laboratory abnormalities may include elevated ESR, anemia (normochromic, normocytic), abnormal liver function studies, elevated serum ß2 microglobulin levels, rheumatoid factor.

•

A definite diagnosis SS can be made with a salivary gland biopsy.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Adequate fluid replacement. Ameliorate skin dryness by gently blotting dry after bathing, leaving a small amount of moisture, and then applying a moisturizer.

•

Proper oral hygiene to reduce the incidence of caries

GENERAL Rx

•

Use artificial tears frequently.

•

Pilocarpine 5 mg PO qid is useful to improve dryness. A cyclosporine 0.05% ophthalmic emulsion (Restasis) may also be useful for dry eyes. Recommended dose is one drop bid in both eyes.

•

Cevimeline (Evoxac), a cholinergic agent with muscarinic agonist activity, 30 mg PO tid is effective for the treatment of dry mouth in patients with Sjögren's syndrome.

•

Interferon alfa, 150 IU tid for 12 wk has been shown to significantly improve stimulated whole saliva output and decrease complaints of xerostomia

•

Periodic dental and ophthalmology evaluations to screen for complications

PEARLS & CONSIDERATIONS COMMENTS

Unusual presentations of SS may occur in association with polymyalgia rheumatica, chronic fatigue syndrome, FUO, and inflammatory myositis. SUGGESTED READINGS Kassan SS, Moutsopoulos HM: Clinical manifestations and early diagnosis of Sjogren syndrome. Arch Intern Med 2004; 164:1275.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Sleep Apnea, Obstructive JEFFREY S. DURMER, M.D., PH.D.

BASIC INFORMATION DEFINITION

The American Academy of Sleep Disorders defines obstructive sleep apnea as “characterized by repetitive episodes of upper airway obstruction that occur during sleep, usually associated with a reduction in blood oxygen saturation.” SYNONYMS

Sleep apnea syndrome Obstructive sleep apnea-hypopnea syndrome Complex sleep apnea syndrome

ICD-9CM CODES

780.57 Obstructive sleep apnea syndrome EPIDEMIOLOGY & DEMOGRAPHICS

Obstructive sleep apnea (OSA) occurs most frequently in 40- to 65-year-old men (4%) and women (2%). The prevalence is higher in obese and hypertensive individuals. Pediatric OSA most frequently occurs in preschoolaged children (2%) and is associated with hypertrophy of the tonsils and adenoids, but can be similar to adult apnea in obese children. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Systemic hypertension, type II diabetes, stroke, or heart failure

•

History of snoring, witnessed apneas, frequent arousals and/or nocturnal urination, and excessive daytime somnolence.

•

Obesity with body mass index >27 kg/m2, neck circumference >43 cm (17 in.) in men.

•

Working memory impairment, inability to concentrate, short-temperedness, inattention, and hyperactivity in children.

•

Examination of oropharynx may reveal erythema caused by snoring and lateral narrowing secondary to large tonsils, pendulous uvula, excessive soft tissue, prominent tongue, and retrognathia.

•

Patient's bed partner may report loud snoring, episodic choking sounds, disrupted sleep with repetitive arousals, thrashing movements of extremities during sleep.

•

Decreased libido, mood swings, and depression.

ETIOLOGY

Narrowing of upper airway secondary to: •

Obesity

•

Macroglossia

•

Tonsillar and adenoid hypertrophy

•

Micrognathia

•

Muscular weakness

•

Use of alcohol or sedatives at bedtime

Upper airway muscular weakness secondary to: •

Neuromuscular disorders

•

Metabolic disorders

•

Primary CNS disorder (e.g., stroke, Down's syndrome)

•

Proposed genetic predisposition

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Excessive daytime somnolence

•

Inadequate sleep time

•

Pulmonary disease

•

Heart disease

•

Parkinsonism

•

Narcolepsy

•

Hypothyroidism

•

Anemia

•

Sleep fragmentation

•

Sleep-related asthma

•

Sleep-related GERD

•

Periodic limb movement disorder

•

Restless legs syndrome

•

Parasomnias

•

Psychophysiologic insomnia

•

Panic disorder

WORKUP

•

Medical history should include questions about snoring, witnessed apneas, sleep fragmentation, and excessive daytime sleepiness. Additional history concerning morning headaches, alcohol intake, weight gain, and mood/personality changes also may help implicate apnea.

•

Sleep apnea can be confirmed by overnight polysomnography (PSG) (gold standard). Testing is performed during the patient's habitual sleep hours and ideally includes all stages of sleep and body positions. Patients with sleep apnea have more than five apneic/hypopneic episodes per hour (termed apnea hypopnea index, or AHI) with desaturations of at least 3% by oximetry or coincidental arousals. Overnight oximetry tests can suggest the presence of sleep apnea but are not sufficient to rule out sleep apnea.

•

Portable monitors that measure respiratory flow are available but they lack the EEG, EMG, and technical observations necessary to diagnose sleep apnea with reliable accuracy. The use of such devices is usually related to limited availability of polysomnography or adjustment of OSA therapy.

LABORATORY TESTS

•

TSH level is indicated in suspected hypothyroidism.

•

CBC (with iron studies) is indicated for detecting anemia.

•

Pulmonary function tests are indicated for detecting related pulmonary disorders.

•

ECG is indicated for detecting related heart disease.

IMAGING STUDIES

Radiography of soft tissues in the neck in patients with suspected anatomic abnormalities

TREATMENT NONPHARMACOLOGIC THERAPY

•

Weight loss in overweight patients including bariatric surgery.

•

Avoidance of sedating medications and alcohol.

•

Sleep hygiene training.

•

Elimination of the supine sleeping position.

•

For mild to moderate obstructive sleep apnea in select patient populations (e.g., retrognathia) an oral appliance (constructed by a qualified dentist) may be useful to push the mandible forward.

•

Uvulopalatopharyngoplasty (UPPP, both standard and laser-assisted [LAUP]) in patients with significant obstruction of retropalatal airway can treat snoring but is not an accepted therapy for OSA.

•

Nasal septoplasty in patients with nasoseptal deformity may reduce snoring but is not an accepted therapy for OSA.

•

Adenotonsillectomy in children is often curative if indicated by an overnight PSG.

ACUTE GENERAL Rx

•

Nighttime treatment with continuous positive airway pressure (CPAP) provides immediate resolution of sleep apnea. Symptoms of excessive daytime somnolence may linger and necessitate further investigation or medical therapy.

•

Complex apnea (a combination of obstructive and central apnea) may necessitate therapy with bilevel PAP or require a period of adaptation with repeated nocturnal respiratory measures to demonstrate efficacy.

•

Tracheostomy: reserved for life-threatening cases that are unresponsive to other treatments.

•

Nasal steroids in allergy or sinusitis patients.

CHRONIC Rx

•

CPAP therapy

•

Weight loss

COMPLEMENTARY & ALTERNATIVE MEDICINE

Treatment with low-dose mirtazapine may reduce the AHI in patients with mild OSA. DISPOSITION

•

Most patients improve with weight loss, CPAP, or oral appliance therapy.

•

Complex apnea syndrome may result in Cheyne-Stokes respiratory patterns that can complicate CPAP therapy.

•

Overall success rate for UPPP is about 40% for snoring; much less effective for apnea.

•

Weight loss over time may reduce the need for CPAP pressure or obviate its use entirely.

REFERRAL

•

Sleep physician for proper study type(s) or complex symptoms

•

Dental referral for patients unresponsive to weight loss and CPAP

•

Consider surgical evaluation in select patients (i.e., need for mandibular/maxilla advancement)

PEARLS & CONSIDERATIONS

•

In a primary care setting, patients with high risk of sleep apnea are those who meet two of the following three criteria: (1) snoring, (2) persistent daytime sleepiness or drowsiness while driving, (3) obesity or hypertension.

•

Children with OSA may have symptoms of excessive daytime somnolence, hyperactivity, insomnia, inattention, declining academic performance, growth retardation, and a history of recurrent ear or throat infections.

•

Some patients with sleep apnea experience nocturnal dysrhythmias (bradycardia, paroxysmal tachyarrhythmias). In cardiac patients, trials using atrial overdrive pacing have demonstrated a reduction in the number of episodes of sleep apnea without reduction in the total sleep time.

•

The use of vagal nerve stimulators (VNS) in epilepsy patients has been associated with an increase in apneas and hypopneas. VNS-related respiratory events may be reduced by altering VNS stimulation parameters or by initiating CPAP.

EVIDENCE

The following therapies have been evaluated with varying levels of clinical evidence: Randomized controlled trials (RCTs) demonstrate that nasal CPAP is an effective treatment of moderate to severe obstructive sleep apnea-hypopnea syndrome [124] [125] and is more effective than placebo in improving sleepiness and several quality of life and depression measures in people with obstructive sleep apnea.[[3]] Treatment of OSA with CPAP shows a significant improvement in left ventricular ejection fraction and daytime systolic blood pressure in people with heart failure compared with those without CPAP.[[4]] CPAP therapy provides secondary ischemic stroke prevention in patients with moderately severe apnea.[[5]] RCTs demonstrate that mandibular advancement devices (oral appliances) are effective in treating moderate to severe OSA [129] [130] and show significant improvement in measures of daytime sleepiness and sleep disordered breathing when compared with no treatment in moderately severe OSA.[[8]] CPAP is significantly more effective than oral appliances in improving the AHI and minimum oxygen saturation during sleep,[[3]] as well as functional outcomes and quality of life measures.[[9]] In patients with mild obstructive sleep apnea-hypopnea syndrome, an oral mandibular advancement appliance is significantly more effective in improving AHI at 12 months and at 4-year follow-up compared with uvulopalatopharyngoplasty. Both interventions are equivalent in terms of daytime sleepiness and quality of life measures. Patients treated with uvulopalatopharyngoplasty, however, have better contentment scores. [133] [134] [135] A systematic review failed to find randomized controlled trials demonstrating the efficacy of surgical treatments for obstructive sleep apnea.[[13]] Variability in experimental design as well as limited sample sizes and a lack of common outcomes measures further limits the comparison of studies related to surgical treatments.[[14]]

Evidence-Based Referenceces 1. Montserrat JM, et al: Effectiveness of CPAP treatment in daytime function in sleep apnea syndrome: a randomized controlled study with an optimized placebo. Am J Respir Crit Care Med 2001; 164:608613. 2. Faccenda JF, et al: Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001; 163:344348.Reviewed in: Clin Evid 11:2249-2265, 2004. 3. White J, Cates C, Wright J: Continuous positive airways pressure for obstructive sleep apnoea. Cochrane Database Syst Rev 2001; 4: 4. Kaneko Y, et al: Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003; 348:1233-1241. 5. Martinez-Garcia MA, et al: Continuous positive airway pressure treatment prevents new vascular events after ischemic stroke. Chest 2005; 128(4):2123. 6. Hans MG, et al: Comparison of two dental devices for treatment of obstructive sleep apnea syndrome (OSAS). Am J Orthod Dentofac Orthop 1997; 111:562-570.Reviewed in: Clin Evid 11:2249-2265, 2004. 7. Mehta A, et al: A randomized controlled study of a mandibular advancement splint for obstructive sleep apnea. Am J Respir Crit Care Med 2001; 163:1457-1461.Reviewed in: Clin Evid 11:2249-2265, 2004. 8. Bloch KE, et al: A randomized, controlled crossover trial of two oral appliances for sleep apnea treatment. Am J Respir Crit Care Med 2000; 162:246-251.Reviewed in: Clin Evid 11:2249-2265, 2004. 9. Engleman HM, et al: Randomized crossover trial of two treatments for sleep apnoea/hypopnea syndrome: continuous positive airway pressure and mandibular repositioning splint. Am J Respir Crit Care Med 2002; 166:855-859.Reviewed in: Clin Evid 11:2249-2265, 2004. 10. Wilhelmsson B, et al: A prospective randomized study of a dental appliance compared with uvulopalatopharyngoplasty in the treatment of obstructive sleep apnoea. Acta Otolaryngol 1999; 119:503-509.Reviewed in: Clin Evid 11:2249-2265, 2004. 11. Walker-Engstrom ML, et al: Quality of life assessment of treatment with dental appliance or UPPP in patients with mild to moderate obstructive sleep apnoea. A prospective randomized 1-year follow-up study. J Sleep Res 2000; 9:303-308.Reviewed in: Clin Evid 11:2249-2265, 2004. 12. Walker-Engstrom ML, et al: 4-year follow-up of treatment with dental appliance or uvulopalatopharyngoplasty in patients with obstructive sleep apnea: a randomized study. Chest 2002; 121:739-746. 13. Bridgman SA, Dunn KM, Ducharme F: Surgery for obstructive sleep apnoea. Cochrane Database Syst Rev 1998; 1: 14. Sundaram S, et al: Surgery for obstructive sleep apnea. Cochrane Database Syst Rev 2005; 4:CD001004

SUGGESTED READINGS American Academy of Pediatrics: Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2002; 109:704. American Academy of Sleep Medicine: International classification of sleep disorders: diagnostic and coding

manual, ed 2. Westchester, IL, Author, 2005. Beebe DW: Neurobehavioral effects of obstructive sleep apnea: an overview and heuristic model. Curr Opin Pulm Med 2005; 11(b):494-500. Chervin RD, et al: Inattention, hyperactivity and symptoms of sleep-disordered breathing. Pediatrics 2002; 109:449. Flemons WW: Obstructive sleep apnea. N Engl J Med 2002; 347:498. Garrigue A, et al: Benefit of atrial pacing in sleep apnea syndrome. N Engl J Med 2002; 346:404. Guilleminault C, Lee JH, Chan A: Pediatric obstructive sleep apnea syndrome. Arch Pediatr Adolesc Med 2005; 159(b):775-785.Review. Marzec M, et al: Effects of vagal nerve stimulation on sleep-related breathing in epilepsy patients. Epilepsia 2003; 44:930. Qureshi A, Lee-Chiong TL: Medical treatment of obstructive sleep apnea. Semin Respir Crit Care Med 2005; 26(b):96-108.Review. Sharabi Y, Rabin K, Grossman E: Sleep apnea-induced hypertension: mechanisms of vascular changes. Expert Rev Cardiovasc Ther 2005; 3(b):937-940.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Smallpox FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Smallpox infection is due to the variola virus, a DNA virus member of the genus Orthopoxvirus. It is a human virus with no known nonhuman reservoir of disease. Natural infection occurs following implantation of the virus on the oropharyngeal or respiratory mucosa.

ICD-9CM CODES

050.9 Smallpox NOS V01.3 Smallpox exposure 050.0 Smallpox, hemorrhagic (pustular) 050.1 Variola minor (alastrim) 050.0 Variola major EPIDEMIOLOGY & DEMOGRAPHICS

•

Smallpox infection was eliminated from the world in 1977. The last cases of smallpox, from laboratory exposure, occurred in 1978. The threat of bioterrorism has brought on renewed interest in smallpox virus.

•

Routine vaccination against smallpox ended in 1972.

•

Smallpox is spread from one person to another by infected saliva droplets that expose a susceptible person who has face-to-face contact with the ill person.

•

Persons with smallpox are most infectious during the first wk of illness, when the largest amount of virus is present in saliva; however, some risk of transmission lasts until all scabs have fallen off.

•

The incubation period is about 12 days (range: 7 to 17 days) following exposure.

•

Contaminated clothing or bed linen could also spread the virus. Special precautions need to be taken to ensure that all bedding and clothing of patients are cleaned appropriately with bleach and hot water. Disinfectants such as bleach and quaternary ammonia can be used for cleaning contaminated surfaces.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Initial symptoms include high fever, fatigue, and headaches and back aches. A characteristic rash, most prominent on the face, arms, and legs, follows in 2 to 3 days ( Fig. 1-251 ).

•

The rash starts with flat red lesions that evolve at the same rate. The rash follows a centrifugal pattern.

•

Lesions are firm to the touch, domed, or umbilicated. They become pus-filled and begin to crust early in the second wk.

•

Scabs develop and then separate and fall off after about 3 to 4 wk. Depigmentation persists at the base of the skin lesions for 3 to 6 mo after illness. Scarring is usually most extensive on the face.

•

Associated with the rash may be fever, headache, generalized malaise, vomiting, and colicky abdominal pain.

•

Variola major may produce a rapidly fatal toxemia in some patients.

•

Complications of smallpox include dehydration, pneumonia, blepharitis, conjunctivitis, and corneal ulcerations.

FIGURE 1-251 Appearance of the rash of smallpox on day 6 to 7. All of the lesions are in the same stage of development. (From Gorbach SL: Infectious diseases, ed 2, Philadelphia, 1998, WB Saunders.)

ETIOLOGY

Smallpox is caused by the variola virus. There are at least two strains of the virus, the most virulent known as variola major and a less virulent strain known as variola minor (elastrim).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Rash from other viral illnesses (e.g., hemorrhagic chicken pox, measles, coxsackievirus)

•

Abdominal pain may mimic appendicitis

•

Meningococcemia

•

Insect bites

•

Impetigo

•

Dermatitis herpetiformis

•

Pemphigus

•

Papular urticaria

WORKUP & LABORATORY TESTS

•

Laboratory examination requires high-containment (BL-4) facilities.

•

Electron microscopy of vesicular scrapings can be used to distinguish poxvirus particles from varicellazoster virus or herpes simplex. To obtain vesicular or pustular fluid it may be necessary to open lesions with the blunt edge of a scalpel. A cotton swab may be used to harvest the fluid.

•

In absence of electron microscopy, light microscopy can be used to visualize variola viral particles (Guarnieri bodies) following Giemsa staining.

•

Polymerase chain reaction (PCR) techniques and restriction fragment-length polymorphisms can rapidly identify variola.

IMAGING STUDIES

Chest x-ray in patients with suspected pneumonia

TREATMENT NONPHARMACOLOGIC THERAPY

•

Supportive therapy

•

IV hydration in severe cases

•

A suspect case of smallpox should be placed in strict respiratory and contact isolation

ACUTE GENERAL Rx

•

There is no proven treatment for smallpox. Vaccination administered within 3 to 4 days may prevent or significantly ameliorate subsequent illness. Vaccinia immune globulin can be used for treatment of vaccine complications and for administration with vaccine to those for whom vaccine is otherwise contraindicated.

•

Patients can benefit from supportive therapy (e.g., IV fluids, acetaminophen for pain or fever).

•

Antibiotics are indicated only if secondary bacterial infections occur. Penicillase-resistant antimicrobial agents should be used if smallpox lesions are secondarily infected.

•

Topical idoxuridine should be considered for corneal lesions.

DISPOSITION

•

Mortality for variola major is 20% to 50%. Variola minor has a mortality rate of 1%.

•

After severe smallpox, pitted lesions (most commonly on the face) are seen in up to 80% of survivors.

•

Panophthalmitis and blindness from viral keratitis or secondary eye infection occur in 1% of patients.

•

Arthritis caused by viral infection of the metaphysis of growing bones occurs in 2% of children.

REFERRAL

ID consultation and notification of local health authorities is mandatory in all cases of smallpox.

PEARLS & CONSIDERATIONS

•

The smallpox virus is fragile and in the event of an aerosol release of smallpox, all viruses will be inactivated or dissipated within 1 to 2 days. Buildings exposed to the initial aerosol release of the virus do not need to be decontaminated. By the time the first cases are identified, typically 2 wk after release, the virus in the building will be gone. Infected patients, however, will be capable of spreading the virus and possibly contaminating surfaces while they are sick. Standard hospital-grade disinfectants such as quaternary ammonias are effective in killing the virus on surfaces and should be used for disinfecting hospitalized patients' rooms or other contaminated surfaces. In the hospital setting, patients' linens should be autoclaved or washed in hot water with bleach added. Infectious waste should be placed in biohazard bags and autoclaved before incineration.

•

Symptomatic patients with suspected or confirmed smallpox are capable of spreading the virus. Patients should be placed in medical isolation to avoid spread of the virus. In addition, people who have come into close contact with smallpox patients should be vaccinated immediately and closely watched for symptoms of smallpox.

COMMENTS

•

In people exposed to smallpox, the vaccine can lessen the severity of or even prevent illness if given within 4 days of exposure.

•

Vaccine against smallpox contains another live virus called vaccinia. The vaccine does not contain smallpox virus. Smallpox vaccination produces a skin lesion that is infectious. Vaccine virus in the skin lesion can be transferred to others if the skin lesion is touched directly or if the bandage is handled casually with ungloved hands. The vaccination site is infectious until the scab falls off, approximately 21 days after vaccination.

•

Primary vaccination confers full immunity to smallpox in more than 95% of persons for up to 10 yr.

SUGGESTED READINGS Breman JG, Henderson DA: Diagnosis and management of smallpox. N Engl J Med 2002; 346:1300.

Frey SE, et al: Clinical responses to undiluted and diluted smallpox vaccine. N Engl J Med 2002; 346:1265. Henderson DA, et al: Smallpox as a biological weapon. JAMA 1999; 281:2127.www.bt.cdc.gov/Agent/Smallpox/SmallpoxGen.asp

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Somatization Disorder STUART J. EISENDRATH, M.D.

BASIC INFORMATION DEFINITION

Somatization disorder refers to a pattern of recurring multiple somatic complaints that begin before the age of 30 yr and persist over several years. Patients complain of multiple sites of pain (a minimum of four), GI symptoms (a minimum of two), a sexual or reproductive symptom, and a pseudoneurologic symptom. These cannot be explained by a medical condition or are in excess to expected disability from a coexisting medical condition. SYNONYMS

Briquet's syndrome Nonorganic physical symptoms Medically unexplained symptoms Functional somatic symptoms

ICD-9CM CODES

300.81 Somatization disorder EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE (IN U.S.): Lifetime rates of 0.25% to 2% in women, < 0.2% in men PEAK INCIDENCE: Typically before age 25 yr PREDOMINANT SEX: Women are more commonly affected in the U.S. by 10:1 ratio PREDOMINANT AGE: Onset occurs before age 30 yr and usually in adolescence. GENETICS: In males, there is a high risk of associated substance abuse or antisocial personality disorder. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Onset is characteristically in the teens; course is marked by frequent, unexplained, and frequently disabling pain and physical complaints.

•

Patient frequently undergoes multiple procedures and seeks treatment from multiple physicians. Symptom focus rotates periodically with new physicians sought for new complaints.

•

Patient often has a comorbid psychiatric disorder, most commonly generalized anxiety, panic disorder, or depression.

ETIOLOGY

•

Believed to be the physical expression of psychologic distress; there appears to be a biological predisposition.

•

May be more common in individuals without sufficient verbal or intellectual capacity to communicate psychologic distress, individuals with alexithymia (inability to describe emotional states), or individuals from cultural backgrounds that consider emotional distress as an undesirable quality.

•

Some aspects of somatization behavior possibly learned from somatizing parents.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Undifferentiated somatoform disorder (ICD-10 F45.1, DMS-IV 300.81): one or more physical complaints that cannot be explained by a medical condition are present for at least 6 mo (note: Somatization disorder is more severe and less common).

•

Conversion disorder: there is an alteration or loss of voluntary motor or sensory function without demonstrable physical cause and related to a psychologic stress or a conflict (note: With multiple complaints, the diagnosis of conversion is not made).

•

Pain disorder: distinguished from somatization disorder by the latter featuring multiple nonpain symptoms.

•

Factitious disorder (e.g., Munchausen's syndrome) and malingering: the psychologic basis of the complaints in somatization disorder is not conscious as in factitious disorder where the goal is to be in the patient role and malingering, in which symptoms are also produced consciously for some secondary gain.

WORKUP

•

Rule out a general medical condition.

•

If somatization is suspected on the basis of a history of repeated, multiple, unexplained complaints, restraint in ordering tests is recommended.

LABORATORY TESTS

No specific laboratory tests are required. IMAGING STUDIES

No specific imaging studies are required.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Legitimize patient's complaints.

•

Minimize diagnostic investigation and symptomatic treatment. Only do invasive testing or procedures when there are clear-cut signs, not just symptom reports.

•

Set attainable treatment goals. Patients may benefit from realizing that even though they cannot be cured, that they will be cared for. This may help reassure them that they will continue to have a relationship with the physician.

•

Treat coexisting psychiatric conditions such as depression and anxiety.

ACUTE GENERAL Rx

•

At each visit do a brief physical examination focusing on the area of complaint.

•

Gently praise increased functioning rather than focusing on symptoms.

•

Explore recent life events and ask how the patient is handling these.

•

Convey empathy with the patient's suffering and psychosocial difficulties.

•

No specific pharmacologic therapy has been clearly proven effective, although a number of agents including gabapentin and St. John's wort have been useful in some studies.

CHRONIC Rx

•

Provide one primary care practitioner to manage care.

•

Avoid confronting the patient regarding the psychological origin of symptoms.

•

Ensure follow-up visits at regular (e.g., 2- to 4-wk intervals that are not symptom-contingent; i.e., maintain the regularity even if the symptoms improve).

•

Avoid invasive or expensive diagnostic procedures unless there are clear signs of new illness, not just symptoms.

•

Diagnose and treat mood or anxiety disorders.

•

Cognitive behavior therapy groups have been helpful for patients with unexplained somatic symptoms and can dramatically improve functioning.

DISPOSITION

A chronic condition with frequent exacerbations REFERRAL

If the patient is open to discussing psychological issues a referral for psychotherapy can be made.

PEARLS & CONSIDERATIONS Patients with somatization disorder respond best to establishing a regular, working relationship with a primary care provider. Avoiding confrontations about the origins of symptoms, investigating symptoms when related to actual signs of disease, and gently investigating concurrent stressors will help avoid most of the common problems with this population. SUGGESTED READINGS Allen LA, et al: Cognitive-behavioral therapy for somatization disorder: a randomized controlled trial. Arch Intern Med 2006; 166(14):1512.

Barsky AJ, et al: Distinctive patterns of medical care utilization in patients who somatize. Med Care 2006; 44(9):803. Mai F: Somatization disorder: a practical review. Can J Psychiatry 2004; 49(10):652.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Spinal Cord Compression LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Spinal cord compression is the neurologic loss of spine function. Lesions may be complete or incomplete and develop gradually or acutely. Incomplete lesions often present as distinct syndromes, as follows:

•

Central cord syndrome

•

Anterior cord syndrome

•

Brown-Séquard syndrome

•

Conus medullaris syndrome

•

Cauda equina syndrome

ICD-9CM CODES

344.89 Brown-Séquard syndrome 344.60 Cauda equina syndrome 336.8

Conus medullaris syndrome

Other lesions listed by site PHYSICAL FINDINGS & CLINICAL PRESENTATION

Clinical features reflect the amount of spinal cord involvement:

•

Motor loss and sensory abnormalities

•

Babinski testing usually positive

•

Clonus

•

Gradual compression, often manifested by progressive difficulty walking, clonus with weight bearing, and involuntary spasm; development of sensory symptoms; bladder dysfunction (late)

•

Central cord syndrome: results in a variable quadriparesis with the upper extremities more severely involved than the lower extremities; some sensory sparing

•

Anterior cord syndrome: results in motor, pain, and temperature loss below the lesion

•

Brown-Séquard syndrome: 1.

Spinal cord syndrome caused by injury to either half of the spinal cord and resulting in the loss of motor function, position, vibration, and light touch on the affected side

2.

Pain and temperature sense loss on the opposite side

•

Conus medullaris syndrome: results in variable motor loss in the lower extremities with loss of bowel and bladder function

•

Cauda equina syndrome: typical low back pain, weakness in both lower extremities, saddle anesthesia, and loss of voluntary bladder and bowel control

ETIOLOGY

•

Trauma

•

Tumor

•

Infection

•

Inflammatory processes

•

Degenerative disk conditions with spinal stenosis

•

Acute disk herniation

•

Cystic abnormalities

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

See “Etiology.”

•

Section II describes the differential diagnosis of paraplegia.

WORKUP

•

Spinal cord compression: requires an immediate referral for radiographic and neurologic assessment

•

Laboratory results usually unremarkable unless infectious or inflammatory causes suspected

IMAGING STUDIES

•

Depend on the suspected etiology

•

MRI usually required

TREATMENT Urgent surgical decompression is usually indicated as soon as the etiology is established. DISPOSITION

Important indicators regarding prognosis (Leventhal): •

The greater the distal motor and sensory sparing, the greater the expected recovery.

•

When a plateau of recovery is reached, no further improvement is expected.

•

The quicker the recovery, the greater the recovery.

REFERRAL

Immediate referral for radiographic and neurologic evaluation and treatment in all suspected cases of spinal cord compression SUGGESTED READINGS Baines MJ: Spinal cord compression—a personal and palliative care perspective. Clin Oncol (R Coll Radiol) 2002; 14(2):135. Banerjee R, Stanley J, Palumbo M: Spinal Epidural Hematoma induced by leukemia. Orthopedics 2004; 27:864. Benjamin R: Neurologic complications of prostate cancer. Am Fam Physician 2002; 65(9):1834. Buchner M, Schiltenwolf M: Cauda equina syndrome caused by intervertebral lumbar disc prolapse: mid-term results of 22 patients and literature review. Orthopedics 2002; 25:727. Carlson GD, et al: Sustained spinal cord compression. Part I: time-dependent effect on long-term pathophysiology. J Bone Joint Surg 2003; 85:86. Carlson GD, et al: Sustained spinal cord compression. Part II: effect of methylprednisolone on regional blood flow and recovery of somatosensory evoked potentials. J Bone Joint Surg 2003; 85:95. Casey AT, et al: Rheumatoid arthritis of the cervical spine: current techniques for management. Orthop Clin North Am 2002; 33(2):291. Jagas M, et al: Vertebroplasty with methacrylate bone cement and radiotherapy in the treatment of spinal metastases with epidural spinal cord compression. Ortop Traumatol Rehabil 2005; 7(5):491. Kadanka Z, et al: Approaches to spondylotic cervical myelopathy: conservative versus surgical in a 3-year follow-up study. Spine 2002; 27(20):2205. Malcolm GP: Surgical disorders of the cervical spine: presentation and management of common disorders. J Neurosurg Psychiatry 2002; 73(Suppl 1):134. Matsunaga S, et al: Trauma-induced myelopathy in patients with ossification of the posterior longitudinal ligament. J Neurosurg 2002; 97(2 Suppl):172. Mohanty SP, Venkatram N: Does neurological recovery in thoracolumbar and lumbar burst fractures depend on the extent of canal compromise?. Spinal Cord 2002; 40(6):295. Rades D, et al: Do bladder cancer patients with metastatic spinal cord compression benefit from radiotherapy alone?. Urology 2007; 69(6):1081.

Shimomura T, et al: Prognostic factors for deterioration of patients with cervical spondylotic myelopathy after nonsurgical treatment. Spine 2007; 32:2474. Sorar M, et al: Cervical compression myelopathy: is fusion the main prognostic indicator?. J Neurosurg Spine 2007; 6(6):531 Tang HJ, et al: Spinal epidural abscess—experience with 46 patients and evaluation of prognostic factors. J Infect 2002; 45(2):76. Venkitaraman R, et al: Outcome of early detection and radiotherapy for occult spinal cord compression. Radiother Oncol 2007; 85:469.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Spinal Epidural Abscess GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

A spinal epidural abscess (SEA) is a focal suppurative infection occurring in the spinal epidural space.

ICD-9CM CODES

324.1 Spinal epidural abscess EPIDEMIOLOGY & DEMOGRAPHICS

Incidence (IN U.S.): •

2 to 25 cases/100,000 hospitalized patients/yr

•

May be increasing over the past 3 decades

PREDOMINANT AGE: •

Median age of onset approximately 50 yr (35 yr in intravenous drug users)

•

Peak incidence in seventh and eighth decades of life

PHYSICAL FINDINGS & clinical presentation

The presentation of SEA can be nonspecific. •

Fever, malaise, and back pain are the most consistent early symptoms.

•

Pain is often focal. It may initially be mild but can progress to become severe.

•

As the disease progresses, root pain can occur, followed by motor weakness, sensory changes, bladder and bowel dysfunction, and paralysis.

•

Physical findings may be limited to fever or spinal tenderness.

•

The evolution to neurologic deficits can occur as quickly as a few hours, or over weeks to months.

•

Once paralysis occurs, it may quickly become irreversible without the appropriate intervention.

ETIOLOGY

•

Pyogenic bacteria account for the majority of cases in the U.S. Immigrants from tuberculosis-endemic areas may present with tuberculous SEAs. Fungi and parasites can also cause this condition. The most common causative organism is Staphylococcus aureus. Most posterior EAs thought to originate from distant focus (e.g., skin and soft tissue infections), while anterior EAs commonly associated with diskitis or vertebral osteomyelitis. No source found in approximately one third of cases.

•

Associated predisposing conditions include diabetes mellitus, alcoholism, cancer, AIDS, and chronic renal failure, or following epidural anesthesia, spinal surgery or trauma, or intravenous drug use. No predisposing condition is found in approximately 20% of patients.

•

Damage to the spinal cord can be caused by direct compression of the spinal cord, vascular compromise, bacterial toxins, and inflammation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Herniated disc

•

Vertebral osteomyelitis and diskitis

•

Metastic tumors

•

Meningitis

LABORATORY TESTS

•

WBC may be normal or elevated.

•

ESR usually elevated over 30 mm/hr.

•

Blood cultures are positive in approximately 60% of patients with SEA.

•

CSF cultures positive in 19%, but lumbar puncture unnecessary, and may be contraindicated.

•

Once imaging is done, CT-guided aspiration or open biopsy should be done to determine causative organism. Abscess content culture positive in 90%.

IMAGING STUDIES

•

MRI with gadolinium is the imaging modality of choice; CT scan with contrast may show the abscess but is less sensitive than MRI.

•

CT with myelography is more sensitive for cord compression.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Surgical decompression is the mainstay of treatment. Decompression within the first 24 hr has been related to an improved prognosis.

•

Nonsurgical treatment is effective in some patients, but failure rate may be excessive. This approach should not be considered but should only be attempted in the absence of signs of compressive myelopathy and with very careful follow-up.

ACUTE GENERAL Rx

•

In addition to surgery, antibiotics directed at the most likely organism should be initiated.

•

If the organism is unknown, broad coverage against staphylococci, streptococci and gram-negative bacilli should be initiated. The regimen can be adjusted according to culture results. Therapy should continue for at least 4 to 6 wk.

CHRONIC Rx

Neurologic deficits may remain despite aggressive treatment. DISPOSITION

Irreversible paralysis and death can occur in up to 25% of patients. REFERRAL

All cases should be referred to a neurosurgeon and an infectious diseases specialist.

PEARLS & CONSIDERATIONS It is critically important to recognize this process early; the prognosis is generally excellent if treatment is initiated while symptoms are localized and before evidence of myelopathy develops. SUGGESTED READINGS Curry WT, et al: Spinal epidural abscess: clinical presentation, management, and outcome. Surg Neurol 2005; 63(4):364. Moriya M, et al: Successful management of cervical spinal epidural abscess without surgery. Intern Med 2005; 44(10):1110. Savage K, Holtom PD, Zalavras CG: Spinal epidural abscess: early clinical outcome in patients treated medically. Clin Orthop Relat Res 2005; 439:56. Torgovnick J, Sethi N, Wyss J: Spinal epidural abscess: clinical presentation, management and outcome. Surg Neurol 2005; 63:364.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Spinal Stenosis, Lumbar JORGE A. VILLAFUERTE, M.D.

BASIC INFORMATION DEFINITION

Spinal stenosis is the pathologic condition caused by the compressing or narrowing of the spinal canal, nerve root canal, or intervertebral foramina at the lumbar region. SYNONYMS

Central spinal stenosis Lateral spinal stenosis Spondylosis

ICD-9CM CODES

724.02 Spinal stenosis lumbar, lumbosacral EPIDEMIOLOGY & DEMOGRAPHICS

More common between 50 and 60 yr of age PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms caused by direct mechanical compression or indirect vascular compression of the nerve roots or the cauda equina

•

Neurogenic claudication: leg, buttock, or back pain precipitated by walking and relieved by sitting

•

Pain may radiate down to ankles and is associated with numbness, tingling, and weakness

•

Taking a flexed posture reduces symptoms because it increases the available space in the lumbar spinal canal

•

Decreased lumbar extension

•

Normal peripheral pulses

•

Positive Romberg's sign (decreased proprioception)

•

Wide-based gait

•

Reduced knee and ankle reflex

•

Urine incontinence

ETIOLOGY

Spinal stenosis may be primary or secondary •

•

Primary stenosis (congenital or developmental narrowing) 1.

Idiopathic

2.

Achondroplasia

3.

Morquio-Ullrich syndrome

Secondary stenosis (acquired) 1.

Degenerative (hypertrophy of the articular processes, disk degeneration, ligamentum flavum hypertrophy, spondylolisthesis)

2.

Fracture/trauma

3.

Postoperative (postlaminectomy)

4.

Paget's disease

5.

Ankylosing spondylitis

6.

Tumors

7.

Acromegaly

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Osteoarthritis of the knee or hip

•

Acute cauda equina syndrome, due to compression by epidural abscess or tumors

•

Pain and weakness caused by multiple myeloma or osteomyelitis

•

Intermittent claudication-peripheral vascular disease

•

Peripheral neuropathy such as that caused by a herniated nucleus pulposus

•

Scoliosis or spondylolisthesis

•

Rheumatoid diseases: ankylosing spondylitis, Reiter's syndrome, fibromyalgia

WORKUP

History, physical examination, and specific imaging studies IMAGING STUDIES

•

Lumbar spine film sensitivity 66%, specificity 93%.

•

Ultrasound of the spinal canal has also been used.

•

CT scan of the lumbosacral spine: sensitivity (75% to 85%), specificity (80%).

•

MRI of the lumbosacral spine: sensitivity (80% to 90%), specificity (95%).

•

Myelogram: sensitivity (77%), specificity (72%). Absolute stenosis is defined as the anterior-posterior (AP) diameter of the spinal canal 3 days, carries with it a 15% to 20% chance of miscarriage.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Profuse bleeding and cramping has a higher association with miscarriage than bleeding without cramping, which is more consistent with a threatened miscarriage.

•

Cervical dilation with history or finding of fetal tissue at cervical os may be present.

•

In cases of missed abortion, uterine size may be smaller than menstrual dating, in contrast to molar gestation, where size may be greater than dates.

ETIOLOGY

•

In a general overview the etiology can be classified in terms of maternal (environmental) and fetal (genetic) factors, with the majority of miscarriages being related to genetic or chromosomal causes

•

Causes: uterine anomalies (unicornuate uterus risk = 50%, bicornuate or septate uterus risk = 25% to 30%), incompetent cervix (iatrogenic or congenital, associated with 20% of midtrimester losses), diethylstilbestrol exposure in utero (T-shaped uterus), submucous leiomyomas, intrauterine adhesions or synechiae, luteal phase or progesterone deficiency, autoimmune disease such as anticardiolipin antibodies, uncontrolled diabetes mellitus, HLA associations between mother and father, infections such as TB, Chlamydia, Ureaplasma, smoking and alcohol use, irradiation, and environmental toxins

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Normal pregnancy

•

Hydatidiform molar gestation

•

Ectopic pregnancy

•

Dysfunctional uterine bleeding

•

Pathologic endometrial or cervical lesions

WORKUP

•

All patients with bleeding in the first trimester should have an evaluation for possible ectopic pregnancy.

•

If there are three early, prior pregnancy losses, a workup and treatment for recurrent miscarriage should begin before next conception. If there is a strong history for second-trimester loss, consideration for cerclage should be given, especially if the history is consistent with incompetent cervix (e.g., painless cervical dilation).

LABORATORY TESTS

•

Type and antibody screen is used to evaluate for the need for Rh immune globulin.

•

During the preconception period, Hgb A1C, anticardiolipin antibody, lupus anticoagulant, factor V, Leiden, MTHFR, Antithrombin III, Prothrombin gene 2210A, karyotyping, endometrial biopsy with progesterone level, and cervical cultures or serum antibodies can be checked for suspected disease processes.

•

Progesterone level < 5 mg/dl indicates nonviable gestation vs. > 25 mg/dl, which suggests a good prognosis.

IMAGING STUDIES

Transabdominal or transvaginal sonogram (preferably) can be used in combination with menstrual dating and

serum quantitative hCG to document pregnancy location, fetal heart presence, gestational sac size, and adnexal pathology.

TREATMENT NONPHARMACOLOGIC THERAPY

Depending on the patient's clinical status, desire to continue the pregnancy, and certainty of the diagnosis, expectant management can be considered. In pregnancies < 6 wk or > 14 wk, complete expulsion of fetal tissue usually occurs and surgical intervention such as dilation and curettage (D&C) can be avoided. ACUTE GENERAL Rx

•

Incomplete miscarriage between 6 and 14 wk can be associated with large amounts of blood loss, and thus these patients should undergo D&C.

•

In cases of missed abortion, if fetal demise has occurred > 6 wk before or gestational age is > 14 wk, there is an increased risk of hypofibrinogenemia with disseminated intravascular coagulation, and thus D&C should be performed early in the disease course. Can consider use of misoprostol (Cytotec) 200 mg po q6h × 4 doses.

•

Threatened abortions may be managed expectantly, watching for signs of cervical dilation or sonographic evidence of missed abortion.

•

If surgical intervention is required, preoperative use of 40 U of oxytocin (Pitocin) in 1000 ml lactated Ringer's solution may be used to decrease the amount of bleeding and shorten the operative time.

•

Postoperatively all patients undergoing a D&C should receive antibiotics (doxycycline 100 mg bid for 7 days), methylergonovine (Methergine) 0.2 mg q6h for four doses, and Motrin or NSAIDs prn for pain.

•

In all cases of first- or second-trimester bleeding in Rh-negative patients, Rh immune globulin 300 µg should be given to prevent Rh sensitization.

REFERRAL

Refer to OB/GYN.

PEARLS & CONSIDERATIONS “Spontaneous pregnancy loss” has been recommended to avoid the term “abortion” and acknowledge the emotional aspects of losing a pregnancy. SUGGESTED READINGS Griebel CP, et al: Management of spontaneous abortion. Am Fam Physician 2005; 72:1243.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Sporotrichosis GEORGE O. ALONSO, M.D., GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Sporotrichosis is a granulomatous disease caused by Sporothrix schenckii. SYNONYMS

Lymphocutaneous sporotrichosis Cutaneous sporotrichosis Pulmonary sporotrichosis

ICD-9CM CODES

117.1 Sporotrichosis EPIDEMIOLOGY & DEMOGRAPHICS

PREDOMINANT SEX: The most common form, lymphocutaneous sporotrichosis, occurs equally in both sexes. Males predominate in both pulmonary and osteoarticular sporotrichosis. PREDOMINANT AGE: Generally, lymphocutaneous sporotrichosis occurs in persons 35 yr of age or younger, and pulmonary sporotrichosis occurs in persons between the ages of 30 to 60 yr. GENETICS: Neonatal Infection: At least one case of transmission from the cheek lesion of the mother to the skin of the infant has been reported. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Cutaneous disease

•

•

1.

Arises at the site of inoculation

2.

Initial lesion usually located on the distal part of an extremity, although any area may be affected, including the face

3.

Variable incubation period of approximately 3 wk once introduced into the skin

4.

Granulomatous reaction provoked

5.

Lesion becomes papulonodular, erythematous, elastic, variable in size

6.

Subsequently, nodule becomes fluctuant, undergoes central necrosis, breaks down, discharges mucoid pus from which fungus may be isolated

7.

Indolent ulcer with raised erythematous or violaceous borders

8.

Secondary lesions: Develop along superficial lymphatic channels

b.

Evolve in the same manner as the primary lesion, with subsequent inflammation, induration, and suppuration

Fixed, or plaque form 1.

Erythematous verrucous, ulcerated, or crusted lesions

2.

Does not spread locally

3.

Does not involve lymphatic vessels

4.

Rarely undergoes spontaneous resolution

5.

More often persists for years without systemic symptoms and within a setting of normal laboratory examinations

Osteoarticular involvement 1.

Most common extracutaneous form

2.

Usually presents as monoarticular arthritis

3.

Left untreated, may progress to:

4.

•

a.

a.

Synovitis

b.

Osteitis

c.

Periostitis

d.

All involving elbows, knees, wrists, and ankles

Joint inflamed a.

Associated with an effusion

b.

Painful on motion

Early pulmonary disease

1.

2.

3.

4.

Usually associated with a paucity of clinical findings a.

Low-grade fever

b.

Cough

c.

Fatigue

d.

Malaise

e.

Weight loss

Untreated a.

Cavitary pulmonary disease

b.

Frank pulmonary dysfunction

Meningitis uncommon a.

Except perhaps in the immunocompromised patient

b.

Presents with few signs or symptoms of neurologic involvement

Few reported cases a.

Infection of the ocular adnexa

b.

Endophthalmitis without antecedent trauma

c.

Infection of the testes and epididymis

ETIOLOGY

•

•

•

Sporothrix schenckii 1.

Global in distribution

2.

Often isolated from soil, plants, and plant products

3.

Majority of case reports from tropical and subtropical regions of the Americas

Occupational or recreational exposure 1.

Hay

2.

Straw

3.

Sphagnum moss

4.

Timber

5.

Thorny plants (e.g., roses and barberry bushes)

Animal contact 1.

Armadillos

2.

Cats

3.

Squirrels

•

Human-to-human transmission

•

Tattooing

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

•

•

•

•

Fixed, or plaque, sporotrichosis 1.

Bacterial pyoderma

2.

Foreign body granuloma

3.

Tularemia

4.

Anthrax

5.

Other mycoses: blastomycosis, chromoblastomycosis

Lymphocutaneous sporotrichosis 1.

Nocardia brasiliensis

2.

Leishmania braziliensis

3.

Atypical mycobacterial disease: M. marinum, M. kansasii

Pulmonary sporotrichosis 1.

Pulmonary TB

2.

Histoplasmosis

3.

Coccidioidomycosis

Osteoarticular sporotrichosis 1.

Pigmented villonodular synovitis

2.

Gout

3.

Rheumatoid arthritis

4.

Infection with M. tuberculosis

5.

Atypical mycobacteria: M. marinum, M. kansasii, M. avium-intracellulare

Meningitis

WORKUP

1.

Histoplasmosis

2.

Cryptococcosis

3.

TB

•

The diagnosis should be considered in individuals who are occupationally exposed to soil, decaying plant matter, and thorny plants (gardeners, horticulturists, farmers) who present with chronic nonhealing ulcers or lesions with or without associated arthritis or pulmonary symptoms.

•

Diagnosis is made by culture: 1.

Pus

2.

Joint fluid

3.

Sputum

4.

Blood

5.

Skin biopsy

•

Isolation of the fungus from any site is considered diagnostic of infection.

•

Saprophytic colonization of the respiratory tract has been described.

•

A positive blood culture may indicate infection in an immunocompromised host.

•

Increasingly sensitive laboratory culturing systems may detect the fungus in the normal host.

•

Biopsy specimens are diagnostic if characteristic cigar-shaped, round, oval, or budding yeast forms are seen.

•

Despite special staining, the yeast may remain difficult to detect unless multiple sections are examined.

•

No standard method of serologic testing is available.

•

Previously described techniques have been hampered by the presence of antibody in the absence of infection.

LABORATORY TESTS

•

CBCs and serum chemistries are generally normal.

•

Elevated ESR is seen with extracutaneous disease.

•

CSF analysis in meningeal disease reveals:

•

1.

Lymphocytic pleocytosis

2.

Elevated protein

3.

Hypoglycorrhachia

Nested PCR assay represents a future clinical modality to rapidly detect Sporothrix schenckii.

IMAGING STUDIES

•

Chest x-ray examination: unilateral or bilateral upper lobe cavitary or noncavitary lesions

•

Radiographic findings of affected joints: 1.

Loss of articular cartilage

2.

Periosteal reaction

3.

Periarticular osteopenia

4.

Cystic changes

TREATMENT NONPHARMACOLOGIC THERAPY

Local heat and prevention of bacterial superinfection in cutaneous or plaque form ACUTE GENERAL Rx

CUTANEOUS AND LYMPHOCUTANEOUS SPOROTRICHOSIS: •

Itraconazole at doses of 100 to 200 mg/day is the drug of choice and should be given for 3 to 6 mo.

•

Use saturated solution of potassium iodide (SSKI) 5 to 10 drops PO tid or 1.5 ml PO tid, gradually increasing to 40 to 50 drops PO tid or 3 ml PO tid after meals.

•

Maximum tolerated dose should be continued until cutaneous lesions have resolved, approximately 6 to 12 wk.

•

Adjunctive therapy with heat is useful and occasionally curative.

•

Side effects: 1.

Nausea

2.

Anorexia

3.

Diarrhea

4.

Parotid or lacrimal gland hypertrophy

5.

Acneiform rash

DEEP-SEATED MYCOSES (e.g., osteoarticular, noncavitary pulmonary disease): •

•

•

Itraconazole 1.

Appropriate initial chemotherapy

2.

Probably as effective as amphotericin B

3.

Less toxic than amphotericin B

4.

Better tolerated than ketoconazole

5.

100 to 200 mg bid for 1 to 2 yr with continued lifelong suppressive therapy in selected patients

6.

Absence of relapses from 40 to 68 mo has been documented when at least 200 mg/day administered for 24 mo

7.

Insufficient data for use in disseminated disease (e.g., fungemia and meningitis)

Parenteral amphotericin B, total course of 2 to 2.5 g or more, results in cure in approximately two thirds of cases 1.

Relapses are common.

2.

Amphotericin B–resistant isolates of Sporothrix schenckii have been reported.

3.

Remains the drug of choice for severely ill patients with disseminated disease.

4.

In cavitary pulmonary disease, given perioperatively as an adjunct to surgical resection.

5.

In meningitis, amphotericin B may be used alone or in combination with 5-fluorocytosine.

Fluconazole 1.

Less effective than itraconazole

2.

Requires daily doses of 400 mg/day for lymphocutaneous disease and 800 mg/day for visceral or osteoarticular disease

CHRONIC Rx

For lymphocutaneous and visceral disease, therapy with itraconazole 200 mg/day for periods of 24 mo or

greater; newer agents such as voriconazole and posaconazole might be useful in refractory to standard therapy but existing data for these new agents is very limited at present. DISPOSITION

•

Prognosis for cutaneous disease is good.

•

Prognosis is less satisfactory for extracutaneous disease, especially if associated with abnormal immunologic states or other underlying systemic diseases.

REFERRAL

To surgeon; with an established diagnosis of pulmonary sporotrichosis, cavitary lesions require resection of involved tissue

PEARLS & CONSIDERATIONS COMMENTS

•

In patients with underlying immunosuppression (e.g., hematologic malignancy or infection with HIV), progression of the initial infection may develop into multifocal extracutaneous sporotrichosis.

•

In this subset of patients, dissemination of cutaneous lesions is accompanied by hematogenous spread to lungs, bone, mucous membranes, CNS.

•

Osteoarticular and pulmonary manifestations predominate with the development of polyarticular arthritis and osteolytic bone lesions.

•

In the absence of therapy, the infection is ultimately fatal.

•

Patients with underlying immunosuppressive states should be carefully evaluated even when presenting with single cutaneous lesions.

•

Diagnostic modalities should include: 1.

Radiographic examination of chest

2.

Technetium pyrophosphate bone scan

3.

Culture of synovial fluid, blood, skin lesion(s)

•

In patients with AIDS, itraconazole appears to be the drug of choice, although meningitis and pulmonary disease may warrant the use of amphotericin B.

•

In patients with AIDS, lifetime suppressive therapy with itraconazole should follow initial therapy given the potential for relapse and dissemination.

SUGGESTED READINGS Bernardes-Engermann AR, et al: Development of an enzyme-linked immunosorbent assay for the serodiagnosis of several clinical forms of sporotrichosis. Med Mycol 2005; 43(6):487. Da Rosa AC, et al: Epidemiology of sporotrichosis; a study of 304 cases in Brazil. J Am Acad Dermatol 2005; 52(3 Pt 1):451. Neyra E, et al: Epidemiology of human sporotrichosis investigated by amplified fragment length polymorphism. J Clin Microbiol 2005; 43(3):1348. Schubach AO, Schubach TM, Barros MB: Epidemic cat-transmitted sporotrichosis. N Engl J Med 2005; 353(11):1185.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Squamous Cell Carcinoma FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Squamous cell carcinoma (SCC) is a malignant tumor of the skin arising in the epithelium. SYNONYMS

SCC Skin cancer

ICD-9CM CODES

173.9 Skin neoplasm, site unspecified EPIDEMIOLOGY & DEMOGRAPHICS

•

SCC is the second most common cutaneous malignancy, comprising 20% of all cases of nonmelanoma skin cancer.

•

Incidence is highest in lower latitudes (e.g., southern U.S., Australia).

•

Male:female ratio of 2:1.

•

Incidence increases with age and sun exposure.

•

Average age at diagnosis is 66 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

SCC commonly affects scalp, neck region, back of hands, superior surface of the pinna, and the lip.

•

The lesion may have a scaly, erythematous macule or plaque.

•

Telangiectasia, central ulceration may also be present ( Fig. 1-252 ).

•

Most SCC present as exophytic lesions that grow over a period of months.

FIGURE 1-252 Squamous cell carcinoma. Nodular hyperkeratotic lesion with central erosion. (From Noble J et al: Textbook of primary care medicine, ed 3, St Louis, 2001, Mosby.)

ETIOLOGY

Risk factors include UVB radiation and immunosuppression (renal transplant recipients have a threefold increased risk).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Keratoacanthomas

•

Actinic keratosis

•

Amelanotic melanoma

•

Basal cell carcinoma

•

Benign tumors

•

Healing traumatic wounds

•

Spindle cell tumors

•

Warts

WORKUP

Diagnosis is made with full-thickness skin biopsy (incisional or excisional).

TREATMENT ACUTE GENERAL Rx

•

Electrodesiccation and curettage for small SCCs (< 2 cm in diameter), superficial tumors and lesions located in extremity and trunk.

•

Tumors thinner than 4 mm can be managed by simple local removal.

•

Lesions between 4 and 8 mm thick or those with deep dermal invasion should be excised.

•

Tumors penetrating the dermis can be treated with several modalities, including excision and Mohs' surgery, radiation therapy, and chemotherapy.

•

Metastatic SCC can be treated with cryotherapy and combination of chemotherapy using 13-cis- retinoic acid and interferon a-2A.

DISPOSITION

•

Survival is related to size, location, degree of differentiation, immunologic status of the patient, depth of invasion, and presence of metastases. Risk factors for metastasis include lesions on the lip or ear, increasing lesion depth, and poor cell differentiation.

•

Patients whose tumors penetrate through the dermis or exceed 8 mm in thickness are at risk of tumor recurrence.

•

The most common metastatic locations are regional lymph nodes, liver, and lung.

•

Tumors on the scalp, forehead, ears, nose, and lips also carry a higher risk.

•

SCCs originating in the lip and pinna metastasize in 10% to 20% of cases.

•

Five-year survival for metastatic squamous cell carcinoma is 34%.

REFERRAL

Oncology referral for metastatic SCC

PEARLS & CONSIDERATIONS COMMENTS

SCC arising in areas of prior radiation, thermal injury, and areas of chronic ulcers or chronic draining sinuses are more aggressive and have a higher frequency of metastases than those originating in actinic damaged skin.

EVIDENCE

There is insufficient evidence for the use of radiation therapy after surgery to prevent recurrence of squamous cell carcinoma.[[1]] A 40% reduction in incidence of squamous cell carcinoma was found with daily application of sunscreen to head, neck, arms, and hands compared with discretionary application in a 4.5-year randomized controlled trial.[[2]]

Evidence-Based Referenceces 1. Green A, Marks R: Squamous cell carcinoma of the skin (non-metastatic). Clin Evid 2005; 13:2142.

2. Green A, et al: Daily sunscreen application and betacarotene supplementation in prevention of basal cell and squamous cell carcinomas of the skin: a randomised controlled trial. Lancet 1999; 354:723.Reviewed in: Clin Evid 11:2203, 2004.

SUGGESTED READINGS Stulberg DL, et al: Diagnosis and treatment of basal cell and squamous cell carcinomas. Am Fam Physician 2004; 70:1481.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Stasis Dermatitis PURVA AGARWAL, M.D.

BASIC INFORMATION DEFINITION

Stasis dermatitis refers to an inflammatory skin disease of the lower extremities, commonly seen in patients with chronic venous insufficiency. ( Fig. 1-253 )

FIGURE 1-253 Moderate stasis dermatitis with hyperpigmentation and bilateral venous insufficiency. (Courtesy Department of Dermatology, University of North Carolina at Chapel Hill. From Goldstein BG, Goldstein AO: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

SYNONYMS

Chronic venous insufficiency

ICD-9CM CODES

459.81 Stasis dermatitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Stasis dermatitis occurs more frequently in the elderly

•

Rarely seen before the age of 50 yr

•

Estimated to occur in up to 6% to 7% of the patients > 50 yr

•

Occurs in woman more often than men, perhaps related to lower extremity venous impairment aggravated through pregnancy

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Insidious onset

•

Pruritus

•

Chronic edema usually described as “brawny” edema as stasis dermatitis pathologically is associated with dermal fibrosis

•

Erythema

•

Scaly

•

Eczematous patches

•

Commonly located over the medial malleolus

•

Progressive pigment changes can occur as a result of extravasation of red blood cells and hemosiderin deposition within the cutaneous tissue.

•

Secondary infections can occur

ETIOLOGY

•

•

Stasis dermatitis is thought to occur as a direct result from any insult or injury of the lower extremity venous system leading to venous insufficiency including: 1.

Deep vein thrombosis

2.

Trauma

3.

Pregnancy

4.

Vein stripping

5.

Vein harvesting in patients requiring coronary artery bypass grafting (CABG)

Venous insufficiency subsequently results in venous hypertension, causing skin inflammation and the aforementioned physical findings and clinical presentation.

DIAGNOSIS The diagnosis of stasis dermatitis is primarily made by a detailed history and physical examination. DIFFERENTIAL DIAGNOSIS

•

Contact dermatitis

•

Atopic dermatitis

•

Cellulitis

•

Tinea dermatophyte infection

•

Pretibial myxedema

•

Nummular eczema

•

Lichen simplex chronicus

•

Xerosis

•

Asteatotic eczema

•

Deep vein thrombosis

WORKUP

Directed at excluding potential life-threatening causes (e.g., deep vein thrombosis) and complications (e.g., cellulites and sepsis). LABORATORY TESTS

Generally not very helpful unless a secondary infection is present. IMAGING STUDIES

•

X-rays, CT scans, and MRIs are generally not very helpful.

•

Doppler studies are indicated in any patient suspected of having a deep vein thrombosis.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Leg elevation above heart level for 30 min 3 to 4 times a day (avoid in arterial occlusive diseases).

•

Compression stocking with a gradient of at least 30 to 40 mm Hg. In obese patients, intermittent pneumatic compression pump is recommended.

•

For weeping skin lesions, wet to dry dressing changes are helpful.

ACUTE GENERAL Rx

•

The mainstay of treatment of stasis dermatitis is to control leg edema and prevent venous stasis ulcers from developing.

•

In patients with acute stasis dermatitis, a compression (Unna) boot can be applied.

•

Topical corticosteroid creams or ointments (e.g., triamcinolone 0.1% bid) are used frequently to help reduce inflammation and itching.

•

Secondary infections should be treated with appropriate antibiotics. Most secondary infections are the result of Staphylococcus or Streptococcus organisms.

•

Diuretics for controlling edema.

•

Aspirin (300 to 325 mg) promotes healing of chronic venous ulcers.

CHRONIC Rx

•

Patients with chronic stasis dermatitis can be treated with topical emollients (e.g., white petrolatum, lanolin, Eucerin).

•

Topical dressings (e.g., DuoDerm) are effective in the treatment of chronic venous stasis ulcers.

•

Surgical therapy: Venous stripping Superficial and deep perforator vein ligation Endovenous stenting

REFERRAL

•

Dermatology

•

Vascular surgery

•

Indications for referral: Nonhealing ulcers Uncertainty in the diagnosis Associated arterial insufficiency Persistent stasis dermatitis Suspected contact dermatitis Consideration of superficial venous surgery

PEARLS & CONSIDERATIONS COMMENTS

Inflammatory skin changes from stasis dermatitis are thought to result from poor oxygen perfusion to the lowerextremity skin tissue. SUGGESTED READINGS Felty CL, Rooke TW: Compression therapy for chronic venous insufficiency. Semin Vasc Surg 2005; 18(1):36. Mussa FF: Iliac vein stenting for chronic venous insufficiency. Tex Heart Inst J 2007; 34(1):60. Pascarella L, Schonbein GW, Bergan JJ: Microcirculation and venous ulcers: a review. Ann Vasc Surg 2005; 19(6):921. Yuwono HS: Diagnosis and treatment in the management of chronic venous insufficiency. Clin Hemorheol Microcirc 2000; 23(2–4):233.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Status Epilepticus JOHN E. CROOM, M.D., PH.D., SUZETTE LAROCHE, M.D.

BASIC INFORMATION DEFINITION

The term status epilepticus refers to continuous seizure activity lasting at least 5 min, or two or more discrete seizures between which there is incomplete recovery of consciousness. SYNONYMS

Generalized convulsive status epilepticus Nonconvulsive status epilepticus Complex partial status epilepticus Absence status epilepticus

ICD-9CM CODES

345.3 Grand mal status EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 100,000 to 152,000 cases per year PREDOMINANT SEX: Male = female PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

In convulsive status epilepticus, patients are unresponsive and have obvious tonic, clonic, or tonic-clonic movements of the extremities.

•

Presentation of patients in nonconvulsive status epilepticus varies from complete unresponsiveness with little or no observable motor activity to confusion with or without repetitive behaviors or automatisms.

ETIOLOGY

•

Preexisting epilepsy with breakthrough seizures or low anticonvulsant drug levels

•

Central nervous system (CNS) infection or tumor

•

Drug/alcohol toxicity or withdrawal

•

Metabolic disturbance

•

Hypoxia

•

Head trauma

•

Stroke

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Coma

•

Encephalopathy

•

Psychogenic unresponsiveness

WORKUP

Because convulsive status epilepticus is an emergency with substantial morbidity and mortality, treatment must be early and aggressive, not postponed until an etiology is determined. LABORATORY TESTS

•

While treatment is being initiated: glucose, electrolytes, BUN, ABG, drug levels, CBC, UA, toxicology screen.

•

Lumbar puncture in patients with fever or other signs/symptoms suspicious of CNS infection and all patients who are HIV positive.

IMAGING STUDIES

CT or MRI of the brain is recommended as soon as possible after seizures have been controlled.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Give oxygen by nasal cannula or nonrebreathing mask.

•

Maintain blood pressure, monitor ECG.

•

Obtain IV access.

•

Endotracheal intubation for refractory status epilepticus or signs of respiratory distress.

ACUTE GENERAL Rx

•

0 to 5 minutes: Thiamine 100 mg IV and glucose 50 mg D50 by IV push (2 ml/kg D25 in children) unless hyperglycemic.

•

5 to 10 minutes: Lorazepam 2 mg/min IV up to 0.1 mg/kg.

•

> 10 minutes: Fosphenytoin 20 mg/kg, Fosphenytoin equivalents (PE) IV up to 150 mg/min (if not available, use phenytoin 20 mg/kg IV at up to 50 mg/min). Can be followed by an additional 5 to 10 mg/kg PE IV if seizures persist.

•

> 45 minutes (refractory status epilepticus): Load phenobarbital 20 mg/kg IV or induce general anesthesia with midazolam, propofol, or pentobarbital by continuous intravenous drip.

•

An electroencephalogram (EEG) should be obtained to evaluate for nonconvulsive status epilepticus in any patient who does not regain consciousness within 1 to 2 hr of cessation of convulsive activity and for all patients requiring general anesthesia for seizure control.

CHRONIC Rx

Chronic treatment with anticonvulsants should be considered for all patients presenting with status epilepticus, particularly if there is significant risk of recurrence (e.g., known epilepsy, brain lesion, epileptiform EEG abnormalities). DISPOSITION

•

Favorable if status is treated promptly and there is no underlying acute symptomatic cause such as an underlying CNS lesion.

•

Overall mortality is 22%, but higher in the elderly (38%) and substantially lower in children (2.5%). Difference in mortality is mainly because status epilepticus in the elderly is more often the result of an acute symptomatic cause.

REFERRAL

All patients with refractory status epilepticus should be evaluated by a neurologist or epilepsy specialist.

PEARLS & CONSIDERATIONS COMMENTS

•

Because of varied clinical presentations of status epilepticus, there is no clinical basis for being certain that seizures have stopped unless the patient regains full consciousness.

•

EEG provides the only definitive information about seizure cessation.

•

All patients being treated with continuous IV infusion of anesthetic agents should have continuous EEG monitoring to assess treatment response.

EVIDENCE

In the Veterans Affairs cooperative randomized controlled trial, status epilepticus was terminated within 20 min in 64.9% of patients treated with lorazepam (0.1 mg/kg), 58.2% treated with phenobarbital (15 mg/kg), 55.8% treated with diazepam (0.15 mg/kg) and phenytoin (18 mg/kg), and 43.6% treated with phenytoin alone.[[1]] The San Francisco Emergency Medical Services Study, a randomized controlled trial, found that prehospital administration of intravenous benzodiazepines safely and effectively terminated convulsive status epilepticus in up to 60% of patients.[[2]] A meta-analysis comparing treatments for refractory status epilepticus found no difference in mortality between midazolam, pentobarbital, and propofol.[[3]] A retrospective review of all EEGs recorded in an academic hospital on comatose patients with no overt signs of seizure activity found nonconvulsive status epilepticus in 8% of patients.[[4]] In a study of EEGs performed following cessation of convulsive status epilepticus, discrete electrographic seizures were found in 48% and nonconvulsive status epilepticus was found in 14%.[[5]]

Evidence-Based Referenceces 1. N Engl J Med 1998; 339:792. 2. N Engl J Med 2001; 345:631. 3. Epilepsia 2002; 43:146. 4. Neurology 2000; 54:340. 5. Epilepsia 1998; 39:833.

SUGGESTED READINGS Gaitanis JN, Drislane FW: Status epilepticus: a review of different syndromes, their current evaluation, and treatment. Neurologist 2003; 9(2):61. Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Stevens-Johnson Syndrome FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Stevens-Johnson syndrome (SJS) is a severe vesiculobullous form of erythema multiforme affecting skin, mouth, eyes, and genitalia. SYNONYMS

SJS Herpes iris Febrile mucocutaneous syndrome

ICD-9CM CODES

695.1 Stevens-Johnson syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

SJS affects predominantly children and young adults.

•

Male:female ratio of 2:1.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The cutaneous eruption is generally preceded by vague, nonspecific symptoms of low-grade fever and fatigue occurring 1 to 14 days before the skin lesions. Cough is often present. Fever may be high during the active stages.

•

Bullae generally occur on the conjunctiva, mucous membranes of the mouth, nares, and genital regions.

•

Corneal ulcerations may result in blindness.

•

Ulcerative stomatitis results in hemorrhagic crusting.

•

Flat, atypical target lesions or purpuric maculae may be distributed on the trunk or be widespread ( Fig. 1254 ).

•

The pain from oral lesions may compromise fluid intake and result in dehydration.

•

Thick, mucopurulent sputum and oral lesions may interfere with breathing.

FIGURE 1-254 Stevens-Johnson syndrome. (From Stein JH: Internal medicine, ed 5, St Louis, 1998, Mosby.)

ETIOLOGY

•

Drugs (e.g., phenytoin, penicillins, phenobarbital, sulfonamides) are the most common cause.

•

Upper respiratory tract infections (e.g., Mycoplasma pneumoniae) and herpes simplex viral infections have also been implicated in SJS.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Toxic erythema (drugs or infection)

•

Pemphigus

•

Pemphigoid

•

Urticaria

•

Hemorrhagic fevers

•

Serum sickness

•

Staphylococcus scalded-skin syndrome

•

Behçet's syndrome

WORKUP

•

Diagnosis is generally based on clinical presentation and characteristic appearance of the lesions.

•

Skin biopsy is generally reserved for when classic lesions are absent and diagnosis is uncertain.

LABORATORY TESTS

CBC with differential, cultures in cases of suspected infection IMAGING STUDIES

Chest x-ray may show patchy changes in patients with pulmonary involvement.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Withdrawal of any potential drug precipitants

•

Careful skin nursing to prevent secondary infection

ACUTE GENERAL Rx

•

Treatment of associated conditions, (e.g., acyclovir for herpes simplex virus infection, erythromycin for mycoplasma infection)

•

Antihistamines for pruritus

•

Treatment of the cutaneous blisters with cool, wet Burow's compresses

•

Relief of oral symptoms by frequent rinsing with lidocaine (Xylocaine Viscous)

•

Liquid or soft diet with plenty of fluids to ensure proper hydration

•

Treatment of secondary infections with antibiotics

•

Corticosteroids: use remains controversial; when used, prednisone 20 to 30 mg bid until new lesions no longer appear, then rapidly tapered

•

Topical steroids: may use to treat papules and plaques; however, should not be applied to eroded areas

•

Vitamin A: may be used for lacrimal hyposecretion

DISPOSITION

•

Prognosis varies with severity of disease. It is generally good in patients with limited disease; however, mortality may approach 10% in patients with extensive involvement.

•

Oral lesions may continue for several months.

•

Scarring and corneal abnormalities may occur in 20% of patients.

REFERRAL

•

Hospital admission in a unit used for burn care is recommended in severe cases.

•

Urethral involvement may necessitate catheterization.

•

Ocular involvement should be monitored by an ophthalmologist.

PEARLS & CONSIDERATIONS COMMENTS

Risk of recurrence of SJS is 30% to 40%. AUTHOR: FRED F. FERRI, M.D. Stomatitis

BASIC INFORMATION DEFINITION

Stomatitis is inflammation involving the oral mucous membranes. SYNONYMS

Heterogeneous grouping of unrelated illnesses, each with their own designation(s)

ICD-9CM CODES

528.0 Stomatitis 054.2 (herpetic) 528.2 (aphthous) 112.0 (monilial) PHYSICAL FINDINGS & clinical presentation

WHITE LESIONS: Candidiasis (thrush) Caused by yeast infection (Candida albicans) Examination: white, curdlike material that when wiped off leaves a raw bleeding surface Epidemiology: seen in the very young and the very old, those with immunodeficiency (AIDS, cancer), persons with diabetes, and patients treated with antibacterial agents Other

•

Leukoedema: filmy opalescent-appearing mucosa, which can be reverted to normal appearance by stretching. This condition is benign.

•

White sponge nevus: thick, white corrugated folds involving the buccal mucosa. Appears in childhood as an autosomal dominant trait. Benign condition.

•

Darier's disease (keratosis follicularis): white papules on the gingivae, alveolar mucosa, and dorsal tongue. Skin lesions also present (erythematous papules). Inherited as an autosomal dominant trait.

•

Chemical injury: white sloughing mucosa.

•

Nicotine stomatitis: whitened palate with red papules.

•

Lichen planus: linear, reticular, slightly raised striae on buccal mucosa. Skin is involved by pruritic violaceous papules on forearms and inner thighs.

•

Discoid lupus erythematosus: lesion resembles lichen planus.

•

Leukoplakia: white lesions that cannot be scraped off; 20% are premalignant epithelial dysplasia or squamous cell carcinoma.

•

Hairy leukoplakia: shaggy white surface that cannot be wiped off; seen in HIV infection, caused by EBV.

RED LESIONS: •

Candidiasis may present with red instead of the more frequent white lesion (see “White Lesions”). Median rhomboid glossitis is a chronic variant.

•

Benign migratory glossitis (geographic tongue): area of atrophic depapillated mucosa surrounded by a keratotic border. Benign lesion, no treatment required.

•

Hemangiomas.

•

Histoplasmosis: ill-defined irregular patch with a granulomatous surface, sometimes ulcerated.

•

Allergy.

•

Anemia: atrophic reddened glossal mucosa seen with pernicious anemia.

•

Erythroplakia: red patch usually caused by epithelial dysplasia or squamous cell carcinoma.

•

Burning tongue (glossopyrosis): normal examination; sometimes associated with denture trauma, anemia, diabetes, vitamin B12 deficiency, psychogenic problems.

DARK LESIONS (BROWN, BLUE, BLACK): •

Coated tongue: accumulation of keratin; harmless condition that can be treated by scraping

•

Melanotic lesions: freckles, lentigines, lentigo, melanoma, Peutz-Jeghers syndrome, Addison's disease

•

Varices

•

Kaposi's sarcoma: red or purple macules that enlarge to form tumors; seen in patients with AIDS

RAISED LESIONS:

•

Papilloma

•

Verruca vulgaris

•

Condyloma acuminatum

•

Fibroma

•

Epulis

•

Pyogenic granuloma

•

Mucocele

•

Retention cyst

BLISTERS: •

Primary herpetic gingivostomatitis

Caused by herpes simplex virus type 1 or less frequently type 2 Course: day 1: malaise, fever, headache, sore throat, cervical lymph-adenopathy; days 2 and 3: appearance of vesicles that develop into painful ulcers of 2 to 4 mm in diameter; duration of up to 2 wk Recurrent intraoral herpes: rare, recurrences typically involve only the keratinized epithelium (lips)

•

Pemphigus and pemphigoid

•

Hand-foot-mouth disease: caused by coxsackievirus group A

•

Erythema multiforme

•

Herpangina: caused by echovirus

•

Traumatic ulcer

•

Primary syphilis

•

Perlèche (or angular cheilitis)

•

Recurrent aphthous stomatitis (canker sores)

•

Behçet's syndrome (aphthous ulcers, uveitis, genital ulcerations, arthritis, and aseptic meningitis)

•

Reiter's syndrome (conjunctivitis, urethritis, and arthritis with occasional oral ulcerations)

•

Unknown cause

Course: solitary or multiple painful ulcers may develop simultaneously and heal over 10 to 14 days. The size of the lesions and the frequency of recurrences are variable.

DIAGNOSIS WORKUP

WHITE LESIONS: Candidiasis (thrush) diagnosis: ovoid yeast and hyphae seen in scrapings treated with KOH culture BLISTERS:

•

Exfoliative cytology

•

Viral culture

•

Immunofluorescence for herpes antigen

TREATMENT WHITE LESIONS: Candidiasis (thrush) treatment: •

Topical with nystatin or clotrimazole

•

Systemic with ketoconazole or fluconazole

BLISTERS: •

Supportive

•

Consider acyclovir

RECURRENT INTRAORAL HERPES: Topical corticosteroids or systemic steroids for severe cases SUGGESTED READINGS Amir J, et al: Treatment of herpes simplex gingivostomatitis with acyclovir in children: a randomized double blind placebo controlled study. BMJ 1997; 314:1800. Khandwala A, et al: 5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers. Clinical demonstration of acceleration of healing and resolution of pain. Oral Surg Oral Med Oral Pathol 1997; 83:222.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Strabismus MELVYN KOBY, M.D.

BASIC INFORMATION DEFINITION

Strabismus is a condition of the eyes in which the visual axes of the eyes are not straight in the primary position or in which the eyes do not follow each other in the different positions of gaze. SYNONYMS

Esotropia Exotropia Restrictive eye movement

ICD-9CM CODES

378.9 Strabismus EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 2% of all children PEAK INCIDENCE: Childhood PREDOMINANT SEX: None PREDOMINANT AGE: Birth to 5 yr of age GENETICS: None known PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Conjugate gaze loss in both eyes with the eyes focusing independently ( Fig. 1-255 )

•

Amblyopia

FIGURE 1-255 A, Note the nasal deviation of the right eye with the corneal light reflection temporally displaced on the right eye and centered in the left pupil, indicating an esotropia. B, Divergent strabismus of the left eye, defining an exotropia. (From Hodkelman [ed]: Primary pediatric care, ed 3, St Louis, 1997, Mosby.)

ETIOLOGY

•

Many cases are congenital.

•

Accomodative cases occur later with focusing.

•

Rarely, there is neurologic disease or severe refractive errors.

•

Hereditary common, with hyperopia (far-sightedness) most common.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Measuring eye position and movement

•

Vision testing

•

Refractive errors

•

CNS tumors

•

Orbital tumors

•

Brain and CNS dysfunction

WORKUP

•

Eye examination

•

Visual field

•

MRI to rule out tumors when develops later with no apparent cause

LABORATORY TESTS

Generally not needed IMAGING STUDIES

Necessary only if other neurologic findings are found

TREATMENT NONPHARMACOLOGIC THERAPY

•

Glasses

•

Patching—best between 3 to 7 yr old; vision most improved by 3 to 6 mo

•

Prisms

•

Atropine—same as patching most of time although patching may give better results in resistant cases

CHRONIC Rx

•

Glasses

•

Alternate eye patching

•

Surgery

•

Prisms

DISPOSITION

•

The earlier the condition is treated, the more likely it is that the child will have normal vision in both eyes.

•

After age 7 yr, visual loss is usually permanent from amblyopia.

REFERRAL

•

Early for full rehabilitation of eye cosmetically and functionally

•

To an ophthalmologist for management (usually)

EVIDENCE

A systematic review of randomized controlled trials of surgical and nonsurgical treatments for intermittent distance exotropia found that the literature consists mainly of retrospective case reviews, which are difficult to compare and analyze because of large variations in definition, intervention criteria, and outcome measures. The reviewers noted, however, that there seems to be general agreement that nonsurgical treatment is most appropriate in small-angle deviations or as a supplement to surgery. They found studies that supported early surgical intervention and others that supported late surgical intervention, and so were unable to draw conclusions about the optimal timing of surgical intervention. They also noted that recent work suggests that bilateral surgery may be the most effective surgical procedure. [[1]] A systematic review of the literature concerning the surgical treatment of strabismus in adults identified one randomized controlled trial, which found that surgical treatment was significantly more effective than chemodenervation with botulinum toxin A.[[2]]

Evidence-Based Referenceces 1. Richardson S, Gnanaraj L: Interventions for intermittent distance exotropia. Cochrane Database Syst Rev 2003; 2: 2. Mills MD, et al: Strabismus surgery for adults. A report by the American Academy of Ophthalmology. Ophthalmology 2004; 111:1255.

SUGGESTED READINGS Donahue SP: Pediatric strabismus. N Engl J Med 2007; 356:1040.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Stroke RICHARD S. ISAACSON, M.D.

BASIC INFORMATION DEFINITION

Stroke describes acute brain injury caused by decreased blood supply or hemorrhage. SYNONYMS

Cerebrovascular accident (CVA)

ICD-9CM CODES

436 Acute stroke EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Occurs in 5 to 10/100,000 persons < 40 yr of age

•

Occurs in 10 to 20/100,000 persons > 65 yr of age

PEAK INCIDENCE: 80 to 84 yr PREVALENCE (IN U.S.): Estimated at 5.8 million persons PREDOMINANT SEX: Incidence is 30% higher in males PHYSICAL FINDINGS & CLINICAL PRESENTATION

Motor and/or sensory and/or cognitive deficits, depending on distribution and extent of involved vascular territory. More common manifestations include contralateral motor weakness or sensory loss, as well as language difficulties (aphasia; predominantly left-sided lesions) and visuospatial/neglect phenomena (predominantly right-sided lesions). Onset is usually sudden; however, this depends on specific etiology. ETIOLOGY

•

70% to 80% are caused by ischemic infarcts; 20% to 30% are hemorrhagic.

•

80% of ischemic infarcts are from occlusion of large or small vessels caused by atherosclerotic vascular disease (due to hypertension, hyperlipidemia, diabetes, tobacco abuse), 15% are caused by cardiac embolism, 5% are from other causes, including hypercoagulable states and vasculitis.

•

Small vessel occlusion is most often caused by lipohyalinosis precipitated by chronic hypertension.

•

Risk factors for ischemic stroke are described in Box 1-11 .

BOX 1-11 Risk Factors for Ischemic Stroke Nonmodifiable: Age, gender, race, sociocultural Family history of premature vascular disease Modifiable: Diabetes, hypertension, hyperlipidemia Smoking (prior smoker 1.3 × risk, current smoker 2.1 × risk) Alcohol (1-2 drinks/day decreases risk × 0.75 vs. no alcohol; >2 drinks/day increases risk) Waist circumference Atrial fibrillation History of transient ischemic attack (TIA) History of congestive heart failure (left ventricular [LV] ejection fraction females in persons < 40 yr of age; then female:male ratio of 3:2 in persons > 40 yr old PREDOMINANT AGE: >50 yr GENETICS: •

First-degree relatives have a 4% to 9% risk of intracranial aneurysms (as compared with about 2% in the general population) and these may tend to rupture at a younger age and at a smaller size than sporadic ones. Recommendations on screening unaffected family members depend on the number of relatives with aneurysms. There may also be a familial predisposition to multiple aneurysms.

•

Increased incidence in some inherited systemic diseases (e.g., autosomal dominant polycystic kidney disease and connective tissue diseases such as Ehlers-Danlos syndrome).

•

No single gene has yet been identified for intracranial aneurysm formation or rupture.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Patients typically present with sudden onset of a severe headache with maximal intensity at onset. Additional findings may include nuchal rigidity, nausea, and vomiting.

•

Transient loss of consciousness occurs in 45% of patients.

•

Focal neurologic deficits may be present.

•

Funduscopic examination may reveal subhyaloid hemorrhage.

ETIOLOGY

•

Key distinction is aneurysmal (nontraumatic etiology in > 60% of cases, most commonly after rupture of saccular “berry” aneurysms) vs. nonaneurysmal (traumatic) SAH

•

Others: Arteriovenous malformation (AVM), angioma, fusiform or mycotic aneurysm, dissecting and tumorrelated aneurysms

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Intraparenchymal hemorrhage

•

Subarachnoid extension of an extracranial arterial dissection or intracerebral hemorrhage

•

Meningoencephalitis (e.g., hemorrhagic meningoencephalitis caused by HSV)

•

Headache associated with sexual activity (e.g., coital/postcoital headache; usually acute onset of severe headache around time of orgasm)

WORKUP

•

CT scan without contrast is initial test of choice, with a sensitivity of 90% or higher in the first 12 to 24 hr. If CT is negative and there is a high clinical suspicion for SAH, lumbar puncture must be considered as there is an approximately 7% (or 1 in 14) chance of having a SAH. Spinal fluid is considered positive if there is xanthochromia and if there is a constant amount of red cells in each LP tube. LP performed < 12 hr after onset of headache may be falsely negative for xanthochromia.

•

If CT scan is unavailable, transfer patient immediately.

•

ECG (nonspecific ST-and T-wave changes, “cerebral T-waves”).

LABORATORY TESTS

PT, PTT, platelet count at a minimum for clotting abnormality IMAGING STUDIES

CT scan ( Fig. 1-260 ) followed by cerebral angiography if hemorrhage is confirmed. May also use Transcranial Doppler (TCD) as a baseline to more adequately assess for vasospasm later

FIGURE 1-260 Noncontrast CT demonstrates diffuse subarachnoid hemorrhage. The rounded area of hyperdensity anterior to the suprasellar cistern represents an aneurysm of the anterior communicating artery. (From Specht N [ed]: Practical guide to diagnostic imaging, St Louis, 1998, Mosby.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Intubation as necessary

•

Bed rest, isotonic fluids

•

Neurosurgical or interventional neuroradiologic referral mandatory if aneurysm or arteriovenous malformation demonstrated by angiography; also, invasive ICP monitoring and/or ventriculostomy may be required on an emergent basis (e.g., deteriorating level of consciousness and/or development of hydrocephalus); elevated ICP is associated with a worse patient outcome, particularly if ICP does not respond to treatment

ACUTE GENERAL Rx

•

Short-acting analgesics (e.g., morphine 1 to 4 mg IV) and sedation (e.g., midazolam 1 to 5 mg IV); avoid oversedation and watch neurologic examination closely

•

Seizure prophylaxis controversial (consider phenytoin 15 to 20 mg/kg IV load, 100 mg TID maintenance)

•

Vasospasm prophylaxis (nimodipine 60 mg PO q4h)

•

BP control (e.g., labetalol 10 to 40 mg IV q30 min); lower BP for unprotected aneurysms vs. higher BP if protected (post-coiling/clipping)

•

Stool softeners

•

Hypertonic saline (HS) solutions have been used in various concentrations (e.g., 7.5%, 10%, 23.5%) to treat elevated ICP and augment cerebral blood flow (CBF); in one study, HS 23.5% bolus (2 ml/kg IV x 1) exerted an early CBF-augmenting effect which lasted for up to 7.5 hr; despite this evidence, there are limited studies in this area and the exact recommended doses have yet to be determined; neurosurgical consultation is mandatory for persistently elevated ICP management

•

Vasospasm occurs in 20% to 30% of patients and peaks at about 1 wk; monitor closely for this. Consider TCD monitoring in high-risk patients. “Triple H” therapy for prevention of vasospasm includes hemodilution, hypertension (consider pressors), and hypervolemia. Goals of Triple H include a hematocrit of 30%, central venous pressure of 8 to 12 mm Hg, and enough artificially induced hypertension to prevent or reverse new neurologic deficits

•

Patients with any persistent new neurologic deficit who do not respond to medical treatment should have urgent catheter angiography to confirm the presence of vasospasm, followed by intraarterial papaverine and/or balloon angioplasty in those cases

•

While a systematic review of randomized trials suggested a positive effect of antiplatelet therapy after aneurysmal SAH, a randomized controlled trial concluded that aspirin did not reduce the risk of delayed ischemic neurological deficit

CHRONIC Rx

It is unclear whether the increased risk for recurrent aneurysms justifies continued screening. A review of 752 cases found the cumulative incidence of recurrent SAH was 3.2% (22 times higher than expected in comparable populations). Risk factors for recurrence were smoking, age, and multiple aneurysms at the time of the initial SAH. The issue requires further study. DISPOSITION

Approximately 35% early mortality, 45% at 1 mo REFERRAL

Transfer as soon as possible to a facility with neurosurgical care.

PEARLS & CONSIDERATIONS COMMENTS

About 20% of patients experience warning signs within 3 mo before aneurysm rupture, including moderate or severe headache (“sentinel headache”), dizziness, nausea and vomiting, transient motor or sensory deficits, loss of consciousness, or visual disturbances.

EVIDENCE

Oral nimodipine (60 mg every 4 hours) significantly reduces the proportion of patients with poor outcome and ischemic neurologic deficits after aneurysmal SAH. Limited evidence suggests that the timing of surgery is not a critical factor in determining outcome following an SAH, although results from one trial suggest that patients who undergo early surgery (day 0-3) tend to fare best. Antifibrinolytic therapy does not improve clinical outcome following SAH, as the benefit gained from a reduction of rebleeding is offset by an increase in poor outcome caused by cerebral ischemia. A randomized trial comparing neurosurgical clipping vs. endovascular coiling in 2143 patients with ruptured intracranial aneurysms showed the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data also suggested that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling. A prospective pilot study of 19 patients confirmed the safety and feasibility of continuous high-dose intravenous magnesium sulfate (MgSO4) for the prevention of cerebral vasospasm and ischemic cerebral injury. A randomized, double-blind, placebo-controlled trial with MgSO4 (64 mmol/day IV) is currently under way. A randomized trial of intravenous magnesium vs. nimodipine showed comparable results between groups. A randomized trial of mild intraoperative hypothermia during surgery for intracranial aneurysm did not improve neurologic outcomes. There is no evidence of a beneficial or adverse effect of corticosteroids, and we are unable to cite evidence that meets our criteria for the other treatments for SAH. SUGGESTED READINGS Beck J, et al: Sentinel headache and the risk of rebleeding after aneurysmal subarachnoid hemorrhage. Stroke 2006; 37(11):2733.Epub Sept 28, 2006 Bederson JB, et al: Recommendations for the management of patients with unruptured intracranial aneurysms: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation 2000; 102(18):2300. Brisman JL, et al: Cerebral aneurysms. N Engl J Med 2006; 355:928.

Dorhout Mees S, et al: Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Library 2007; 3:CD000277 Edlow JA: Diagnosis of subarachnoid hemorrhage. Neurocri Care 2005; 2(2):99. Edlow JA, Caplan LR: Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med 2000; 342:29. Edlow JA, Wyer PC: How good is a negative cranial computed tomographic scan result in excluding subarachnoid hemorrhage?. Ann Emerg Med 2000; 36:507. Feigin V, et al: Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane Database Syst Rev 2005; 20(3):CD004583 Heuer GG, et al: Relationship between intracranial pressure and other clinical variables in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 2004; 101(3):408. Krischek B, Inoue I: The genetics of intracranial aneurysms. J Hum Genet 2006; 51:587. Molyneux A, et al: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002; 26(9342):360.1267 Morgenstern LB, et al: Worst headache and subarachnoid hemorrhage: prospective modern computed tomography and spinal fluid analysis. Ann Emerg Med 1998; 32:297. Morris PG, et al: Anxiety and depression after spontaneous subarachnoid hemorrhage. Neurosurgery 2004; 54(1):47.discussion 52 Pickard JD, et al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989; 298:636. Qureshi AI, Suarez JI: Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000; 28(9):3301. Raaymakers TWthe MARS Study Group: Aneurysms in relatives of patients with subarachnoid hemorrhage. Frequency and risk factors. Neurology 1999; 53:982. Roos YB, et al: Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Library 2004; 1: Schmid-Elsaesser R, et al: Intravenous magnesium versus nimodipine in the treatment of patients with aneurismal subarachnoid hemorrhage: a randomized study. Neurosurg 2006; 58:1054. Suarez JI: Editorial comment: salting the brain to improve CBF in SAH patients. Stroke 2003; 34:1396. Todd MM: Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 2005; 352:135. Treggiari MM, et al: Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage. J Neurosurg 2003; 98:978. Tseng MY, et al: Effect of hypertonic saline on cerebral blood flow in poor-grade patients with subarachnoid hemorrhage. Stroke 2003; 34:1389. Van den Bergh WB, et al: Randomized controlled trial of acetylsalicylic acid in aneurysmal subarachnoid hemorrhage: the MASH study. Stroke 2006; 37:2326. Wermer MJ, et al: Incidence of recurrent subarachnoid hemorrhage after clipping for ruptured intracranial

aneurysms. Stroke 2005; 36:2394. Whitfield PC, Kirkpatrick PJ: Timing of surgery for aneurysmal subarachnoid haemorrhage. Cochrane Library 2004; 1: Yahia AM, et al: The safety and feasibility of continuous intravenous magnesium sulfate for prevention of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. Neurocrit Care 2005; 3(1):16.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Subclavian Steal Syndrome DANIEL MATTSON, M.D., M.SC.(MED.)

BASIC INFORMATION DEFINITION

Subclavian steal syndrome is an occlusion or severe stenosis of the proximal subclavian artery leading to decreased antegrade flow or retrograde flow in the ipsilateral vertebral artery and neurologic symptoms referable to the posterior circulation. SYNONYMS

Proximal subclavian (or innominate) artery stenosis or occlusion

ICD-9CM CODES

435.2 Subclavian steal syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

Similar to that of other manifestations of atherosclerosis (coronary artery disease, cerebrovascular disease, or peripheral vascular disease)

•

Affects middle-aged persons (men somewhat younger than women on average) with arteriosclerotic risk factors including family history, smoking, diabetes mellitus, hyperlipidemia, hypertension, sedentary lifestyle

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Symptoms: •

Many patients are asymptomatic.

•

Upper extremity ischemic symptoms: fatigue, exercise-related aching, coolness, numbness of the involved upper extremity.

•

Neurologic symptoms are reported by 25% of patients with known unilateral subclavian steal. These include brief spells of: 1.

Vertigo

2.

Diplopia

3.

Decreased vision

4.

Oscillopsia

5.

Gait unsteadiness

These spells are only occasionally provoked by exercising the ischemic upper extremity (classic subclavian

steal). Left subclavian steal is more common than right, but the latter is more serious.

•

Posterior circulation stroke related to subclavian steal is rare.

•

Innominate artery stenosis can cause decreased right carotid artery flow and cerebrovascular symptoms of the anterior cerebral circulation, but this is uncommon.

Physical findings: •

Delayed and smaller volume pulse (wrist or antecubital) in the affected upper extremity

•

Lower blood pressure in the affected upper extremity

•

Supraclavicular bruit

NOTE: Inflating a blood pressure cuff will increase the bruit if it originates from a vertebral artery stenosis and decrease the bruit if it originates from a subclavian artery stenosis. ETIOLOGY & PATHOGENESIS

Etiology: •

Atherosclerosis

•

Arteritis (Takayasu's disease and temporal arteritis)

•

Embolism to the subclavian or innominate artery

•

Cervical rib

•

Chronic use of a crutch

•

Occupational (baseball pitchers and cricket bowlers)

Pathogenesis: The vertebral artery originates from the subclavian artery. For subclavian steal to occur, the occlusion must be proximal to the takeoff of the vertebral artery. On the right side, only a small distance separates the bifurcation of the innominate artery and the takeoff of the vertebral artery, explaining why the condition occurs less commonly on the right side. Occlusion of the innominate artery must affect right carotid artery flow.

DIAGNOSIS

•

See “History,” “Physical Findings,” and “Imaging Studies.”

•

The carotid arteries should be evaluated at least noninvasively in all cases.

DIFFERENTIAL DIAGNOSIS

•

Posterior circulation TIA (and stroke)

•

Upper extremity ischemia

WORKUP

1.

Distal subclavian artery stenosis/occlusion

2.

Raynaud's syndrome

3.

Thoracic outlet syndrome

•

Noninvasive upper extremity arterial flow studies

•

Doppler sonography of the vertebral, subclavian, and innominate arteries

•

Arteriography

TREATMENT

•

In most patients the disease is benign and requires no treatment other than atherosclerosis risk factor modification and aspirin. Symptoms tend to improve over time as collateral circulation develops.

•

Vascular surgical reconstruction requires a thoracotomy; it may be indicated in innominate artery stenosis or when upper extremity ischemia is incapacitating.

AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Subdural Hematoma

BASIC INFORMATION DEFINITION

A subdural hematoma is bleeding into the subdural space, caused by rupture of bridging veins between the brain and venous sinuses.

ICD-9CM CODES

432.1 Subdural hematoma SYNONYMS

Acute subdural hematoma Chronic subdural hematoma Subdural hemorrhage EPIDEMIOLOGY & DEMOGRAPHICS

Nearly all cases are caused by trauma, although the trauma may be quite trivial. Patients are commonly at the extremes of age. Coagulation abnormalities, especially use of anticoagulation in the elderly, is a significant risk factor. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Vague headache, often worse in morning than evening.

•

Some apathy, confusion, and clouding of consciousness is common, although frank coma may complicate late cases. Chronic subdural hematomas may cause a dementia picture.

•

Neurologic symptoms may be transient, simulating TIA.

•

Almost any sign of cortical dysfunction may occur, including hemiparesis, sensory deficits, or language abnormalities, depending on which part of the cortex is compressed by the hematoma.

•

New-onset seizures should raise the index of suspicion.

ETIOLOGY

Traumatic rupture of cortical bridging veins, especially where stretched by underlying cerebral atrophy

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Epidural hematoma

•

Subarachnoid hemorrhage

•

Mass lesion (e.g., tumor)

•

Ischemic stroke

•

Intraparenchymal hemorrhage

WORKUP

•

CT scan is sensitive for diagnosis and should be performed in a timely fashion ( Fig. 1-261 ).

•

Hematocrit, platelet count, PTT, and PT/INR should be routinely checked.

FIGURE 1-261 Subdural hematomas. A noncontrasted computed tomography scan of an acute subdural hematoma (A) shows a crescentic area of increased density in the right posterior parietal region between the brain and the skull (black and white arrows). An area of intraparenchymal hemorrhage (H) is also seen; a chronic subdural hematoma for a different patient is shown in (B). There is an area of decreased density in the left frontoparietal region (arrows) effacing the sulci, compressing the anterior horn of the left lateral ventricle, and shifting the midline somewhat to the right. (From Mettler FA [ed]: Primary care radiology, Philadelphia, 2000, WB Saunders.)

TREATMENT NONPHARMACOLOGIC THERAPY

Small subdural hematomas may be left untreated and the patient observed, but if there is an underlying cause, such as anticoagulation, this should be rapidly corrected to prevent further accumulation of blood. ACUTE GENERAL Rx

•

Neurosurgical drainage of blood from subdural space via burr hole is the definitive procedure, although it is common for the hematoma to reaccumulate.

•

There is an increased risk of seizures, which should be treated appropriately if they arise.

DISPOSITION

Admit to hospital, may require ICU admission. Neurosurgical evacuation may be required. REFERRALS

Neurology, neurosurgery, critical care

PEARLS & CONSIDERATIONS

•

The very young and very old are particularly susceptible to subdural hematomas.

•

Relatively minor trauma may cause a subdural hematoma.

•

Caution should be taken in interpreting CT findings in the subacute stage, where blood appears as isodense to brain, and therefore the distance from the cortical sulci to the skull needs to be evaluated.

EVIDENCE

There are no RCTs to guide the selection of treatment in SDH. In particular, no defined criteria for selecting patients who would benefit from surgical evacuation exist. Advanced age and severity of underlying cerebral lesions were negatively correlated with outcome in a large retrospective study of patients who received surgical intervention. [249] [250] Review of the literature does not show a clear benefit for prophylactic antiepileptic medications in SDH.[[3]] Use of factor IX complex vs. FFP for reversal of warfarin-induced bleeding was associated with improved speed of anticoagulation reversal by factor IX complex in an RCT. No studies, however, establish that rapid reversal improves outcome.[[4]] A recent retrospective analysis suggested no difference in outcome between craniotomy vs. decompressive craniectomy in acute traumatic SDH, but found advanced age and evidence of herniation independently correlated with poor outcome.[[5]]

Evidence-Based Referenceces 1. Neurosurg Rev 1997; 20(b):239-244. 2. Clin Neurol Neurosurg 2005; 107(b):223-229. 3. Cochrane Database Syst Rev 2005; 3:CD004893 4. Neurosurgery 1999; 45(5):1113-1118.discussion 1118–1119 5. J Clin Neurosci 2006; 13(7):718.Epub, 2006

SUGGESTED READINGS Adhiyaman V, et al: Chronic subdural haematoma in the elderly. Postgrad Med J 2002; 78(b):71-75. Chen JC, Levy ML: Causes, epidemiology, and risk factors of chronic subdural hematoma. Neurosurg Clin N Am 2000; 11(3):399. Voelker JL: Nonoperative treatment of chronic subdural hematoma. Neurosurg Clin N Am 2000; 11(3):507.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Suicide MITCHELL D. FELDMAN, M.D., M.PHIL.

BASIC INFORMATION DEFINITION

Suicide refers to successful and unsuccessful attempts to kill oneself. Suicide ideation is defined as the presence of passive or active thoughts about a premature end of life. SYNONYMS

Self-murder

ICD-9CM CODES Categorized by method (e.g., poisoning) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Suicide is among the top 10 leading causes of death and the seventh leading cause of years of potential life lost in the U.S.

•

Suicide ideation is present in 7% to 10% of primary care patients.

•

Overall rate in U.S. is 11 cases/100,000 persons.

•

Rate in men is 18.7 cases/100,000 persons.

•

Rate in women is 4.4 cases/100,000 persons.

PEAK INCIDENCE: > 65 yr of age for completed suicide PREDOMINANT AGE: •

Increases with age (13.1 cases/100,000 persons aged 15 to 24 yr, 16.9 cases/100,000 persons aged 65 to 74 yr, and 23.5 cases/100,000 persons aged 75 to 84 yr)

•

Third leading cause of death in ages 15 to 24 in U.S.

GENETICS: •

Biologic factors may increase the risk of suicide directly (e.g., by increasing impulsivity) or indirectly (e.g., by predisposing to a mental illness).

•

Family history of suicide is associated with suicidal behavior.

•

Pediatric trials suggest that selective serotonin reuptake inhibitors (SSRIs) are associated with slight increased risk of suicidal behavior.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Methods used in attempted (unsuccessful) suicides differ from those used in completed suicides.

•

Overdose used in > 70% of attempted suicides.

•

About 60% of completed suicides are accomplished with firearms. Hanging is the second most common method for completed suicides.

•

Several risk factors for completed suicide include psychiatric illness such as depression or anxiety, middle age or advanced age, white race, male gender, a recent divorce or separation, comorbid substance abuse (particularly when intoxicated), previous history of suicide attempts, fatal plan (e.g., firearms or hanging), history of violence, and family history of suicide. Concurrent chronic physical illness increases the risk for suicide greatly (e.g., the risk for suicide among AIDS or renal dialysis patients is nearly 30 times that of the general population).

ETIOLOGY

•

Individuals with a mental disorder or substance abuse are responsible for > 90% of all suicides.

•

The concurrence of more than one condition (e.g., depression and alcohol abuse) greatly increases the risk of suicide.

•

Hopelessness is a strong predictor of suicide potential.

•

Same-gender sexual orientation has been shown to exert an independent influence on suicide attempts.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Some disorders are associated with self-injurious behavior that is not suicidal. Borderline personality disorder, for example, manifests with self-mutilation without active suicidal intent. Eating disorders are harmful and may be fatal, but death is rarely the goal.

•

Some suicidal behavior is intended as a “call for help.” In these situations individuals usually design the suicide so that they will be discovered before significant damage has been done.

WORKUP

•

The physician must directly inquire into the presence of suicidal ideation. Approximately one half to two thirds of individuals who commit suicide visit physicians within 1 mo of taking their lives.

•

Explicit suicidal intent, hopelessness, and a well-formulated plan indicate high risk. Clinicians can use the mnemonic SAL: Is the method Specific? Is it Available? Is it Lethal?

•

The concurrence of multiple psychiatric problems, substance abuse, and multiple physical problems increases the risk.

•

Covert suicidal ideation occurs in patients primarily with multiple vague physical complaints, depression, anxiety, or substance abuse.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Major immediate intervention: placement of the patient in a safe environment (usually hospitalization in a psychiatric unit or a medical unit with continuous observation)

•

Long-term: psychotherapy aimed at factors that underlie the decision to pursue suicide or at the risk factors contributing to suicidal behavior

•

Substance abuse treatment (e.g., AA, NA) when substance abuse is present

ACUTE GENERAL Rx

•

Benzodiazepines are useful in reducing the extreme anxiety and dysphoria in a suicidal patient; however, these agents are depressive and should be used only when patient is in a safe environment.

•

Antipsychotics can be used if psychosis is present (e.g., voices telling patient to hurt self).

•

Mood stabilizers and antidepressants should be started in the acute setting but may have up to a 2-wk latency period.

CHRONIC Rx

•

Therapy should be aimed at the underlying condition (e.g., antidepressants for depression, anxiolytics or antidepressants for anxiety, ongoing substance abuse treatment for substance abuse history, or psychotherapy for chronic low self-esteem, hopelessness).

•

In elderly, loneliness and medical disability are major reasons for suicide and therefore major targets for intervention.

DISPOSITION

•

Prior suicide attempt is the best predictor for completed suicides (i.e., patients who attempt suicide once are at high risk for completing suicide in the future).

•

Conditions associated with suicide (e.g., depression, physical ailments) are usually chronic and recurring.

REFERRAL

Patients with active suicidal ideation and intent should be referred to specialty mental health.

PEARLS & CONSIDERATIONS

•

Past suicidal behavior is strongly associated with an increased risk for subsequent suicidal behavior.

•

Most people who die by suicide are suffering from a treatable mental disorder, usually depression, but few have seen a specialty mental health provider.

•

Although many patients are reluctant to seek and actively engage in mental health treatment, up to 75% of those who complete suicide have seen a primary care provider in the prior 30 days.

PREVENTION

The U.S. Preventive Services Task Force has produced the following document: Gaynes BN et al: Screening for suicide risk in adults: a summary of the evidence for the U.S. Preventive Services Task Force, Ann Intern Med 140:822, 2004.

EVIDENCE

Cognitive-behavioral therapy (CBT) There is limited evidence from randomized studies that CBT is of benefit in reducing further suicide attempts in patients who have previously attempted suicide. A randomized controlled trial (RCT) compared CBT vs. enhanced usual care over 18 months in 120 adults who had recently attempted suicide. This study found that treatment with CBT resulted in significantly lower reattempt rate compared with usual care (24% vs. 41%) and had significantly reduced rate of self-reported depression.[[1]] Electroconvulsive therapy (ECT) The use of ECT in the short-term management of suicidality is supported by expert opinion. Recommendations from the American Psychiatric Association are that, because ECT is associated with a rapid and robust antidepressant response and a rapid diminution in associated suicidal thoughts, ECT may be recommended as a treatment for severe episodes of major depression that are accompanied by suicidal thoughts or behaviors. [[2]] Further recommendations are that, because there is no evidence of a long-term reduction of suicide risk with ECT, continuation or maintenance treatment with pharmacotherapy or with ECT is recommended after an acute ECT course.[[2]] Interpersonal therapy A systematic review of 13 RCTs analyzed the efficacy of interpersonal therapy in the treatment of depressive spectrum disorders using a metaanalytic approach. Four metaanalyses were performed, showing that interpersonal therapy was superior to placebo, similar to treatment with medication alone (and efficacy did not increase when combined with medication), and superior to CBT.[[3]] Recommendations from the American Psychiatric Association are that, in patients with suicidality, psychothera-pies such as interpersonal psychotherapy and CBT may be considered appropriate treatments for suicidal behavior, especially in the context of depression.[[2]]

Evidence-Based Referenceces 1. Brown GK, et al: Cognitive therapy for the prevention of suicide attempts: a randomized controlled trial. JAMA 2005; 294:563-570. 2. American Psychiatric Association: Practice guideline for the assessment and treatment of patients with suicidal behaviors, Arlington, VA, American Psychiatric Association, 2003. $c 3. de Mello MF, et al: A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci 2005; 255:75-82.

SUGGESTED READINGS Feldman MD, et al: Let's not talk about it: suicide inquiry in primary care. Ann Fam Med 2007; 5(b):412-418.

Mann JJ, et al: Suicide prevention strategies: a systematic review. JAMA 2005; 294(16):2064.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Superior Vena Cava Syndrome SEAN I. SAVITZ, M.D., BHARAT K. KANTHARIA, M.D.

BASIC INFORMATION DEFINITION

Superior vena cava syndrome is a set of symptoms that results when a mediastinal mass compresses the superior vena cava (SVC) or the veins that drain into it.

ICD-9CM CODES

453.2 Vena cava thrombosis EPIDEMIOLOGY & DEMOGRAPHICS

•

The superior vena cava syndrome occurs in 15,000 persons in the U.S. every year.

•

Mirrors lung cancer (especially small cell carcinoma) and lymphoma: see “Lung Neoplasm” and “Lymphoma” in Section I.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

The pathophysiology of the syndrome involves the increased pressure in the venous system draining into the superior vena cava, producing edema of the head, neck, and upper extremities. Symptoms develop over a period of 2 weeks in one third of patients. Symptoms: •

Shortness of breath

•

Chest pain

•

Cough

•

Dysphagia, hoarseness, stridor

•

Headache

•

Syncope

•

Visual trouble

Signs:

•

Chest wall vein distention ( Fig. 1-262 )

•

Neck vein distention

•

Facial edema

•

Upper extremity swelling

•

Cyanosis

FIGURE 1-262 Superior vena cava obstruction causing dilated veins and plethora of the upper trunk and neck in a patient with bronchial carcinoma. Patients with superior vena cava obstruction are occasionally referred to dermatologists with suspected contact allergy (eyelid swelling) or angioedema (facial or hand swelling). (From White GM, Cox NH [eds]: Diseases of the skin, a color atlas and text, ed 2, St. Louis, 2006, Mosby.)

ETIOLOGY

•

Lung cancer (80% of all cases, of which half are small cell lung cancer)

•

Lymphoma (15%)

•

Thymoma

•

Tuberculosis

•

Goiter

•

Aortic aneurysm (arteriosclerotic or syphilitic)

•

SVC thrombosis

•

1.

Primary: associated with a central venous catheter

2.

Secondary: as a complication of SVC syndrome associated with one of the abovementioned causes

Inflammatory process, fibrosing mediastinitis

DIAGNOSIS CT of the chest wth contrast is the most useful diagnostic study. MRI is usually adequate to establish the diagnosis of superior vena cava obstruction and to assist in the differential diagnosis of probable cause. DIFFERENTIAL DIAGNOSIS

The syndrome is characteristic enough to exclude other diagnoses. The differential diagnosis concerns the underlying etiologies listed previously. WORKUP

•

Chest x-ray

•

Chest CT with contrast or MRI (in patient who cannot tolerate contrast medium)

•

Venography: warranted only when an intervention (e.g., stent or surgery) is planned

•

Percutaneous needle biopsy (usually the initial diagnostic modality used to establish a histologic diagnosis)

•

Bronchoscopy

•

Mediastinoscopy

•

Thoracotomy

TREATMENT Although invasive procedures such as mediastinoscopy or thoracotomy are associated with higher than usual risk of bleeding, a tissue diagnosis is usually needed before commencing therapy. Management is guided by the severity of the symptoms and the underlying etiology. Emergency empiric radiation is indicated in critical situations such as respiratory failure or central nervous system signs associated with increased intracranial pressure.

•

Treatment of the underlying malignancy: 1.

Radiotherapy: the majority of tumors causing the SVC syndrome are sensitive to radiotherapy

2.

Systemic/chemotherapy

•

Anticoagulant or fibrinolytic therapy in patients who do not respond to cancer treatment within a week or if an obstructing thrombus has been documented.

•

Loop diuretics are often used, but their effect is limited.

•

Upright positioning and fluid restriction until collateral channels develop and allow for clinical regression are useful modalities for SVC syndrome secondary to benign disease.

•

Steroids (dexamethasone 4 mg q6h) may be useful in reducing the tumor burden in lymphoma and thymoma.

•

Percutaneous self-expandable stents that can be placed under local anesthesia with radiologic manipulation are useful in the treatment of SVC syndrome to bypass the obstruction, especially in cases associated with malignant tumors.

•

Surgical bypass grafting is infrequently used to treat the superior vena cava syndrome.

REFERRAL

To a thoracic surgeon, pulmonary specialist, or oncologist AUTHORS: FRED F. FERRI, M.D., and TOM J. WACHTEL, M.D. Syncope

BASIC INFORMATION DEFINITION

Syncope is the transient loss of consciousness that results from an acute global reduction in cerebral blood flow. Syncope should be distinguished from other causes of transient loss of consciousness.

ICD-9CM CODES

720.2 Syncope EPIDEMIOLOGY & DEMOGRAPHICS

•

Syncope accounts for 3% to 5% of emergency room visits.

•

30% of the adult population will experience at least one syncopal episode during their lifetime.

•

Incidence of syncope is highest in elderly men and young women.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Blood pressure: if low, consider orthostatic hypotension; if unequal in both arms (difference > 20 mm Hg), consider subclavian steal or dissecting aneurysm. (note: Blood pressure and heart rate should be recorded in the supine and standing positions.) If there is drop in BP but no change in HR, the patient may be on a beta blocker or may have an autonomic neuropathy.

•

Pulse: if patient has tachycardia, bradycardia, or irregular rhythm, consider arrhythmia.

•

Heart: if there are murmurs present suggestive of AS or IHSS, consider syncope secondary to left ventricular outflow obstruction; if there are JVD and distal heart sounds, consider cardiac tamponade.

•

Carotid sinus pressure: can be diagnostic if it reproduces symptoms and other causes are excluded; a pause > 3 sec or a systolic BP drop > 50 mm Hg without symptoms or < 30 mm Hg with symptoms when sinus pressure is applied separately on each side for < 5 sec is considered abnormal. This test should be avoided in patients with carotid bruits or cerebrovascular disease; ECG monitoring, IV access, and bedside atropine should be available when carotid sinus pressure is applied.

ETIOLOGY

•

•

•

Neurally mediated syncope 1.

Psychophysiologic (emotional upset, panic disorders, hysteria)

2.

Visceral reflex (micturition, defecation, food ingestion, coughing, ventricular contraction; glossopharyngeal neuralgia)

3.

Carotid sinus pressure

4.

Reduction of venous return caused by Valsalva maneuver

Orthostatic hypotension 1.

Hypovolemia

2.

Vasodilator medications

3.

Autonomic neuropathy (diabetes, amyloid, Parkinson's disease, multisystem atrophy)

4.

Pheochromocytoma

5.

Carcinoid syndrome

Cardiac 1.

2.

Reduced cardiac output a.

Left ventricular outflow obstruction (aortic stenosis, hypertrophic cardiomyopathy)

b.

Obstruction to pulmonary flow (pulmonary embolism, pulmonic stenosis, primary pulmonary hypertension)

c.

MI with pump failure

d.

Cardiac tamponade

e.

Mitral stenosis

f.

Reduction of venous return (atrial myxoma, valve thrombus)

g.

ß-blockers

Arrhythmias or asystole

a.

Extreme tachycardia (>160 to 180 bpm)

b.

Severe bradycardia ( 1 min), amnesia or lethargy after LOC suggests seizure rather than syncope.

•

Patient's activity at the time of syncope:

•

1.

Micturition, coughing, defecation: consider syncope secondary to decreased venous return.

2.

Turning head or while shaving: consider carotid sinus syndrome.

3.

Physical exertion in a patient with murmur: consider aortic stenosis.

4.

Arm exercise: consider subclavian steal syndrome.

5.

Assuming an upright position: consider orthostatic hypotension.

Associated events:

•

1.

Chest pain: consider MI, pulmonary embolism.

2.

Palpitations: consider arrhythmias.

3.

Incontinence (urine or fecal) and tongue biting are associated with seizure or syncope.

4.

Brief, transient shaking after LOC may represent myoclonus from global cerebral hypoperfusion and not seizures. However, sustained tonic/clonic muscle action is more suggestive of seizure.

5.

Focal neurologic symptoms or signs point to a neurologic event such as a seizure with residual deficits (e.g., Todd's paralysis) or cerebral ischemic injury.

6.

Psychologic stress: syncope may be vasovagal.

Review current medications, particularly antihypertensive and psychotropic drugs.

LABORATORY TESTS

Routine blood tests rarely yield diagnostically useful information and should be done only if they are specifically suggested by the results of the history and physical examination. The following are commonly ordered tests. •

Pregnancy test should be considered in women of childbearing age

•

CBC to rule out anemia, infection

•

Electrolytes, BUN, creatinine, magnesium, calcium to rule out electrolyte abnormalities and evaluate fluid status

•

Serum glucose level

•

Cardiac isoenzymes should be obtained if the patient gives a history of chest pain before the syncopal episode

•

ABGs to rule out pulmonary embolus, hyperventilation (when suspected)

•

Evaluate drug and alcohol levels when suspecting toxicity

IMAGING STUDIES

•

Echocardiogram is useful to rule out major pathology such as AS, IHSS, atrial myxoma, and left ventricular dysfunction.

•

If seizure is suspected, CT scan and/or MRI of the head and EEG may be useful.

•

If head trauma or neurologic signs on examination, CT or MRI may be helpful.

•

If pulmonary embolism is suspected, ventilation-perfusion scan should be done.

•

If arrhythmias are suspected, a 24-hr Holter monitor and admission to a telemetry unit is appropriate. Generally, Holter monitoring is rarely useful, revealing a cause for syncope in < 3% of cases. Loop recorders that can be activated after syncopal episode to retrieve information about the cardiac rhythm during the preceding 4 min add considerable diagnostic yield in patients with unexplained syncope.

•

Implantable cardiac monitors that function as permanent loop recorders or implantable cardioverterdefibrillators, which are placed subcutaneously in the pectoral region with the patient under local anesthesia, may be useful in patients with cardiac syncope.

•

Electrophysiologic studies may be indicated in patients with structural heart disease and/or recurrent syncope.

•

ECG to rule out arrhythmias; may be diagnostic in 5% to 10% of patients.

TILT-TABLE TESTING

•

Useful to support a diagnosis of neurally mediated syncope or orthostatic hypotension. Head-up tilt-table (HUT) testing should be performed after ruling out structural cardiac abnormalities of the heart (e.g., valvular stenosis, left ventricular dysfunction, hypertrophied cardiomyopathy by echocardiography). Patients older than age 50 should also have stress testing before tilt-table testing. Positive results would preclude tilt-table testing.

•

Indicated in patients with recurrent episodes of unexplained syncope as well as for patients in high-risk occupations (e.g., pilots, bus drivers) ( Fig. 1-263 ).

•

It is performed by keeping the patient in an upright posture on a tilt table with footboard support. The angle of the tilt table varies from 60 to 80 degrees. The duration of upright posture during tilt-table testing varies from 25 to 45 min. Provocative measures such as intravenous isoproterenol or sublingual nitroglycerine may be used during tilt-table test.

•

The hallmark of neurally mediated syncope is severe hypotension associated with a paradoxical bradycardia triggered by a specific stimulus. The diagnosis of orthostatic hypotension is made by observance of a drop in systolic blood pressure of 20 mm Hg or a drop in diastolic blood pressure of 10 mm Hg within 3 min of upright tilt table testing. A number of patients may have delayed orthostatic hypotension, with falls in blood pressure beyond 30 min.

PSYCHIATRIC EVALUATION

FIGURE 1-263 Head-up tilt test performed on an 18-year-old woman with a history of syncope associated with pain, preceded by a prodrome of dizziness, graying vision, and diaphoresis. A similar prodrome preceded syncope during the test. Note the precipitous, nearly simultaneous, decline of heart rate and blood pressure after an initial rise in heart rate. Vital signs returned to normal rapidly after the head was lowered. (Courtesy Robert F. Sprung, University of Utah. In Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders.)

PSYCHIATRIC EVALUATION

•

May be indicated in young patients without heart disease who have frequently recurring transient loss of consciousness and other somatic symptoms.

•

Generalized anxiety disorder, pain disorder, and major depression predispose patients to neurally mediated reactions and may result in syncope.

TREATMENT GENERAL THERAPY

•

Teach patients to recognize and avoid triggering factors leading to syncope. Advise patients to assume a recumbent position to maintain cerebral perfusion when they develop premonitory symptoms.

•

Ensure proper hydration; consider TED stockings and salt tablets.

•

Eliminate medications that may induce hypotension.

PHARMACOLOGIC Rx

•

Pharmacologic approaches include beta-adrenergic receptor blockers (if not contraindicated) as first-line therapy. Other agents that are used include selective serotonin reuptake inhibitors (SSRIs), methylxanthines, anticholinergic agents, and alpha agonists. A progressive approach to pharmacologic therapy is advisable.

•

Syncope caused by orthostatic hypotension is treated with volume replacement in patients with intravascular volume depletion. Also consider midodrine to promote venous return via adrenergic-mediated vasoconstriction and fludrocortisone for its mineralocorticoid effects to increase intravascular volume.

NONPHARMACOLOGIC Rx

•

Permanent dual-chamber pacemaker with algorithm for rapid pacing at detection of sudden rate drop may help those patients who have recurrent refractory symptomatic neurocardiogenic syncope associated with bradycardia documented spontaneously or at the time of HUT testing.

•

Other nonpharmacologic and more definitive therapies vary with the underlying etiology of syncope (e.g., pacemaker in patients with syncope secondary to complete heart block; cardiac defibrillator in patients with ventricular tachyarrhythmias; radiofrequency ablation for supraventricular tachyarrhythmias; surgery for stenotic valvular heart disease).

•

Varies with the underlying etiology of syncope (e.g., pacemaker in patients with syncope secondary to complete heart block).

•

Syncope caused by orthostatic hypotension is treated with volume replacement in patients with intravascular volume depletion. Also consider midodrine to promote venous return via adrenergic-mediated vasoconstriction and Florinef for its mineralocorticoid effects to increase intravascular volume.

DISPOSITION

Prognosis varies with the age of the patient and the etiology of the syncope. Generally:

•

Benign prognosis (very low 1-yr morbidity) in patients: 1.

Age serum osmolarity

•

Urinary sodium usually >40 mEq/L with normal dietary salt intake

•

Normal BUN, creatinine (indicative of normal renal function and absence of dehydration), normal TSH

•

Decreased uric acid

IMAGING STUDIES

Chest x-ray to rule out neoplasm or infectious process

TREATMENT NONPHARMACOLOGIC THERAPY

Fluid restriction to 500 to 800 ml/day with close monitoring of levels of urinary and plasma electrolytes. Adequate intake of dietary protein and salt should be encouraged. ACUTE GENERAL Rx

•

In emergency situations (seizures, coma) SIAD can be treated with combination of: 1.

Hypertonic saline solution (slow infusion of 250 ml of 3% NaCl). Infuse 3% saline (513 mmol/L) at a rate of 1 to 2 ml/kg of body weight per hour to increase the serum sodium level by 1 to 2 mmol/L/hr.

2.

Furosemide, 20 to 40 mg IV. This combination increases the serum sodium by causing diuresis of urine that is more dilute than plasma and prevents extracellular fluid volume expansion.

•

The rapidity of correction varies depending on the degree of hyponatremia and if the hyponatremia is acute or chronic; generally the serum sodium should be corrected only halfway to normal in the initial 24 hr. A prudent approach is to increase serum sodium by 12 mmol/L over a period of 24 hr increases the risk of osmotic demyelination.

•

Conivaptan (Vaprisol) is an intravenous (20 to 40 mg/day) vasopressin receptor antagonist useful in selected hospitalized patients with moderate-to-severe hyponatremia. Potential problems associated with its use are infusion-site reactions (50% of patients) and risk of osmotic demyelination if serum sodium levels are corrected too rapidly. Oral vasopressin-receptor antagonists (tolvaptan, lixivaptan, satavaptan) are pending FDA approval.

CHRONIC Rx

•

Depending on the underlying etiology, fluid restriction may be needed indefinitely. Monthly monitoring of electrolytes is recommended in patients with chronic SIAD.

•

Demeclocycline (Declomycin) 300 to 600 mg PO bid reduces urinary osmolality and increases serum sodium levels. It may be useful in patients with chronic SIAD (e.g., secondary to neoplasm) but use with caution in patients with hepatic disease; its side effects include nephrogenic diabetes insipidus (DI) and photosensitivity. This medication is also very expensive.

•

Successful treatment of chronic nephrogenic SIAD with urea to induce osmotic diuresis has been reported in children and adults. However, oral intake of urea (30 g/day) is generally poorly tolerated

DISPOSITION

•

Prognosis varies depending on the cause. Generally, prognosis is benign when SIAD is caused by an infectious process.

•

Morbidity and mortality are high (>40%) when serum sodium concentration is 0.5 g/day or 3+ if quantitation not performed, cellular casts)

8.

Neurologic disorder (seizures, psychosis [in absence of offending drugs or metabolic derangement])

9.

Hematologic disorder: a.

Hemolytic anemia with reticulocytosis

b.

Leukopenia (< 4000/mm3 total on two or more occasions)

c.

Lymphopenia (< 1500/mm3 on two or more occasions)

d.

Thrombocytopenia (< 100,000/mm3 in the absence of offending drugs)

10. Immunologic disorder: a.

Positive SLE cell preparation

b.

Anti-DNA (presence of antibody to native DNA in abnormal titer)

c.

Anti-Sm (presence of antibody to Smith nuclear antigen)

d.

False-positive STS known to be positive for at least 6 mo and confirmed by negative TPI or FTA tests

11. ANA: an abnormal titer of ANA by immunofluorescence or equivalent assay at any time in the absence of drugs known to be associated with “drug-induced lupus” syndrome LABORATORY TESTS

Suggested initial laboratory evaluation of suspected SLE: •

Immunologic evaluation: ANA, anti-DNA antibody, anti-Sm antibody

•

Other laboratory tests: CBC with differential, platelet count (Coombs' test if anemia detected), urinalysis (24-hr urine collection for protein if proteinuria is detected), PTT and anticardiolipin antibodies in patients with thrombotic events, BUN, creatinine to evaluate renal function

IMAGING STUDIES

•

Chest x-ray for evaluation of pulmonary involvement (e.g., pleural effusions, pulmonary infiltrates)

•

Echocardiogram to screen for significant valvular heart disease (present in 18% of patients with SLE); echocardiography can identify a subset of lesions (valvular thickening and dysfunction) other than verrucous (Libman-Sacks) endocarditis that are prone to hemodynamic deterioration

TREATMENT NONPHARMACOLOGIC THERAPY

Patients with photosensitivity should avoid sunlight and use high-factor sunscreen. GENERAL Rx

•

Joint pain and mild serositis are generally well controlled with NSAIDs; antimalarials are also effective (e.g., hydroxychloroquine [Plaquenil]).

•

Cutaneous manifestations are treated with the following:

•

1.

Topical corticosteroids; intradermal corticosteroids are helpful for individual discoid lesions, especially in the scalp

2.

Antimalarials (e.g., hydroxychloroquine [Plaquenil] and quinacrine)

3.

Sunscreens that block ultraviolet (UV) A and UVB radiation

4.

Immunosuppressive drugs (methotrexate or azathioprine) are used as steroid-sparing drugs

Renal disease (lupus nephritis) 1.

The use of high-pulsed doses of cyclophosphamide given at monthly intervals is more effective in preserving renal function than is treatment with glucocorticoids alone. The present standard of care with monthly high-dose IV cyclophosphamide has been challenged on several fronts. Alternative ways of administering cyclophosphamide in much lower doses for shorter periods have emerged. The combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone in patients with lupus nephritis. For patients with proliferative lupus nephritis, short-term therapy with IV cyclophosphamide followed by maintenance therapy with mycophenolate mofetil or azathioprine appears to be more efficacious and safer than long-term therapy with IV cyclophosphamide. In the treatment of severe proliferative lupus nephritis, mycophenolate mofetil represents an excellent alternative to cyclophosphamide.

2.

The use of plasmapheresis in combination with immunosuppressive agents (to prevent the rebound phenomenon of antibody levels after plasmapheresis) is generally reserved for rapidly progressive renal failure or life-threatening systemic vasculitis.

•

CNS involvement: treatment generally consists of corticosteroid therapy; however, its efficacy is uncertain, and it is generally reserved for organic brain syndrome. Anticonvulsants and antipsychotics are also indicated in selected cases; headaches are treated symptomatically.

•

Hemolytic anemia: treatment of Coombs'-positive hemolytic anemia consists of high doses of corticosteroids; nonhemolytic anemia (secondary to chronic disease) does not require specific therapy.

•

Thrombocytopenia 1.

Initial treatment consists of corticosteroids.

2.

In patients with poor response to steroids, encouraging results have been reported with the use of danazol, vincristine, and immunoglobulins. Combination chemotherapy with cyclophosphamide and prednisone combined with vincristine, vincristine and procarbazine, or etoposide may be useful in patients with severe refractory idiopathic thrombocytopenic purpura.

3.

Splenectomy generally does not cure the thrombocytopenia of SLE, but it may be necessary as an adjunct in managing selected cases.

•

Infections are common because of compromised immune function secondary to SLE and the use of corticosteroid, cytotoxic, and antimetabolite drugs; pneumococcal bacteremia is associated with high mortality rate.

•

Close monitoring for exacerbation of the disease and for potential side effects from medications (corticosteroids, cytotoxic agents) with frequent laboratory evaluation and office visits is necessary in all patients with SLE.

•

Valvular heart disease is present in 18% of patients with SLE. The prevalence of infective endocarditis is approximately 1% (similar to the prevalence after prosthetic valve surgery, but greater than that following rheumatic valvulitis). Valvular heart disease in patients with SLE frequently changes over time (e.g., vegetations can appear unexpectedly for the first time, resolve, or change in size or appearance). These frequent changes are temporarily unrelated to other clinical features of SLE and can be associated with substantial morbidity and mortality.

•

Newer treatment modalities include the use of rituximab (a chimeric human-murine monoclonal antibody directed against CD20 on B cells and their precursors) to induce substantial remissions in patients previously unresponsive to conventional agents. Intravenous immunoglobulins are also increasingly being used in the treatment of patients with resistant lupus.

DISPOSITION

•

Most patients with lupus experience remissions and exacerbations.

•

The leading cause of death in SLE is infection (one third of all deaths); active nephritis causes approximately 18% of deaths, and CNS disease causes 7% of deaths; the survival rate is 75% over the first 10 yr. Blacks and Hispanics generally have a worse prognosis.

•

Symptomatic pericarditis occurs in one fourth of patients with SLE at some point during the course of the disease. Asymptomatic involvement is estimated to be more than 60% based on autopsy reports.

•

Renal histologic studies and evaluation of renal function are useful in determining disease activity and predicting disease outcome (e.g., serum creatinine levels > 3 mg/dl or evidence of diffuse proliferative involvement on renal biopsy are poor prognostic factors).

•

Atherosclerosis occurs prematurely in patients with SLE and is independent of traditional risk factors for cardiovascular disease.

•

Antiphospholipid syndrome with thrombotic manifestations is a major predictor of irreversible organ damage and death in patients with SLE.

REFERRAL

•

Rheumatology consultation in all patients with SLE

•

Hematology consultation in patients with significant hematologic abnormalities (e.g., severe hemolytic anemia or thrombocytopenia)

•

Nephrology consultation in patients with significant renal involvement

EVIDENCE

We are unable to cite evidence that meets our criteria for many treatments for SLE. Another systematic review found that, in patients with proliferative lupus nephritis, cyclophosphamide plus corticosteroids reduced the risk of doubling serum creatinine compared with corticosteroids alone, although there was no impact on mortality, and the risk of ovarian failure was increased in the cyclophosphamide group. The reviewers concluded that cyclophosphamide combined with corticosteroids is the best option for preserving renal function, and that the smallest effective dose and the shortest duration of treatment should be used.[[1]] This same systematic review found that azathioprine plus corticosteroids reduced the risk of death from any cause compared with corticosteroids alone, but it had no impact on renal outcomes.[[1]]

Evidence-Based Referencece 1. Flanc RS, et al: Treatment for lupus nephritis. Reviewed. Cochrane Library, 3. Chichester, UK: John Wiley; 2004.

SUGGESTED READINGS D'Cruz DP, et al: Systemic lupus erythematosus. Lancet 2007; 369:587. Fine DM: Pharmacologic therapy of lupus nephritis. JAMA 2005; 293:3053. Remmers EF, et al: STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 2007; 357:977.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

T Tabes Dorsalis EROBOGHENE E. UBOGU, M.D.

BASIC INFORMATION DEFINITION

Tabes dorsalis is a form of tertiary neurosyphilis affecting the dorsal columns of the spinal cord and peripheral nerves, characterized by paroxysmal pain, particularly in the abdomen and legs; sensory ataxia; normal strength; autonomic dysfunction, and Argyll-Robertson pupils. SYNONYMS

Posterior spinal sclerosis Tabetic neurosyphilis Syphilitic myeloneuropathy

ICD-9CM CODES

094.0 Tabes dorsalis, ataxia, locomotor EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): Rare, but increasing with HIV/AIDS PEAK INCIDENCE: 15 to 20 yr after initial infection PREVALENCE (IN U.S.): Rare; more common with HIV/AIDS epidemic. 10% of untreated cases of syphilis develop neurosyphilis, of which 2% to 5% may develop tabes dorsalis. PREDOMINANT SEX: Male PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Argyll-Robertson pupil in 50% (pupil reacts poorly to light but well to accommodation)

•

Loss of position and vibration at ankles (wide-based gait; inability to walk in the dark: sensory ataxia)

•

Loss of deep pain sensation, resulting in deep foot ulcers

•

Degenerative joint disease, especially in knees caused by severe neuropathy (Charcot joints)

•

Normal strength with areflexia in the legs

•

Lightning pains in the legs

•

Severe intermittent visceral pains, such as gastrointestinal, laryngeal (visceral crises)

•

Autonomic dysfunction (urinary and fecal incontinence)

ETIOLOGY

Infectious (Treponema pallidum)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Vitamin B12 deficiency (subacute combined degeneration of the spinal cord)

•

Vitamin E deficiency

•

Chronic nitrous oxide abuse

•

Spinal cord neoplasm (involving conus medullaris)

•

Lyme disease

WORKUP

Thorough neurologic history and examination LABORATORY TESTS

•

Lumbar puncture for elevated VDRL and FTA-ABS titers. False-positive CSF VDRL titers may occur with traumatic tap. CSF mononuclear pleocytosis (> 5 white cells/microL) with increased protein support the diagnosis.

•

Serum venereal disease research laboratory test (VDRL). This may be normal in 25% to 30% of patients. Serum microhemagglutination-Treponema Pallidum (MHA-TP) or Fluorescent Treponemal AntigenAntibody test (FTA-ABS) is necessary if clinical suspicion high.

•

False-positive serum VDRL may occur in Lyme disease, nonvenereal treponematoses, genital herpes simplex, pregnancy, SLE, alcoholic cirrhosis, scleroderma, and mixed connective tissue disease.

IMAGING STUDIES

Not necessary if diagnosis confirmed

TREATMENT ACUTE GENERAL Rx

•

Procaine penicillin 2 to 4 million U IM qd, along with probenecid 500 mg PO qid, for 14 days, or aqueous penicillin G 3 to 4 million U IV q4h for 10 to 14 days.

•

If penicillin allergic, doxycycline 200 mg PO bid for 4 wk.

•

Many of the symptoms—degenerative neuropathic joint disease, lightning pains—persist after treatment.

CHRONIC Rx

•

Physical therapy

•

Analgesics, carbamazepine, gabapentin, or steroids may help “lightning” pain

•

Supportive care (wheelchair, toileting issues, etc.)

DISPOSITION

Close follow-up required. Repeat lumbar puncture every 6 mo until CSF pleocytosis normalizes. If pleocytosis does not normalize in 6 mo or CSF is still abnormal in 2 yr, repeat treatment. Further indication for retreatment: if there is a fourfold increase in titers or a failure of titers > 1:32 to decrease at least fourfold by 12 to 24 mo. REFERRAL

Joint replacement in moderate cases

PEARLS & CONSIDERATIONS COMMENTS

Diagnosis should be considered in all patients with a progressive neuropsychiatric disorder with signs of spinal cord dysfunction and peripheral neuropathy.

EVIDENCE

There is no evidence from randomized controlled trials to guide treatment of tabes dorsalis. SUGGESTED READINGS Centers for Disease Control and Prevention: 2002 sexually transmitted diseases treatment guidelines. MMWR Morb Mortal Wkly Rep 2002; 51(RR-6): Conde-Sendin MA, et al: Current clinical spectrum of neurosyphilis in immunocompetent patients. Eur Neurol 2004; 52:29. Timmermans M, Carr J: Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry 2004; 75:1727.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Takayasu's Arteritis MEL ANDERSON, M.D.

BASIC INFORMATION DEFINITION

Takayasu's arteritis refers to a chronic systemic granulomatous vasculitis primarily affecting large arteries (aorta and its branches). SYNONYMS

Pulseless disease Aortitis syndrome Aortic arch arteritis

ICD-9CM CODES

446.7 Takayasu disease or syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

Most cases have been reported from Japan, China, India, and Mexico

•

Exact incidence and prevalence is not known

•

Incidence in the U.S. 2.6/1 million

•

Females > males 9:1

•

Seen predominantly in patients < 30 yr old

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Takayasu's arteritis most frequently involves the aortic arch and its branches and can manifest as:

•

Arm claudication, weakness, and numbness

•

Amaurosis fugax, diplopia, headache, and postural dizziness

•

Systemic symptoms 1.

Low-grade fever

2.

Malaise

3.

Weight loss

4.

Fatigue

5.

Arthralgia and myalgia

•

Vascular bruits of the carotid artery, subclavian artery, and aorta

•

Discrepancy of blood pressures between the upper extremities

•

Absent pulses

•

Hypertension

•

Retinopathy

•

Aortic insufficiency murmur

ETIOLOGY

•

The cause of Takayasu's arteritis is unknown. A delayed hypersensitivity to mycobacteria and spirochetes is a theory but remains to be substantiated.

•

Infiltration of inflammatory cells into the vasa vasorum and media of large elastic arteries leads to thickening and narrowing or obliteration as well as aneurysmal dilation.

DIAGNOSIS Criteria have been established for the diagnosis of Takayasu's arteritis by the American College of Rheumatology in 1990 and include: •

Age of disease < 40 yr

•

Claudication of extremities

•

Decreased brachial artery pulse

•

Systolic BP difference > 10 mm Hg between left and right arms

•

Bruit over subclavian arteries or aorta

•

Abnormal arteriogram

•

Takayasu's arteritis is diagnosed if at least three of the six criteria are present, giving a sensitivity of 90% and a specificity of 98%

DIFFERENTIAL DIAGNOSIS

Other causes of inflammatory aortitis must be excluded:

•

Giant cell arteritis

•

Syphilis

•

Tuberculosis

•

SLE

•

Rheumatoid arthritis

•

Buerger's disease

•

Behçet's disease

•

Cogan's syndrome

•

Kawasaki disease

•

Spondyloarthropathies

WORKUP

Any young patient with findings of absence pulses and loud bruits merits a workup for Takayasu's arteritis. The workup generally includes blood testing to look for signs of inflammation and imaging studies with the angiogram being the diagnostic gold standard. LABORATORY TESTS

•

CBC may reveal an elevated WBC count

•

ESR is elevated in active disease

IMAGING STUDIES

•

Ultrasound: Carotid, thoracic, and abdominal ultrasound are useful adjunctive imaging studies in diagnosing occlusive disease resulting from Takayasu's arteritis ( Fig. 1-266 ).

•

Doppler and noninvasive upper and lower extremity studies are helpful in assessing blood flow and absent pulses.

•

CT scan is used to assess the thickness of the aorta.

•

Angiogram can show narrowing of the aorta and/or branches of the aorta, aneurysm formation, and poststenotic dilation. Angiographic findings are classified as four types: 1.

Type I: Lesions involve only the aortic arch and its branches.

2.

Type II: Lesions only involving the abdominal aorta and its branches.

3.

Type III: Lesions involving the aorta above and below the diaphragm.

4.

Type IV: Lesions involving the pulmonary artery.

FIGURE 1-266 Angiogram of a child with Takayasu's arteritis showing massive bilateral carotid dilation, stenosis, and poststenotic dilation. (From Behrman RE: Nelson textbook of pediatrics, ed 16, Philadelphia, 2000, WB Saunders.)

TREATMENT ACUTE GENERAL Rx

•

Corticosteroids are the treatment of choice. Prednisone 40 to 60 mg PO qd or 1 mg/kg/day is used for 3 mo.

•

Patients are monitored for symptoms and by following the ESR. If symptoms have resolved and the ESR is normal, attempts to taper prednisone are made.

CHRONIC Rx

•

Patients who cannot be tapered off the corticosteroids or who have relapse of the disease are given methotrexate 0.15 to 0.35 mg/kg or approximately 15 mg/wk.

•

Cyclophosphamide 1 to 2 mg/kg/day can be given with glucocorticoids as adjunctive therapy in relapse or treatment-resistant patients.

DISPOSITION

•

Treatment improves symptoms within days with relief of ischemic claudication, return of pulses on examination, and reversal of lumen narrowing on angiograms. However, some patients may continue to have progression of arterial lesions despite therapy.

•

With the addition of a second agent in patients with treatment resistance or relapse, 50% remission has been seen.

•

Mortality results are mixed, showing high rates in reports from Asia and lower rates in studies done in the U.S. (2%).

•

Death can occur suddenly from ruptured aneurysm, myocardial infarction, and stroke.

REFERRAL

Whenever the diagnosis of vasculitis is suspected, a rheumatology consult is appropriate. Vascular surgery and cardiology consultations are recommended for any evidence of carotid, peripheral, and coronary artery disease or if a large abdominal aneurysm is found.

PEARLS & CONSIDERATIONS

With long term corticosteroid use, consider measures to protect against bone loss. Bisphosphonates have been studied prospectively with corticosteroid use in this fashion; remember to ensure adequate dietary calcium and vitamin D intake as well. COMMENTS

The long-term prognosis of treated patients with Takayasu's disease is good, with > 90% of patients surviving more than 15 yr. SUGGESTED READINGS Arend WP, et al: American College of Rheumatology 1990 criteria for the classification of Takayasu's arteritis. Arthr Rheum 1990; 33:1129. Hahn-Kover K, Folzenlogen D: Diagnosis of Takayasu arteritis. J Clin Rheumatol 2005; 11(3):170. Mwipatayi B, et al: Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 2005; 75(3):110. Seko Y: Giant cell and Takayasu arteritis. Curr Opin Rheumatol 2007; 19(1):39 Weyend CM, Goronzy JJ: Mechanisms of disease: medium and large vessel vasculitis. N Engl J Med 2003; 349:160.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tapeworm Infestation GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

Four species of adult tapeworm may infect humans as the definitive host: Taenia saginata (beef tapeworm), Taenia solium (pork tapeworm), Diphyllobothrium latum (fish tapeworm), and Hymenolepis nana. In addition, T. solium may infect humans in its larval form (cysticercosis), and several animal tapeworms (see “Echinococcosis” in Section I) may cause infection in an analogous manner. SYNONYMS

Cysticercosis (larval infection by T. solium)

ICD-9CM CODES

123.9 Tapeworm infestation EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Diagnosed primarily in immigrants

•

Varies widely by country of origin and dietary practices

PREVALENCE (IN U.S.): •

T. saginata: < 0.1%

•

D. latum: < 0.05%

•

T. solium: < 0.1%

•

H. nana: sporadic, often in setting of outbreak

PREDOMINANT SEX: Equal sex distribution PREDOMINANT AGE: •

T. saginata, T. solium, D. latum: 20 to 39 yr of age

•

H. nana in setting of institution outbreaks: children

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

Adult worms 1.

Attach to bowel mucosa

2.

Feed and grow

3.

Cause minimal or no symptoms or sequelae

Cysticercosis 1.

Mass lesions of brain (neurocysticercosis), soft tissue, viscera

2.

Neurocysticercosis may cause seizures, hydrocephalus

Prolonged infection with D. latum 1.

Vitamin B12 deficiency

2.

Megaloblastic anemia

ETIOLOGY

TAPEWORM: •

Adult worm resides in small or large bowel; proglottids and eggs passed in stool.

•

Eggs are ingested by the animal intermediate host.

•

Eggs hatch into larvae.

•

Larvae disseminate largely in skeletal muscle, brain, viscera.

•

Humans eat infected beef (T. saginata), infected pork (T. solium), or infected fish (D. latum).

•

Larvae mature into adults within the GI lumen.

•

H. nana infection is acquired by ingesting eggs in human or rodent feces.

CYSTICERCOSIS: •

Humans ingest eggs of T. solium in food contaminated with human feces that contain the eggs.

•

Eggs hatch into larvae in gut.

•

Larvae disseminate widely through tissues (particularly soft tissue and CNS) forming cystic lesions containing either viable or nonviable larvae.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Section II describes the differential diagnosis of intestinal helminths. WORKUP

•

Stool examination for eggs or proglottids (tapeworm)

•

Cerebral CT scan (neurocysticercosis)

•

Serum antibody (neurocysticercosis)

IMAGING STUDIES

•

Tapeworm: incidental finding on upper GI series

•

Neurocysticercosis: 1.

Cerebral cysts are readily demonstrated by CT scan or MRI.

2.

Calcified lesions are an incidental finding.

TREATMENT ACUTE GENERAL Rx

•

All patients with intestinal tapeworm infections should be treated with a single oral dose of praziquantel. 1.

T. solium: 5 mg/kg

2.

T. saginata: 20 mg/kg

3.

D. latum: 10 mg/kg

4.

H. nana: 25 mg/kg

•

An alternative therapy to praziquantel for tapeworm infections is niclosamide, 2 gm by mouth once or 500 mg by mouth daily for 3 days.

•

Therapy that may be considered for symptomatic cysticercosis:

•

1.

May regress spontaneously

2.

Surgery

3.

Albendazole 15 mg/kg PO qd in three doses for 28 days

4.

Praziquantel 50 mg/kg PO qd in three doses for 15 days

Therapy contraindicated with: 1.

Ocular infections

2.

Cerebral infections in which local inflammation caused by destruction of the parasite may cause significant damage

CHRONIC Rx

•

Retreatment if required

•

Avoidance of undercooked pork, meat, or fish

•

Cysticercosis: proper hand washing, proper disposal of human waste

DISPOSITION

•

Neurologic follow-up for patients with neurocysticercosis

•

Ophthalmologic follow-up for patients with ocular involvement

REFERRAL

Patients treated for neurocysticercosis should be evaluated by a physician experienced in managing this infection, if possible.

PEARLS & CONSIDERATIONS

COMMENTS

T. solium is the most dangerous of the tapeworms because of the potential for cysticercosis by means of autoinfection. SUGGESTED READINGS Buyuk Y, et al: Non-ruptured hydatid cyst can lead to death by spread of cyst content into bloodstream: an autopsy case. Eur J Gastroenterol Hepatol 2005; 17(6):671. DeGiorgio C, Pietsch-Escueta S, Tsang V: Sero-prevalence of Taenia solium cysticercosis and Taenia solium taeniasis in California, USA. Acta Neurol Scand 2005; 111(2):84. Flisser A, et al: Short report: evaluation of a self-detection tool for tapeworm carriers for use in public health. Am J Trop Med Hyg 2005; 72(5):510. Infanger M, et al: Surgical and medical management of rare echinococcosis of the extremities. Pre- and postoperative long-term chemotherapy. Scand J Infect Dis 2005; 37(11):954. Liu YM, et al: Acute pancreatitis cause by tapeworm in the biliary tract. AM J Trop Med Hyg 2005; 73(2):377.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tardive Dyskinesia MITCHELL D. FELDMAN, M.D., M.PHIL., SHALINI PATEL, M.D.

BASIC INFORMATION DEFINITION

Tardive dyskinesia (TD) is a syndrome of involuntary movements associated with the long-term use of antipsychotic medication, particularly dopamine-blocking neuroleptics. Patients usually exhibit rapid, repetitive, stereotypic movements mostly involving the oral, lingual, trunk, and limb areas. SYNONYMS

Tardive syndrome Tardive dystonia

ICD-9CM CODES

333.82 Tardive dyskinesia EPIDEMIOLOGY & DEMOGRAPHICS

•

The disorder is caused by dopamine-blocking neuroleptics (e.g., haloperidol).

•

Incidence is declining with the use of newer generation antipsychotics.

•

At least 20% of patients treated with standard neuroleptic drugs are affected with TD, and approximately 5% are expected to develop TD with each year of neuroleptic treatment.

•

The risk is greatest in the early years of exposure and in elderly patients.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Typically appears with the reduction or withdrawal of the antipsychotics.

•

TD is characterized by: Primarily involves the tongue, lips, and jaw. A combination of tongue twisting and protrusion, lip smacking and puckering, and chewing movements in a repetitive and stereotypic fashion is often observed. Slow, writhing movements of the arms and legs. The involuntary mouth movements in TD may be voluntarily suppressed by patients. They are also suppressed by voluntary actions such as putting food in the mouth or talking.

ETIOLOGY

TD is generally thought to result from chronic exposure to dopamine receptor blocking agents—drugs primarily used to treat psychosis. TD has not been reported with dopamine depleters (e.g., reserpine) and is seldom reported with atypical antipsychotic drugs. Some drugs for nausea (e.g., metoclopramide and prochlorperazine) and depression (e.g., amoxapine, fluoxetine, and paroxetine) can also cause TD. Recent evidence suggests that TD may result from antipsychotic-induced damage to striatal cholinergic neurons.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Huntington's chorea

•

Excessive treatment with l-dopa

•

Tourette's syndrome

•

Wilson's disease

•

Sydenham's chorea

WORKUP

Diagnosis of exclusion with emphasis on complete neuropsychiatric history (including medication history) and examination. IMAGING STUDIES

Brain imaging normal in TD.

TREATMENT ACUTE GENERAL Rx

•

Treatment predicated on prevention-limiting the indications for neuroleptics and using the lowest effective dose and withdrawing them when feasible.

•

Use atypical antipsychotics if possible. Clozapine, risperidone, and olanzapine have lower reported rates of TD in long-term studies.

CHRONIC Rx

•

Clozapine has best evidence for improvement of symptoms in TD. Risperidone, olanzapine, and amisulpride also have been shown to benefit.

•

Piracetam, an antioxidant and neuronal enhancer, was effective in reducing symptoms of TD in randomized clinical trial with short-term follow-up.

•

Benzodiazepines, vitamin E, vitamin B6, donepezil, clonazepam, and melatonin may be helpful, but controlled trial evidence is weak.

DISPOSITION

Potentially irreversible, long-term adverse effect of treatment with firstgeneration antipsychotic medications.

REFERRAL

Movement disorder specialist if symptoms are severe.

PEARLS & CONSIDERATIONS

•

Neuroleptics should be resumed to treat TD in the absence of active psychosis only as a last resort for persistent, disabling, and treatment-resistant TD.

•

Worsening in overall psychopathology in schizophrenia is longitudinally associated with the emergence of TD.

SUGGESTED READINGS Bhoopathi PS, et al: Benzodiazepines for neuroleptic-induced tardive dyskinesia. Cochrane Database Syst Rev 2006; 3:CD000205 Libov I, et al: Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry 2007; 68(b):1031-1037. Margolese HC, et al: Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia. Can J Psychiatry 2005; 50(11):703. Rosenheck RA: Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics. Br J Psychiatry 2007; 191:238-245. Skidmore F, Reich SG: Tardive dystonia. Curr Treat Options Neurol 2005; 7(3):231.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tarsal Tunnel Syndrome LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Tarsal tunnel syndrome is a rare entrapment neuropathy that develops as a result of compression of the posterior tibial nerve in the tunnel formed by the flexor retinaculum behind the medial malleolus of the ankle ( Fig. 1-267 ). This retinaculum arises from the medial malleolus and inserts into the medial aspect of the calcaneus.

FIGURE 1-267 Anatomy of tarsal tunnel syndrome. Transverse view of ankle. FDL, Flexor digitorum longus; FHL, flexor hallucis longus tendon; TN, tibial nerve (single contour), posterior tibial artery, veins; TP, tibialis posterior tendon. Tendons and neurovascular elements are included into individual fibrous septa that connect periosteum with the deep fascia. (From Canoso J: Rheumatology in primary care, Philadelphia, 1997, WB Saunders.)

ICD-9CM CODES

355.5 Tarsal tunnel syndrome SYNONYMS

None EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: Unknown PREDOMINANT SEX: Female = male PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms are often vague in contrast to other compression neuropathies such as carpal tunnel syndrome.

•

Neuritic symptoms along the course of the posterior tibial nerve in the sole and heel.

•

The Valleix phenomenon (proximal radiation of the pain) may occur.

•

Swelling over tarsal tunnel.

•

Possible positive Tinel's sign.

•

Possible reproduction of symptoms with sustained eversion of hindfoot or digital compression of tunnel.

•

Sensory loss and motor changes unusual.

ETIOLOGY

Space-occupying lesions (ganglia, varicosities, lipomas, synovial hypertrophy) or local tendonitis Possibly traction on nerve

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Plantar fasciitis

•

Peripheral neuropathy

•

Proximal radiculopathy

•

Local tendinitis

•

Peripheral vascular disease

•

Morton's neuroma

ELECTRICAL STUDIES

Electrodiagnostic testing is often inconclusive. Delayed sensory conduction or increased motor latency may be seen.

TREATMENT

•

NSAIDs

•

Immobilization for 4 to 6 wk with ankle orthosis or fracture cast boot

•

Medial heel wedge or orthotic to minimize heel eversion

•

Local steroid injection into tunnel (avoiding the posterior tibial nerve) if symptoms persist

DISPOSITION

Many patients are successfully treated conservatively. REFERRAL

For surgical decompression if needed. Results of surgery are mixed unless an obvious compressive lesion is found.

PEARLS & CONSIDERATIONS The disorder is controversial and there are many unanswered questions regarding its diagnosis and incidence. The condition may be difficult to differentiate from plantar fasciitis and the two conditions may occur together. SUGGESTED READINGS Aldridge T: Diagnosing heel pain in adults. Am Fam Physician 2004; 70:332. Bracilovic A, et al: Effect of foot and ankle position on tarsal tunnel compartment volume. Foot Ankle Int 2006; 27:431. Campbell SE: MRI of sports injuries of the ankle. Clin Sports Med 2007; 25(4):727. Gorter K, et al: Variation in diagnosis and management of common foot problems by GPs. Fam Pract 2001; 18(6):569. Labib SA, et al: Heel pain triad (HPT): the combination of plantar fasciitis, posterior tibial tendon dysfunction and tarsal tunnel syndrome. Foot Ankle Int 2002; 23(3):212.

Mizel MS, et al: Evaluation and treatment of chronic ankle pain. Instr Course Lect 2004; 53:311. Mondelli M, Morana P, Padua L: An electrophysiological severity scale in tarsal tunnel syndrome. Acta Neurol Scand 2004; 109:284. Pecina M: Diagnostic tests for tarsal tunnel syndrome. J Bone Joint Surg Am 2002; 84-A(9):1714. Pessis E, et al: Nerve and vascular entrapment in athletes. J Radiol 2007; 88:156.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Temporomandibular Joint Syndrome WEN-CHIH WU, M.D.

BASIC INFORMATION DEFINITION

Temporomandibular joint (TMJ) syndrome refers to a group of disorders leading to symptoms of the temporomandibular joint. SYNONYMS

Temporomandibular dysfunction Painful temporomandibular joint

ICD-9CM CODES

524.60 Temporomandibular joint pain-dysfunction syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

15% of the population have TMJ disorders

•

Females > males 4:1

•

Occurs between the second and fourth decades of life

•

Usually unilateral, affecting either side with equal frequency

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Otalgia

•

Odontalgia

•

Headaches (frontal, temporal, retroorbital)

•

Tinnitus

•

Dizziness

•

Clicking or popping sounds with movement of the TMJ

•

Joint locking

•

Tender to palpation

•

Limited range of motion of the TMJ

ETIOLOGY

•

Multifactorial, encompassing local anatomic anomalies to familiar disease processes that can involve the TMJ.

•

Myofascial pain-dysfunction syndrome: the most common cause of TMJ syndrome and results from teeth grinding and clenching the jaw (bruxism)

•

Internal TMJ derangement: abnormal connection of the articular disk to the mandibular condyle

•

Degenerative joint disease

•

Rheumatoid arthritis

•

Gouty arthritis

•

Pseudogout

•

Ankylosing spondylitis

•

Trauma

•

Prior surgery (orthodontic, intraarticular steroid injection)

•

Tumors

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Can be made based on history and physical examination in most cases. Includes the list as mentioned previously under Etiology. Myofascial pain-dysfunction syndrome, internal TMJ derangement, and degenerative joint disease represent > 90% of all causes of TMJ syndrome. WORKUP

Radiographic imaging evaluation is helpful to exclude anatomic or systemic causes of disease. LABORATORY TESTS

Laboratory examination is not very helpful. IMAGING STUDIES

•

Plain x-rays: The most common x-rays are the panoramic, transorbital, and transpharyngeal views in both opened and closed positions.

•

Arthrography is helpful in looking for meniscus involvement.

•

CT scan is very accurate in diagnosing meniscal and osseous derangements of the TMJ.

•

MRI can better visualize soft tissue inflammation, if present.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Soft diet to rest the muscles of mastication

•

Heat 15 to 20 min 4 to 6 times per day

•

Massage of the masseter and temporalis muscles

•

Formed splints or bite appliances

•

Range-of-motion exercises

ACUTE GENERAL Rx

•

Nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 PO mg tid prn, naproxen 500 PO mg bid prn, titrated to relieve symptoms

•

Muscle relaxants: diazepam 2.5 to 5 mg PO tid prn

•

In degenerative joint disease of the TMJ, intraarticular steroid injection can be tried

CHRONIC Rx

•

Most of the above mentioned treatment is used for myofascial paindysfunction syndrome; however, it can be applied to other causes of TMJ syndrome. Surgery is usually a measure of last resort in patients who are refractory to nonpharmacologic and acute general treatment.

•

Surgical procedures include: 1.

Meniscoplasty

2.

Meniscectomy

3.

Subcondylar osteotomy

4.

TMJ reconstruction

DISPOSITION

The course depends on the underlying etiology; however, a lengthy course with exacerbations of symptoms can be expected. REFERRAL

All patients with TMJ syndrome refractory to conservative nonpharmacologic and acute therapy should be referred to a periodontist, oral maxillofacial surgeon, or ENT surgeon.

PEARLS & CONSIDERATIONS Patients with rheumatoid arthritis involving the TMJ usually will have bilateral involvement. COMMENTS

Frequently, emotional stress initiates the myofascial pain-dysfunction, which accounts for 85% of all cases of TMJ syndrome.

EVIDENCE

A systematic review of occlusal adjustment in the management of temporomandibular disorders (TMD) found no difference between occlusal adjustment and control groups (reassurance or no treatment) in terms of symptom-based outcomes.[[1]] There is insufficient evidence for or against the use of stabilization splint therapy for the treatment of temporomandibular pain dysfunction syndrome.[[2]] Acupuncture had a positive influence on the signs and symptoms of TMJ syndrome.[[3]]

Evidence-Based Referenceces 1. Koh H, Robinson PG: Occlusal adjustment for treating and preventing temporomandibular joint disorders. Cochrane Database Syst Rev 2003; 1:(Cochrane Review). 2. Al-Ani MZ, et al: Stabilisation splint therapy for temporomandibular pain dysfunction syndrome (Cochrane Review). Reviewed. Cochrane Library, 2. Chichester, UK: John Wiley; 2004. 3. Smith P, et al: The efficacy of acupuncture in the treatment of temporomandibular joint myofascial pain: a randomised controlled trial. J Dent 2007; 35(3):259.Epub 2006 Nov 13.

SUGGESTED READINGS Dimitroulis G: The role of surgery in the management of disorders of the temporomandibular joint: a critical review of the literature. Part 1 and Part 2. Int J Oral Maxillofac Surg 2005; 34(2):107.34(3):231:2005 Herb K, et al: Temporomandibular joint pain and dysfunction. Curr Pain Headache Rep 2006; 10(6):408. Sommer OJ, et al: Cross-sectional and functional imaging of the temporomandibular joint: radiology, pathology, and basic biomechanics of the jaw. Radiographics 2003; 23(6):e14.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Testicular Neoplasms FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Testicular neoplasms are primary cancers originating in a testis. SYNONYMS

Testis tumor Testicular cancer

ICD-9CM CODES

186.9

Testicular neoplasm

M906/3

(seminoma)

M9101/3 (embryonal carcinoma or teratoma) M9100/3 (choriocarcinoma) EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 2 to 3 cases/100,000 men/yr PREVALENCE: 1% to 2% of all cancers in males PREDOMINANT AGE: Can occur in any age but most common in young adults; average age for embryonal cell carcinoma: 30 yr; average age for seminoma: 36 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Any mass within the testicle should be considered cancer until proven otherwise. It may be found by the patient who brings it to the attention of a physician or it may be found by a physician on a routine examination.

•

Symptoms other than scrotal or testicular swelling are typically absent unless the cancer has metastasized. Occasionally a patient may complain of scrotal fullness or heaviness.

•

Testicular palpation should be performed with two hands. Transillumination may distinguish a solid mass (e.g., cancer) and a fluid-filled lesion (e.g., hydrocele or spermatocele). The mass is nontender, indeed less sensitive than a normal testicle.

ETIOLOGY & PATHOLOGY

•

Cryptorchidism (undescended testes) even if corrected by orchiopexy; however, treatment of undescended testis before puberty decreases the risk of testicular cancer.

•

Pathology. Cell type Seminoma

42

Embryonal cell carcinoma

26

Teratocarcinoma

26

Teratoma

5

Choriocarcinoma

1

Other rare types: Yolk sac carcinoma Mixed germ cell tumors Carcinoid tumor Sertoli cell tumors Leydig cell tumors Lymphoma Metastatic cancer to the testes

•

Frequency %

TNM staging system for testicular cancer

T0 No apparent primary T1 Testis only (excludes rete testis) T2 Beyond the tunica albuginea T3 Rete testis or epididymal involvement T4 Spermatic cord 1.

Spermatic cord

2.

Scrotum

N0 No nodal involvement N1 Ipsilateral regional nodal involvement N2 Contralateral or bilateral abdominal or groin nodes N3 Palpable abdominal nodes or fixed groin nodes N4 Juxtaregional nodes

M0 No distant metastases M1 Distant metastases present

The clinical stages consist of stage A, with tumor confined to the testis and cord structures; stage B, with tumor confined to the retroperitoneal lymph nodes; and stage C, with tumor involving the abdominal viscera or disease above the diaphragm.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Spermatocele

•

Varicocele

•

Hydrocele

•

Epididymitis

•

Epidermoid cyst of the testicle

•

Epididymis tumors

WORKUP

Physical examination, laboratory tests, and imaging studies (Section III, “Testicular Mass”) LABORATORY TESTS

•

Serum human chorionic gonadotropin (hCG)

•

Serum alpha-fetoprotein (AFP)

One or both of these tumor markers will be elevated in 70% of cases of testicular cancer. •

Testicular biopsy is contraindicated.

IMAGING STUDIES

•

Ultrasound

•

CT scan or MRI of pelvis and abdomen

•

Chest x-ray

TREATMENT

•

Surgical exploration of the testicle through an inguinal incision with a noncrushing clamp placed on the cord before direct testicular examination. If a mass is confined within the body of the testicle, an orchiectomy is performed

•

Retroperitoneal lymph node dissection for clinical stage A and low stage B (lymph nodes under 6 cm in greatest diameter) provides cure in 70%

•

Chemotherapy: cisplatin, vinblastine, and bleomycin 1.

Not indicated in clinical stage A

2.

Controversial in low stage B

3.

Cornerstone of treatment in high stage B or stage C

•

Radiation therapy for stage A and low stage B seminoma provides cure in 85%

•

Posttreatment surveillance for testicular cancer survivors (annually) 1.

General maintenance

2.

Fertility assessment

3.

Sexuality status

4.

Skin examination (increased risk of dysplastic nevi)

5.

Testicular examination (3% to 4% risk of second testicular cancer)

6.

Serum tumor markers (hCG, AFP)

7.

Chest x-ray (for late relapse)

8.

Complications of cisplatin: hypertension, hyperlipidemia, renal failure, hypomagnesemia, hearing loss, tinnitus, peripheral neuropathy, and infertility

EVIDENCE

A randomized trial of paraaortic (PA) vs. PA plus ipsilateral iliac lymph node radiation for stage I testicular seminoma found low recurrence rates for either treatment and reduced hematologic, gastrointestinal, and gonadal toxicity with adjuvant radiotherapy confined to the PA nodes.[[1]]

Evidence-Based Referencece 1. Fossa SD, et al: Optimal planning target volume for stage I testicular seminoma: a Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol 1999; 17:1146.

SUGGESTED READINGS Feldman DR, et al: Medical treatment of advanced testicular cancer. JAMA 2008; 299(b):672-684. Petterson A, et al: Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007; 356:1835. Shaw J: Diagnosis and treatment of testicular cancer. Am Fam Physician 2008; 77(b):469-474.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Testicular Torsion FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Testicular torsion is a twisting of the spermatic cord leading to cessation of testicular blood flow, ischemia, and infarction if left untreated. SYNONYMS

Spermatic cord torsion

ICD-9CM CODES

608.2 Testicular torsion EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: Affects 1:4000 males younger than 25 years PREDOMINANT AGE: Two thirds of all cases occur between the ages of 12 and 18 yr, but may occur at any age, including antenatally. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Typical sequence is sudden onset of hemiscrotal pain, then swelling, nausea, and vomiting without fever or urinary symptoms.

•

Physical examination may reveal a tender firm testis, high-riding testis, horizontal lie of testis, absent cremasteric reflex, and no pain with elevation of testis. Absence of the cremasteric reflex (stroking or pinching the medial thigh normally causes contraction of the cremaster muscle and elevation of the testis) is the most sensitive physical finding.

•

Painless testicular swelling occurs in 10%.

•

One out of three patients reports previous episodes of spontaneously remitting scrotal pain.

•

In the neonate, testicular torsion should be presumed in patients with a painless, discolored hemiscrotal swelling.

•

In rare cases, torsion may involve an undescended testicle. In such situations an empty hemiscrotum is palpated together with a tender lump in the inguinal area.

ETIOLOGY

•

There are two types of testicular torsion: extravaginal caused by nonadherence of the tunica vaginalis to the dartos layer and intravaginal due to malrotation of the spermatic cord with the tunica vaginalis. Intravaginal torsion accounts for 90% of cases.

•

Torsion usually occurs in the absence of any precipitating events. Trauma accounts for 36 yr.

•

Early and late postoperative complications can occur and generally manifest in arrhythmias from atrial and ventricular tachycardias, and diminished exercise tolerance from RV failure.

•

A prolonged QRS duration in the preoperative ECG predicts an increased risk of postoperative supraventricular and ventricular arrhythmias. Prolongation of QRS beyond 180 ms identifies patients at increased risk of ventricular tachycardia after surgery.

•

Ventricular arrhythmias can lead to sudden cardiac death in 8.3% of surgically repaired patients by age 35.

•

Reduced exercise capacity is usually secondary to chronic pulmonary regurgitation or residual RV outflow tract obstruction. The precise indications and timing for undergoing pulmonary valve replacement after TOF repair are under research. An RV end-diastolic volume index of 150 ml/m2 is a practical cutoff value for pulmonic valve replacement.

•

TEI index (a measurement of myocardial performance) by echocardiography, increased serum brain natriuretic peptide (BNP) levels, and a decreased peak O2 consumption on exercise testing help to identify significant pulmonic valve lesions before they are clinically symptomatic.

•

Women with repaired TOF should be assessed by a cardiologist before considering pregnancy to determine if pulmonic valve replacement is needed first.

•

Selected patients with normal RV pressures and function, without evidence of residual shunt, and without atrial or ventricular tachyarrhythmias are eligible to participate in competitive sports.

REFERRAL

•

Infants and children with cyanotic heart disease should be referred to a pediatric cardiologist for further diagnostic evaluation. On diagnosing TOF, patients should be referred to centers experienced in palliative and complete surgical repair.

•

Adult patients with repaired TOF should be co-managed with cardiology.

PEARLS & CONSIDERATIONS

•

TOF was first described by the French physician Etienne Fallot in 1888.

•

The first palliative surgical treatment for TOF was performed by Dr. Alfred Blalock at Johns Hopkins University in 1945 (Taussig-Blalock shunt).

•

The first surgical repair for TOF was performed by Dr. C. Walton Lillehei at the University of Minnesota in 1954.

COMMENTS

•

The severity of right ventricular outflow tract obstruction is the primary determinant of clinical symptoms and outcome.

•

Coexisting cardiac abnormalities occur in nearly 40% of patients with TOF, including patent ductus arteriosus, atrial septal defect, multiple VSDs, absence of a pulmonary artery, complete AV septal defects, and anomalous coronary arteries.

•

TOF requires bacterial endocarditis prophylaxis before any dental work or nonsterile surgical procedures, such as surgery on the bowel or bladder.

•

Screening of patients with TOF for 22q11 deletions is helpful to detect concomitant immune deficiency syndromes.

•

Long-term follow-up of children with surgically corrected TOF is warranted. Even hemodynamically stable, they are at risk for neurodevelopment delay at school age.

SUGGESTED READINGS Dave HH, et al: Early insertion of a pulmonary valve for chronic regurgitation helps restoration of ventricular dimensions. Ann Thorac Surg 2005; 80(b):1615-1620. Graham Jr TP, et al: Task Force 2: congenital heart disease. J Am Coll Cardiol 2005; 45(b):1326-1333. Shinebourne E, et al: Tetralogy of Fallot: from fetus to adult. Heart 2006; 92(b):1353-1359. Warnes CA: The adult with congenital heart disease: born to be bad?. J Am Coll Cardiol 2005; 46(b):1-8.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thalassemias FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Thalassemias are a heterogeneous group of disorders of hemoglobin synthesis that have in common a deficient synthesis of one or more of the polypeptide chains of the normal human hemoglobin, resulting in a quantitative abnormality of the hemoglobin thus produced. There are no qualitative changes such as those encountered in the hemoglobinopathies (e.g., sickle cell disease). SYNONYMS

Mediterranean anemia Cooley's anemia

ICD-9CM CODES

282.4 Thalassemia EPIDEMIOLOGY & DEMOGRAPHICS

•

Thalassemia is among the most common genetic disorders worldwide. 4.83% of the world's population carry globin variants, including 1.67% of the population who are heterozygous for alpha-thalassemia and beta-thalassemia.

•

The highest concentration of alpha-thalassemia is found in Southeast Asia and the African west coast. For example, in Thailand the prevalence is 5% to 10%. It is also common among blacks, with a prevalence of approximately 5%.

•

The worldwide prevalence of beta-thalassemia is approximately 3%; in certain regions of Italy and Greece the prevalence reaches 15% to 30%. This high prevalence can be found in Americans of Italian or Greek descent.

•

The distribution of thalassemia in Europe and Africa parallels that of malaria, suggesting that thalassemic persons are more resistant to the parasite, thus permitting evolutionary survival advantage.

CLASSIFICATION

BETA THALASSEMIA:

•

Beta (+) thalassemia (suboptimal beta-globin synthesis)

•

Beta (o) thalassemia (total absence of beta-globin synthesis)

•

Delta-beta thalassemia (total absence of both delta-globin and beta-globin synthesis)

•

Lepore hemoglobin (synthesis of small amounts of fused delta-beta-globin and total absence of delta- and beta-globin)

•

Hereditary persistence of fetal hemoglobin (HPHF) (increased hemoglobin F synthesis and reduced or absence of delta- and beta-globin)

ALPHA THALASSEMIA: •

Silent carrier (three alpha-globin genes present)

•

Alpha thalassemia trait (two alpha-globin genes present)

•

Hemoglobin H disease (one alpha-globin gene present)

•

Hydrops fetalis (no alpha-globin gene)

•

Hemoglobin constant sprint (elongated alpha-globin chain)

THALASSEMIC HEMOGLOBINOPATHIES: Hb Terre Haute, Hb Quong Sze, HbE, Hb Knossos PHYSICAL FINDINGS & CLINICAL PRESENTATION

BETA THALASSEMIA: •

Heterozygous beta thalassemia (thalassemia minor): no or mild anemia, microcytosis and hypochromia, mild hemolysis manifested by slight reticulocytosis and splenomegaly

•

Homozygous beta thalassemia (thalassemia major): intense hemolytic anemia; transfusion dependency; bone deformities (skull and long bones); hepatomegaly; splenomegaly; iron overload leading to cardiomyopathy, diabetes mellitus, and hypogonadism; growth retardation; pigment gallstones; susceptibility to infection

•

Thalassemia intermedia caused by combination of beta and alpha thalassemia or beta thalassemia and Hb Lepore: resembles thalassemia major but is milder

ALPHA THALASSEMIA: •

Silent carrier: no symptoms.

•

Alpha thalassemia trait: microcytosis only.

•

Hemoglobin H disease: moderately severe hemolysis with microcytosis and splenomegaly.

•

The loss of all four alpha-globin genes is incompatible with life (stillbirth of hydropic fetus). Note: Pregnancies with hydrops fetalis are associated with a high incidence of toxemia.

ETIOLOGY

•

Beta thalassemia: it is caused by more than 200 point mutations and, rarely, by deletions. The reduction of beta-globin synthesis results in redundant alpha-globin chains (Heinz bodies), which are cytotoxic and cause intramedullary hemolysis and ineffective erythropoiesis. Fetal hemoglobin may be increased.

•

Alpha thalassemia: several mutations can result in insufficient amounts of alpha globin available for combination with non–alpha globins.

DIAGNOSIS LABORATORY TESTS

BETA THALASSEMIA: •

Microcytosis (MCV: 55 to 80 FL)

•

Normal RDW (RBC distribution width)

•

Smear: nucleated RBCs, anisocytosis, poikilocytosis, polychromatophilia, Pappenheimer and Howell-Jolly bodies

•

Hemoglobin electrophoresis: absent or reduced hemoglobin A, increased fetal hemoglobin, variable increase in the amount of hemoglobin A2

•

Markers of hemolysis: elevated indirect bilirubin and LDH, decreased haptoglobin

ALPHA THALASSEMIA: •

Microcytosis in the absence of iron deficiency.

•

Hemoglobin electrophoresis is normal, except for the presence of hemoglobin H in hemoglobin H disease.

TREATMENT

•

Thalassemia minor: no treatment but avoid iron administration for incorrect diagnosis of iron deficiency.

•

Beta thalassemia major (and hemoglobin H disease): 1.

Transfusion as required together with chelation of iron with desferrioxamine (by intravenous or subcutaneous administration, 8 to 12 hr nightly, 5 to 6 days a week at a dose of 2 to 6 g/day using a portable infusion pump).

2.

Splenectomy for hypersplenism if present.

3.

Bone marrow transplantation. Although hematopoietic stem-cell transplantation is the only curative approach for thalassemia, it has been limited by the high cost and scarcity of HLAmatched donors. Before transplantation it is necessary to administer myeloablative regimens to eradicate the endogenous thalassemic bone marrow. Commonly used agents are hydroxyurea, azathioprine, fludarabine, busulfan, and cyclophosphamide.

4.

Hydroxyurea may increase the level of hemoglobin F.

PEARLS & CONSIDERATIONS

•

Polymerase chain reaction (PCR) can be used to detect point mutations or deletions in chorionic-villous samples, enabling first-trimester, DNA-based testing for thalassemia.

•

Preimplantation genetic diagnosis can be extended to HLA typing on embryonic biopsies allowing the selection of an embryo that is not affected by thalassemia and that may also serve as a stem-cell donor for a previously affected child within the same family.

SUGGESTED READING Round D, Rachmilewitz E: Beta thalassemia. N Engl J Med 2005; 353:1135-1146.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thoracic Outlet Syndrome LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Thoracic outlet syndrome is the term used to describe a condition producing upper extremity symptoms thought to result from neurovascular compression at the thoracic outlet. Three types are described based on the point of compression: (1) cervical rib and scalenus syndrome, in which abnormal scalene muscles or the presence of a cervical rib may cause compression; (2) costoclavicular syndrome, in which compression may occur under the clavicle; and (3) hyperabduction syndrome, in which compression may occur in the subcoracoid area.

ICD-9CM CODES

353.0 Thoracic outlet syndrome EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: Varies from source to source; presence of cervical ribs in 0.5% to 1% of population (50% bilateral), but most are asymptomatic PREDOMINANT SEX: Female > male (3.5:1) PREDOMINANT AGE: Rare under 20 yr of age PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms and signs are related to the degree of involvement of each of the various structures at the level of the first rib.

•

True venous or arterial involvement is not common.

•

Diagnosis is most often used in the consideration of neural pain affecting the arm, which would suggest involvement of the brachial plexus. 1.

Arterial compression: pallor, paresthesias, diminished pulses, coolness, digital gangrene, and a supraclavicular bruit or mass

2.

Venous compression: edema and pain; thrombosis causing superficial venous dilation about the shoulder

3.

“True” neural compression: lower trunk (C8, T1) findings with intrinsic weakness and diminished sensation to the finger and small fingers and ulnar aspect of the forearm

4.

Possible supraclavicular tenderness

5.

Provocative tests (Adson's, Wright's): may reproduce pain but are of disputed usefulness

ETIOLOGY

•

Congenital cervical rib or fibrous extension of cervical rib ( Fig. 1-270 )

•

Abnormal scalene muscle insertion

•

Drooping of shoulder girdle resulting from generalized hypotonia or trauma

•

Narrowed costoclavicular interval as a result of downward and backward pressure on shoulder (sometimes seen in individuals who carry heavy backpacks)

•

Acute venous thrombosis with exercise (effort thrombosis)

•

Bony abnormalities of first rib

•

Abnormal fibromuscular bands

•

Malunion of clavicle fracture

FIGURE 1-270 A, Compression caused by a cervical rib (arrow). B, Abnormal scalene muscle insertions that may cause compression at the cervicobrachial region (arrow). (From Mercier LR: Practical orthopedics, ed 5, St Louis, 2000, Mosby.)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Carpal tunnel syndrome

•

Cervical radiculopathy

•

Brachial neuritis

•

Ulnar nerve compression

•

Reflex sympathetic dystrophy

•

Superior sulcus tumor

WORKUP

Except for venous or arterial pathology, no ancillary diagnostic tests are reliable for diagnostic confirmation. IMAGING STUDIES

•

Arteriography or venography when vascular pathology is strongly suspected clinically

•

Cervical spine radiographs to rule out cervical disk disease

•

Chest film to rule out lung tumor

•

EMG, NCV studies to rule out carpal tunnel syndrome, cervical radiculopathy

TREATMENT ACUTE GENERAL Rx

•

Sling for pain relief

•

Physical therapy modalities plus shoulder girdle–strengthening exercises

•

Postural reeducation

•

NSAIDs

DISPOSITION

•

Surgery: generally successful for vascular disorders

•

Nonsurgical treatment: often successful for patients with pain as the primary symptom

REFERRAL

For vascular surgery consultation when venous or arterial impairment is present

PEARLS & CONSIDERATIONS COMMENTS

•

True thoracic outlet syndrome is probably an uncommon condition.

•

Diagnosis is often used to describe a wide variety of clinical symptoms.

•

Considerable disagreement exists regarding the frequency of this disorder.

EVIDENCE

Home exercise treatment program provides relief to patients with thoracic outlet syndrome symptoms.

Evidence-Based Referencece 1. Lindgren KA: Conservative treatment of thoracic outlet syndrome: a 2-year follow-up. Arch Phys Med Rehab 1997; 78:373.

SUGGESTED READINGS Kaymak B, Ozcakar L: Complex regional pain syndrome in thoracic outlet syndrome. Br J Sports Med 2004; 38:364. Malas FU, et al: Etiologic factors in thoracic outlet syndrome. Orthopedics 2007; 30(6):425. Monica JT, et al: Thoracic outlet syndrome with subclavian artery thrombosis undetectable by magnetic resonance angiography. J Bone Joint Surg 2007; 89:1589. Sanders RJ, et al: Diagnosis of thoracic outlet syndrome. J Vasc Surg 2007; 46:601. Urschel HC, Kourlis H: Thoracic outlet syndrome: a 50-year experience at Baylor University Medical Center. Proc (Bayl Univ Med Cent) 2007; 20(2):125. Wehbe MA, Leinberry CF: Current trends in treatment of thoracic outlet syndrome. Hand Clin 2004; 20:119.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thromboangiitis Obliterans PRANAV M. PATEL, M.D.

BASIC INFORMATION DEFINITION

Thromboangiitis obliterans (TAO), or Buerger's disease, is a nonatherosclerotic inflammatory disease that commonly affects the small- and medium-sized arteries, veins, and nerves of the upper and lower extremities. SYNONYMS

Buerger's disease Presenile gangrene

ICD-9CM CODES

443.1 Thromboangiitis obliterans (Buerger's disease) EPIDEMIOLOGY & DEMOGRAPHICS

•

TAO is most prevalent in the Middle East, Far East, and Asia, where the prevalence can be as high as 45% to 63%.

•

In the U.S., the prevalence has been estimated at 12.6 to 20 cases/100,000 persons.

•

A genetic predisposition has been proposed based on the higher incidence in Israel among Jews of Ashkenazi ancestry with peripheral artery disease.

•

The symptoms almost always begin before the age of 40 yr, and almost all the patients affected are smokers.

•

TAO was initially thought to affect almost exclusively men. It still predominantly affects young men; however, more recently there has been an increase in the prevalence of TAO in women. This increase may be a result of an increase in smoking among women.

•

Death from TAO is rare.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

TAO generally begins with hand or foot ischemia due to involvement of the distal small arteries and veins of the limbs.

•

In 70% to 80% of cases, rest pain and diminished sensation from ischemic neuropathy is seen. Sometimes this can lead to ischemic ulcerations of the toes or feet before diagnosis of TAO is made.

•

Rest pain generally occurs on the forefoot, causing continuous pain and, therefore, patients may sleep with their legs dangling downward.

•

Ischemia of the upper limbs is clinically evident in 40% to 50% of patients, but may be detected in 63% of patients by the Allen's test.

•

There is evidence of prolonged capillary refill with dependent rubor, and migratory thrombophlebitis.

•

Systemic involvement, intestinal involvement, and central nervous system involvement are rare.

ETIOLOGY

•

Unknown.

•

Exposure to tobacco is essential for initiation and progression of the disease (a small number of cases have been reported to be attributed to the use of chewing tobacco).

•

Studies have suggested the presence of impaired endothelium-dependent vasorelaxation in the peripheral vasculature in patients with TAO.

•

There is no evidence to suggest that hypercoagulability abnormalities play a role in the disease mechanism.

•

There is no overwhelming evidence to suggest a predominantly genetic or immunologic etiology for TAO.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Limb ischemia resulting from emboli or atherosclerotic occlusive disease

•

Antiphospholipid antibody syndrome

•

Autoimmune disorders

•

Acrocyanosis

•

Carpal tunnel syndrome

•

CREST (calcinosis cutis, Raynaud's phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) syndrome

•

Systemic lupus erythematosus

•

Diabetes mellitus

•

Repetitive vibratory equipment use

•

Hypothenar hammer syndrome

•

Raynaud's phenomenon

•

Ergotamine intoxication

•

Polyarteritis nodosa

•

Cannabis arteritis

•

Peripheral neuropathy

WORKUP

The diagnosis of TAO is rendered difficult by the lack of specific clinical, radiological, and biological features in the disease. Point scoring systems are available to aid with the diagnosis; however, at this time no criteria is validated or accepted internationally. The diagnosis is therefore made by trying to eliminate differential diagnoses and to search for other signs of the disease: 1.

Peripheral vascular disease occurring predominantly in men before the age of 40 yr

2.

Typically, affects the arms and the legs and not just the lower extremities as arteriosclerosis does

3.

Found solely in tobacco smokers, with improvement in those who abstain

4.

Associated with migratory thrombophlebitis

5.

No other atherosclerotic risk factors (e.g., diabetes, cholesterol, or hypertension) •

Angiographic criteria (see “Imaging Studies”)

•

TAO is an inflammatory disease; however, in contrast to all of the major arteritis, fibrinoid necrosis of the arterial wall is not observed and the vascular wall is preserved. This feature distinguishes TAO from other types of systemic vasculitis and from arteriosclerosis, in which there is usually disruption of the internal elastic lamina and the media.

LABORATORY TESTS

TAO can not be diagnosed on the basis of a specific laboratory test. The primary goal of a laboratory workup in patients thought to have the disease is to exclude other disease processes in the differential diagnosis. IMAGING STUDIES

•

Noninvasive vascular studies help differentiate proximal occlusive disease characteristic of arteriosclerosis from distal disease typical of TAO.

•

Echocardiography should be performed in patients thought to have TAO in order to exclude a proximal source of emboli as the cause of distal vessel occlusion.

•

Angiography findings in TAO include: Involvement of distal small- and medium-size vessels Occlusions are segmental, multiple, smooth, and tapered Collateral circulation gives a “tree root” or “spider leg” appearance Both upper and lower extremities are involved

TREATMENT NONPHARMACOLOGIC THERAPY

Abstaining from smoking is the only way to stop the progression of the disease. Medical and surgical treatments will prove to be futile if the patient continues to smoke. Exacerbation of ischemic ulcers is directly related to tobacco use. ACUTE GENERAL Rx

•

The goal of medical treatment is to provide relief of ischemic pain and healing of ischemic ulcers. If the patient does not completely abstain from tobacco, medical measures will not be helpful.

•

Treatment with intravenous iloprost (a prostaglandin analogue) has been shown to be effective in improving symptoms and reducing the amputation rate among patients with TAO.

•

Epidural anesthesia and hyperbaric oxygen have a vasodilator effect and have been shown to aid in pain relief from ischemic ulcers.

CHRONIC Rx

•

Surgical bypass procedures and sympathectomy, as with medical treatment, will not be efficacious unless the patient stops smoking.

•

Surgical bypass may be difficult because the occlusions of TAO are distal.

•

Sympathectomy leads to increased blood flow by decreasing the vasoconstriction of distal vessels and also has been shown to aid in the healing and relief of pain from ischemic ulcers.

•

Debridement must be done on necrotic ulcers if needed.

•

Amputation is frequently required for gangrenous digits.

•

There is limited data on experimental gene transfer to induce therapeutic angiogenesis in TAO.

DISPOSITION

The course of TAO can be dramatically changed by the cessation of tobacco smoking. If a patient continues to smoke, recurrent exacerbation of ischemic ulcers, necrosis, and gangrene leading to small digit amputations are inevitable. REFERRAL

Smoking cessation counseling, rheumatology consultation, and vascular surgery consultation are recommended in any young smoker with claudication and ischemic ulcers, especially if both the upper and lower extremities are involved.

PEARLS & CONSIDERATIONS COMMENTS

Smoking cessation is mandatory. In individuals who quit smoking, prognosis is markedly improved. PATIENT/FAMILY EDUCATION

Patients with TAO must be warned about tobacco use and secondhand smoke. Information for patients: •

Vascular Disease Foundation (http://www.vdf.org

•

Mayo Foundation for Medical Education and Research (http://www.mayoclinic.com

EVIDENCE

) )

The discontinuation of tobacco use is the only definitive therapy for TAO.[[1]] Prostacyclin analogues may help patients with critical limb ischemia seen in TAO.[[2]] Recent experimental genetic and cell-based therapeutic approaches have been proposed to help in the treatment of TAO; however, further study is required. [59] [60]

Evidence-Based Referenceces 1. Olin JW, et al: Thromboangiitis obliterans (Buerger's disease). N Engl J Med 2000; 343:864-869. 2. Fiessinger JN, et al: Trial of iloprost versus aspirin treatment for critical limb ischemia of thromboangiitis obliterans: the TAO study. Lancet 1990; 335:555-557. 3. Kim DI, et al: Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger's disease. Stem Cells 2006; 24:1194-1200. 4. Kim SW, et al: Successful stem cell therapy using umbilical cord blood derived multi-potent stem cells for Buerger's disease and ischemic limb disease animal model. Stem Cells 2006; 24:1620-1626.

SUGGESTED READINGS Puéchal X, et al: Thromboangiitis obliterans or Buerger's disease: challenges for the rheumatologist. Rheumatology 2007; 46(b):192-199.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thrombophlebitis, Superficial FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Superficial thrombophlebitis is inflammatory thrombosis in subcutaneous veins. Superficial suppurative thrombophlebitis is an inflammation of the vein wall due to the presence of microorganisms occurring as a complication of either dermal infection or use of an indwelling intravenous catheter. SYNONYMS

Phlebitis Superficial suppurative thrombophlebitis

ICD-9CM CODES

451.0 Thrombophlebitis, superficial EPIDEMIOLOGY & DEMOGRAPHICS

•

20% of superficial thrombophlebitis cases are associated with occult DVT.

•

Catheter-related thrombophlebitis incidence is 100:100,000. The disease occurs more frequently when plastic catheters are inserted in the lower extremities. The mean duration of preceding venous cannulation is 4.8 days and the latent interval from removal of the catheter to development of symptoms ranges from 2 to 10 days.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Subcutaneous vein is palpable, tender; tender cord is present with erythema and edema of the overlying skin and subcutaneous tissue.

•

Induration, redness, and tenderness are localized along the course of the vein. This linear appearance rather than circular appearance is useful to distinguish thrombophlebitis from other conditions (cellulitis, erythema nodosum).

•

There is no significant swelling of the limb (superficial thrombophlebitis generally does not produce swelling of the limb).

•

Low-grade fever may be present. High fever and chills are suggestive of septic phlebitis.

•

Superficial suppurative thrombophlebitis may be difficult to identify because local findings of inflammation may be absent. Fever is present in >70% of cases but rigors are rare. Local findings (warmth, erythema, tenderness, swelling, lymphangitis) are present in only one third of patients.

ETIOLOGY

•

Trauma to preexisting varices.

•

Intravenous cannulation of veins (most common cause).

•

Abdominal cancer (e.g., carcinoma of pancreas).

•

Infection: Staphylococcus aureus was the most common pathogen, found in 65% to 78% of the cases of superficial suppurative thrombophlebitis before 1970; now most cases are due to Enterobacteriaceae, especially Klebsiella-Enterobacter spp. These agents are acquired nosocomially and are often resistant to multiple antibiotics. Infection with fungi or gram-negative aerobic bacilli is often seen in patients who are receiving broad-spectrum antibiotics at the time of the superficial suppurative phlebitis.

•

Hypercoagulable state.

•

DVT.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Lymphangitis

•

Cellulitis

•

Erythema nodosum

•

Panniculitis

•

Kaposi's sarcoma

WORKUP

Laboratory evaluation to exclude infectious etiology and imaging studies to rule out DVT in suspected cases LABORATORY TESTS

•

CBC with differential, blood cultures, culture of IV catheter tip (when secondary to intravenous cannulation). Bacteremia occurs in 80%-90% of the cases of superficial suppurative thrombophlebitis.

•

Culture of the catheter may be misleading because even though bacteria are isolated in 60% of the cases, a positive culture does not correlate with inflammation.

•

Exploratory venotomy may be necessary in suspected superficial suppurative thrombophlebitis.

IMAGING STUDIES

•

Serial ultrasound or venography in patients with suspected DVT

•

CT scan of abdomen in patients with suspected malignancy (Trousseau's syndrome: recurrent migratory thrombophlebitis)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Warm, moist compresses.

•

It is not necessary to restrict activity; however, if there is extensive thrombophlebitis, bed rest with the leg elevated will limit the thrombosis and improve symptoms.

ACUTE GENERAL Rx

•

NSAIDs to relieve symptoms

•

Treatment of septic thrombophlebitis with antibiotics with adequate coverage of Enterobacteriaceae and Staphylococcus. Initial empirical treatment with a semisynthetic penicillin (IV Nafcillin 2 g q4 to 6h plus either an aminoglycoside [gentamicin 1 mk/kg IV q8h] or a third-generation cephalosporin [cefotaxime] or a quinolone [ciprofloxacin]).

•

Ligation and division of the superficial vein at the junction to avoid propagation of the clot in the deep venous system when the thrombophlebitis progresses toward the junction of the involved superficial vein with deep veins.

•

The role of antifungal therapy for superficial suppurative thrombophlebitis due to C. albicans is controversial. Most of these infections can be cured by vein excision. Because of the propensity of these infections for hematogenous spread, a 10- to 14-day course of amphotericin B or fluconazole is advisable.

DISPOSITION

Clinical improvement within 7 to 10 days REFERRAL

Surgical referral in selected cases (see “Acute General Rx”)

PEARLS & CONSIDERATIONS COMMENTS

•

Patients with positive cultures should be evaluated and treated for endocarditis.

•

Suppurative thrombophlebitis is a particular problem in burned patients, for whom it represents a common cause of death due to infection.

•

Septic thrombophlebitis is more common in IV drug addicts.

SUGGESTED READING Gillespie P, et al: Cannula related suppurative thrombophlebitis in the burned patient. Burns 2000; 26:200-204.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thrombotic Thrombocytopenic Purpura FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by thrombocytopenia (often accompanied by purpura) and microangiopathic hemolytic anemia; neurologic impairment, renal dysfunction, and fever may also be present. SYNONYMS

TTP

ICD-9CM CODES

446.6 Thrombotic thrombocytopenic purpura EPIDEMIOLOGY & DEMOGRAPHICS

•

TTP primarily affects females between 10 and 50 yr of age.

•

Frequency is 3.7 cases/yr/1 million persons.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Purpura (secondary to thrombocytopenia)

•

Jaundice, pallor (secondary to hemolysis)

•

Mucosal bleeding

•

Fever

•

Fluctuating levels of consciousness (secondary to thrombotic occlusion of the cerebral vessels)

ETIOLOGY

•

The exact cause of TTP remains unknown. Recent studies reveal that there is platelet aggregation as a result of abnormalities in circulating von Willebrand factor caused by endothelial injury.

•

Many drugs, including clopidogrel, penicillin, antineoplastic agents, oral contraceptives, quinine, and ticlopidine, have been associated with TTP. Other precipitating causes include infectious agents, pregnancy, malignancies, allogenic bone marrow transplantation, and neurologic disorders.

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

DIC

•

Malignant hypertension

•

Vasculitis

•

Eclampsia or preeclampsia

•

Hemolytic-uremic syndrome (typically encountered in children, often following a viral infection)

•

Gastroenteritis as a result of a serotoxin-producing serotype of Escherichia coli

•

Medications: clopidogrel, ticlopidine, penicillin, antineoplastic chemotherapeutic agents, oral contraceptives

WORKUP

•

A comprehensive history, physical examination, and laboratory evaluation usually confirms the diagnosis.

•

The disease often begins as a flulike illness ultimately followed by clinical and laboratory abnormalities.

•

An algorithm for the diagnosis of TTP is described in Section III.

LABORATORY TESTS

•

Severe anemia and thrombocytopenia

•

Elevated BUN and creatinine

•

Evidence of hemolysis: elevated reticulocyte count, indirect bilirubin, LDH, decreased haptoglobin

•

Urinalysis: hematuria (red cells and red cell casts in urine sediment) and proteinuria

•

Peripheral smear: severely fragmented RBCs (schistocytes)

•

No laboratory evidence of DIC (normal FDP, fibrinogen)

TREATMENT ACUTE GENERAL Rx

•

Discontinue potential offending agents.

•

The America Association of Blood Banks, the American Society for Apheresis, and the British Committee for Standards in Haematology recommend daily plasma exchange with replacement of 1.0 to 1.5 times the predicted plasma volume of the patient as standard therapy for TTP. The British guidelines recommend that plasma exchange therapy be continued for a minimum of 2 days after the platelet count returns to normal (> 150,000 per cubic millimeter).

•

Corticosteroids (prednisone 1 to 2 mg/kg/day) may be effective alone in patients with mild disease or may be administered concomitantly with plasmapheresis plus plasma exchange with FFP.

•

Vincristine has been used in patients refractory to plasmapheresis.

•

Use of antiplatelet agents (ASA, dipyridamole) is controversial.

•

Platelet transfusions are contraindicated except in severely thrombocytopenic patients with documented bleeding.

•

Splenectomy is performed in refractory cases.

CHRONIC Rx

•

Relapsing TTP may be treated with plasma exchange.

•

Remission of chronic TTP that is unresponsive to conventional therapy has been reported after treatment with cyclophosphamide and the monoclonal antibody rituximab.

•

Splenectomy done while the patients are in remission has been used in some centers to decrease the frequency of relapse in TTP.

DISPOSITION

•

Survival of patients with TTP currently exceeds 80% with plasma exchange therapy.

•

Relapse occurs in 20% to 40% of patients who have TTP in remission.

REFERRAL

Surgical referral for splenectomy in selected patients (see “Acute General Rx” and “Chronic Rx”)

PEARLS & CONSIDERATIONS COMMENTS

Thrombotic microangiopathy can also be associated with administration of cyclosporine and mitomycin C, and with HIV infection.

EVIDENCE

Plasma exchange vs. plasma infusion with fresh frozen plasma is associated with a significantly higher response rate (increase in platelet count) and lower mortality rate in patients receiving treatment with aspirin and dypridamole for TTP.[[1]] There is no significant difference in outcome between plasma exchange with fresh frozen plasma vs. exchange with cryoprecipitate-poor plasma as initial treatment for patients with TTP.[[2]]

Evidence-Based Referenceces 1. Rock GA, et al: Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 1991; 325:393. 2. Zeigler ZR, et al: Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP). J Clin Apheresis 2001; 16:19.

SUGGESTED READING George JN: Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thyroid Carcinoma FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Thyroid carcinoma is a primary neoplasm of the thyroid. There are four major types of thyroid carcinoma: papillary, follicular, anaplastic, and medullary. SYNONYMS

Papillary carcinoma of thyroid Follicular carcinoma of thyroid Anaplastic carcinoma of thyroid Medullary carcinoma of thyroid

ICD-9CM CODES

193 Malignant neoplasm of thyroid EPIDEMIOLOGY & DEMOGRAPHICS

•

Thyroid cancer is the most common endocrine cancer, with an annual incidence of 14,000 new cases in the U.S. and about 1100 deaths.

•

Female:male ratio of 3:1.

•

Most common type (50% to 60%) is papillary carcinoma.

•

Median age at diagnosis: 45 to 50 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Presence of thyroid nodule

•

Hoarseness and cervical lymphadenopathy

•

Painless swelling in the region of the thyroid

ETIOLOGY

•

Risk factors: prior neck irradiation

•

Multiple endocrine neoplasia II (medullary carcinoma)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Multinodular goiter

•

Lymphocytic thyroiditis

•

Ectopic thyroid

WORKUP

The workup of thyroid carcinoma includes laboratory evaluation and diagnostic imaging. However, diagnosis is confirmed with fine-needle aspiration (FNA) or surgical biopsy. The characteristics of thyroid carcinoma vary with the type: •

•

•

•

Papillary carcinoma 1.

Most frequently occurs in women during second or third decades

2.

Histologically, psammoma bodies (calcific bodies present in papillary projections) are pathognomonic; they are found in 35% to 45% of papillary thyroid carcinomas

3.

Majority are not papillary lesions but mixed papillary follicular carcinomas

4.

Spread is via lymphatics and by local invasion

Follicular carcinoma 1.

More aggressive than papillary carcinoma

2.

Incidence increases with age

3.

Tends to metastasize hematogenously to bone, producing pathologic fractures

4.

Tends to concentrate iodine (useful for radiation therapy)

Anaplastic carcinoma 1.

Very aggressive neoplasm

2.

Two major histologic types: small cell (less aggressive, 5-yr survival approximately 20%) and giant cell (death usually within 6 mo of diagnosis)

Medullary carcinoma 1.

Unifocal lesion: found sporadically in elderly patients

2.

Bilateral lesions: associated with pheochromocytoma and hyperparathyroidism; this combination is known as MEN-II and is inherited as an autosomal dominant disorder

LABORATORY TESTS

•

Thyroid function studies are generally normal. TSH, T4, and serum thyroglobulin levels should be obtained before thyroidectomy in patients with confirmed thyroid carcinoma

•

Increased plasma calcitonin assay in patients with medullary carcinoma (tumors produce thyrocalcitonin)

IMAGING STUDIES

•

Thyroid scanning with iodine-123 or technetium-99m can identify hypofunctioning (cold) nodules, which are more likely to be malignant. However, warm nodules can also be malignant.

•

Thyroid ultrasound can detect solitary solid nodules that have a high risk of malignancy. However, a negative ultrasound does not exclude diagnosis of thyroid carcinoma.

•

FNA biopsy is the best method to assess a thyroid nodule (refer to “Thyroid Nodule” in Section I).

TREATMENT ACUTE GENERAL Rx

•

Papillary carcinoma 1.

•

•

•

Total thyroidectomy is indicated if the patient has: a.

Extrapyramidal extension of carcinoma

b.

Papillary carcinoma limited to thyroid but a positive history of irradiation to the neck

c.

Lesion >2 cm

2.

Lobectomy with isthmectomy may be considered in patients with intrathyroid papillary carcinoma < 2 cm and no history of neck or head irradiation; most follow surgery with suppressive therapy with thyroid hormone because these tumors are TSH responsive. The accepted practice is to suppress serum TSH concentrations to < 0.1 µU/ml.

3.

Radiotherapy with iodine-131 (after total thyroidectomy), followed by thyroid suppression therapy with triiodothyronine, can be used in metastatic papillary carcinoma.

Follicular carcinoma 1.

Total thyroidectomy followed by TSH suppression as noted previously

2.

Radiotherapy with iodine-131 followed by thyroid suppression therapy with triiodothyronine is useful in patients with metastasis

Anaplastic carcinoma 1.

At diagnosis, this neoplasm is rarely operable; palliative surgery is indicated for extremely large tumor compressing the trachea.

2.

Management is usually restricted to radiation therapy or chemotherapy (combination of doxorubicin, cisplatin, and other antineoplastic agents); these measures rarely provide significant palliation.

Medullary carcinoma 1.

Thyroidectomy should be performed.

2.

Patients and their families should be screened for pheochromocytoma and hyperparathyroidism.

DISPOSITION

Prognosis varies with the type of thyroid carcinoma: 5-yr survival approaches 80% for follicular carcinoma and is approximately 5% with anaplastic carcinoma.

PEARLS & CONSIDERATIONS COMMENTS

Family members of patients with medullary carcinoma should be screened; DNA analysis for the detection of mutations in the RET gene structure permits the identification of MEN IIA gene carriers. AUTHOR: FRED F. FERRI, M.D. Thyroid Nodule

BASIC INFORMATION DEFINITION

A thyroid nodule is an abnormality found on physical examination of the thyroid gland; nodules can be benign (70%) or malignant.

ICD-9CM CODES

241.0 Nodule, thyroid EPIDEMIOLOGY & DEMOGRAPHICS

•

Palpable thyroid nodules occur in 4% to 7% of the population.

•

Thyroid nodules can be found in 50% of autopsies; however, only 1 in 10 is palpable.

•

Malignancy is present in 5% to 30% of palpable nodules.

•

Incidence of thyroid nodules increases after 45 yr of age. They are found more frequently in women.

•

History of prior head and neck irradiation increases the risk of thyroid cancer.

•

Increased likelihood that nodule is malignant: nodule increasing in size or > 2 cm, regional lymphadenopathy, fixation to adjacent tissues, age < 40 yr, symptoms of local invasion (dysphagia, hoarseness, neck pain, male sex, family history of thyroid cancer or polyposis [Gardner syndrome]), rapid growth during levothyroxine therapy.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Palpable, firm, and nontender nodule in the thyroid area should prompt suspicion of carcinoma. Signs of metastasis are regional lymphadenopathy, inspiratory stridor.

•

Signs and symptoms of thyrotoxicosis can be found in functioning nodules.

ETIOLOGY

•

History of prior head and neck irradiation

•

Family history of pheochromocytoma, carcinoma of the thyroid, and hyperparathyroidism (medullary carcinoma of the thyroid is a component of MEN-II)

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

•

Thyroid carcinoma

•

Multinodular goiter

•

Thyroglossal duct cyst

•

Epidermoid cyst

•

Laryngocele

•

Nonthyroid neck neoplasm

•

Branchial cleft cyst

WORKUP

•

Fine-needle aspiration (FNA) biopsy is the best diagnostic study; the accuracy can be > 90%, but it is directly related to the level of experience of the physician and the cytopathologist interpreting the aspirate.

•

FNA biopsy is less reliable with thyroid cystic lesions; surgical excision should be considered for most thyroid cysts not abolished by aspiration.

•

A diagnostic approach to thyroid nodule is described in Section III.

LABORATORY TESTS

•

TSH, T4, and serum thyroglobulin levels should be obtained before thyroidectomy in patients with confirmed thyroid carcinoma on FNA biopsy.

•

Serum calcitonin at random or after pentagastrin stimulation is useful when suspecting medullary carcinoma of the thyroid and in anyone with a family history of medullary thyroid carcinoma.

•

Serum thyroid autoantibodies (see “Thyroiditis” in Section I) are useful when suspecting thyroiditis.

IMAGING STUDIES

•

Thyroid ultrasound is done in some patients to evaluate the size of the thyroid and the number, composition (solid vs. cystic), and dimensions of the thyroid nodule; solid thyroid nodules have a higher incidence of malignancy, but cystic nodules can also be malignant.

•

The introduction of high-resolution ultrasonography has made it possible to detect many nonpalpable nodules (incidentalomas) in the thyroid (found at autopsy in 30% to 60% of cadavers). Most of these lesions are benign. For most patients with nonpalpable nodules that are incidentally detected by thyroid imaging, simple follow-up neck palpation is sufficient.

•

Thyroid scan can be performed with technetium-99m pertechnetate, iodine-123, or iodine-131. Iodine isotopes are preferred because 35% to 8% of nodules that appear functioning on pertechnetate scanning may appear nonfunctioning on radioiodine scanning. A thyroid scan:

•

1.

Classifies nodules as hyperfunctioning (hot), normally functioning (warm), or nonfunctioning (cold); cold nodules have a higher incidence of malignancy.

2.

Scan has difficulty evaluating nodules near the thyroid isthmus or at the periphery of the gland.

3.

Normal tissue over a nonfunctioning nodule might mask the nodule as “warm” or normally functioning.

Both thyroid scan and ultrasound provide information about the risk of malignant neoplasia based on the characteristics of the thyroid nodule, but their value in the initial evaluation of a thyroid nodule is limited because neither provides a definite tissue diagnosis.

TREATMENT GENERAL Rx

•

Evaluation of results of FNA 1.

Normal cells: may repeat biopsy during present evaluation or reevaluate patient after 3 to 6 mo of suppressive therapy (l-thyroxine, prescribed in doses to suppress the TSH level to 0.1 to 0.5) a.

Failure to regress indicates increased likelihood of malignancy.

b.

Reliance on repeat needle biopsy is preferable to routine surgery for nodules not responding to thyroxine.

2.

Malignant cells: surgery

3.

Hypercellularity: thyroid scan a.

Hot nodule: 131I therapy if the patient is hyperthyroid

b.

Warm or cold nodule: surgery (rule out follicular adenoma vs. carcinoma)

DISPOSITION

Variable with results of FNA biopsy REFERRAL

Surgical referral for FNA biopsy

PEARLS & CONSIDERATIONS COMMENTS

•

Most solid, benign nodules grow, therefore an increase in nodule volume alone is not a reliable predictor of malignancy.

•

Surgery is indicated in hard or fixed nodule, presence of dysphagia or hoarseness, and rapidly growing solid masses regardless of “benign” results on FNA.

•

Suppressive therapy of malignant thyroid nodules postoperatively with thyroxine is indicated. The use of suppressive therapy for benign solitary nodules is controversial.

•

The preferred approach when repeated FNA fails to yield an adequate specimen remains a challenge. Immunohistochemical markers (galectin-3, human bone marrow endothelial cell [HBME-1]) have shown promise in preliminary studies. Routine calcitonin measurement for early detection of medullary carcinoma remains controversial due to the low frequency of this cancer and the high cost associated with case detection.

SUGGESTED READINGS Castro MR, Gharib H: Continuing controversies in the management of thyroid nodules. Ann Intern Med 2005; 142:926. Shetty SK, et al: Significance of incidental thyroid lesions detected on CT: correlation among CT, sonography, and pathology. Am J Roentgenol 2006; 187:1349.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thyroiditis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Thyroiditis is an inflammatory disease of the thyroid. It is a multifaceted disease with varying etiology, different clinical characteristics (depending on the stage), and distinct histopathology. Thyroiditis can be subdivided into three common types (Hashimoto's, painful, painless) and two rare forms (suppurative, Riedel's). To add to the confusion, there are various synonyms for each form, and there is no internationally accepted classification of autoimmune thyroid disease. SYNONYMS

Hashimoto's thyroiditis: chronic lymphocytic thyroiditis, chronic autoimmune thyroiditis, lymphadenoid goiter Painful subacute thyroiditis: subacute thyroiditis, giant cell thyroiditis, de Quervain's thyroiditis, subacute granulomatous thyroiditis, pseudogranulomatous thyroiditis Painless postpartum thyroiditis: subacute lymphocytic thyroiditis, postpartum thyroiditis Painless sporadic thyroiditis: silent sporadic thyroiditis, subacute lymphocytic thyroiditis Suppurative thyroiditis: acute suppurative thyroiditis, bacterial thyroiditis microbial inflammatory thyroiditis, pyogenic thyroiditis Riedel's thyroiditis: fibrous thyroiditis

ICD-9CM CODES

245.2 Hashimoto's thyroiditis 245.1 Subacute thyroiditis 245.9 Silent thyroiditis 245.0 Suppurative thyroiditis 245.3 Riedel's thyroiditis PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Hashimoto's: patients may have signs of hyperthyroidism (tachycardia, diaphoresis, palpitations, weight loss) or hypothyroidism (fatigue, weight gain, delayed reflexes) depending on the stage of the disease. Usually there is diffuse, firm enlargement of the thyroid gland; thyroid gland may also be of normal size (atrophic form with clinically manifested hypothyroidism).

•

Painful subacute: exquisitely tender, enlarged thyroid, fever; signs of hyperthyroidism are initially present; signs of hypothyroidism can subsequently develop.

•

Painless thyroiditis: clinical features are similar to subacute thyroiditis except for the absence of tenderness of the thyroid gland.

•

Suppurative: patient is febrile with severe neck pain, focal tenderness of the involved portion of the thyroid, erythema of the overlying skin.

•

Riedel's: slowly enlarging hard mass in the anterior neck; often mistaken for thyroid cancer; signs of hypothyroidism occur in advanced stages.

ETIOLOGY

•

Hashimoto's: autoimmune disorder that begins with the activation of CD4 (helper) T-lymphocytes specific for thyroid antigens. The etiologic factor for the activation of these cells is unknown.

•

Painful subacute: possibly postviral; usually follows a respiratory illness; it is not considered to be a form of autoimmune thyroiditis.

•

Painless thyroiditis: it frequently occurs postpartum.

•

Suppurative: infectious etiology, generally bacterial, although fungi and parasites have also been implicated; it often occurs in immunocompromised hosts or following a penetrating neck injury.

•

Riedel's: fibrous infiltration of the thyroid; etiology is unknown.

•

Drug induced: lithium, interferon alfa, amiodarone, interleukin-2.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

The hyperthyroid phase of Hashimoto's, subacute, or silent thyroiditis can be mistaken for Graves' disease.

•

Riedel's thyroiditis can be mistaken for carcinoma of the thyroid.

•

Painful subacute thyroiditis can be mistaken for infections of the oropharynx and trachea or for suppurative thyroiditis.

•

Factitious hyperthyroidism can mimic silent thyroiditis.

WORKUP

•

The diagnostic workup includes laboratory and radiologic evaluation to rule out other conditions that may mimic thyroiditis (see “Differential Diagnosis”) and to differentiate the various forms of thyroiditis.

•

The patient's medical history may be helpful in differentiating the various types of thyroiditis (e.g., presentation following childbirth is suggestive of silent [postpartum, painless] thyroiditis; occurrence following a viral respiratory infection suggests subacute thyroiditis; history of penetrating injury to the neck indicates suppurative thyroiditis).

LABORATORY TESTS

•

TSH, free T4: may be normal, or indicative of hypo- or hyperthyroidism depending on the stage of the thyroiditis.

•

WBC with differential: increased WBC with “shift to the left” occurs with subacute and suppurative thyroiditis.

•

Antimicrosomal antibodies: detected in > 90% of patients with Hashimoto's thyroiditis and 50% to 80% of patients with silent thyroiditis.

•

Serum thyroglobulin levels are elevated in patients with subacute and silent thyroiditis; this test is nonspecific but may be useful in monitoring the course of subacute thyroiditis and distinguishing silent thyroiditis from factitious hyperthyroidism (low or absent serum thyroglobulin level).

IMAGING STUDIES

24-hr radioactive iodine uptake (RAIU) is useful to distinguish Graves' disease (increased RAIU) from thyroiditis (normal or low RAIU).

TREATMENT ACUTE GENERAL Rx

•

Treat hypothyroid phase with levothyroxine 25 to 50 µg/day initially and monitor serum TSH initially every 6 to 8 wk.

•

Control symptoms of hyperthyroidism with ß-blockers (e.g., propranolol 20 to 40 mg PO q6h).

•

Control pain in patients with subacute thyroiditis with NSAIDs. Prednisone 20 to 40 mg qd may be used if NSAIDs are insufficient, but it should be gradually tapered off over several weeks.

•

Use IV antibiotics and drain abscess (if present) in patients with suppurative thyroiditis.

DISPOSITION

•

Hashimoto's thyroiditis: long-term prognosis is favorable; most patients recover their thyroid function.

•

Painful subacute thyroiditis: permanent hypothyroidism occurs in 10% of patients.

•

Painless thyroiditis: 6% of patients have permanent hypothyroidism.

•

Suppurative thyroiditis: there is usually full recovery following treatment.

•

Riedel's thyroiditis: hypothyroidism occurs when fibrous infiltration involves the entire thyroid.

REFERRAL

Surgical referral in patients with compression of adjacent neck structures and in some patients with suppurative thyroiditis SUGGESTED READINGS Bindra A, Braunstein GD: Thyroiditis. Am Fam Physician 2006; 73:1769. Pearce EN, et al: Thyroiditis. N Engl J Med 2003; 348:2646.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Thyrotoxic Storm MARIE ELIZABETH WONG, M.D.

BASIC INFORMATION DEFINITION

Thyrotoxic storm is the abrupt and severe exacerbation of thyrotoxicosis.

ICD-9CM CODES

242.9 Thyrotoxic storm 242.0 With goiter 242.2 Multinodular 242.3 Adenomatous 242.8 Thyrotoxicosis factitia PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Goiter

•

Tremor, tachycardia, fever

•

Warm, moist skin

•

Lid lag, lid retraction, proptosis

•

Altered mental status (psychosis, coma, seizures)

•

Other: evidence of precipitating factors (infection, trauma)

ETIOLOGY

•

Major stress (e.g., infection, MI, DKA) in an undiagnosed hyperthyroid patient

•

Inadequate therapy in a hyperthyroid patient

DIAGNOSIS The clinical presentation is variable. The patient may present with the following signs and symptoms:

•

Fever

•

Marked anxiety and agitation, psychosis

•

Hyperhidrosis, heat intolerance

•

Marked weakness and muscle wasting

•

Tachyarrhythmias, palpitations

•

Diarrhea, nausea, vomiting

•

Elderly patients may have a combination of tachycardia, CHF, and mental status changes

DIFFERENTIAL DIAGNOSIS

•

Psychiatric disorders

•

Alcohol or other drug withdrawal

•

Pheochromocytoma

•

Metastatic neoplasm

WORKUP

•

Laboratory evaluation to confirm hyperthyroidism (elevated free T4, decreased TSH)

•

Evaluation for precipitating factors (e.g., ECG and cardiac enzymes in suspected MI, blood and urine cultures to rule out sepsis)

•

Elimination of disorders noted in the differential diagnosis (e.g., psychiatric history, evidence of drug and alcohol abuse)

LABORATORY TESTS

•

Free T4, TSH

•

CBC with differential

•

Blood and urine cultures

•

Glucose

•

Liver enzymes

•

BUN, creatinine

•

Serum calcium

•

CPK

IMAGING STUDIES

Chest x-ray to exclude infectious process, neoplasm, CHF in suspected cases

TREATMENT NONPHARMACOLOGIC THERAPY

•

Nutritional care: replace fluid deficit aggressively (daily fluid requirement may reach 6 L); use solutions containing glucose and add multivitamins to the hydrating solution.

•

Monitor for fluid overload and CHF in the elderly and in those with underlying cardiovascular or renal disease.

•

Treat significant hyperthermia with cooling blankets.

ACUTE GENERAL Rx

•

•

•

Inhibition of thyroid hormone synthesis 1.

Administer propylthiouracil (PTU) 300 to 600 mg initially (PO or via NG tube), then 150 to 300 mg q6h.

2.

If the patient is allergic to PTU, use methimazole (Tapazole) 80 to 100 mg PO or PR followed by 30 mg PR q8h.

Inhibition of stored thyroid hormone 1.

Iodide can be administered as sodium iodine 250 mg IV q6h, potassium iodide (SSKI) 5 gtt PO q8h, or Lugol's solution, 10 gtt q8h. It is important to administer PTU or methimazole 1 hr before the iodide to prevent the oxidation of iodide to iodine and its incorporation in the synthesis of additional thyroid hormone.

2.

Corticosteroids: dexamethasone 2 mg IV q6h or hydrocortisone 100 mg IV q6h for approximately 48 hr is useful to inhibit thyroid hormone release, impair peripheral conversion of T3 from T4, and provide additional adrenocortical hormone to correct deficiency (if present).

Suppression of peripheral effects of thyroid hormone 1.

ß-Adrenergic blockers: Administer propranolol 80 to 120 mg PO q4 to 6h. Propranolol may also be given IV 1 mg/min for 2 to 10 min under continuous ECG and blood pressure monitoring. ßAdrenergic blockers must be used with caution in patients with severe CHF or bronchospasm. Cardioselective ß-blockers (e.g., esmolol or metoprolol) may be more appropriate for patients with bronchospasm, but these patients must be closely monitored for exacerbation of bronchospasm because these agents lose their cardioselectivity at high doses.

•

Control of fever with acetaminophen 325 to 650 mg q4h; avoidance of aspirin because it displaces thyroid hormone from its binding protein

•

Consider digitalization of patients with CHF and atrial fibrillation (these patients may require higher than usual digoxin doses)

•

Treatment of any precipitating factors (e.g., antibiotics if infection is strongly suspected)

DISPOSITION

Patients with thyrotoxic crisis should be treated and appropriately monitored in the ICU. REFERRAL

Endocrinology referral is appropriate in patients with thyrotoxic crisis.

PEARLS & CONSIDERATIONS COMMENTS

If the diagnosis is strongly suspected, therapy should be started immediately without waiting for laboratory confirmation.

AUTHOR: FRED F. FERRI, M.D. Tinea Capitis

BASIC INFORMATION DEFINITION

Tinea capitis is a dermatophyte infection of the scalp. SYNONYMS

Ringworm of the scalp, ringworm of the head, gray patch tinea capitis, black dot tinea capitis, tinea tonsurans, superficial mycosis, dermatophytosis, kerion

ICD-9CM CODES

110.0 Tinea capitis EPIDEMIOLOGY & DEMOGRAPHICS

Tinea capitis is the most common dermatophytosis of childhood, primarily affecting children between 3 and 7 yr of age. About 3% to 8% of American children are affected, and 34% of household contacts are asymptomatic carriers. African American children are particularly susceptible. Adult and geriatric populations are less frequently affected, possibly because of the fungistatic effect of the sebum found in older persons. In urban populations, large family size, low socioeconomic status, and crowded living conditions may contribute to an increased incidence of tinea capitis. The predominant etiologic agent of tinea capitis in the U.S. and in Western Europe has changed from Microsporum audouinii to Trichophyton tonsurans in the past 50 years. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Triad of scalp scaling, alopecia, and cervical adenopathy.

•

Primary lesions including plaques, papules, pustules, or nodules on the scalp (usually occipital region).

•

Secondary lesions include scales, alopecia (usually reversible), erythema, exudates, and edema.

•

Two distinctly different forms: Gray patch: Lesions are scaly and well demarcated. The hairs within the patch break off a few millimeters above the scalp. One or several lesions may be present; sometimes the lesions join to form larger ones. Black dot: Early lesions with erythema and scaling patch are easily overlooked until areas of alopecia develop. Hairs within the patches break at the surface of the scalp, leaving behind a pattern of swollen black dots.

•

Scalp pruritus may be present.

•

Fever, pain, and lymphadenopathy (commonly postcervical) with inflammatory lesions.

•

Kerion: inflamed, exudative, pustular, boggy, tender nodules exhibiting marked edema, and hair loss seen in severe tinea capitis. Caused by immune response to the fungus. May lead to some scarring.

•

Favus: production of scutula (hair matted together with dermatophyte hyphae and keratin debris), characterized by yellow cup-shaped crusts around hair shafts. A fetid odor may be present.

ETIOLOGY

Most commonly caused by the Trichophyton (80% of the cases in the U.S.) or Microsporum genera. Most common causative species for black dot tinea capitis is T. tonsurans and for gray patch tinea capitis are M. andouinii and M. canis. Transmission occurs via infected persons or asymptomatic carriers, fallen infected hairs, animal vectors, and fomites. M. audouinii is commonly spread by dogs and cats. Infectious fungal particles may remain viable for many months.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Alopecia areata, impetigo, pediculosis, trichotillomania, traction alopecia, folliculitis, pseudopelade, seborrhea/atopic dermatitis, psoriasis, carbuncles, pyoderma, lichen ruber planus, lupus erythematosus WORKUP

•

KOH testing of hair shaft extracted from the lesion, not the scale, because the T. tonsurans spores attach to or reside inside hair shafts and will rarely be found in the scales.

•

Wood's ultraviolet light fluoresces blue-green on hair shafts for Microsporum infections but will fail to identify T. tonsurans.

•

Fungal culture of hairs and scales on fungal medium such as Sabouraud's agar may be used to confirm the diagnosis, especially if uncertain.

•

Histology of biopsies with fungal staining in cases where mycology tests are negative because of treatment initiation.

TREATMENT

•

Griseofulvin—gold standard FDA-approved treatment with excellent long-term safety profile. Micronized and ultramicronized preparations are absorbed better, and side effects are infrequent, especially when administered with fatty meals. Periodic monitoring of hematologic, liver, and renal function may be indicated, especially in prolonged treatment over 8 weeks. Children: higher doses of 20 to 25 mg/kg/d orally (to a maximum of 0.5 to 1.0 gram per day) now recommended for at least 6 to 8 weeks (until hair regrowth occurs or 2 weeks beyond cure to prevent relapse). Adults: 250 mg orally bid or 500 mg qd (or tid for a few cases of black dot type) for 4 to 12 weeks.

•

New alternative treatments: oral terbinafine, itraconazole, or fluconazole are comparable in efficacy and safety to griseofulvin, with shorter treatment and better patient compliance. Monitoring of CBC, liver function tests, and renal function may be indicated.

•

The adjuvant use of antifungal shampoos is recommended for all patients and household contacts. Shampoo like selenium sulfide 2.5% used for 5 minutes or ketoconazole shampoo used 2 to 3 times/week can help prevent infection or eradicate asymptomatic carrier state by inhibiting fungal growth.

•

Severe inflammatory kerion can be managed with additional prednisone 1 mg/kg/day and erythromycin.

PEARLS & CONSIDERATIONS COMMENTS

•

Confirming the diagnosis of tinea capitis with a laboratory specimen is important because misdiagnosis will result in delay or improper treatment.

•

Patients and their families should look for sources of infections and disinfect contaminated objects such as combs, brushes, towels, and headgear. Avoid sharing personal hygiene utensils.

•

Culture of hairs and scalp dander facilitates carrier identification and prevention.

•

Pets that are infected or asymptomatic carriers should be treated.

•

Recommend follow-up visit every 2 to 4 weeks using Wood's light, microscopic study, and fungal culture. A mycologically documented cure is the goal of treatment.

SUGGESTED READINGS Elewski BE: Tinea capitis: a current perspective. J Am Acad Dermatol 2000; 41:1-20. Gilbert DN, et al: The Sanford Guide to Antimicrobial Therapy 2005, Hyde Park, VT, Antimicrobial Therapy, 2005. Goldstein AO, et al: Mycotic infections: effective management of conditions involving the skin, hair, and nails. Geriatrics 2000; 55(b):40-52. Mohrenschlager M, et al: Pediatric tinea capitis: recognition and management. Am J Clin Dermatol 2005; 6(b):203-213. Roberts BJ, Friedlander SF: Tinea capitis: a treatment update. Pediatr Ann 2005; 34(b):191-200. Seebacher C, et al: Tinea capitis: ringworm of the scalp. Mycoses 2007; 50(b):218-226. Shy R: Tinea corporis and tinea capitis. Pediatr Rev 2007; 28(b):164-174. Strober BE: Tinea capitis. Dermatol Online J 2000; 7(1):12. Trovato MJ, et al: Tinea capitis: current concepts in clinical practice. Cutis 2006; 77(b):93-99.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tinea Corporis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Tinea corporis is a dermatophyte fungal infection caused by the genera Trichophyton or Microsporum. SYNONYMS

Ringworm Body ringworm Tinea circinata

ICD-9CM CODES

110.5 Tinea corporis EPIDEMIOLOGY & DEMOGRAPHICS

•

The disease is more common in warm climates.

•

There is no predominant age or sex.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Typically appears as single or multiple annular lesions with an advancing scaly border; the margin is slightly raised, reddened, and may be pustular.

•

The central area becomes hypopigmented and less scaly as the active border progresses outward ( Fig. 1271 ).

•

The trunk and legs are primarily involved.

•

Pruritus is variable.

•

It is important to remember that recent topical corticosteroid use can significantly alter the appearance of the lesions.

FIGURE 1-271 Annular lesion (tinea corporis). Note raised erythematous scaling border and central clearing. (From Noble J et al: Textbook of primary care medicine, ed 3, St Louis, 2001, Mosby.)

ETIOLOGY

Trichophyton rubrum is the most common pathogen.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Pityriasis rosea

•

Erythema multiforme

•

Psoriasis

•

SLE

•

Syphilis

•

Nummular eczema

•

Eczema

•

Granuloma annulare

•

Lyme disease

•

Tinea versicolor

•

Contact dermatitis

WORKUP

Diagnosis is usually made on clinical grounds. It can be confirmed by direct visualization under the microscope of a small fragment of the scale using wet mount preparation and potassium hydroxide solution; dermatophytes appear as translucent branching filaments (hyphae) with lines of separation appearing at irregular intervals. LABORATORY TESTS

•

Microscopic examination of hyphae

•

Mycotic culture is usually not necessary

•

Biopsy is indicated only when the diagnosis is uncertain and the patient has failed to respond to treatment

TREATMENT NONPHARMACOLOGIC THERAPY

Affected areas should be kept clean and dry. ACUTE GENERAL Rx

•

•

Various creams are effective; the application area should include normal skin about 2 cm beyond the affected area: 1.

Miconazole 2% cream (Monistat-Derm) applied bid for 2 wk

2.

Clotrimazole 1% cream (Mycelex) applied and gently massaged into the affected areas and surrounding areas bid for up to 4 wk

3.

Naftifine 1% cream (Naftin) applied qd

4.

Econazole 1% (Spectazole) applied qd

Systemic therapy is reserved for severe cases and is usually given up to 4 wk; commonly used agents: 1.

Ketoconazole (Nizoral), 200 mg qd

2.

Fluconazole (Diflucan), 200 mg qd

3.

Terbinafine (Lamisil), 250 mg qd

DISPOSITION

Majority of cases resolve without sequelae within 3 to 4 wk of therapy. REFERRAL

Dermatology referral in patients with persistent or recurrent infections SUGGESTED READINGS Friedlander SF, et al: Terbinafine in the treatment of trichophytin tinea capitis. Pediatrics 2002; 109:602. Hainer BL: Dermatophyte infections. Am Fam Physician 2003; 67:101. Weinstein A, Berman B: Topical treatment of common superficial tinea infections. Am Fam Physician 2002; 65:2095.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tinea Cruris FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Tinea cruris is a dermatophyte infection of the groin. SYNONYMS

Jock itch Ringworm

ICD-9CM CODES

110.3 Tinea cruris EPIDEMIOLOGY & DEMOGRAPHICS

•

Most common during the summer

•

Men are affected more frequently than women

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Erythematous plaques have a half-moon shape and a scaling border.

•

The acute inflammation tends to move down the inner thigh and usually spares the scrotum; in severe cases the fungus may spread onto the buttocks.

•

Itching may be severe.

•

Red papules and pustules may be present.

•

An important diagnostic sign is the advancing well-defined border with a tendency toward central clearing ( Fig. 1-272 ).

FIGURE 1-272 Tinea cruris. A halfmoon-shaped plaque has a well-defined, scaling border. (From Habif TB: Clinical dermatology: a color guide to diagnosis and therapy, ed 3, St Louis, 1996, Mosby.)

ETIOLOGY

•

Dermatophytes of the genera Trichophyton, Epidermophyton, and Microsporum. T. rubrum and E. floccosum are the most common causes.

•

Transmission from direct contact (e.g., infected persons, animals). The patient's feet should be evaluated as a source of infection because tinea cruris is often associated with tinea pedis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Intertrigo

•

Psoriasis

•

Seborrheic dermatitis

•

Erythrasma

•

Candidiasis

•

Tinea versicolor

WORKUP

Diagnosis is based on clinical presentation and demonstration of hyphae microscopically using potassium hydroxide. LABORATORY TESTS

•

Microscopic examination

•

Cultures are generally not necessary

TREATMENT NONPHARMACOLOGIC THERAPY

•

Keep infected area clean and dry.

•

Use of boxer shorts is preferred to regular underwear.

ACUTE GENERAL Rx

•

Drying powders (e.g., Miconazole nitrate [Zeasorb AF]) may be useful in patients with excessive perspiration.

•

Various topical antifungal agents are available: miconazole (Lotrimin), terbinafine (Lamisil), sulconazole nitrate (Exelderm), betamethasone dipropionate/clotrimazole (Lotrisone).

•

Oral antifungal therapy is generally reserved for cases unresponsive to topical agents. Effective medications are itraconazole (Sporonax) 100 mg/day for 2 to 4 wk, ketoconazole (Nizoral) 200 mg qd, fluconazole (Diflucan) 200 mg qd, and terbinafine (Lamisil) 250 mg qd.

DISPOSITION

Most cases respond promptly to therapy with complete resolution within 2 to 3 wk. SUGGESTED READING Hainer BL: Dermatophyte infections. Am Fam Physician 2003; 67:101.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tinea Pedis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Tinea pedis is a dermatophyte infection of the feet. SYNONYMS

Athlete's foot

ICD-CM CODES

110.4 Tinea pedis EPIDEMIOLOGY & DEMOGRAPHICS

•

Most common dermatophyte infection

•

Increased incidence in hot humid weather. Occlusive footwear is a contributing factor

•

Occurrence is rare before adolescence

•

More common in adult males

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Typical presentation is variable and ranges from erythematous scaling plaques ( Fig. 1-273 ) and isolated blisters to interdigital maceration.

•

The infection usually starts in the interdigital spaces of the foot. Most infections are found in the toe webs or in the soles.

•

Fourth or fifth toes are most commonly involved.

•

Pruritus is common and is most intense following removal of shoes and socks.

•

Infection with tinea rubrum often manifests with a moccasin distribution affecting the soles and lateral feet.

FIGURE 1-273 Tinea pedis. (From Goldstein BG, Goldstein AO: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

ETIOLOGY

Dermatophyte infection caused by T. rubrum, T. mentagrophytes, or less commonly E. floccosum

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Contact dermatitis

•

Toe web infection

•

Eczema

•

Psoriasis

•

Keratolysis exfoliativa

•

Juvenile plantar dermatosis

WORKUP

•

Diagnosis is usually made by clinical observation.

•

Laboratory testing, when performed, generally consists of a simple potassium hydroxide (KOH) preparation with mycologic examination under a light microscope to confirm the presence of dermatophytes.

LABORATORY TESTS

•

Microscopic examination of a scale or the roof of a blister with 10% KOH under low or medium power will reveal hyphae.

•

Mycologic culture is rarely indicated in the diagnosis of tinea pedis.

•

Biopsy is reserved for when the diagnosis remains in question after testing or failure to respond to treatment.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Keep infected area clean and dry. Aerate feet by using sandals when possible.

•

Use 100% cotton socks rather than nylon socks to reduce moisture.

•

Areas likely to become infected should be dried completely before being covered with clothes.

ACUTE GENERAL Rx

•

Butenafine Hcl 1% (Mentax) cream applied bid for 1 wk or qd for 4 wk is effective in interdigital tinea pedis.

•

Ciclopirox 0.77 % (Loprox) cream applied bid for 4 wk is also effective.

•

Clotrimazole 1% (Lotrimin AF) cream is an OTC treatment. It should be applied to affected and surrounding area bid for up to 4 wk.

•

Naftifine (Naftin) 1 % cream applied qd or gel applied bid for 4 wk also produces a significantly high cure rate.

•

When using topical preparations, the application area should include normal skin about 2 cm beyond the affected area.

•

Areas of maceration can be treated with Burow's solution soaks for 10 to 20 min bid followed by foot elevation.

•

Oral agents (fluconazole 150 mg once/wk for 4 wk) can be used in combination with topical agents in resistant cases.

PEARLS & CONSIDERATIONS

Combination therapy of antifungal and corticosteroid (clotrimazole/betamethasone [Lotrisone]) should only be used when the diagnosis of fungal infection is confirmed and inflammation is a significant issue.

EVIDENCE

A systematic review found that topical allylamines are significantly more effective than placebo for the treatment of fungal infections of the foot. Allylamines were found to be slightly more effective than azoles, although they are more expensive.[[1]] Terbinafine cream has been shown to be more effective than placebo for the treatment of interdigital tinea pedis.[[2]] Terbinafine cream and butenafine cream have been shown to be more effective than placebo for the treatment of moccasin-type tinea pedis. There was no significant difference in cure rates between the treatment groups in this randomized controlled trial (RCT).[[3]] A systematic review compared various oral antifungals for treatment of tinea pedis. Terbinafine and itraconazole were found to be more effective than placebo in two RCTs. There was no difference in efficacy between fluconazole and itraconazole; terbinafine was found to be more effective than griseofulvin.[[4]]

Evidence-Based Referenceces 1. Crawford F, et al: Topical treatments for fungal infections of the skin and nails of the foot. Cochrane Database Syst Rev 1999; 3: 2. Korting HCfor the LAS-INT-06 Study Group, et al: One week terbinafine 1% cream (Lamisil) once daily is effective in the treatment of interdigital tinea pedis: a vehicle controlled study. Med Mycology 2000; 39:335.Reviewed in: Clin Evid 13:2060, 2005. 3. Syed TA, et al: Butenafine 1% versus terbenafine 1% in cream for the treatment of tinea pedis. A placebo controlled double-blind comparative study. Clin Drug Invest 2000; 19:393.Reviewed in: Clin Evid 11:2128, 2004. 4. Bell-Syer SEM, et al: Oral treatments for fungal infections of the skin of the foot (Cochrane Review). Reviewed. Cochrane Library, 1. Chichester, UK: John Wiley; 2004.

SUGGESTED READING Weinstein A, Berman B: Topical treatment of common superficial tinea infections. Am Fam Physician 2002; 65:2095.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tinea Versicolor JUDITH NUDELMAN, M.D.

BASIC INFORMATION DEFINITION

Tinea versicolor is a fungal infection of the skin caused by the yeast Pityrosporum orbiculare (Malassezia furfur). SYNONYMS

Pityriasis versicolor

ICD-9CM CODES

111.0 Tinea versicolor EPIDEMIOLOGY & DEMOGRAPHICS

•

Increased incidence in adolescence and young adulthood

•

More common during the summer (hypopigmented lesions are more evident when the skin is tanned)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most lesions begin as multiple small, circular macules of various colors.

•

The macules may be darker or lighter than the surrounding normal skin and will scale with scraping.

•

Most frequent site of distribution is trunk.

•

Facial lesions are more common in children (forehead is most common facial site).

•

Eruption is generally of insidious onset and asymptomatic.

•

Lesions may be hyperpigmented in blacks.

•

Lesions may be inconspicuous in fair-complexioned individuals, especially during the winter.

•

Most patients become aware of the eruption when the involved areas do not tan ( Fig. 1-274 ).

FIGURE 1-274 The classic presentation of tinea versicolor with white, oval, or circular patches on tan skin. (From Habif TB: Clinical dermatology: a color guide to diagnosis and therapy, ed 3, St Louis, 1996, Mosby.)

ETIOLOGY

The infection is caused by the lipophilic yeast P. orbiculare (round form) and P. ovale (oval form); these organisms are normal inhabitants of the skin flora; factors that favor their proliferation are pregnancy, malnutrition, immunosuppression, oral contraceptives, and excess heat and humidity.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Vitiligo

•

Pityriasis alba

•

Secondary syphilis

•

Pityriasis rosea

•

Seborrheic dermatitis

WORKUP

Diagnosis is based on clinical appearance; identification of hyphae and budding spores (spaghetti and meatballs appearance) with microscopy confirms diagnosis. LABORATORY TESTS

Microscopic examination using potassium hydroxide confirms diagnosis when in doubt.

TREATMENT NONPHARMACOLOGIC THERAPY

Sunlight accelerates repigmentation of hypopigmented areas. ACUTE GENERAL Rx

•

Topical treatment: selenium sulfide 2.5% suspension (Selsun or Exsel) applied daily for 10 min for 7 consecutive days results in a cure rate of 80% to 90%.

•

Antifungal topical agents (e.g., miconazole, ciclopirox, clotrimazole) are also effective but generally expensive.

•

Oral treatment is generally reserved for resistant cases. Effective agents are ketoconazole (Nizoral) 200 mg qd for 5 days, or single 400-mg dose (cure rate > 80%), fluconazole (Diflucan) 400 mg given as a single dose (cure rate > 70% at 3 wk after treatment), or itraconazole 200 mg/day for 5 days.

DISPOSITION

The prognosis is good, with death of the fungus usually occurring within 3 to 4 wk of treatment; however, recurrence is common.

PEARLS & CONSIDERATIONS COMMENTS

Patients should be informed that the hypopigmented areas will not disappear immediately after treatment and that several months may be necessary for the hypopigmented areas to regain their pigmentation. AUTHOR: FRED F. FERRI, M.D. Tinnitus

BASIC INFORMATION DEFINITION

Tinnitus is an unwanted auditory perception of internal origin, usually localized and rarely heard by others. It usually involves a high-pitched sound with a buzzing or ringing quality. SYNONYM

Ringing in the ear(s)

ICD-9CM CODES

388.30 Tinnitus EPIDEMIOLOGY & DEMOGRAPHICS

Tinnitus increases with age. The most recent prevalence statistics from the National Center for Health Statistics (1999) indicate that tinnitus affects approximately 18% of the population. The American Tinnitus Association reports that 50 million Americans have tinnitus. It is slightly more common in men, frequently associated with hearing impairment, and more common in Caucasians than African Americans. The prevalence is double in the southern states compared to the northern states. It is most prevalent at ages 40 to 70 yr. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Patient complaints are of sounds in ears: determine onset, localization, pitch, loudness, duration, and nature: can be pulsatile, or described as ringing, buzzing, cricketlike, hissing, humming, or whistling.

•

Objective tinnitus is pulsatile, with bursts of sound energy coinciding with the pulse.

ETIOLOGY

•

Mechanism poorly understood; central in origin, it may originate at any point along the auditory pathway. Theories include injured cochlear hair cells, spontaneous activity in auditory nerve fibers, hyperactivity in the auditory nuclei in the brainstem, or a reduction in suppressive activity of the central auditory cortex.

•

Medications implicated in tinnitus: aspirin, NSAIDs, aminoglycosides, chloramphenicol, erythromycin, tetracycline, vancomycin, bleomycin, cisplatin, mechlorethamine, vincristine, bumetanide, ethacrynic acid, furosemide, chloroquine, heavy metals, heterocyclic antidepressants, quinine.

•

Classified as either objective or subjective. Subjective causes: (1) otologic: hearing loss, Meniere's disease, acoustic neuroma, cerumen impaction; (2) ototoxic medications; (3) neurologic: multiple sclerosis, head injury; (4) metabolic: thyroid disorder, hyperlipidemia, vitamin B12 deficiency; (5) psychogenic: depression, anxiety, fibromyalgia; and (6) infectious: otitis media, Lyme disease, meningitis, syphllis Objective causes: (1) vascular: arterial bruit, venous hum, AV malformation, vascular tumors; (2) neurologic: palatomyoclonus, idiopathic stapedial muscle spasm; and (3) patulous (lax) Eustachian tube

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Subjective vs. objective tinnitus WORKUP

•

History of exposure to ototoxic substances or disease processes that predispose to tinnitus

•

Association with depression: screen for depression

LABORATORY TESTS

•

Audiometry, tympanometry, pitch masking

•

Evaluate for metabolic abnormalities: thyroid disease, hyperlipidemia, anemia, B12 deficiency, zinc deficiency, CBC, complete blood chemistry

•

Electronystagmograph: Meniere's disease

IMAGING STUDIES

•

MRI/CT: Consider brain imaging to rule out multiple sclerosis, acoustic neuroma, brainstem tumor

•

MRI/MRA for pulsatile tinnitus

TREATMENT NONPHARMACOLOGIC THERAPY

Unknown effectiveness: psychotherapy, biofeedback, acupuncture, tinnitus-masking devices ACUTE GENERAL Rx

•

No FDA-approved medications: possibly beneficial are tricyclic antidepressants (one randomized controlled trial [RCT])

•

Benzodiazapines possibly effective

•

Lidocaine not found to be effective

CHRONIC Rx

Tinnitus retraining therapy: education, support, counseling and feedback device, multidisciplinary team. Duration of therapy is > 1 yr; success rates of 80%, but no RCTs have been done. COMPLEMENTARY & ALTERNATIVE MEDICINE

•

Possibly effective: acupuncture, relaxation therapy, hypnosis (based on systemic reviews)

•

Ginkgo biloba not found to be effective (based on one systemic review, one RCT)

DISPOSITION

Evaluate for all treatable causes, careful history to raise awareness of pulsatile tinnitus; determine subjective vs. objective REFERRAL

ENT, neurology

PEARLS & CONSIDERATIONS COMMENTS

•

Up to 18% of population may have tinnitus, with 0.5% severely effected; be aware of high prevalence.

•

Be aware of concurrent depression; screen and treat for it. Treat all treatable underlying causes.

PREVENTION

Avoid ototoxic drugs and loud, chronic noise exposure. PATIENT/FAMILY EDUCATION

•

American Tinnitus Association: 800-634-8978, www.ata.org

•

American Academy of Audiology: 800-AAA-2336, www.audiology.org

•

Hear USA: www.hearusa.org

•

Counsel families and patients that tinnitus may be irreversible and that they should be aware of the condition's effect on their lives.

EVIDENCE

Patients with difficulty sleeping as a result of tinnitus reported a significant overall improvement with melatonin in a crossover randomized controlled trial. Patients with bilateral tinnitus had significantly more improvement with melatonin than patients with unilateral tinnitus.[[1]] There is little evidence to support the use of Ginkgo biloba in the treatment of tinnitus.[[2]] There is insufficient evidence about the effects of masking to comment on whether it is effective in the treatment of tinnitus.[[2]]

Evidence-Based Referenceces 1. Rosenberg SI, et al: Effect of melatonin on tinnitus. Laryngoscope 1998; 108:305. 2. Waddell A: Tinnitus. Reviewed. Clin Evid, 12. London: BMJ Publishing Group; 2004:798.

SUGGESTED READINGS Crummer RW: Diagnostic approach to tinnitus. Am Fam Physician 2004; 69(1):120. Waddell A: Tinnitus: clinical evidence concise. Am Fam Physician 2004; 69(3):591. Lockwood A: Tinnitus. Neurology Clinics 2005; 23:893. Lockwood A: Tinnitus. N Engl J Med 2002; 347(12):904.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Torticollis LONNIE R. MERCIER, M.D.

BASIC INFORMATION DEFINITION

Torticollis is a contraction or contracture of the muscles of the neck that causes the head to be tilted to one side. It is usually accompanied by rotation of the chin to the opposite side with flexion ( Fig 1-275 ). Usually it is a symptom of some underlying disorder. This term is often used incorrectly in cases when the torticollis may simply be positional.

FIGURE 1-275 Torticollis. In this child, the right sternocleidomastoid muscle is contracted. (From Brinker MR, Miller MD: Fundamentals of orthopaedics, Philadelphia, 1999, WB Saunders.)

SYNONYMS

Twisted neck “Wry neck”

ICD-9CM CODES

723.5

Spastic (intermittent) torticollis

754.1

Congenital muscular (sternocleidomastoid)

300.11 Hysterical 714.0

Rheumatoid

333.83 Spasmodic PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

Congenital muscular torticollis: 1.

Palpable soft tissue “mass” in the sternocleidomastoid shortly after birth

2.

Mass gradually subsides, leaving a shortened, contracted sternocleidomastoid muscle

3.

Head characteristically tilted toward the side of the mass and rotated in the opposite direction

4.

Facial asymmetry and other secondary changes persisting into adulthood

Spasmodic torticollis: 1.

“Spasms” in the cervical musculature; may be bilateral and uncontrollable

2.

Head often tilted toward the affected side

Findings in other cases depend on etiology.

ETIOLOGY

Torticollis has been attributed to more than 50 different causes: •

Localized fibrous shortening of unknown cause involving the sternocleidomastoid, leading to the condition termed congenital muscular torticollis

•

Spasmodic torticollis: of uncertain etiology, possibly a variant of dystonia musculorum deformans

•

Infection, specifically pharyngitis, tonsillitis, retropharyngeal abscess

•

Miscellaneous rare causes: congenital musculoskeletal deformities, trauma, inflammation from rheumatoid arthritis, vestibular disturbances, posterior fossa tumor, syringomyelia, neuritis of spinal accessory nerve, and drug reactions

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Usually involves separating each disorder from the others

•

Acquired positional disorders (e.g., ocular disturbances, acute disk herniation)

WORKUP

•

Workup is dependent on the clinical situation.

•

Laboratory studies are usually not helpful unless infection or rheumatoid disease is suspected.

•

Section II describes a differential diagnosis for the evaluation and therapy of neck pain.

•

Any child with a gradually increasing torticollis should have a complete eye examination.

IMAGING STUDIES

•

Plain radiographs in cases of trauma or to rule out congenital abnormalities

•

MRI in appropriate cases

•

Electrodiagnostic studies: only rarely indicated to rule out neurologic causes

TREATMENT

•

Congenital muscular torticollis: gentle stretching exercises carried out by the parent

•

Spasmodic torticollis: physical therapy, psychotherapy, cervical braces, biofeedback, and pain control

•

Other forms: treated according to etiology

DISPOSITION

•

Most patients with congenital muscular torticollis respond well to conservative treatment.

•

Spasmodic torticollis is often resistant to normal conservative treatment.

•

Prognosis of other forms of torticollis is dependent on etiology.

REFERRAL

•

Torticollis often requires a multidisciplinary approach unless the etiology is obvious.

•

Children usually do not require any specific studies; however, an orthopedic consultation is recommended.

•

Fixed deformity in the child; may need orthopedic referral for surgical release.

SUGGESTED READINGS Crowner BE: Cervical dystonia: disease profile and clinical management. Phys Ther 2007; 87:1511. Ferreira JJ, et al: The management of cervical dystonia. Expert Opin Pharmacother 2007; 8(2):129. Hosalkar HS, et al: Congenital osseous anomalies of the upper cervical spine. J Bone Joint

Surg 2008; 90A:337. Papadimitriou NG, et al: Acute torticollis after isolated stress fracture of the first rib in a child. J Bone Joint Surg 2005; 87A:2537. Parikh SN, Crawford AH, Choudhary S: Magnetic resonance imaging in the evaluation of infantile torticollis. Orthopedics 2004; 27:509. Slawek J, et al: Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections. Funct Neurol 2007; 22(2):95.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tourette's Syndrome CINDY ZADIKOFF, M.D.

BASIC INFORMATION DEFINITION

Tics are sudden, brief, intermittent involuntary or semivoluntary movements (motor tics) or sounds (phonic or vocal tics) that mimic fragments of normal behavior. Tourette's syndrome (TS) is an inherited neuropsychiatric disorder characterized by multiple motor and vocal tics that change during the course of the illness. Onset is before age 18. SYNONYMS

Gilles de la Tourette syndrome

ICD-9CM CODES

307.23 Gilles de la Tourette disorder EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE (IN U.S.): Unknown. Estimates range from 0.7% to 5%. PREDOMINANT SEX: Male:female ratio of 3:1 PREDOMINANT AGE: Typical age of onset is between 2 to 15 yr. Mean is 5 to 7 yr. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Neurologic examination is normal.

•

Vocal tics (clearing of throat, repetitive short phrases, e.g., “You bet,” swearing [coprolalia]).

•

Motor tics can be simple (e.g., blinking, grimacing, head jerking) or complex (e.g., gesturing). Tics wax, wane, and change over time. Often they can be suppressed for short periods. Commonly they are preceded by an urge to perform the tic.

•

Often TS is associated with a variety of behavioral symptoms, most commonly ADHD and OCD.

ETIOLOGY

There is a large genetic contribution to TS. There is a strong family history of OCD or TS in patients with tics,

and twin studies provide evidence for importance of genetic factors. However, although multiple candidate genes have been identified no simple mutation has been found thus far. Dopamine is thought to be one of the major neurotransmitters involved.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Sydenham's chorea—occurs after infection with group A streptococcus.

•

PANDAS—pediatric autoimmune neurolopsychiatric disorder associated with streptococcal infection.

•

Sporadic tic disorders—these tend to be motor or vocal but not both.

•

Head trauma.

•

Drug intoxication—there are many drugs that are known to induce or exacerbate tic disorder, including methylphenidate, amphetamines, pemoline, anticholinergics, and antihistamines.

•

Postinfectious encephalitis.

•

Inherited disorders—these include Huntington's disease, Hallervorden Spatz, and neuroacanthocytosis. All these should have other abnormalities on neurologic examination.

WORKUP

Clinical observation and history to confirm diagnosis LABORATORY TESTS

No definitive laboratory tests. IMAGING STUDIES

CT scan and MRI of brain are normal and unnecessary in the absence of abnormal neurologic examination.

TREATMENT NONPHARMACOLOGIC THERAPY

Multidisciplinary: parents, teachers, psychologists, school nurses ACUTE GENERAL Rx

Dopamine-blocking agents may be used to reduce severity of tics acutely (e.g., haloperidol 0.25 mg po qhs initially). CHRONIC Rx

Tics only require treatment when they interfere with psychosocial, educational, and occupational functioning of a person. TICS

•

Clonidine—many choose this as a first line agent because of fewer long-term side effects. Start at 0.05 mg and slowly titrate to about 0.45 mg daily (needs tid/qid dosing). May also help with symptoms of ADHD.

•

Guanfacine (Tenex), another alpha agonist similar to clonidine but can be administered once daily. Typical starting dose is 0.5 mg titrating to 1 to 3 mg qd.

•

Tetrabenazine—dopamine-depleting agent that is not currently available in the U.S. Avoids many of the typical side effects of the neuroleptics.

•

Atypical antipsychotics such as ziprasidone (Geodon), risperidone (Risperdal), and olanzapine (Zyprexa). These have fewer side effects than typical neuroleptics.

•

Dopamine-blocking agents—neuroleptics (Pimozide, Haldol, Prolixin). These should be avoided until other options have been exhausted.

•

Dopamine agonists—recent small, open label studies have found that ropinirole and pramipexole in low doses may be effective in reducing tic severity.

ADHD

Stimulants (dextroamphetamine, methylphenidate) are useful for symptoms of ADHD but may exacerbate tics. OCD

SSRIs, such as fluoxetine, are the most effective. DISPOSITION

•

In the later teen years, intensity and frequency of tics diminish.

•

One third of patients will achieve significant remission although complete, lifelong remission is rare.

•

One third will have mild, persistent, but “unimpairing” tics.

REFERRAL

To neurologist to confirm initial diagnosis

PEARLS & CONSIDERATIONS Tics do not need treatment unless they interfere with an individual's ability to function. COMMENTS

Patient education may be obtained from the Tourette's Syndrome Association (TSA), 4240 Bell Blvd., Bayside, NY 11361-2864; phone: (800) 237-0717, (718) 224-2999; www.tsa-usa.org .

EVIDENCE

Evidence for specific therapies is limited. A recent double-blind, placebo-controlled study confirmed that methylphenidate (as compared with clonidine) does not actually cause a worsening of tics.[[1]]

Evidence-Based Referencece 1. Neurology 2002; 58:527-536.

SUGGESTED READINGS Jankovic J: Tourette's syndrome. N Engl J Med 2001; 345:1184. Jankovic J: Tics and Tourette's syndrome. In: Jankovic J, Tolosa E, ed. Parkinson's Disease and Movement Disorders, Philadelphia: Lippincott Williams & Wilkins; 2002. Kurlan R: Future and alternative therapies in Tourette syndrome. Adv Neurol 2006; 99:248. Pringsheim T: Tics. Curr Opin Neurol 2003; 16:523-527. Sandor P: Pharmacological management of tics in patients with TS. J Psychosom Res 2003; 55:41-48.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Toxic Shock Syndrome DENNIS M. WEPPNER, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Toxic shock syndrome is an acute febrile illness resulting in multiple organ system dysfunction caused most commonly by a bacterial exotoxin. Disease characteristics also include hypotension, vomiting, myalgia, watery diarrhea, vascular collapse, and an erythematous sunburnlike cutaneous rash that desquamates during recovery.

ICD-9CM CODES

040.89 Toxic shock syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

Case reported incidence peak: 14 cases/100,000 menstruating women/yr in 1980; has since fallen to 1 case/100,000 persons

•

Occurs most commonly between ages 10 and 30 yr in healthy, young menstruating white females

•

Case fatality ratio of 3%

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Fever (=38.9° C)

•

Diffuse macular erythrodermatous rash that desquamates 1 to 2 wk after disease onset in survivors

•

Orthostatic hypotension

•

GI symptoms: vomiting, diarrhea, abdominal tenderness

•

Constitutional symptoms: myalgia, headache, photophobia, rigors, altered sensorium, conjunctivitis, arthralgia

•

Respiratory symptoms: dysphagia, pharyngeal hyperemia, strawberry tongue

•

Genitourinary symptoms: vaginal discharge, vaginal hyperemia, adnexal tenderness

•

End-organ failure

•

Severe hypotension and acute renal failure

•

Hepatic failure

•

Cardiovascular symptoms: DIC, pulmonary edema, ARDS, endomyocarditis, heart block

ETIOLOGY

•

Menstrually associated TSS: 45% of cases associated with tampons, diaphragm, or vaginal sponge use

•

Nonmenstruating associated TSS: 55% of cases associated with puerperal sepsis, post–cesarean section endometritis, mastitis, wound or skin infection, insect bite, pelvic inflammatory disease, and postoperative fever

•

Causative agent: S. aureus infection of a susceptible individual (10% of population lacking sufficient levels of antitoxin antibodies), which liberates the disease mediator TSST-1 (exotoxin)

•

Other causative agents: coagulase-negative streptococci producing enterotoxins B or C, and exotoxin A producing group A ß-hemolytic streptococci

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Staphylococcal food poisoning

•

Septic shock

•

Mucocutaneous lymph node syndrome

•

Scarlet fever

•

Rocky Mountain spotted fever

•

Meningococcemia

•

Toxic epidermal necrolysis

•

Kawasaki's syndrome

•

Leptospirosis

•

Legionnaires' disease

•

Hemolytic-uremic syndrome

•

Stevens-Johnson syndrome

•

Scalded skin syndrome

•

Erythema multiforme

•

Acute rheumatic fever

WORKUP

Broad-spectrum syndrome with multiorgan system involvement and variable but acute clinical presentation, including the following:

1.

Fever =38.1° C

2.

Classic desquamating (1 to 2 wk) rash

3.

Hypotension/orthostatic SBP 90 or less

4.

Syncope

5.

Negative throat/CSF cultures

6.

Negative serologic test for Rocky Mountain spotted fever, rubeola, and leptospirosis

7.

Clinical involvement of three or more of the following: a.

Cardiopulmonary: ARDS, pulmonary edema, endomyocarditis, second- or third-degree AV block

b.

CNS: altered sensorium without focal neurologic findings

c.

Hematologic: thrombocytopenia (PLT < 100 k)

d.

Liver: elevated LFT results

e.

Renal: > 5/HPF, negative urine cultures, azotemia, and increased creatinine double normal

f.

Mucous membrane involvement: vagina, oropharynx, conjunctiva

g.

Musculoskeletal: myalgia, CPK twice normal

h.

GI: vomiting, diarrhea

LABORATORY TESTS

•

Pan culture (cervix/vagina, throat, nasal passages, urine, blood, CSF, wound) for Staphylococcus, Streptococcus, or other pathogenic organisms

•

Electrolytes to detect hypokalemia, hyponatremia

•

CBC with differential and clotting profile for anemia (normocytic/normochromic), thrombocytopenia, leukocytosis, coagulopathy, and bacteremia

•

Chemistry profile to detect decreased protein, increased AST, increased ALT, hypocalcemia, elevated BUN/creatinine, hypophosphatemia, increased LDH, increased CPK

•

Urinalysis to detect WBC (> 5/HPF), proteinemia, microhematuria

•

ABGs to assess respiratory function and acid-base status

•

Serologic tests considered for Rocky Mountain spotted fever, rubeola, and leptospirosis

IMAGING STUDIES

•

Chest x-ray examination to evaluate pulmonary edema

•

ECG to evaluate arrhythmia

•

Sonography/CT scan/MRI considered if pelvic abscess or TOA suspected

TREATMENT NONPHARMACOLOGIC THERAPY

•

For optimal outcome: high index of suspicion and early and aggressive supportive management in an ICU setting

•

Aggressive fluid resuscitation (maintenance of circulating volume, CO, SBP)

•

Thorough search for a localized infection or nidus: incision and drainage, debridement, removal of tampon or vaginal sponge

•

Central hemodynamic monitoring, Swan-Ganz catheter and arterial line for surveillance of hemodynamic status and response to therapy

•

Foley catheter to monitor hourly urine output

•

Possible MAST trousers as temporary measure

•

Acute ventilator management if severe respiratory compromise

•

Renal dialysis for severe renal impairment

•

Surgical intervention for indicated conditions (i.e., ruptured TOA, wound abscess, mastitis)

ACUTE GENERAL Rx

•

Isotonic crystalloid (normal saline solution) for volume replacement following “7-3” rule

•

Electrolyte replacement (K+, Ca+)

•

PRBC/coagulation factor replacement/FFP to treat anemia or D&C

•

Vasopressor therapy for hypotension refractory to fluid volume replacement (i.e., dopamine beginning at 2 to 5 µg/kg/min)

•

Naloxone infusion (i.e., 0.5 mg/kg/hr) to improve SBP by blocking endogenous endorphin effects

•

Parenteral antibiotic therapy; ß-lactamase resistant antibiotic (methicillin, nafcillin, or oxacillin) initiated early

•

Broad-spectrum antibiotic added if concurrent sepsis suspected

•

Tetracycline added if considering Rocky Mountain spotted fever

CHRONIC Rx

•

Severely ill patient: may require prolonged hospitalization and supportive management with gradual recovery and/or sequelae from severe endorgan involvement (ARDS or renal failure requiring dialysis)

•

Majority of patients: complete recovery

•

Early late-onset complications (within 2 wk):

•

1.

Skin desquamation

2.

Impaired digit sensation

3.

Denuded tongue

4.

Vocal cord paralysis

5.

ATN

6.

ARDS

Late-onset complications (after 8 wk):

•

1.

Nail splitting/loss

2.

Alopecia

3.

CNS sequelae

4.

Renal impairment

5.

Cardiac dysfunction

Recurrent TSS: 1.

More common in menstrually related cases

2.

Less common in patient treated with ß-lactamase–resistant antistaphylococcal antibiotics

3.

Patients with history of TSS: if suspect signs and symptoms occur, should have high index of suspicion and low threshold for evaluation and treatment

PREVENTION

•

Avoidance of tampons or use of low-absorbency tampons only (< 4 hr in situ) and alternate with napkins

•

Education for patients concerning signs and symptoms of TSS

•

Avoidance of tampons for patients with history of TSS

DISPOSITION

•

Complete recovery for most patients

•

Long-term management of early- and late-onset complications for minority of patients

REFERRAL

•

For multidisciplinary management, involving primary physician, gynecologist, internist, infectious disease specialist, and other supportive care specialists

•

To tertiary level hospital

PEARLS & CONSIDERATIONS COMMENTS

Patient information available from American College of Gynecologists and Obstetricians.

EVIDENCE

In patients with bacterial sepsis or septic shock, treatment with polyclonal intravenous immunoglobulin (IVIG) has been shown to significantly reduce both overall and sepsis-related mortality, but larger multicenter trials are needed to support these findings. [106] [107] Existing evidence has not determined whether any particular vasopressor agent has superiority in the management of septic shock.[[3]] Treatment with a long course of low-dose corticosteroids has been shown to significantly reduce 28-day allcause mortality, and intensive care unit and hospital mortality in patients with severe sepsis or septic shock, compared with control groups. [[4]] A randomized controlled trial has found that early goal-directed therapy, commenced in the emergency department before admission to the intensive care unit, provides significant benefits with respect to outcome (including in-hospital mortality) in patients with severe sepsis and septic shock.[[5]]

Evidence-Based Referenceces 1. Alejandria MM, et al: Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev 2002; 1:(Cochrane Review). 2. Darenberg J, et al: Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003; 37:333. 3. Müllner M, et al: Vasopressors for shock. Cochrane Database Syst Rev 2004; 2:(Cochrane Review). 4. Annane D, et al: Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev 2004; 1:(Cochrane Review). 5. Rivers EEarly Goal-Directed Therapy Collaborative Group, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368.

SUGGESTED READINGS Issa NC, et al: Staphylococcal toxic shock syndrome: suspicion and prevention are keys to control. Postgrad Med 2001; 110(4):55. Miche CA, Shah V: Managing toxic shock syndrome. Nursing Times 2003; 99(5):26.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Toxoplasmosis GLENN G. FORT, M.D., M.P.H., MICHELE HALPERN, M.D., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Toxoplasmosis is an infection caused by the protozoal parasite Toxoplasma gondii.

ICD-9CM CODES

130.9 Toxoplasmosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

3% to 70% of healthy adults

•

Increases with age

•

Increases with certain activities

•

1.

Slaughterhouse workers

2.

Cat owners

Increases with certain geographic locations: high prevalence of cats

PEAK INCIDENCE: Temperate climates PREDOMINANT SEX: Equal gender distribution PREDOMINANT AGE: •

Infancy (congenital infection)

•

Prevalence increases with age

GENETICS: Congenital Infection:

•

Incidence and severity vary with the trimester of gestation during which the mother acquired infection. 1.

10% to 25% (first trimester)

2.

30% to 54% (second trimester)

3.

60% to 65% (third trimester)

•

Congenital infection occurring in the first trimester is the most severe.

•

89% to 100% of infections in the third trimester are asymptomatic.

•

Risk to the fetus is not correlated with symptoms in the mother.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

Acquired (immunocompetent host) 1.

80% to 90% asymptomatic

2.

Adenopathy (usually cervical)

3.

Fever

4.

Myalgias

5.

Malaise

6.

Sore throat

7.

Maculopapular rash

8.

Hepatosplenomegaly

9.

Chorioretinitis rare

Acquired (in patients with AIDS) 1.

•

•

89% of symptomatic cases a.

Encephalitis

b.

Intracerebral mass lesions

2.

Pneumonitis

3.

Chorioretinitis

4.

Other end organ

Acquired (immunocompromised patients) 1.

Encephalitis

2.

Myocarditis (especially in heart transplant patients)

3.

Pneumonitis

Ocular infection in the immunocompetent host

•

1.

Congenital infection

2.

Blurred vision

3.

Photophobia

4.

Pain

5.

Loss of central vision if macula involved

6.

Focal necrotizing retinitis

7.

Typically presents in second or third decade

Congenital 1.

Results from acute infection acquired by the mother within 6 to 8 wk before conception or during gestation

2.

Usually, asymptomatic mother

3.

No sign of disease

4.

Chorioretinitis

5.

Blindness

6.

Epilepsy

7.

Psychomotor or mental retardation

8.

Intracranial calcifications

9.

Hydrocephalus

10. Microcephaly 11. Encephalitis 12. Anemia 13. Thrombocytopenia 14. Hepatosplenomegaly 15. Lymphadenopathy 16. Jaundice 17. Rash 18. Pneumonitis 19. Most infected infants are asymptomatic at birth ETIOLOGY

•

•

Toxoplasma gondii 1.

Ubiquitous intracellular protozoan

2.

Present worldwide

3.

Cat is definitive host

Human infection 1.

Ingestion of oocysts shed by cats

2.

Ingestion of meat containing tissue cysts

3.

Vertical transmission

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

•

•

•

•

Lymphadenopathy 1.

Infectious mononucleosis

2.

CMV mononucleosis

3.

Cat-scratch disease

4.

Sarcoidosis

5.

Tuberculosis

6.

Lymphoma

7.

Metastatic cancer

Cerebral mass lesions in immunocompromised host 1.

Lymphoma

2.

Tuberculosis

3.

Bacterial abscess

Pneumonitis in immunocompromised host 1.

Pneumocystis jirovecii (carinii) pneumonia

2.

Tuberculosis

3.

Fungal infection

Chorioretinitis 1.

Syphilis

2.

Tuberculosis

3.

Histoplasmosis (competent host)

4.

CMV

5.

Syphilis

6.

Herpes simplex

7.

Fungal infection

8.

Tuberculosis (AIDS patient)

Myocarditis 1.

•

Organ rejection in heart transplant recipients

Congenital infection

1.

Rubella

2.

CMV

3.

Herpes simplex

4.

Syphilis

5.

Listeriosis

6.

Erythroblastosis fetalis

7.

Sepsis

WORKUP

•

•

Acute infection, immunocompetent host 1.

CBC

2.

Toxoplasma serology (IgG, IgM) in serial blood specimens 3 wk apart

3.

Lymph node biopsy if diagnosis uncertain

Immunocompromised host 1.

2.

3.

4.

•

CNS symptoms a.

Cerebral CT scan or MRI if CNS symptoms present

b.

Spinal tap, if safe

c.

Brain biopsy if no response to empiric therapy

Ocular symptoms a.

Funduscopic examination

b.

Serologic studies

c.

Rarely, vitreous tap

Pulmonary symptoms a.

Chest x-ray examination

b.

Bronchoalveolar lavage

c.

Transbronchial or open lung biopsy

Myocarditis a.

Cardiac enzymes

b.

Electrocardiogram

c.

Endomyocardial biopsy for definitive diagnosis

Toxoplasmosis in pregnancy

1.

2.

3. •

Initial maternal screening with IgM and IgG a.

If negative, mother at risk of acute infection and should be retested monthly

b.

If both IgG and IgM positive, obtain IgA and IgE ELISA, AC/HS test

c.

IgA and IgE ELISA, AC/HS test elevated in acute infection

d.

Ig high for 1 yr or more

e.

IgG repeated 3 to 4 wk later to determine if titer is stable

Acute maternal infection not excluded or documented a.

Fetal blood sampling (for culture, Ig, IgA, IgE)

b.

Amniotic fluid PCR

Fetal ultrasound every other week if maternal infection documented

Congenital toxoplasmosis 1.

Placental histology

2.

Specific IgM or IgA in infant's blood

LABORATORY TESTS

•

Antibody studies 1.

More than one test necessary to establish diagnosis of acute toxoplasmosis

2.

IgM antibody

3.

4.

5.

a.

Appears 5 days into infection

b.

Peaks at 2 wk

c.

Falls to low level or disappears within 2 mo

d.

May persist at low levels for 1 yr or more

Antibody not measurable a.

Ocular toxoplasmosis

b.

Reactivation

c.

Immunocompromised hosts

IgA ELISA, IgE ELISA, and IgE ASAGA a.

More sensitive tests

b.

Disappear more rapidly than Ig, establishing diagnosis of acute infection

IgG antibody a.

Appears 1 to 2 wk after infection

b.

Peaks at 6 to 8 wk

c.

Gradually declines over months to years

IMAGING STUDIES

•

Chest x-ray examination if pulmonary involvement suspected

•

Cerebral CT scan or MRI if encephalitis suspected

TREATMENT NONPHARMACOLOGIC THERAPY

•

•

Selected cases of ocular infection 1.

Photocoagulation

2.

Vitrectomy

3.

Lentectomy

Selected cases of congenital cerebral infection 1.

Ventricular shunting

ACUTE GENERAL Rx

•

Acute infection, immunocompetent host 1.

•

•

Acute infection, immunocompromised host, non-AIDS 1.

Treat even if asymptomatic

2.

Duration Until 4 to 6 wk after resolution of all signs and symptoms

b.

Usually 6 mo or longer

Treat if symptomatic

Acute or reactivated infection, AIDS 1.

Treat in all cases

2.

Induction course

3.

•

a.

Reactivated infection, immunocompromised host, non-AIDS 1.

•

No treatment, unless severe and persistent symptoms or vital organ damage

a.

3 to 6 wk

b.

Maintenance therapy continued for life; consider discontinuation of suppressive therapy if the patient has a good response to highly active antiretroviral therapy and if the CD4 count remains >200 cell/mm3 for more than 3 mo

Empiric therapy a.

AIDS with positive IgG

b.

Multiple ring-enhancing lesions on cerebral CT scan or MRI

c.

Response seen by day 7 in 71% and day 14 in 91%

Ocular infection

•

•

1.

Treat in all cases

2.

Therapy continued for 1 mo or longer if needed

3.

Response seen in 70% within 10 days

4.

Retreat as needed

5.

Steroids may be indicated

6.

Surgical treatment in selected cases

Treatment regimens 1.

Pyrimethamine 100 to 200 mg loading dose once PO, then 25 mg PO qd (50 to 75 mg in AIDS) plus

2.

Leucovorin 10 to 20 mg PO qd plus

3.

Sulfadiazine 1 to 1.5 g PO q6h Other treatment options (if sulfahypersensitivity or allergy is present): pyrimethamine 50 to 75 mg/day orally with leucovorin 10 to 20 mg/day po and either (1) clindamycin 600 mg iv or po q6h, or (2) clarithromycin 1 gm po bid, or (3) dapsone 100 mg/day po, or (4) atovaquone 750 mg po q6h.

Acute infection in pregnancy 1.

Treat immediately

2.

Risk of fetal infection reduced by 60% with treatment a.

b.

•

First trimester i.

Spiramycin 3 g PO qd in two to four divided doses

ii.

Sulfadiazine 4 g PO qd in four divided doses

Second and third trimester i.

Sulfadiazine as above plus

ii.

Pyrimethamine 25 mg PO qd plus

iii.

Leucovorin 5 to 15 mg PO qd

iv.

Spiramycin as above

Congenital infection 1.

Sulfadiazine 50 mg/kg PO bid plus

2.

Pyrimethamine 2 mg/kg PO for 2 days, then 1 mg/kg PO, three times weekly plus

3.

Leucovorin 5 to 20 mg PO three times weekly

4.

Minimum duration of treatment: 12 mo

CHRONIC Rx

•

Maintenance therapy in AIDS patients because of the high risk (80%) of relapse 1.

Pyrimethamine 25 mg PO qd

2.

Sulfadiazine 500 mg PO qid

3.

Leucovorin 10 to 20 mg PO qd

DISPOSITION

•

•

Prognosis 1.

Excellent in the immunocompetent host

2.

Good in ocular infection (although relapses are common)

Treatment of acute infection in pregnancy 1.

•

•

Reduces incidence and severity of congenital toxoplasmosis

Treatment of congenital infection 1.

Improvement in intellectual function

2.

Regression of retinal lesions

AIDS 1.

70% to 95% response to therapy

REFERRAL

•

•

To infectious disease expert: 1.

Immunocompromised hosts

2.

Pregnant women

3.

Difficulty in making a diagnosis or deciding on treatment

To pediatric infectious disease expert: 1.

•

•

Congenital infection

To obstetrician: 1.

Pregnant seronegative mother

2.

Acute seroconversion

To ophthalmologist: 1.

Congenital infection

2.

Any case of ocular infection

PEARLS & CONSIDERATIONS COMMENTS

•

Prevention of toxoplasmosis is most important in seronegative pregnant women and immunocompromised hosts.

•

Patient instructions: 1.

Cook meat to 66° C.

2.

Cook eggs.

3.

Do not drink unpasteurized milk.

4.

Wash hands thoroughly after handling raw meat.

5.

Wash kitchen surfaces that come in contact with raw meat.

6.

Wash fruits and vegetables.

7.

Avoid contact with materials potentially contaminated with cat feces.

EVIDENCE

Treatment of toxoplasmosis in pregnancy Two systematic reviews in women with acute toxoplasmosis in pregnancy found little evidence to suggest a benefit for mother or baby from treatment with current antiparasitics compared with no treatment. [113] [114]

However, a long-term multicenter observational study concluded that even though prenatal antibiotic therapy for toxoplasmosis infection during pregnancy had no impact on the fetomaternal transmission rate, it did reduce the rate of sequelae among the infected infants. Also, starting treatment early resulted in significantly fewer severely affected children.[[3]] Treatment and prophylaxis of toxoplasmic encephalitis in HIV-infected patients A European multicenter trial found no difference in efficacy during acute treatment between pyrimethamine plus sulfadiazine or pyrimethamine plus clindamycin.[[4]] This trial also found that during maintenance therapy the relapse rate was twice as high among patients in the group receiving pyrimethamine plus clindamycin.[[4]] A small, randomized controlled trial (RCT) found that trimethoprimsulfamethoxazole was as effective and better tolerated than pyrimethamine-sulfadiazine.[[5]] A trial of patients in the early stages of HIV infection in sub-Saharan Africa found that there was no significant difference between trimethoprim-sulfamethoxazole vs. placebo terms of preventing toxoplasmosis.[[6]] A systematic review found no significant difference between trimethoprimsulfamethoxazole vs. dapsone (alone or in combination with pyrimethamine) in the prevention of toxoplasmosis in HIV-infected patients.[[7]] An RCT found that, in patients who were able to tolerate it, dapsone/pyrimethamine was a more effective prophylactic treatment for toxoplasmic encephalitis in HIV-infected people vs. aerosolized pentamidine. However, 30% of patients were unable to tolerate dapsone/pyrimethamine.[[8]] We were unable to cite any evidence that meets our criteria concerning the newer agents azithromycin and atovaquone.

Evidence-Based Referenceces 1. Wallon M, et al: Congenital toxoplasmosis: systematic review of evidence of efficacy of treatment in pregnancy. BMJ 1999; 318:1511.Reviewed in: Clin Evid 12:1058, 2004. 2. Peyron F, et al: Treatments for toxoplasmosis in pregnancy. Cochrane Database Syst Rev 1999; 3: 3. Foulon W, et al: Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year. Am J Obstet Gynecol 1999; 180:410. 4. Katlama C, et al: Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis 1996; 22:268. 5. Torre D, et al: Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Antimicrob Agents Chemother 1998; 42(6):1346. 6. Anglaret X, et al: Early chemoprophylaxis with trimethroprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomized trial. Lancet 1999; 353:1463.Reviewed in: Clin Evid 12:1004, 2004. 7. Bucher HC, et al: Meta-analysis of prophylactic treatments against Pneumocystis carinii pneumonia and toxoplasma encephalitis in HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 15:104.Reviewed in: Clin Evid 12:1004, 2004. 8. Opravil M, et al: Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients. Clin Infect Dis 1995; 20:531.

SUGGESTED READINGS Boyer KM, et al: Risk factors for Toxoplasma gondii infection in mothers of infants with congenital toxoplasmosis: implications for prenatal management and screening. Am J Obstet Gynecol 2005; 192(2):564. Campbell AL, et al: First case of toxoplasmosis following small bowel transplantation and systematic review of tissue-invasive toxoplasmosis following noncardiac solid organ transplantation. Transplantation 2006; 81(3):408. Fricker-Hidalgo H, et al: Disseminated toxoplasmosis with pulmonary involvement after heart transplantation. Transpl Infect Dis 2005; 7(1):38. Kravetz JD, Federman DG: Prevention of toxoplasmosis in pregnancy: knowledge of risk factors. Infect Dis Obstet Gynecol 2005; 13(3):161. Kravetz JD, Federman DG: Toxoplasmosis in pregnancy. Am J Med 2005; 118:212. Montoya JG, Rosso F: Diagnosis and management of toxoplasmosis. Clin Perinatol 2005; 32(3):705. Soheilian M, et al: Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology 2005; 112(11):1876.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tracheitis GLENN G. FORT, M.D., M.P.H., JOSEPH R. MASCI, M.D., HARVEY M. SHANIES, M.D., PH.D.

BASIC INFORMATION DEFINITION

Bacterial tracheitis is an acute infectious disease affecting the trachea and large conducting airways. Tracheal inflammation may be caused by a large number of inhaled stimuli, but bacterial infection is a life-threatening illness associated with purulent secretions and subglottic edema. SYNONYMS

Bacterial tracheobronchitis Pseudomembranous croup Membranous laryngotracheobronchitis

ICD-9CM CODES

464.10 Tracheitis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Uncommon

•

May be the most common cause of acute upper airway obstruction requiring admission to pediatric ICUs

PEAK INCIDENCE: Three fourths of cases reported in winter PREDOMINANT SEX: Boys > girls in one series PREDOMINANT AGE: •

1 mo to 8 yr

•

Almost all < 13 yr (most < 3 yr)

GENETICS: Down syndrome is a possible predisposing factor.

Congenital Infection: Some cases found in those with anatomic abnormalities of the upper airways. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Croupy or “brassy” cough

•

Inspiratory stridor (frequent)

•

Wheezing (unusual)

•

Fever (often > 102° F)

•

Thick, purulent secretions expectorated 1.

Minority of patients expectorate “ricelike” pellets.

2.

Most patients are unable to mobilize secretions. a.

Become inspissated

b.

Form pseudomembranes

ETIOLOGY

•

Staphylococcus aureus

•

Haemophilus influenzae

•

ß-Hemolytic streptococcal infection

•

Secondary to viral infections of the respiratory tract

•

1.

Primary influenza

2.

RSV

3.

Parainfluenza

Many cases follow measles 1.

Especially when accompanied by chest radiographic infiltrates

2.

Sometimes fatal outcome

3.

Associated with prolonged endotracheal intubation

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Viral croup

•

Epiglottitis

•

Diphtheria

•

Necrotizing herpes simplex infection in the elderly

•

CMV in immunocompromised patients

•

Invasive aspergillosis in immunocompromised patients

WORKUP

Direct laryngoscopy

1.

Typical secretions a.

May form pseudomembranes

b.

Airway obstruction

2.

Normal epiglottis rules out epiglottitis

3.

Possible subglottic edema

LABORATORY TESTS

•

WBC is sometimes elevated.

•

On differential, left shift is almost universal.

•

Gram stain and culture of tracheal secretions confirm diagnosis.

•

Blood cultures are positive in a minority.

IMAGING STUDIES

•

•

Lateral x-ray examination of neck 1.

Normal epiglottis

2.

Vague density or a “dripping candle” appearance of tracheal mucosa 1.

Secretions

b.

Pseudomembranes

Chest radiograms 1.

Not diagnostic

2.

Should not be performed on patients in acute respiratory distress, because severe or fatal upper airway obstruction can develop suddenly

•

Pneumonic infiltrates frequent

•

Atelectasis: unusual but can lead to lobar collapse

TREATMENT NONPHARMACOLOGIC THERAPY

•

•

•

Aggressive maintenance of a patent airway 1.

Laryngoscopy or bronchoscopy used diagnostically and therapeutically to strip away pseudomembranes

2.

Voluminous and tenacious secretions suctioned from the underlying friable mucosa a.

May extend from between the vocal cords to the main carina

b.

Larger channels of rigid instruments for more effective suctioning

Prevention of complete large airway obstruction 1.

Nasotracheal intubation

2.

Humidification of inspired gas

3.

Frequent saline instillation and suctioning

4.

Intubation with general anesthesia, performed in the operating room, is preferred by some

Ventilatory support necessary with initial management in ICU

ACUTE GENERAL Rx

•

Antibiotic therapy: start immediately, generally continued for 1 to 2 wk

•

Initial therapy directed against H. influenzae and S. aureus (e.g., cefotaxime and vancomycin)

•

Oral therapy is usually sufficient after 5 or 6 days of IV administration

DISPOSITION

•

Most patients are extubated in 5 to 6 days after initiating antibiotic therapy.

•

Anoxic encephalopathy is reported in 7% of survivors.

REFERRAL

Suspected diagnosis

PEARLS & CONSIDERATIONS COMMENTS

•

Infants are at increased risk of airway obstruction because of the small airway dimension.

•

Presence of pneumonia and a staphylococcal etiology are thought to worsen prognosis.

•

Reported complications: toxic shock syndrome, persistent postextubation stridor, pneumothorax, and volutrauma

SUGGESTED READINGS Gaugler C, et al: Neonatal necrotizing tracheobronchitis: three case reports. J Perinatol 2004; 24(4):259. Kinebuchi S, et al: Tracheo-bronchitis associated with Crohn's disease improved on inhaled corticotherapy. Intern Med 2004; 43(9):829. Salamone FN, et al: Bacterial tracheitis reexamined: is there a less severe manifestation?. Otolaryngol Head Neck Surg 2004; 131(6):871.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Transfusion Reaction, Hemolytic SEAN I. SAVITZ , M.D.

BASIC INFORMATION DEFINITION

Hemolytic transfusion reaction is an acute intravascular hemolysis caused by mismatches in the ABO system. It is cause fixing Ig and IgG antibodies to group A and B RBCs. Hemolytic transfusion reactions can also be caused by minor antige they are usually less severe. In delayed serologic transfusion reactions, hemolysis with hemoglobinemia is unusual; in th reactions the only manifestations may be the development of a newly positive Coombs' test and fever. ICD-9CM CODES 999.8 Other transfusion reaction EPIDEMIOLOGY & DEMOGRAPHICS

Acute intravascular hemolysis occurs in < 1 in 50,000 transfusions. PHYSICAL FINDINGS & CLINICAL PRESENTATION ( Table 1-47 )

• Hypotension • Pain at the infusion site • Fever, tachycardia, chest or back pain, dyspnea • Often, severe reactions occur in surgical patients under anesthesia who are unable to give any warning signs TABLE 1-47 -- Signs and Symptoms of Acute Adverse Reactions to Blood Transfusion Acute hemolytic X X X X X X X X X Febrile nonhemolytic

X X X X

Nonimmune hemolysis

Acute lung injury Allergic X

X X

X Massive transfusion complications

Anaphylaxis X X X X X X X X X Passive cytokine infusion X X X

Hypervolemia

X

Bacterial sepsis X X X

X X X Air embolus

X X

Disc Chest Facial Back/Lumbar at In Reaction Fever Chills/Rigors Nausea/Vomiting Discomfort/Pain Flushing Wheezing/Dyspnea Pain Site From Goldman L, Bennett JC (eds): Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders. ETIOLOGY

Most fatal hemolytic reactions are caused by clerical errors and mislabeled specimens.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

• Bacterial contamination of blood • Hemoglobinopathies WORKUP

The transfusion must be stopped immediately. The blood bank must be notified, and the donor transfusion bag must be r bank along with a freshly drawn posttransfusion specimen. LABORATORY TESTS

• Positive Coombs' test, elevated BUN, creatinine, and bilirubin • Hemoglobinuria (wine-colored urine), hemoglobinemia (pink plasma) • Decreased Hct, decreased serum haptoglobin

TREATMENT NONPHARMACOLOGIC THERAPY

• Stop transfusion immediately. Test anticoagulated blood from the recipient for the presence of free Hgb in the plasma. • Monitor vital signs. ACUTE GENERAL Rx

• Vigorous IV hydration to maintain urine flow at > 100 ml/hr until hypotension is corrected and hemoglobinuria clears. IV furo necessary to maintain adequate renal flow. • The addition of mannitol may prevent renal damage (controversial). • Monitor for the presence of DIC. • Use of IV steroids is controversial. DISPOSITION

Mortality exceeds 50% in severe transfusion reactions.

PEARLS & CONSIDERATIONS COMMENTS

Hemolysis caused by minor antigen systems is generally less severe and may be delayed 5 to 10 days after transfusion. AUTHOR: FRED F. FERRI, M.D.

Transient Ischemic Attack

BASIC INFORMATION DEFINITION

Transient ischemic attack (TIA) refers to a transient neurologic dysfunction caused by focal brain or retinal ischemia with less than 60 min and followed by a full recovery of function. Acute brain ischemia is a medical emergency requiring prom evaluation and potential intervention. SYNONYMS

TIA ICD-9CM CODES 435.9 Unspecified transient cerebral ischemia EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 49 cases/100,000 persons/yr PEAK INCIDENCE: >60 yr PREDOMINANT SEX: Males > females PHYSICAL FINDINGS & CLINICAL PRESENTATION

• During an episode, neurologic abnormalities are confined to discrete vascular territory.

• Typical carotid territory symptoms are ipsilateral monocular visual disturbance, contralateral homonymous hemianopsia, co or sensory dysfunction, and language dysfunction (dominant hemisphere) alone or in combination.

• Typical vertebrobasilar territory symptoms are binocular visual disturbance, vertigo, diplopia, dysphagia, dysarthria, and mo dysfunction involving the ipsilateral face and contralateral body. ETIOLOGY

• Cardioembolic • Large vessel atherothrombotic disease •

Lacunar disease • Hypoperfusion with fixed arterial stenosis • Hypercoagulable states

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

• Hypoglycemia • Seizures • Migraine • Subdural hemorrhage • Mass lesions • Vestibular disease • Section II describes the differential diagnosis of neurologic deficits, focal and multifocal. WORKUP

• Thorough history and physical examination • Ancillary investigations including neuroimaging aimed at identifying the etiology quickly LABORATORY TESTS

• CBC with platelets • PT (INR) and PTT • Glucose

• Lipid profile • ESR (if clinical suspicion for infectious or inflammatory process) • Urinalysis • Chest x-ray • ECG and consider cycling cardiac enzymes • Other tests as dictated by suspected etiology IMAGING STUDIES

• Head CT scan to exclude hemorrhage including a subdural hemorrhage

• MRI and MRA. (In several studies, MRI with diffusion-weighted imaging has identified early ischemic brain injury in up to 50 and in such cases the patient has had a stroke). MRA of the brain and neck can identify large vessel intracranial and extrac arteriovenous malformations, and aneurysms

• Carotid Doppler studies identify carotid stenosis; neck ultrasound can also visualize stenoses of the vertebrobasilar arteries • Echocardiography if cardiac source is suspected • Telemetry for hospitalized patients for at least 24 hr. May consider 24-hr Holter if patient is being discharged

• CT angiogram or supraaortic vessel MRA if considering carotid endarterectomy or carotid stent. Four-vessel angiogram if D does not agree with MRA/CTA.

TREATMENT NONPHARMACOLOGIC THERAPY

• Carotid endarterectomy for carotid territory TIA associated with an ipsilateral stenosis of 70% to 99%: should be done by a experienced with and performs this procedure frequently. The procedure should be performed as soon as the patient is fit f within 2 weeks of TIA. Carotid stenting is also being performed in patients who are not surgical candidates. Trials are comp surgery for carotid disease. •

Modification of risk factors including smoking cessation. ACUTE GENERAL Rx

• Depends on etiology.

• If the time of the onset of symptoms is clear, and there are significant deficits on neurologic examination, and brain hemorr out, then the patient may be a candidate for thrombolytic therapy, and it is advisable to discuss the case with a neurologist cerebrovascular disease.

• Acute anticoagulation: no data supporting benefits in the acute setting. Heparin is considered for new-onset atrial fibrillation carotid disease causing recurrent transient neurologic symptoms especially in the setting before carotid endarterectomy or considered for basilar artery thrombosis given concern for progression to brainstem stroke with high morbidity and mortalit • Section III, “Transient Ischemic Attacks,” describes a treatment algorithm. CHRONIC Rx

• For cardioembolic TIA, long-term anticoagulation is considered. Stroke patients with atrial fibrillation or demonstrated cardi shown to benefit from long-term warfarin therapy. Target INR of 2.5 is recommended.

• For noncardioembolic TIA, first line of treatment has traditionally been aspirin. No significant benefit of high-dose aspirin (u been conclusively found over lower doses (75 mg to 325 mg/day). A baby aspirin (81 mg/day) is therefore appropriate.

• Aspirin/dipyridamole extended-release capsules (Aggrenox, 1 capsule po bid) is now recommended as a first-line therapy TIA. In a study of patients with TIA or stroke, aspirin/dipyridamole reduced subsequent cerebrovascular events to a greater alone. Clopidrogel is equally effective to aspirin in secondary prevention but the combination of aspirin and clopidrogel for p stroke causes more life threatening bleeding than clopidrogel alone. Recommend Aggrenox or oral anticoagulation for patie have TIAs while on aspirin (aspirin failures), but there are no data to support this recommendation.

• In patients with cerebrovascular disease, HMG-CoA reductase inhibitors (statins) have been shown to provide significant p subsequent vascular events such as MI and stroke even for LDLs < 100. Consider starting a statin agent unless LDL is < 7 DISPOSITION

• Studies indicate a significant 90-day risk for stroke in patients with a TIA. The risk varies depending on comorbidities, age, deficits. The 7-point ABCD2 score predicts the risk of ischemic stroke and has been validated on a large number of patient • One-year and 3-yr survival rates are 98% and 94%, respectively. REFERRAL

Recommend referring all patients with TIA for an urgent neurologic evaluation and management. TIA patients should be

same urgency as stroke.

PEARLS & CONSIDERATIONS CAVEAT

Urgently evaluate all patients who present with symptoms suggestive of acute brain ischemia. Do not wait for symptoms distinguish TIA versus stroke, as patients who present with acute neurologic deficits within three hours of symptom onse t-PA.

EVIDENCE

Prolonged antiplatelet therapy significantly reduces the risk of serious vascular events in patients with a prior stroke or TI

A systematic review, which compared dipyridamole plus aspirin with aspirin alone, in patients presenting after TIA or stro clear difference in vascular deaths, but has found that the combination is associated with fewer vascular events.[[2] ] There is no benefit from oral anticoagulation following a TIA in the absence of atrial fibrillation.[[3] ]

Warfarin has been shown to be superior to antiplatelet agents in the prevention of stroke in patients with atrial fibrillation. may be used if there are contraindications to warfarin or the risk of ischemic stroke is low.[[4] ]

In people with atrial fibrillation at a high risk of stroke (but no history of previous stroke or TIA), adjusted-dose warfarin si the combined rate of ischemic stroke or systemic embolism, and reduces the rate of disabling or fatal stroke compared w warfarin plus aspirin.[[5] ] Carotid endarterectomy has been shown to reduce the risk of major stroke or death in patients with symptomatic severe stenosis. Patients with mild stenosis did not benefit from surgery. [136 ] [137 ]

RCTs comparing carotid angioplasty plus stenting vs. endarterectomy, in patients with symptomatic carotid stenosis, hav conflicting results, are limited by trial design, and are ongoing. The Stenting and Angioplasty with Protection in Patients a Endarterectomy (SAPPHIRE) study reported improved outcomes in patients at high risk for surgery who were treated wi ]

In patients with a history of previous stroke or TIA, antihypertensive treatment is associated with a significantly reduced r major cardiovascular events compared with placebo, no treatment, or usual medical care.[[9] ]

Simvastatin 40 mg daily for 5 years has significantly reduced mean total cholesterol by 24%, and has significantly reduce vascular events, and deaths vs. placebo, in people with coronary heart disease, other occlusive vascular disease, or diab a history of cerebrovascular disease.[[10] ] In patients with stroke or TIA, simvistatin 80 mg reduces the risk of stroke and

Statin therapy has reduced the relative risk of a major vascular event, irrespective of a patient's medical history or pretre triglyceride level.[[10] ]

Evidence-Based Referenceces

1. Antithrombotic Trialists' Collaboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for preve myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71.Corrections: BMJ 324:141, 2002. Reviewed in 2004.

2. De Schryver EL, Algra A, van Gijn J: Dipyridamole for preventing stroke and other vascular events in patients with vas Cochrane Database Syst Rev 2002; 1:CD001820

3. Sandercock P, et al: Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke ischaemic attack. Cochrane Database Syst Rev 2002; 4:

4. Freestone B, et al: Stroke prevention. Reviewed . Clin Evid, 11. London: BMJ Publishing Group; 2004:257.

5. Stroke Prevention in Atrial Fibrillation Investigators: Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin p risk patients with atrial fibrillation III randomized clinical trial. Lancet 1996; 348:633.Reviewed in: Clin Evid 11:257, 2004

6. Rothwell PM, et al: Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic ca Lancet 2003; 361:107. 7. Cina CS, Clase CM, Haynes RB: Carotid endarterectomy for symptomatic carotid stenosis. Cochrane Database Syst

8. Yadav JS, et al: Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004; 35

9. The INDANA Project Collaborators: Effect of antihypertensive treatment in patients having already suffered from strok 1997; 28:2557.Reviewed in: Clin Evid 11:257, 2004.

10. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol lowering with simvastat individuals: a randomised placebo-controlled trial. Lancet 2002; 360:7.Reviewed in: Clin Evid 11:257, 2004.

11. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) investigators: High-dose atorvastatin af Engl J Med 2006; 355:549.

SUGGESTED READINGS Albers GW: A review of published TIA treatment recommendations. Neurology 2004; 62:S26. Albers GW, et al: Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2004; 126:483S. Albers GW, et al: Transient ischemic attack—proposal for a new definition. N Engl J Med 2002; 347:1713.

Algra A, et al: Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischem stroke of presumed arterial origin. Stroke 2003; 34:234.

Chaturvedi S, et al: Carotid endarterectomy—an evidence-based review: report of the Therapeutics and Technology Ass Subcommittee of the American Academy of Neurology. Neurology 2005; 65:794.

Diener HC, et al: Aspirin and clopidrogrel compared with clopidogrel alone after recent ischemic stroke or transient ischa risk patients (MATCH): randomized, double-blind, placebo-controlled trial. Lancet 2004; 364:331. Heart Protection Study Collaborative Group: MRC/BHF heart protection study of cholesterol lowering with simvastatin in individuals: a randomized placebo-controlled trial. Lancet 2002; 360:7. Johnston SC: Clinical practice. Transient ischemic attack. N Engl J Med 2002; 347:1687.

Johnston SC, et al: National Stroke Association guidelines for the management of transient ischemic attacks. Annals of N 2006; 60:301. Johnston SC, et al: Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. 2007; 369:283.

Copyright © 2008 Elsevier Inc . All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Trichinosis GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., MAURICE POLICAR, M.D.

BASIC INFORMATION DEFINITION

Trichinosis is an infection by one of various species of Trichinella. SYNONYMS

Trichinella spiralis muscle infection

ICD-9CM CODES

124 Trichinosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): 2.5 mV)

2.

Right ventricular enlargement/ypertrophy (e.g., R wave > S wave in lead V1)

3.

Right axis deviation >100 degrees

4.

Atrial fibrillation

IMAGING STUDIES

•

•

•

Chest x-ray may show: 1.

Evidence of COPD (e.g., flattened diaphragms, barrel chest, dilated pulmonary arteries, and increased retrosternal air space) or restrictive lung disease

2.

Enlarged right atrium

3.

Enlarged right ventricle

Echocardiogram ( Fig. 1-277 ) will: 1.

Detect TR

2.

Estimate the severity of TR

3.

Estimate the pulmonary artery pressure

4.

Exclude vegetation, mass or prolapse

5.

Assess left and right ventricular function

Right-sided heart catheterization shows: 1.

Elevated right atrial and right ventricular end-diastolic pressures

2.

Large V waves

FIGURE 1-277 Two-dimensional echocardiograms with color flow imaging of patients with tricuspid regurgitation. A, Echocardiogram of a patient with severe tricuspid insufficiency. B, Echocardiogram of a patient with severe tricuspid regurgitation. LV, Left ventricle; RA, right atrium; RV, right ventricle. (From Zipes DP, Libby P, Bonow RO, Braunwauld E [eds]: Braunwauld's heart disease, ed 7, Philadelphia, 2005, Elsevier.)

TREATMENT Treatment of TR is usually directed at the underlying cause. NONPHARMACOLOGIC THERAPY

Oxygen therapy is beneficial in patients with functional TR secondary to underlying pulmonary hypertension provoked by alveolar hypoxia. ACUTE GENERAL Rx

•

Functional TR caused by left-sided heart failure is treated in the standard way with preload reduction, afterload reduction, or inotropic therapy (see “Heart Failure”).

•

Reversal of pulmonary hypertension with vasodilators or pulmonary thromboendarterectomy has been shown to reverse functional TR.

•

Structural TR treatment depends on the underlying cause of heart disease.

CHRONIC Rx

•

Tricuspid valve repair is beneficial for severe TR in patients with mitral valve (MV) disease requiring MV surgery but carries a high morbidity/mortality. In rheumatic valvular disease, the 30-day morbidity/mortality rate may be as high as 15% to 20%.

•

Tricuspid annuloplasty may be considered in mild and moderate TR in patients undergoing MV surgery when there is suspicion that their TR will progress despite MV surgery (e.g., pulmonary hypertension, tricuspid annular dilatation, or myxomatous involvement of the tricuspid valve).

•

Tricuspid valve replacement or annuloplasty is reasonable in a symptomatic patient with severe TR and diseased or abnormal tricuspid valve leaflets not amenable to annuloplasty or repair.

DISPOSITION

•

Regardless of the etiology, greater than mild degree of TR is associated with decreased survival.

•

Isolated TR should not pose a significant problem during pregnancy, although greater care may be necessary to protect against diuretic-induced hypoperfusion.

•

Isolated TR with normal right ventricular function does not preclude involvement in competitive sports.

REFERRAL

For patients with significant symptomatic TR, a cardiology consultation is recommended.

PEARLS & CONSIDERATIONS TR caused by tricuspid valve prolapse is often associated with concurrent mitral valve prolapse. COMMENTS

Antibiotic prophylaxis for dental, GI, or GU procedures is no longer recommended in patients with only structural tricuspid valve abnormalities. SUGGESTED READINGS Bonow RO, et al: ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease). Circulation 2006; 48(b):598-675. Raman SV, et al: Tricuspid valve disease: tricuspid valve complex perspective. Curr Prob Cardiol 2002; 27(b):103-142. Trichon BH, O'Connor CM: Secondary mitral and tricuspid regurgitation accompanying left ventricular systolic function: is it important, and how is it treated?. Am Heart J 2002; 144(b):373-376.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tricuspid Stenosis CRAIG MCMACKIN, M.D., WEN-CHIH WU, M.D.

BASIC INFORMATION DEFINITION

Tricuspid stenosis (TS) is an uncommon valvular pathology caused by narrowing of the tricuspid valve orifice resulting in the restriction of right atrial emptying. TS is most often rheumatic in origin. SYNONYMS

Tricuspid valve stenosis TS

ICD-9CM CODES

397.0 Disease of the tricuspid valve EPIDEMIOLOGY & DEMOGRAPHICS

•

Most commonly a result of rheumatic heart disease and almost always occurs with associated mitral or aortic valve disease.

•

Antibiotic therapy has made rheumatic heart disease and TS a rarity in the U.S.

•

Present at autopsy in 15% of patients with rheumatic heart disease, but clinically significant in only 5%.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Symptoms of right heart failure: fatigue, right upper quadrant abdominal pain (because of hepatic congestion), ascites, hepatomegaly, and peripheral edema.

•

Jugular venous distention with a prominent “a” wave is noted along with a palpable hepatic pulsation.

•

Right atrial pulsation may be palpated to the right of the sternum and a diastolic thrill that increases with inspiration may be felt over the left sternal edge.

•

An opening snap and a diastolic murmur are best heard along the left sternal border of the fourth intercostal space and are augmented by inspiration.

ETIOLOGY

•

Rheumatic heart disease results in scarring of the valve leaflets, shortening of the chordae tendineae, and fusion of the commissures, leading to immobility of the valve leaflets and narrowing of the tricuspid valve orifice.

•

Other causes are congenital, infectious (e.g., endocarditis), metabolic or enzymatic (carcinoid syndrome, Whipple's disease, Fabry's disease), and systemic (e.g., lupus endocarditis).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Congenital tricuspid atresia

•

Right heart diastolic dysfunction: endomyocardial fibrosis, constrictive pericarditis

•

Extrinsic compression of the right venticle: severe pectum excavatum, massive ascites, pleural effusion, pericardial effusion, or tumor

•

Obstruction of right atrial emptying: right atrial myxoma, metastatic tumor (e.g., lymphoma), right atrial thrombi, tricuspid valve vegetation

WORKUP

•

Echocardiography is the diagnostic test of choice

•

Chest x-ray examination

•

ECG: atrial arrhythmias, enlarged right atrium

•

Right-heart catheterization in patients for whom echocardiography cannot make a definitive diagnosis

IMAGING STUDIES

•

Echocardiography reveals thickening and shortening of the tricuspid valve leaflets, with restriction of movement of the leaflets and leaflet tips. Evidence of right atrial enlargement is present in most cases.

•

Doppler echocardiography or cardiac catheterization demonstrates a reduced tricuspid valve area (severe: males (4:1)

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Hip pain is the most common complaint. The pain is chronic, intermittent, and located over the lateral thigh.

•

Numbness can be present.

•

Pain is precipitated with prolonged lying or standing on the affected side.

•

Walking, climbing, and running exacerbate the pain.

•

Point tenderness over the greater trochanter is noted.

•

Pain is reproduced with resisted hip abduction.

ETIOLOGY

•

The specific cause of trochanteric bursitis is not known although repetitive high-intensity use of the hip joint, trauma, infection (tuberculosis and bacterial), and crystal deposition can precipitate the disease.

•

Trochanteric bursitis can occur when other conditions such as osteoarthritis of the knee and hip and bunions of the feet cause changes in the patient's gait, placing varus stress on the hip joint.

DIAGNOSIS A detailed physical examination and clinical presentation usually make the diagnosis of trochanteric bursitis. Laboratory tests and x-ray images are helpful adjunctive studies used to exclude other conditions either associated with or mimicking trochanteric bursitis.

DIFFERENTIAL DIAGNOSIS

•

Osteoarthritis of the hip

•

Osteonecrosis of the hip

•

Stress fracture of the hip

•

Osteoarthritis of the lumbar spine

•

Fibromyalgia

•

Iliopsoas bursitis

•

Trochanteric tendonitis

•

Gout

•

Pseudogout

•

Trauma

•

Neuropathy

•

Tuberculosis of the greater trochanter

•

Metastatic bone disease

WORKUP

A workup is indicated if suspected associated conditions exist; otherwise treatment can be started on clinical grounds alone. LABORATORY TESTS

CBC with differential may show elevated white count if infection is present. ESR is elevated in an inflammatory process. IMAGING STUDIES

•

Plain x-rays of the hip are not very helpful in diagnosing trochanteric bursitis. Sometimes calcifications may be seen around the greater trochanter.

•

Bone scan can be done but is usually not necessary.

•

CT and MRI may show bursitis but are usually not warranted because it will not alter treatment.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Heat 15 to 20 min 4 to 6 times per day

•

Ultrasound therapy

•

Rest

•

Partial weight bearing

•

Physical therapy to strengthen back, hip, and knee muscles

ACUTE GENERAL Rx

•

NSAIDs, ibuprofen 800 mg PO tid, or naproxen 500 mg PO bid is used for pain relief.

•

Acetaminophen 500-mg tablet, 1 to 2 tablets PO q6h prn can be used with NSAIDs or alternating with NSAIDs.

•

Corticosteroid injection (30 to 40 mg depomethylprednisolone acetate mixed with 3 ml 1% Xylocaine).

CHRONIC Rx

Although rarely done, surgical removal of the bursa is possible for patients with refractory symptoms or infection. DISPOSITION

•

Most patients respond to NSAIDs and/or nonpharmacologic therapy.

•

If steroid injection is used, approximately 70% of patients respond after the first injection and more than 90% respond to two injections.

•

25% of patients receiving steroid injection may develop a relapse.

REFERRAL

A rheumatology or orthopedics referral is made if steroid injection therapy is needed or if the etiology is thought to be infectious.

PEARLS & CONSIDERATIONS Patients with trochanteric bursitis will commonly complain of “hip” pain. The physical examination readily distinguishes true hip pain from trochanteric bursitis. COMMENTS

•

The absence of pain with flexion and extension differentiates trochanteric bursitis from degenerative joint disease of the hip.

•

Localization of pain over the lateral thigh differentiates trochanteric bursitis from pain caused by meralgia paresthetica located over the anterolateral thigh and pain from osteoarthritis located over the inner thigh groin area.

SUGGESTED READINGS Adkins SB, Figler RA: Hip pain in athletes. Am Fam Physician 2000; 61(7):2109. Canoso JJ: Hip pain. In: Canoso JJ, Kersey R, ed. Rheumatology in primary care, Philadelphia: WB Saunders; 1997. Cardone DA, Tallia AF: Diagnostic and therapeutic injection of the hip and knee. Am Fam Physician 2003; 67:2147. Segal NAMulticenter Osteoarthritis Study Group, et al: Greater trochanteric pain syndrome: epidemiology and associated factors. Arch Phys Med Rehabil 2007; 88(8):988.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tropical Sprue GEORGE O. ALONSO, M.D., GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Tropical sprue is a malabsorption syndrome occurring primarily in tropical regions, including Puerto Rico, India, and Southeast Asia. SYNONYMS

Postinfectious tropical malabsorption “Tropical enteropathy” refers to a subclinical form of tropical sprue.

ICD-9CM CODES

579.1 Tropical sprue EPIDEMIOLOGY & DEMOGRAPHICS

•

Tropical sprue is endemic in tropical regions, Venezuela, Colombia, the Middle East, the Far East, the Caribbean [Puerto Rico, Haiti, Dominican Republic, Cuba], and India.

•

The disease affects mainly adults although it has been reported in all age groups.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

The classic clinical features of tropical sprue are nonspecific and simply reflect the symptom of malabsorption. Onset is generally not insidious and most patients can pinpoint when their disorder began.

•

Diffuse, nonspecific abdominal tenderness and distention. Abdominal pain is crampy in nature.

•

Low-grade fever.

•

Glossitis, cheilosis, hyperkeratosis, hyperpigmentation.

•

Diarrhea, often with mucus and foul-smelling stools due to fat malabsorption.

•

Nausea, which leads to decreased appetite and decreased oral intake.

•

Lactose intolerance often develops early in the course of tropical sprue.

ETIOLOGY

•

Unknown. There is a strong presumption that it is caused by an enteric infection, perhaps in individuals predisposed by some nutritional deficiency.

•

Associated with overgrowth of predominantly coliform bacteria in the small intestine.

DIAGNOSIS

The clinical features of tropical sprue include anorexia, diarrhea, weight loss, abdominal pain, and steatorrhea; these symptoms can develop in expatriates even several months after immigrating to temperate regions. DIFFERENTIAL DIAGNOSIS

•

Celiac disease

•

Parasitic infestation

•

Inflammatory bowel disease

•

Other causes of malabsorption (e.g., Whipple's disease)

•

Lymphoma

•

Pancreatic tumor

•

Intestinal TB

•

Microsporidia-associated HIV enteropathy

WORKUP

Diagnostic workup includes a comprehensive history (especially travel history), physical examination, laboratory evidence of malabsorption (see “Laboratory Tests”), and jejunal biopsy; the biopsy results are nonspecific, with blunting, atrophy, and even disappearance of the villi and subepithelial lymphocytic infiltration. Partial villus atrophy distinguishes tropical sprue histologically from celiac sprue, which reveals flattened mucosa. LABORATORY TESTS

•

Megaloblastic anemia (>50% of cases)

•

Vitamin B12 deficiency, folate deficiency

•

Abnormal D-xylose absorption (72-hour fecal fat determination or serum carotene concentration)

•

Stool examination to exclude Giardia

IMAGING STUDIES

GI series with small bowel follow-through may reveal coarsening of the jejunal folds.

TREATMENT NONPHARMACOLOGIC THERAPY

Monitoring of weight and calorie intake ACUTE GENERAL Rx

•

Folic acid therapy (5 mg bid for 2 wk followed by a maintenance dose of 1 mg tid) will improve anemia and malabsorption in more than two thirds of patients.

•

Tetracycline 250 mg qid for 4 to 6 wk in individuals who have returned to temperate zones, up to 6 mo in patients in endemic areas; ampicillin 500 mg bid for at least 4 wk in patients intolerant to tetracycline.

•

Correction of vitamin B12 deficiency: vitamin B12 1000 µg IM weekly for 4 wk, then monthly for 3 to 6 mo.

•

Correction of other nutritional deficiencies (e.g., calcium, iron).

DISPOSITION

Complete recovery with appropriate therapy REFERRAL

GI referral for jejunal biopsy

PEARLS & CONSIDERATIONS COMMENTS

•

Tropical sprue should be considered in any patient who presents with chronic diarrhea, weight loss, and malabsorption, especially if there is significant travel and exposure history.

•

Important factors in the medical history in addition to travel history are use of medications that may predispose to a small bowel overgrowth, HIV exposure (increased risk of chronic diarrhea), and any surgical procedure that may predispose to blind loop syndrome.

•

Most of the functional changes in tropical sprue may be related to small bowel mucosal damage; however, there is also dysfunctional hormonal regulation of the gut (increased enteroglucagon, motilin levels, decreased postprandial insulin and gastric inhibitory peptide) and decreased ability of the colon to absorb water.

•

Even with prolonged therapy, relapses can occur; however, some may be reexposure to an infecting organism rather than relapsing disease.

AUTHOR: FRED F. FERRI, M.D. Tuberculosis, Miliary

BASIC INFORMATION DEFINITION

Miliary tuberculosis (TB) is an infection of disseminated hematogenous disease, caused by the bacterium Mycobacterium tuberculosis, and is often characterized as resembling millet seeds on examination. Extrapulmonary disease may occur in virtually every organ site. SYNONYMS

Disseminated TB

ICD-9CM CODES

018.94 Miliary tuberculosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): >38% of AIDS patients with TB have disseminated disease, often with concurrent pulmonary and extrapulmonary active sites. (See “Pulmonary Tuberculosis” in Section I.) PEAK INCIDENCE: HIV-positive patients, regardless of age PREVALENCE (IN U.S.): •

Undetermined

•

Highest prevalence 1.

AIDS patients

2.

Minorities

3.

Children

4.

Foreign-born persons

5.

Elderly

PREDOMINANT SEX: •

No specific predilection

•

Male predominance in AIDS, shelters, and prisons reflected in disproportionate male TB incidence

PREDOMINANT AGE: Predominantly among 24- to 45-yr-olds PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

See also “Etiology”

•

Common symptoms

•

1.

High intermittent fever

2.

Night sweats

3.

Weight loss

Symptoms referable to individual organ systems may predominate

1.

Meninges

2.

Pericardium

3.

Liver

4.

Kidney

5.

Bone

6.

GI tract

7.

Lymph nodes

8.

Serous spaces

9.

a.

Pleural

b.

Pericardial

c.

Peritoneal

d.

Joint

Skin

10. Lung: cough, shortness of breath •

Adrenal insufficiency possible caused by infection of adrenal gland

•

Pancytopenia

•

•

•

•

1.

With fever and weight loss or

2.

Without other localizing symptoms or signs or

3.

With only splenomegaly

TB hepatitis 1.

Tender liver

2.

Obstructive enzymes (alkaline phosphatase) elevated out of proportion to minimal hepatocellular enzymes (SGOT, SGPT) and bilirubin

TB meningitis 1.

Gradual-onset headache

2.

Minimal meningeal signs

3.

Malaise

4.

Low-grade fever (may be absent)

5.

Sudden stupor or coma

6.

Cranial nerve VI palsy

TB pericarditis 1.

Effusions resembling TB pleurisy

2.

Cardiac tamponade

Skeletal TB

•

1.

Large joint arthritis (with effusions resembling TB pericarditis)

2.

Bone lesions (especially ribs)

3.

Pott's disease

2.

3.

•

TB spondylitis, especially of lower thoracic spine

b.

Paraspinous TB abscess

c.

Possible psoas abscess

d.

Frequent cord compression (often relieved by steroids)

Genitourinary TB 1.

•

a.

Renal TB a.

Papillary necrosis

b.

Destruction of renal pelvis

c.

Strictures of upper third of ureters

d.

Hematuria

e.

Pyuria with misleading bacterial cultures

f.

Preserved renal function

TB orchitis or epididymitis a.

Scrotal mass

b.

Draining abscess

Chronic prostatic TB

Gastrointestinal TB 1.

Diarrhea

2.

Pain

3.

Obstruction

4.

Bleeding

5.

Especially common with AIDS

6.

Bowel lesions a.

Circumferential ulcers

b.

Short strictures

c.

Calcified granulomas

d.

TB mesenteric caseous adenitis

e.

Abscess, but rare fistula formation

f.

Often difficult to distinguish from granulomatous bowel disease (Crohn's disease)

TB peritonitis 1.

Fluid resembles TB pleurisy

2.

PPD often negative

3.

Tender abdomen

4.

Doughy peritoneal consistency, often with ascites

5.

Peritoneal biopsy indicated for diagnosis

•

•

•

TB lymphadenitis (scrofula) 1.

May involve all node groups

2.

Common adenopathies a.

Cervical

b.

Supraclavicular

c.

Axillary

d.

Retroperitoneal

3.

Biopsy generally needed for diagnosis

4.

Surgical resection of nodes may be necessary

5.

Especially common with AIDS

Cutaneous TB 1.

Skin infection from autoinoculation or dissemination

2.

Nodules or abscesses

3.

Tuberculids (possibly allergic reactions)

4.

Erythema nodosum

Miscellaneous presentations

ETIOLOGY

1.

TB laryngitis

2.

TB otitis

3.

Ocular TB a.

Choroidal tubercles

b.

Iritis

c.

Uveitis

d.

Episcleritis

4.

Adrenal TB

5.

Breast TB

•

See also “Pulmonary Tuberculosis” in Section I

•

Mycobacterium tuberculosis (Mtb), a slow growing, aerobic, non–sporeforming, nonmotile bacillus

•

Humans are the only reservoir for Mtb

•

Pathogenesis:

•

1.

AFB (Mtb) are ingested by macrophages in alveoli, then transported to regional lymph nodes where spread is contained.

2.

Some AFB reach the bloodstream and disseminate widely.

3.

Immediate active disseminated disease may ensue or a latent period may develop.

4.

During latent period, T-cell immune mechanisms contain infection in granulomas until later reactivation occurs as a result of immunosuppression or other undefined factors in conjunction with reactivated pulmonary TB or alone.

Miliary TB may occur as a consequence of the following: 1.

Primary infection: inability to contain primary infection leads to a hematogenous spread and progressive disseminated disease.

2.

In late chronic TB and in those with advanced age or poor immunity, a continuous seeding of the blood may develop and lead to disseminated disease.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Widespread sites of possible dissemination associated with myriad differential diagnostic possibilities

•

Lymphoma

•

Typhoid fever

•

Brucellosis

•

Other tumors

•

Collagen-vascular disease

WORKUP

•

Prompt evaluation is essential

•

Sputum for AFB stain and culture

•

Chest x-ray examination

•

PPD

•

Fluid analysis and culture wherever available

•

•

1.

Sputum

2.

Blood: particularly helpful in patients with AIDS

3.

Urine

4.

CSF

5.

Pleural

6.

Pericardial

7.

Peritoneal

8.

Gastric aspirates

Biopsy of any involved tissue is advisable to make immediate diagnosis 1.

Transbronchial biopsy preferred and easily accessible

2.

Bone marrow

3.

Lymph node

4.

Scrotal mass if present

5.

Any other involved site

6.

Positive granuloma or AFB on biopsy specimen is diagnostic

Imaging studies as needed

LABORATORY TESTS

•

Culture and fluid analysis as described previously

•

Smear-negative sputum often is positive weeks later on culture

•

CBC is usually normal

•

ESR is usually elevated

IMAGING STUDIES

•

Chest x-ray examination (may or may not be positive) (See “Pulmonary Tuberculosis” in Section I)

•

CT scan or MRI of brain

•

1.

Tuberculoma

2.

Basilar arachnoiditis

Barium studies of bowel

TREATMENT NONPHARMACOLOGIC THERAPY

•

Bed rest during acute phase of treatment

•

High-calorie, high-protein diet to reverse malnutrition and enhance immune response to TB

•

Isolation in negative-pressure rooms with high-volume air replacement and circulation (with health care provider wearing proper protective 0.5- to 1-micron filter respirators) 1.

Until three consecutive sputum AFB smears are negative, if pulmonary disease coexists

2.

Isolation not required for closed-space TB infections

ACUTE GENERAL Rx

•

See “Pulmonary Tuberculosis” in Section I.

•

Therapy should be initiated immediately. Do not wait for definitive diagnosis.

•

More rapid response to chemotherapy by disseminated TB foci than cavitary pulmonary TB.

•

Treatment for 6 mo with INH plus rifampin plus PZA.

•

•

1.

Treatment for 12 mo often required for bone and renal TB.

2.

Prolonged treatment often required for CNS and pericardial.

3.

Prolonged treatment often required for all disseminated TB in infants.

Compliance (rigid adherence to treatment regimen) is the chief determinant of success. 1.

Supervised DOT is recommended for all patients.

2.

Supervised DOT is mandatory for unreliable patients.

Steroids are often helpful additions in fulminant miliary disease with the hypoxemia and DIC.

CHRONIC Rx

•

Generally not indicated beyond treatment described previously

•

Prolonged treatment supervised by ID expert required in a few complicated infections caused by resistant organisms

DISPOSITION

•

Monthly follow-up by physician experienced in TB treatment

•

Confirm sensitivity testing, and alter treatment appropriately (see “Pulmonary Tuberculosis” in Section I)

REFERRAL

•

•

To infectious disease expert for: 1.

HIV-positive patient

2.

Patient with suspected drug-resistant TB

3.

Patients previously treated for TB

4.

Patients whose fever has not decreased and sputum (if positive) has not converted to negative in 2 to 4 wk

5.

Patients with overwhelming pulmonary or extrapulmonary tuberculosis

To pulmonary, orthopedic, or GI physicians for examinations or biopsy

PEARLS & CONSIDERATIONS COMMENTS

•

All contacts (especially close household contacts and infants) should be properly tested for PPD conversions > 3 mo following exposure.

•

Those with positive PPD should be evaluated for active TB and properly treated or given prophylaxis.

EVIDENCE

A systematic review compared various treatment regimens in patients with newly diagnosed, active pulmonary tuberculosis. Treatment for < 6 months was associated with higher relapse rates.[[1]] Two randomized controlled trials (RCTs) found no difference in relapse rates when 6-month treatment regimens were compared with longer (8- to 9-month) regimens in patients with newly diagnosed pulmonary tuberculosis. The regimens included different combinations of isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide for initial and continuation treatment. [181] [182] A systematic review identified one RCT, which compared treatment regimens of daily vs. three-timesweekly over 6 months in patients with pulmonary tuberculosis. There was no significant difference in cure rates between the groups at 1 month after completion of the treatment. A clinically important difference between the dosing regimens could not be ruled out.[[4]] A systematic review found insufficient evidence from RCTs demonstrating the efficacy of direct observation of tablet swallowing in the treatment of tuberculosis in low-, middle-, and high-income country settings. There was no significant difference between direct observation and self-treatment for cure or treatment completion.[[5]] However, the most recent American guidelines recommend this form of therapy, based on three key references. [185] [186] [187] [188] A systematic review of RCTs studied the effectiveness of tuberculosis preventive therapy in reducing the risk of active tuberculosis and death in persons infected with HIV. Preventive therapy (with any anti-TB regimen) was associated with a significantly lower incidence of active tuberculosis compared with placebo, but all-cause mortality rates were similar in both groups. Those with a positive tuberculin skin test were more likely to benefit from treatment than those with a negative test.[[10]] Limited evidence from this review suggested that the protective effect of therapy may have declined over the short to medium term. No one regimen was found to be superior; however, short-course multidrug regimens were much more likely to be discontinued due to adverse effects, compared with INH monotherapy.[[10]] A systematic review found that isoniazid is effective for the prevention of active tuberculosis in HIV-negative patients who are at increased risk of developing the infection.[[11]]

Evidence-Based Referenceces 1. Gelband H: Regimens of less than six months for treating tuberculosis. Cochrane Database Syst Rev 1999; 4:(Cochrane Review). 2. East and Central African/British Medical Research Council Fifth Collaborative Study: Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis. Tubercle 1983; 64:153.Reviewed in: Clin Evid 12:1194, 2004. 3. British Thoracic Society: A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis, final report: results during the 36 months after the end of chemotherapy and beyond. Br J Dis Chest 1984; 78:330.Reviewed in: Clin Evid 9:901, 2003. 4. Mwandumba HC, Squire SB: Fully intermittent dosing with drugs for treating tuberculosis in adults (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 5. Volmink J, Garner P: Directly observed therapy for treating tuberculosis (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 6. The Infectious Diseases Society of America, the American Thoracic Society, the Centers for Disease Control and Prevention: Treatment of tuberculosis. MMWR Recomm Rep 2003; 52(RR-11):1. 7. Chaulk CP: Eleven years of community-based directly observed therapy for tuberculosis. JAMA 1995; 274:945. 8. Chaulk CP: Directly observed therapy for treatment completion of tuberculosis: concensus statement of the Public Health Tuberculosis Guidelines Panel. JAMA 1998; 279:943. 9. Weis SE, et al: The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med 1994; 330:1179. 10. Woldehanna S, Volmink J: Treatment of latent tuberculosis infection in HIV infected persons (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 11. Smieja MJ, et al: Isoniazid for preventing tuberculosis in non-HIV infected persons (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS American Thoracic Society, CDC and the Infectious Disease Society of America: Controlling tuberculosis in the United States. MMWR 2005; 54(RR-12):1. Golden MP, Vikram HR: Extrapulmonary tuberculosis: an overview. Am Fam Physician 2005; 72(9):1761. Maher D, et al: Tuberculosis deaths in countries with high HIV prevalence: what is their use as an indicator in tuberculosis programme monitoring and epidemiological surveillance?. Int J Tuberc Lung Dis 2005; 9(2):123. Matsushima T: Miliary tuberculosis or disseminated tuberculosis. Intern Med 2005; 44(7):687. Miyoshi I, et al: Miliary tuberculosis not affecting the lungs but complicated by acute respiratory distress syndrome. Intern Med 2005; 44(6):622. Sharma SK, et al: Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis 2005; 5(7):415. Torgersen J, et al: Molecular epidemiology of pleural and other extrapulmonary tuberculosis: a Maryland state review. Clin Infect Dis 2006; 42(10):1375.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tuberculosis, Pulmonary GEORGE O. ALONSO, M.D., GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D.

BASIC INFORMATION DEFINITION

Pulmonary tuberculosis (TB) is an infection of the lung and, occasionally, surrounding structures, caused by the bacterium Mycobacterium tuberculosis. SYNONYMS

TB

ICD-9CM CODES

011.9 Pulmonary tuberculosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE (IN U.S.): •

Approximately 7 cases/100,000 persons—lowest in reported history

•

>90% of new cases each year from reactivated prior infections

•

9% newly infected

•

Only 10% of patients with PPD conversions (higher [8%/yr] in HIV-positive patients) will develop TB, most within 1 to 2 yr

•

Two thirds of all new cases in racial and ethnic minorities

•

80% of new cases in children in racial and ethnic minorities

•

Occurs most frequently in geographic areas and among populations with highest AIDS prevalence

•

1.

Urban blacks and Hispanics between 25 and 45 yr old

2.

Poor, crowded urban communities

Nearly 36% of new cases from new immigrants

PEAK INCIDENCE:

•

Infancy

•

Teenage years

•

Pregnancy

•

Elderly

•

HIV-positive patients, regardless of age, at highest risk

PREVALENCE (IN U.S.): •

Estimated 10 million people infected

•

Varies widely among population groups

PREDOMINANT SEX: •

No specific predilection

•

Male predominance in AIDS, shelters, and prisons reflected in disproportionate male incidence

PREDOMINANT AGE: •

24 to 45 yr old

•

Childhood cases common among minorities

•

Nursing home outbreaks among elderly

GENETICS: •

Populations with widespread low native resistance have been intensely infected when initially exposed to TB.

•

Following elimination of those with least native resistance, incidence and prevalence of TB tend to decline.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

See “Etiology”

•

Primary pulmonary TB infection generally asymptomatic

•

Reactivation pulmonary TB 1.

Fever

2.

Night sweats

3.

Cough

4.

Hemoptysis

5.

Scanty nonpurulent sputum

6.

Weight loss

•

Progressive primary pulmonary TB disease: same as reactivation pulmonary TB

•

TB pleurisy 1.

Pleuritic chest pain

2.

Fever

3.

Shortness of breath

•

Rare massive, suffocating, fatal hemoptysis secondary to erosion of pulmonary artery within a cavity (Rasmussen's aneurysm)

•

Chest examination

1.

Not specific

2.

Usually underestimates extent of disease

3.

Rales accentuated following a cough (posttussive rales)

ETIOLOGY

•

Mycobacterium tuberculosis (Mtb), a slow-growing, aerobic, non–sporeforming, nonmotile bacillus, with a lipid-rich cell wall 1.

Lacks pigment

2.

Produces niacin

3.

Reduces nitrate

4.

Produces heat-labile catalase

5.

Mtb staining, acid-fast and acidalcohol fast by Ziehl-Neelsen method, appearing as red, slightly bent, beaded rods 2 to 4 microns long (acid-fast bacilli [AFB]), against a blue background

6.

Polymerase chain reaction (PCR) to detect < 10 organisms/ml in sputum (compared with the requisite 10,000 organisms/ml for AFB smear detection)

7.

Culture

8.

9.

a.

Growth on solid media (Löwenstein-Jensen; Middlebrook 7H11) in 2 to 6 wk

b.

Growth in liquid media (BACTEC, using a radioactive carbon source for early growth detection) often in 9 to 16 days

c.

Enhanced in a 5% to 10% carbon dioxide atmosphere

DNA fingerprinting (based on restriction fragment length polymorphism [RFLP]) a.

Facilitates immediate identification of Mtb strains in early growing cultures

b.

False-negatives possible if growth suboptimal

Humans are the only reservoir for Mtb

10. Transmission

•

a.

Facilitated by close exposure to high-velocity cough (unprotected by proper mask or respirators) from patient with AFB-positive sputum and cavitary lesions, producing aerosolized droplets containing AFB, which are inhaled directly into alveoli

b.

Occurs within prisons, nursing homes, and hospitals

Pathogenesis 1.

AFB (Mtb) ingested by macrophages in alveoli, then transported to regional lymph nodes where spread is contained

2.

Some AFB may reach bloodstream and disseminate widely

3.

Primary TB (asymptomatic, minimal pneumonitis in lower or midlung fields, with hilar lymphadenopathy) essentially an intracellular infection, with multiplication of organisms continuing for 2 to 12 wk after primary exposure, until cell-mediated hypersensitivity (detected by positive skin test reaction to tuberculin purified protein derivative [PPD]) matures, with subsequent containment of infection

4.

Local and disseminated AFB thus contained by T-cell–mediated immune responses

5.

6.

7.

8.

9.

a.

Recruitment of monocytes

b.

Transformation of lymphocytes with secretion of lymphokines

c.

Activation of macrophages and histiocytes

d.

Organization into granulomas, where organisms may survive within macrophages (Langhans' giant cells), but within which multiplication essentially ceases (95%) and from which spread is prohibited

Progressive primary pulmonary disease a.

May immediately follow the asymptomatic phase

b.

Necrotizing pulmonary infiltrates

c.

Tuberculous bronchopneumonia

d.

Endobronchial TB

e.

Interstitial TB

f.

Widespread miliary lung lesions

Postprimary TB pleurisy with pleural effusion a.

Develops after early primary infection, although often before conversion to positive PPD

b.

Results from pleural seeding from a peripheral lung lesion or rupture of lymph node into pleural space

c.

May produce a large (sometimes hemorrhagic) exudative effusion (with polymorphonuclear cells early, rapidly replaced by lymphocytes), frequently without pulmonary infiltrates

d.

Generally resolves without treatment

e.

Portends a high risk of subsequent clinical disease, and therefore must be diagnosed and treated early (pleural biopsy and culture) to prevent future catastrophic TB illness

f.

May result in disseminated extrapulmonary infection

Reactivation pulmonary TB a.

Occurs months to years following primary TB

b.

Preferentially involves the apical posterior segments of the upper lobes and superior segments of the lower lobes

c.

Associated with necrosis and cavitation of involved lung, hemoptysis, chronic fever, night sweats, weight loss

d.

Spread within lung occurs via cough and inhalation

Reinfection TB a.

May mimic reactivation TB

b.

Ruptured caseous foci and cavities, which may produce endobronchial spread

Mtb in both progressive primary and reactivation pulmonary TB

a.

Intracellular (macrophage) lesions (undergoing slow multiplication)

b.

Closed caseous lesions (undergoing slow multiplication)

c.

Extracellular, open cavities (undergoing rapid multiplication)

d.

INH and rifampin are cidal in all three sites

e.

PZA especially active within acidic macrophage environment

f.

Extrapulmonary reactivation disease also possible

10. Rapid local progression and dissemination in infants with devastating illness before PPD conversion occurs 11. Most symptoms (fever, weight loss, anorexia) and tissue destruction (caseous necrosis) from cytokines and cell-mediated immune responses 12. Mtb has no important endotoxins or exotoxins 13. Granuloma formation related to tumor necrosis factor (TNF) secreted by activated macrophages

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Necrotizing pneumonia (anaerobic, gram-negative)

•

Histoplasmosis

•

Coccidioidomycosis

•

Melioidosis

•

Interstitial lung diseases (rarely)

•

Cancer

•

Sarcoidosis

•

Silicosis

•

Paragonimiasis

•

Rare pneumonias

WORKUP

1.

Rhodococcus equi (cavitation)

2.

Bacillus cereus (50% hemoptysis)

3.

Eikenella corrodens (cavitation)

•

Sputum for AFB stains

•

Chest x-ray examination

•

PPD

•

1.

Recent conversion from negative to positive within 3 mo of exposure is highly suggestive of recent infection.

2.

Single positive PPD is not helpful diagnostically.

3.

Negative PPD never rules out acute TB.

4.

Be certain that positive PPD does not reflect “booster phenomenon” (prior positive PPD may become negative after several years and return to positive only after second repeated PPD; repeat second PPD within 1 wk), which thus may mimic skin test conversion.

5.

Positive PPD reaction is determined as follows: a.

Induration after 72 hr of intradermal injection of 0.1 ml of 5 TU-PPD

b.

5-mm induration if HIV-positive (or other severe immunosuppressed state affecting cellular immune function), close contact of active TB, fibrotic chest lesions

c.

10-mm induration if in high–medical risk groups (immunosuppressive disease or therapy, renal failure, gastrectomy, silicosis, diabetes), foreign-born high-risk group (Southeast Asia, Latin America, Africa, India), low socioeconomic groups, IV drug addict, prisoner, health care worker

d.

15-mm induration if low risk

6.

Anergy antigen testing (using mumps, Candida, tetanus toxoid) may identify patients who are truly anergic to PPD and these antigens, but results are often confusing. Not recommended.

7.

Patients with TB may be selectively anergic only to PPD.

8.

Positive PPD indicates prior infection but does not itself confirm active disease.

A new diagnostic test for latent tuberculosis infection, known as the quanta-feron test (QFT-G), is now available. This is a blood test that measures interferon response to specific M. tuberculosis antigens. The test is FDA approved and is available in some large TB centers and state health departments. It may assist in distinguishing true positive reactions, from individuals with latent tuberculosis, from PPD reactions related to: non-tuberculous mycobacteria; prior BCG vaccination; or difficult-to-interpret skin test results from persons with dermatologic conditions or immediate allergic reactions to PPD. The diagnostic utility of the test as a replacement or supplement to the standard PPD is not yet fully determined.

LABORATORY TESTS

•

Sputum for AFB stains and culture 1.

•

Induced sputum if patient not coughing productively

Sputum from bronchoscopy if high suspicion of TB with negative expectorated induced sputum for AFB 1.

Positive AFB smear is essential before or shortly after treatment to ensure subsequent growth for definitive diagnosis and sensitivity testing

2.

Consider lung biopsy if sputum negative, especially if infiltrates are predominantly interstitial

•

AFB stain-negative sputum may grow Mtb subsequently

•

Gastric aspirates reliable, especially in HIV-negative patients

•

CBC 1.

2.

Variable values a.

WBCs: low, normal, or elevated (including leukemoid reaction: >50,000)

b.

Normocytic, normochromic anemia often

Rarely helpful diagnostically

•

ESR usually elevated

•

Thoracentesis 1.

•

Exudative effusion a.

Elevated protein

b.

Decreased glucose

c.

Elevated WBCs (polymorphonuclear leukocytes early, replaced later by lymphocytes)

d.

May be hemorrhagic

2.

Pleural fluid usually AFB-negative

3.

Pleural biopsy often diagnostic—may need to be repeated for diagnosis

4.

Culture pleural biopsy tissue for AFB

Bone marrow biopsy is often diagnostic in difficult-to-diagnose cases, especially miliary tuberculosis

IMAGING STUDIES

•

Chest x-ray examination 1.

Primary infection reflected by calcified peripheral lung nodule with calcified hilar lymph node

2.

Reactivation pulmonary TB

3.

a.

Necrosis

b.

Cavitation (especially on apical lordotic views)

c.

Fibrosis and hilar retraction

d.

Bronchopneumonia

e.

Interstitial infiltrates

f.

Miliary pattern

g.

Many of previous may also accompany progressive primary TB

TB pleurisy a.

Pleural effusion, often rapidly accumulating and massive

4.

TB activity not established by single chest x-ray examination

5.

Serial chest x-ray examinations are excellent indicators of progression or regression

TREATMENT NONPHARMACOLOGIC THERAPY

•

Bed rest during acute phase of treatment

•

High-calorie, high-protein diet to reverse malnutrition and enhance immune response to TB

•

Isolation in negative-pressure rooms with high-volume air replacement and circulation, with health care provider wearing proper protective 0.5- to 1-micron filter respirators, until three consecutive sputum AFB smears are negative

ACUTE GENERAL Rx

•

Compliance (rigid adherence to treatment regimen) chief determinant of success. 1.

•

Supervised directly observed therapy (DOT) recommended for all patients and mandatory for unreliable patients

Preferred adult regimen: DOT. 1.

Isoniazid (INH) 15 mg/kg (max 900 mg) + rifampin 600 mg + ethambutol (EMB) 30 mg/kg (max 2500 mg) + pyrazinamide (PZA) (2 g [< 50 kg]; 2.5 g [51 to 74 kg]; 3 g [>75 kg]) thrice weekly for 6 mo

2.

Alternative, more complicated DOT regimens

•

Rifapentine, a rifampin derivative with a much longer serum half-life, was shown to be as effective when administered weekly (with weekly isoniazid) as conventional regimens for drug-sensitive pulmonary tuberculosis in non-HIV-infected patients.

•

Short-course daily therapy: adult.

•

1.

HIV-negative patient: 6 mo total therapy (2 mo INH 300 mg + rifampin 600 mg + EMB 15 mg/kg [max 2500 mg]) + PZA (1.5 g [< 50 kg]; 2 g [51 to 74 kg]; 2.5 g [>75 kg]) daily and until smear negative and sensitivity confirmed; then INH + rifampin daily × 4 mo

2.

HIV-positive patient: 9 mo total therapy (2 mo INH + rifampin + EMB + PZA daily until smear negative and sensitivity confirmed; then INH + rifampin qd × 7 mo)

3.

Continue treatment at least 3 mo following conversion to negative cultures

Drug resistance (often multiple drug resistance [MDRTB]) increased by: 1.

Prior treatment

2.

Acquisition of TB in developing countries

3.

Homelessness

4.

AIDS

5.

Prisoners

6.

IV drug addicts

7.

Known contact with MDRTB

•

Never add single drug to failing regimen.

•

Never treat TB with fewer than two to three drugs or two to three new additional drugs.

•

Monitor for clinical toxicity (especially hepatitis). 1.

Patient and physician awareness that anorexia, nausea, RUQ pain, and unexplained malaise require immediate cessation of treatment

2.

Evaluation of LFTs a.

•

Minimal SGOT/SGPT elevations without symptoms generally transient and not clinically significant

Preventive treatment for PPD conversion only (infection without disease). 1.

Must be certain that chest x-ray examination is negative and patient has no symptoms of TB

2.

INH 300 mg daily for 9 to 12 mo; at least 12 mo if HIV-positive

3.

Most important groups: a.

HIV-positive and other severely immunocompromised patients

b.

Close contact of active TB

c.

Recent converter

d.

Old TB on chest x-ray examination

e.

IV drug addict

f.

Medical risk factor

g.

High-risk foreign country

h.

Homeless

•

Infants generally given prophylaxis immediately if recent contact of active TB (even if infant PPD negative), then retested with PPD in 3 mo (continuing INH if PPD becomes positive and stopping INH if PPD remains negative).

•

Chronic, stable PPD (several years) given INH prophylaxis generally only if patient is < 35 yr old. 1.

INH toxicity may outweigh benefit

2.

Individualize decision

CHRONIC Rx

•

Preventive therapy for suspected INH-resistant organisms is unclear.

CHRONIC Rx

•

Generally not indicated beyond treatment described previously

•

Prolonged treatment, supervised by infectious disease expert, in a few very complicated infections caused by resistant organisms

DISPOSITION

•

Monthly follow up by physician experienced in TB treatment

•

Confirm sensitivity testing and alter treatment appropriately

•

Frequent sputum samples until culture is negative

•

Confirm chest x-ray regression at 2 to 3 mo

REFERRAL

•

•

To infectious disease expert for: 1.

HIV-positive patient

2.

Patient with suspected drug-resistant TB

3.

Patients previously treated for TB

4.

Patients whose fever has not decreased and sputum has not converted to negative in 2 to 4 wk

5.

Patients with overwhelming pulmonary or extrapulmonary tuberculosis

To pulmonologist for bronchoscopy or pleural biopsy

PEARLS & CONSIDERATIONS COMMENTS

•

All contacts (especially close household contacts and infants) should be properly tested for PPD conversions during 3 mo following exposure.

•

Those with positive PPD should be evaluated for active TB and properly treated or given prophylaxis.

EVIDENCE

A systematic review compared various treatment regimens in patients with newly diagnosed, active pulmonary tuberculosis. Treatment for < 6 months was associated with higher relapse rates.[[1]] Two randomized controlled trials (RCTs) found no difference in relapse rates when 6-month treatment regimens were compared with longer (8- to 9-month) regimens in patients with newly diagnosed pulmonary tuberculosis. The regimens included different combinations of isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide for initial and continuation treatment. [199] [200]

A systematic review identified one RCT, which compared treatment regimens of daily vs. three-timesweekly over 6 months in patients with pulmonary tuberculosis. There was no significant difference in cure rates between the groups at 1 month after completion of the treatment. A clinically important difference between the dosing regimens could not be ruled out.[[4]] A systematic review found insufficient evidence from RCTs demonstrating the efficacy of direct observation of tablet swallowing in the treatment of tuberculosis in low-, middle-, and high-income country settings. There was no significant difference between direct observation and self-treatment for cure or treatment completion.[[5]] However, the most recent American guidelines recommend this form of therapy, based on three key references. [203] [204] [205] [206] A systematic review of RCTs studied the effectiveness of tuberculosis preventive therapy in reducing the risk of active tuberculosis and death in persons infected with HIV. Preventive therapy (with any anti-TB regimen) was associated with a significantly lower incidence of active tuberculosis compared with placebo, but all-cause mortality rates were similar in both groups. Those with a positive tuberculin skin test were more likely to benefit from treatment than those with a negative test.[[10]] Limited evidence from this review suggested that the protective effect of therapy may have declined over the short to medium term. No one regimen was found to be superior; however, short-course multidrug regimens were much more likely to be discontinued due to adverse effects, compared with INH monotherapy.[[10]] A systematic review found that isoniazid is effective for the prevention of active tuberculosis in HIV-negative patients who are at increased risk of developing the infection.[[11]]

Evidence-Based Referenceces 1. Gelband H: Regimens of less than six months for treating tuberculosis. Cochrane Database Syst Rev 1999; 4:(Cochrane Review). 2. 2 East and Central African/British Medical Research Council Fifth Collaborative Study: Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis. Tubercle 1983; 64:153.Reviewed in: Clin Evid 12:1194, 2004. 3. British Thoracic Society: A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis, final report: results during the 36 months after the end of chemotherapy and beyond. Br J Dis Chest 1984; 78:330.Reviewed in: Clin Evid 9:901, 2003. 4. Mwandumba HC, Squire SB: Fully intermittent dosing with drugs for treating tuberculosis in adults (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 5. Volmink J, Garner P: Directly observed therapy for treating tuberculosis (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 6. The Infectious Diseases Society of America, the American Thoracic Society, the Centers for Disease Control and Prevention: Treatment of tuberculosis. MMWR Recomm Rep 2003; 52(RR-11):1. 7. Chaulk CP: Eleven years of community-based directly observed therapy for tuberculosis. JAMA 1995; 274:945. 8. Chaulk CP: Directly observed therapy for treatment completion of tuberculosis: concensus statement of the Public Health Tuberculosis Guidelines Panel. JAMA 1998; 279:943. 9. Weis SE, et al: The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med 1994; 330:1179.

10. Woldehanna S, Volmink J: Treatment of latent tuberculosis infection in HIV infected persons (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 11. Smieja MJ, et al: Isoniazid for preventing tuberculosis in non-HIV infected persons (Cochrane Review). Reviewed. Cochrane Library 1, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Aderaye G, et al: The relationship between disease pattern and disease burden by chest radiography, M. tuberculosis load, and HIV status in patients with pulmonary tuberculosis in Addis Ababa. Infection 2004; 32(6):333. American Thoracic Society, CDC, and the Infectious Disease Society of America: Controlling tuberculosis in the United States. MMWR 2005; 54(RR-12):1. Ismail Y: Pulmonary tuberculosis—a review of clinical features and diagnosis in 232 cases. Med J Malaysia 2004; 59(1):56. Rubin EJ: Toward a new therapy for tuberculosis. N Engl J Med 2005; 352:933. van Lettow M, et al: Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi. BMC Infect Dis 2004; 4(1):61. Wei CJ, et al: Computed tomaography features of acute pulmonary tuberculosis. Am J Emerg Med 2004; 22(3):171.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tuberous Sclerosis RUBY SATPATHY, M.D.

BASIC INFORMATION DEFINITION

Tuberous sclerosis (TS) is an inherited neurocutaneous disorder that is characterized by pleomorphic features involving many organ systems, including multiple benign neoplasms (hamartomas) of the brain, kidney, and skin.

ICD-9CM CODES 759.5 EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: TS has an estimated incidence of 1 case per 6000 live births. Thus, it is the second most common neurocutaneous syndrome after neurofibromatosis. PREVALENCE: The disorder affects about 1 in 10,000 persons in the general population. PREDOMINANT SEX AND AGE: TS has no predilection for gender or race. GENETICS: •

TS is an autosomal dominant disorder with almost complete penetrance but a wide range of clinical severity. However, only one third of cases are familial. The apparently nonfamilial cases can represent either spontaneous mutations or mosaicism.

•

Genetic research has identified two TS genes. One is located on chromosome 9 (TSC1 gene) and the other on chromosome 16 (TSC2 gene). About 68% of cases occur as a result of new gene mutations. Because of the genetic transmission and new mutations, antenatal diagnosis is difficult.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Dermatologic manifestations may be the only clues the family physician has to the diagnosis of the disorder, which is also marked by childhood seizures and mental retardation (Figs. 1-280 through 1-282 [15] [16] [17]).

•

The diagnostic criteria for TS were recently revised at a consensus conference. Major and minor features are listed in Table 1-50 .

•

The classic diagnostic triad of seizures, mental retardation, and facial angiofibromas (Vogt's triad) occurs in fewer than 50% of patients with TS.

•

All of the clinical features of TS may not be apparent in the first year of life. Thus, a child is often initially diagnosed with possible or probable TS and the diagnosis of definite TS is made after additional features are identified.

•

Dermatologic manifestations: A careful skin examination of patients at risk for TS continues to be the easiest and most accessible method of establishing the diagnosis ( Table 1-51 ).

•

Neurologic manifestations: These are the leading cause of morbidity and mortality in patients with TS. Brain hamartomas in the form of cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas are often responsible for intractable seizures, most commonly as infantile spasms. Approximately 90% to 96% of TS patients suffer from seizures. Approximately 85% of patients have their first epileptic episode in the first 2 years of life. Behavioral and cognitive dysfunction, including autism and mental retardation, can be seen in 40% to 50% of patients.

•

Renal and pulmonary manifestations: They are strongly associated with TS. Angiomyolipoma is the most common renal lesion found in TS patients. Clinically evident pulmonary involvement in TS patients is relatively rare, with an estimated incidence of 1% to 6%. The most common lesion is lymphangiomyomatosis (LAM), a progressive cystic lung disease with progressive dyspnea and spontaneous pneumothorax in a childbearing woman.

•

Cardiovascular manifestations: These are often the earliest diagnostic findings in patients with TS. Rhabdomyoma is the most common primary cardiac tumour in infants and children. Its incidence in TS patients ranges between 47% and 60%. In fact, 80% to 95% of patients with cardiac rhabdomyomas have TS.

•

The most common ocular findings in TS are retinal hamartomas, appearing in 40% to 50% of patients.

FIGURE 1-280 Hypomelanotic macules (“ash left” spots).

FIGURE 1-281 Facial angiofibromas.

FIGURE 1-282 Shagreen patches.

TABLE 1-50 -- Revised Diagnostic Criteria for Tuberous Sclerosis Complex (TSC) Major features 1.

Facial angiofibromas or forehead plaque

2.

Nontraumatic ungual or periungual fibroma

3.

Hypomelanotic macule (3 or more)

4.

Shagreen patch (connective tissue nevus)

5.

Multiple retinal nodular hamartomas

6.

Cortical tuber

7.

Subependymal nodule

8.

Subependymal giant cell astrocytoma

9.

Cardiac rhabdomyoma, single or multiple

10. Lymphangiomyomatosis 11. Renal angiomyolipoma Minor features

1.

Multiple, randomly distributed pits in dental enamel

2.

Hamartomatous rectal polyps

3.

Bone cysts

4.

Cerebral white matter radial migration lines

5.

Gingival fibromas

6.

Nonrenal hamartomas

7.

Retinal achromic patch

8.

“Confetti” skin lesions

9.

Multiple renal cysts

TABLE 1-51 -- Cutaneous Manifestations Associated with Tuberous Sclerosis Complex (TSC) Diagnostic Cutaneous Lesions Descriptions Age of Onset Prevalence Classification Hypomelanotic macules (“ash leaf” spots) or Fitzpatrick patches

Earliest 97.2% cutaneous lesion; usually present at birth or infancy

Major

Facial angiofibromas Red to pink papules with a smooth surface, symmetrically distributed over the centrofacial areas, sparing the upper lips

Second to fifth year of life; become more prominent with age

74.5%

Major

Shagreen patches

Rare during 48.1% infancy; tend to increase in size and number with age

Major

Molluscum pendulum Multiple soft pedunculated skin growths on neck; rarely in axilla or groin

More common during first decade of life; rare during infancy

22.6%

Minor

Forehead fibrous plaque

Yellowish-brown or skin-colored plaques of variable size and shape, usually located on the forehead or scalp

Common at any age and can be seen at birth or early infancy

18.9%

Major

Periungual fibromas

Skin-colored or reddish nodules seen on the lateral nail groove, nail plate, or along the proximal nail folds; more commonly found on the toes than on the fingers

Present at puberty or soon after; become more common with age

15.1%

Major

“Confetti-like” macules

Multiple 1-2 mm white spots Second decade symmetrically distributed over extremities or adulthood

2.8%

Minor

ETIOLOGY

Leaf-shaped or polygonal white spots enhanced by Wood's lamp examination; more common on the trunk and buttocks

Slightly elevated patch or plaque, usually found on the dorsal body surfaces, especially the lumbosacral area; its rough surface resembles an orange peel; represents a connective tissue nevus, sometimes called collagenoma

TS is an autosomal dominant disorder.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Cutaneous manifestations: •

Nevus anemicus

•

Nevus depigmentosus (nevus achromicus)

•

Vitiligo

WORKUP

•

The dermatologic manifestations of TS are helpful in diagnosing this disorder. When TS has been inherited in the autosomal dominant form, dermatologic signs are almost universally present in one of the patient's parents.

•

No specific prenatal laboratory test is available.

•

Early recognition of TS is vital because prompt implementation of the recommended diagnostic evaluation (neuroimaging studies, electroencephalogram, electrocardiography, renal ultrasonography, and chest computed tomography) may prevent serious clinical consequences.

LABORATORY TESTS

Molecular genetic testing: In recent years, molecular genetic testing for TS has become clinically available. Such testing identifies mutations in the TSC1 and TSC2 genes by one of several methods, most commonly polymerase chain reaction (PCR) amplification of individual exons, followed by DNA sequencing on DNA obtained from a patient's blood sample. DNA testing for TS is potentially useful in several settings: •

First, it can be helpful in confirming a clinical diagnosis of TS, especially in young patients in whom many clinical signs and symptoms have yet to develop.

•

Second, in many families with a history of TS in which there is a sporadic case of TS in a new child, genetic testing can provide reassurance to parents, children, and other family members that they do not carry the TS gene mutation.

•

Third, DNA testing is useful for prenatal diagnosis.

TREATMENT The management of TSC is presently symptomatic. NONPHARMACOLOGIC THERAPY

Genetic counseling should be offered to families with affected members, even though accurate counseling remains difficult because of the variability of gene expression. ACUTE GENERAL Rx/CHRONIC Rx

•

Treatment methods currently available for patients with disfiguring facial angiofibromas include cryosurgery, curettage, dermabrasion, chemical peeling, excision, and laser therapy.

•

Some patients have been treated successfully with antiepileptic medications; unfortunately, there are multiple cases of intractable seizure where medical treatment is ineffective. In some cases of intractable epilepsy, neurosurgical intervention becomes a life-saving option.

•

In such drug-resistant cases of TS, the early administration of vigabatrin (a-vinyl-gamma aminobutyric acid), a selective irreversible inhibitor of GABA-transaminase, has been proven to result in 80% to 100% cessation rates of infantile spasms. Vigabatrin is marketed in many European countries, but remains unavailable in the U.S. and has not been approved by the FDA.

•

Embolization and/or renal sparing surgery are treatment options for renal angiomyolipomas.

•

Oopherectomy, medroxyprogesterone, and tamoxifen use have been advocated in patients with LAM, but therapeutic benefit is unclear. Lung transplantation is reserved for patients with end-stage LAM.

•

Most rhabdomyomas tend to regress with increasing age, although tumour growth has been documented in some at puberty. Surgery is recommended only for life-threatening situations, such as hemodynamic compromise.

•

Oral rapamycin or sirolimus therapy can induce regression of brain astrocytomas associated with TS. Ongoing therapeutic trials with rapamycin in lymphangioleiomyomatosis appear promising.

REFERRAL

A multidisciplinary team including genetics, neurology, ophthalmology, nephrology, dermatology, neurosurgery, and plastic surgery should evaluate children suspected of having TS.

PEARLS & CONSIDERATIONS PREVENTION

It is speculated that if one could establish the prenatal diagnosis of TS and begin using rapamycin early, one might prevent the development of TS manifestations. SUGGESTED READINGS Hurst JS, Wilcoski S: Recognizing an index case of tuberous sclerosis. Am Fam Physician 2001; 61(b):703708. Schwartz RA: Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatology 2007; 57(b):189-202.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Tubular Necrosis, Acute CHAITANYA V. REDDY, D.O.

BASIC INFORMATION DEFINITION

Acute tubular necrosis refers to intrinsic tubular damage induced by hypoperfusion to renal parenchymal cells, particularly tubular epithelium, that results in sodium loss and FENa >1% (fractional excretion of sodium). SYNONYMS

Ischemic or nephrotoxic ARF

ICD-9CM CODES

584.5 With lesion of tubular necrosis Renal failure with (acute) tubular necrosis Tubular necrosis: NOS, acute 997.5 Urinary complications Tubular necrosis (acute) specified as due to procedure EPIDEMIOLOGY & DEMOGRAPHICS

•

Accounts for 90% of intrinsic renal failure.

•

Most common cause of intrinsic renal failure among hospitalized patients, including pediatric and adult, especially on surgical services in patients undergoing major cardiovascular surgery or in intensive care units in patients suffering severe trauma, hemorrhage, sepsis, or volume depletion.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

No apparent physical findings. Clinical features include recent hemorrhage, hypotension, or surgery thereby suggesting ischemic ARF. Recent radiocontrast study, nephrotoxic drugs, history suggestive of rhabdomyolysis, hemolysis, or myeloma may suggest toxin-mediated ARF.

•

Three phases of ischemic ARF: 1.

Initiation phase (hours to days)—renal hypoperfusion, evolving ischemia.

2.

Maintenance phase (1 to 2 wk)—renal cell injury established, GFR stabilizes at its nadir (5 to 10 ml/min), urine output at its lowest, uremic complications arise.

3.

Recovery phase (>2 wk)—renal parenchymal cell repair and regeneration, gradual return of GFR to premorbid levels; may be complicated by a marked diuretic phase due to excretion of retained salt and water and other solutes, continued use of diuretics, or delayed recovery of epithelial cell function (solute and water reabsorption) relative to glomerular filtration.

PATHOLOGIC FINDINGS

•

Ischemic ARF—patchy and focal necrosis of tubule epithelium with detachment from its basement membrane and occlusion of tubule lumens with casts composed of epithelial cells, cellular debris, TammHorsfall mucoprotein (represents the matrix of all urinary casts), and pigments. Also present is leukocyte accumulation in vasa recta (capillaries that return the NaCl and water reabsorbed in the loop of Henle and medullary collecting tubule to the systemic circulation). Morphology of glomeruli and renal vasculature remain normal. Necrosis most severe in pars recta (straight portion of proximal tubule and thick ascending limb of loop of Henle).

•

Nephrotoxic ARF—morphologic changes in convoluted and straight portion of proximal tubule. Tubule cell necrosis less pronounced than in ischemic ARF.

ETIOLOGY

Hypotension or shock, prolonged prerenal azotemia, postoperative sepsis syndrome, rhabdomyolysis, hemolysis (hypercalcemia, hemoglobin, urate, oxalate, myeloma light chains), antimicrobial drugs (acyclovir, foscarnet, aminoglycosides, amphotericin B, pentamidine), radiocontrast (contrast nephropathy), chemotherapy (cisplatin, ifosfamide).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Allergic interstitial nephritis, acute bilateral pyelonephritis WORKUP LABORATORY TESTS

•

Urinalysis for specific gravity (SG), UNa, PCr, PNa, UCr

•

Calculate fractional excretion of sodium (FENa) = [(UNa X PCr) / (PNa X UCr)] >3 100

LABORATORY FINDINGS

FENa >1% UNa >20 mmol/L SG 100,000 colony-forming units per ml from a midstream-catch urine sample. In symptomatic patients, a smaller number of bacteria (between 100 and 10,000 colony-forming units per ml of midstream urine) is recognized as an infection. SYNONYMS

UTI

ICD-9CM CODES

595.0 Acute cystitis 595.3 Trigonitis 595.2 Chronic cystitis 590.1 Acute pyelonephritis 590.0 Chronic pyelonephritis 590.8 Nonspecific pyelonephritis CLASSIFICATION

FIRST INFECTION: The first documented UTI; tends to be uncomplicated and is easily treated. UNRESOLVED BACTERIURIA: UTI in which the urinary tract is not sterilized during therapy. Main causes are bacterial resistance, patient noncompliance with medication, resistance, mixed bacterial infection, rapid reinfection, azotemia, infected stones, Munchausen's, and papillary necrosis. BACTERIAL PERSISTENCE: UTI in which the urine cultures become sterile during therapy, but a persistent source of infection from a site within the urinary tract that was excluded from the high urinary concentrations gives rise to reinfection by the same organism. Causes: infected stone, chronic bacterial prostatitis, atrophic infected kidney, vesicovaginal or enterovesical fistulas, obstructive uropathy, infected pyelocalyceal diverticula, infected ureteral stump following nephrectomy, infected necrotic papillae from papillary necrosis, infected urachal cysts, infected medullary sponge kidney, urethral diverticula, and foreign bodies. REINFECTION: UTI in which a new infection occurs with new pathogens at variable intervals after a previous infection has been eradicated. Relapse: The less common form of recurrent infection; occurs within 2 wk of treatment when the same organism reappears in the same site as the previous infection. Relapsing infections of the urinary tract most commonly occur in pyelonephritis, kidney obstruction from a stone, and prostatitis. EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: In Neonates: More common in boys as a result of anatomic abnormalities. In Preschool Children: More common in girls (4.5% vs. 0.5% for boys). In Adulthood: More common in women, with a 1% to 3% prevalence in nonpregnant women. In pregnancy at 12 wk, the incidence of asymptomatic bacteriuria is similar to nonpregnant women, at 2% to 10%. However, 70% to 80% of women with asymptomatic bacteriuria develop acute pyelonephritis, especially in the second and third trimesters, and suffer a pyelonephritic recurrence rate of 10%. In adults, 65 yr and older, at least 10% of men and 20% of women have bacteriuria. PHYSICAL FINDINGS & clinical presentation

•

UTI presentation is inconsistent and cannot be relied upon to diagnose UTI accurately or to localize the site of infection. Patients complain of: 1.

Urinary frequency, urgency

2.

Dysuria

3.

Urge incontinence

4.

Suprapubic pain

5.

Gross or microscopic hematuria

•

When negative cultures are associated with significant pyuria, vaginal discharge, or hematuria, infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis should be considered.

•

Acute pyelonephritis (PN) presents with fever, flank or abdominal pain, chills, malaise, vomiting, and diarrhea. It is these systemic symptoms that distinguish pyelonephritis from cystitis. Complications of acute pyelonephritis are renal abscess, perinephric abscess, emphysematous pyelonephritis, and pyonephrosis.

ETIOLOGY & PATHOGENESIS

•

•

Four major pathways: 1.

Ascending from the urethra

2.

Lymphatic

3.

Hematogenous

4.

Direct extension from another organ system

Other risk factors: neurologic diseases, renal failure, diabetes; anatomic abnormalities: bladder outlet obstruction, urethral stricture, vesicoureteral reflux, fistula, urinary diversion, megacystis, and infected stones; age; pregnancy; instrumentation, poor patient compliance, poor hygiene, infrequent voider, diaphragm contraceptives, tampon use, douches, and catheters

Catheters: All patients who require a long-term Foley catheter eventually develop significant levels of bacteriuria. Treatment is reserved for those individuals who become symptomatic (i.e., leukocytosis, fever, chills, malaise, loss of appetite, etc.) Using prophylactic antibiotics to treat patients who have chronic catheters is to be discouraged because of the risk of acquiring bacteria that are resistant to antibiotic therapy.

•

•

Once bacteria reach the urinary tract, three factors determine whether the infection occurs ( Box 1-14 ): 1.

Virulence of the microorganism

2.

Inoculum size

3.

Adequacy of the host defense mechanisms

These factors also determine the anatomic level of the UTI.

BOX 1-14

Bacterial factors 1.

The size of the inoculum

2.

The virulence of the infecting organism: a.

3.

Virulence factors: i.

P-fimbriae facilitate the adherence of bacteria to biologic surfaces.

ii.

K-antigens facilitate adherence and protect the organisms from the host-immune response.

iii.

O-antigens are an important source of the systemic reactions, such as fever and shock, that occur with bacterial infections.

iv.

H antigens are associated with flagella and are related to bacterial locomotion.

v.

Hemolysin may potentiate tissue damage and facilitate local bacterial growth.

vi.

Urease alkalinizes the urine and facilitates stone formation, thus potentiating infection.

b.

Biofilms harbor bacteria on prosthetic devices and may be a source of recurrent infections.

c.

The presence of sialosyl galactosyl globoside (SGG) on the surface of kidney cells. This compound is a highly powerful receptor for E. coli bacteria.

d.

Women with a deficiency in human beta-defensin-1 (HBD-1) are at greater risk for urinary tract infection.

Adequacy of host defense mechanisms

Urinary Pathogens: In >95% of UTIs the infecting organism is a member of the Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, or, in young women, Staphylococcus saprophyticus. In contrast, the organisms that commonly colonize the distal urethra and skin of both men and women and the vagina of women are Staphylococcus epidermidis, diphtheroids, lactobacilli, Gardnerella vaginalis, and a variety of anaerobes that rarely cause UTI. Generally, the isolation of two or more bacterial species from a urine culture signifies a contaminated specimen, unless the patient is being managed with an indwelling catheter or urinary diversion or has a chronic complicated infection. Defense Mechanisms against Cystitis: Low pH and high osmolarity, mucopolysaccharide glycosaminoglycan protective layer, normal bladder that empties completely and has no incontinence, and the presence of estrogen

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Interstitial cystitis

•

Vaginitis

•

Urethritis (gonococcal, nongonococcal, Trichomonas)

•

Frequency-urgency syndrome, prostatitis (acute and chronic)

•

Obstructive uropathy

•

Infected stones

•

Fistulas

•

Papillary necrosis

•

Vesicoureteral reflux

LABORATORY TESTS

•

Urinalysis with microscopic evaluation of clean-catch urine for bacteria and pyuria

•

Urine C&S

•

CBC with differential (shows leukocytosis)

•

Antibody-coated bacteria are seen with pyelonephritis

IMAGING STUDIES

•

Warranted only if renal infection or genitourinary abnormality is suspected

•

KUB, VCUG, renal sonogram, IVP, CT scan, and nuclear scan

•

Specialty examination: cystoscopy with occasional retrograde pyelography to rule out obstructive uropathy; stenting the obstruction possibly required

TREATMENT NONPHARMACOLOGIC THERAPY

•

Hot sitz baths, anticholinergics, urinary analgesics

•

For pyelonephritis: bed rest, analgesics, antipyretics, and IV hydration

ACUTE GENERAL Rx

•

Conventional therapy of 7 days; short-term therapy of 1, 3, or 5 days.

•

Agents of choice: amoxicillin/clavulanate, cephalosporins, fluoroquinolones, nitrofurantoin, and trimethoprim with sulfonamide.

•

For pyelonephritis: hospitalization until afebrile and stable, then at home via home care agency with IV antibiotic composed of aminoglycoside plus cephalosporin × 1 wk followed by oral agents (based on sensitivity) for 2 wk. Moderate forms of pyelonephritis have been successfully treated with fluoroquinolone therapy for 21 days, without requiring hospitalization. Most important, complicating factors such as obstructive uropathy or infected stones must be identified and treated.

•

Section III, “Urinary Tract Infection,” describes an approach to the management of UTI.

PEARLS & CONSIDERATIONS

COMMENTS

•

Asymptomatic bacteriuria: occurs in both anatomically normal and abnormal urinary tracts. This can clear spontaneously, persist, or lead to symptomatic kidney infection. Treatment is recommended in patients with vesicoureteral reflux, stones, obstructive uropathy, parenchymal renal disease, diabetes mellitus, and pregnant or immunocompromised patients.

•

Pregnancy: 20% to 40% of pregnant women with untreated bacteriuria develop pyelonephritis. This is associated with prematurity and low-birth-weight infants. Confirmed significant bacteriuria should be treated with an aminopenicillin and cephalosporin.

•

Recurrent UTI: caused by an unresolved infection, vaginal colonization of the originally infecting organism, or reinfection with a new strain. Management of recurrent UTI includes continuous antibiotic prophylaxis, intermittent self-treatment, and postcoital prophylaxis. Prophylaxis is recommended for women who experience two or more symptomatic UTIs over a 6-mo period or three or more episodes over a 12-mo period. 1.

Changes after menopause: lower levels of lactobacilli, decreased estrogen, senile atrophy of the genitalia, and loss of bladder elasticity (compliance).

2.

Biologic factors altering defense systems: the presence of sialosyl galactosyl globoside (SGG) on the surface of the kidney acts as a powerful receptor for E. coli and increases the risk for UTI; the presence of the blood group P1 causes increased binding of E. coli that is resistant to normal infection-fighting mechanisms in the body and it is believed that some individuals are deficient in a compound called human beta-defensin-1 (HBD-1), a naturally occurring antibiotic that fights E. coli within the urinary tract.

Resistance:

•

Because of the overuse of antibiotics, organisms once sensitive to a number of agents are now increasingly more resistant, making effective management of UTI and pyelonephritis more difficult and potentially more dangerous. Most important has been the increasing resistance to TMP-SMX, the current primary care provider drug of choice for acute uncomplicated UTI in women.

•

When choosing a treatment regimen physicians should consider such factors as: 1.

In-vitro susceptibility

2.

Adverse effects

3.

Cost effectiveness

4.

Resistance rates in the respective communities

EVIDENCE

A systematic review examined the optimal duration of antibiotic treatment for uncomplicated UTIs in elderly women. The comparison of short (3 to 6 days) and longer (7 to 14 days) treatments did not show any significant difference, but the methodologic quality and sample size of all the trials were low.[[1]] A systematic review of RCTs examining which treatment is most effective for symptomatic UTIs during pregnancy found no significant differences between treatments with regard to cure rates, recurrent infection, and incidence of preterm delivery.[[2]] A systematic review and a subsequent RCT in women with uncomplicated acute pyelonephritis have found no consistent differences in cure rates between oral trimethoprim/sulfamethoxazole (TMP/SMX), amoxicillin/clavulanic acid, or ciprofloxacin. [18] [19]

Evidence-Based Referenceces 1. Lutters M, Vogt N: Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women (Cochrane Review). Cochrane Library 1, Chichester, UK, John Wiley, 2004. 2. Vazquez JC, Villar J: Treatments for symptomatic urinary tract infections during pregnancy (Cochrane Review). Cochrane Library 1, Chichester, UK, John Wiley, 2004. 3. Pinson AG, et al: Oral antibiotic therapy for acute pyelonephritis: a methodologic review of the literature. J Gen Intern Med 1992; 7:544.Reviewed in: Clin Evid 10:2204, 2003. 4. Richard GA, et al: Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology 1998; 52:5155.Reviewed in: Clin Evid 10:2204, 2003.

AUTHORS: PHILIP J. ALIOTTA, M.D., M.S.H.A., and RUBEN ALVERO, M.D. Urolithiasis

BASIC INFORMATION DEFINITION

Urolithiasis is the presence of calculi within the urinary tract. The five major types of urinary stones are calcium oxalate (>50%), calcium phosphate (10% to 20%), uric acid (8%), struvite (15%), and cystine (3%). SYNONYMS

Nephrolithiasis Renal colic

ICD-9CM CODES

592.9 Urinary calculus EPIDEMIOLOGY & DEMOGRAPHICS

•

Urinary stone disease afflicts 250,000 to 750,000 Americans/yr.

•

Male:female ratio is 4:1. After the sixth decade, the ratio is 1.5:1.

•

Incidence of symptomatic nephrolithiasis is greatest during the summer (resulting from increased humidity and temperatures with increased risk of dehydration and concentrated urine).

•

Calcium oxalate or mixed calcium oxalate/calcium phosphate stones account for 70% of urolithiasis.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Stones may be asymptomatic or may cause the following signs and symptoms from obstruction:

•

Sudden onset of flank tenderness

•

Nausea and vomiting

•

Patient in constant movement, attempting to lessen the pain (patients with an acute abdomen are usually still because movement exacerbates the pain)

•

Pain may be referred to the testes or labium (progression of stone down the urinary ureter)

•

Fever and chills accompanying the acute colic if there is superimposed infection

•

Pain may radiate anteriorly over to the abdomen and result in intestinal ileus

ETIOLOGY

•

Increased absorption of calcium in the small bowel: type I absorptive hypercalciuria (independent of calcium intake)

•

Idiopathic hypercalciuria nephrolithiasis is the most common diagnosis for patients with calcium stones; the diagnosis is made only if there is no hypercalcemia and no known cause for hypercalciuria

•

Increased vitamin D synthesis (e.g., secondary to renal phosphate loss: type III absorptive hypercalciuria)

•

Renal tubular malfunction with inadequate reabsorption of calcium and resulting hypercalciuria

•

Heterozygous mutations in the NPT2a gene result in hypophosphatemia and urinary phosphate loss

•

Hyperparathyroidism with resulting hypercalcemia

•

Elevated uric acid level (metabolic defects, dietary excess)

•

Chronic diarrhea (e.g., inflammatory bowel disease) with increased oxalate absorption

•

Type I (distal tubule) renal tubular acidosis (40 yr of age

•

May occur singly but are often multiple

•

Fewer than half of all fibroids are estimated to produce symptoms

•

Frequently diagnosed incidentally on pelvic examination

•

There is increased familial incidence

•

Potential to enlarge during pregnancy, as well as to regress after menopause

•

Infrequent primary cause of infertility in 1000 mIU/ml (second IS)

•

8 to 9 wk: fetal cardiac activity

•

Molar pregnancy: characteristic cluster of cysts

•

Location of placenta

•

Degree of placental separation: difficult to assess

TREATMENT NONPHARMACOLOGIC THERAPY

•

Pelvic rest: no coitus, douching, or tampons

•

Bed rest, if >20 wk

•

Counseling: genetic, bereavement

ACUTE GENERAL Rx

•

Hemodynamic stabilization

•

Emergency D & C, laparotomy, or cesarean section as necessary

CHRONIC Rx

Depends on diagnosis DISPOSITION

Depends on diagnosis REFERRAL

•

If patient is unstable and needs emergency ob/gyn management and/or surgery

•

If patient has diagnosis of ectopic or molar pregnancy, because immediate surgical treatment is indicated

•

Perinatal consultation for high-risk pregnancy

EVIDENCE

Administration of anti-D immunoglobulin to Rhesus-negative women at 24 weeks and 34 weeks gestation during the first pregnancy reduces the risk of Rhesus-D alloimmunization from 1.5% to 0.2%.[[1]]

Evidence-Based Referencece 1. Crowther CA: Anti-D administration in pregnancy for preventing Rhesus alloimmunization. Cochrane Library, 2, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Coppola PT, Coppola M: Vaginal bleeding in the first 20 weeks of pregnancy. Emerg Med Clin North Am 2003; 21(3):667.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vaginal Malignancy GIL FARKASH, M.D., RUBEN ALVERO, M.D. BASIC INFORMATION DEFINITION

Vaginal malignancy is an abnormal proliferation of vaginal epithelium demonstrating malignant cells below the basement membrane. SYNONYMS

Squamous cell carcinoma of the vagina Adenocarcinoma of the vagina Melanoma of the vagina Sarcoma of the vagina Endodermal sinus tumor

ICD-9CM CODES

184.0 Vagina, vaginal neoplasm EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 0.42 cases/100,000 persons PREVALENCE: Vaginal cancer is the second rarest gynecologic cancer. It comprises 2% of malignancies of the female genital tract. MEAN AGE AT DIAGNOSIS: Predominantly a disease of menopause. Mean age at diagnosis is 60 yr old. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Majority of cases are asymptomatic

•

Postmenopausal vaginal bleeding and/or vaginal discharge are the most common symptoms

•

May also present as pelvic pain or pressure, dyspareunia, dysuria, malodor, or postcoital bleeding

•

May present as a vaginal lesion or abnormal Pap smear

ETIOLOGY

•

The exact etiology is unknown.

•

Vaginal intraepithelial neoplasia is thought to be a precursor for squamous cell carcinoma of the vagina.

•

Chronic pessary use has been associated with vaginal malignancy.

•

Prior pelvic radiation may be a risk factor.

•

Clear-cell adenocarcinoma is related to in utero diethylstilbestrol exposure.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Extension from other primary carcinoma more common than primary vaginal cancer

•

Vaginitis

WORKUP

•

Diagnosis is made histologically by biopsy.

•

Colposcopy and biopsy should follow suspicious Pap smear.

•

Cystoscopy, proctosigmoidoscopy, chest radiography, IV urography, and barium enema may be used for clinical staging.

•

CT scan and MRI are being used to evaluate spread.

•

Staging I to IV ( Fig. 1-286 ).

FIGURE 1-286 Staging system for vaginal cancer. Metastatic disease that involves the bladder or rectum is stage IV-a. Metastatic disease beyond the pelvis is stage IV-b. (From Copeland LJ: Textbook of gynecology, ed 2, Philadelphia, 2000, WB Saunders.)

IMAGING STUDIES

•

Chest radiography, IV urography, and barium enema are used for staging.

•

CT scan and MRI are good for assessing tumor spread.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Radiation therapy is the mainstay of treatment.

•

Stage I tumors that are small and confined to the posterior, upper third of the vagina may be treated with radical surgery.

•

Other stages require a whole-pelvis, interstitial, and/or intracavitary radiation therapy.

•

Chemotherapy is used in conjunction with radiotherapy in rare select cases.

DISPOSITION

Five-year survival ranges from 80% for stage I to 17% for stage IV. REFERRAL

Vaginal cancer should be managed by a gynecologic oncologist and radiation oncologist.

EVIDENCE

A retrospective review of 121 women with vaginal intraepithelial neoplasia (VAIN) found recurrence rates following partial vaginectomy, laser, and 5-fluorouracil of 0, 38, and 59%, respectively, after at least 7 months' follow-up.[[1]] A retrospective review of 71 patients with primary vaginal carcinoma treated with interstitial iridium-192 with or without external beam radiotherapy found that interstitial irradiation resulted in local control in the majority of patients with primary vaginal carcinoma with acceptable morbidity.[[2]] A retrospective review of 84 patients with primary invasive vaginal cancer managed at one institution over a 25-year period found that patients with stage I and II squamous cell vaginal carcinoma managed by initial surgery followed by selective radiotherapy had good outcomes in terms of survival and local tumor control.[[3]]

Evidence-Based Referencece 1. Dodge JA, et al: Clinical features and risk of recurrence among patients with vaginal intraepithelial neoplasia. Gynecol Oncol 2001; 83:363. 2. Tewari KS, et al: Primary invasive carcinoma of the vagina: treatment with interstitial brachytherapy. Cancer 2001; 91:758. 3. Tjalma WA, et al: The role of surgery in invasive squamous carcinoma of the vagina. Gynecol Oncol 2001; 81:360.

SUGGESTED READINGS Kim H, et al: Case report: magnetic resonance imaging of vaginal malignant melanoma. J Comput Assist Tomogr 2003; 27(3):357.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vaginismus BETH J. WUTZ, M.D., RUBEN ALVERO, M.D. BASIC INFORMATION DEFINITION

Vaginismus refers to the involuntary spasm of the vaginal, introital, and/or levator ani muscles, preventing penetration or causing painful intercourse.

ICD-9CM CODES

300.11 Hysterical vaginismus 306.51 Psychogenic or functional vaginismus 625.1

Reflex vaginismus

EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: Estimated at about 11.7% to 42% of women presenting to sexual dysfunction clinics PREVALENCE: Affects approximately 1:200 women PREDOMINANT SEX: Affects only females RISK FACTORS: Any previous sexual trauma, including incest or rape PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Fear of pain with coitus

•

Dyspareunia

•

Orgasmic dysfunction

ETIOLOGY

•

Learned conditioned response to real or imagined painful vaginal experience (e.g., traumatic speculum examination, incest, rape)

•

Vaginitis

•

PID

•

Endometriosis

•

Anatomic anomalies

•

Atrophic vaginitis

•

Mucosal tears

•

Inadequate lubrication

•

Focal vulvitis

•

Painful hymenal tags

•

Scarring secondary to episiotomy

•

Skin disorders

•

Topical allergies

•

Postherpetic neuralgia

DIAGNOSIS WORKUP

•

Thorough history (including sexual history)

•

Careful pelvic examination

•

Behavioral therapy

TREATMENT NONPHARMACOLOGIC THERAPY

•

Deconditioning the response by systematic self-administered progressive dilation techniques using fingers or dilators

•

Behavioral and/or psychosexual therapy

ACUTE GENERAL Rx

•

Botulinum toxin therapy given locally has been shown to relieve the perineal muscle spasms associated with vaginismus, allowing resumption of intercourse. 1.

Acts by preventing neuromuscular transmission, causing muscle weakness

2.

Considered experimental treatment for vaginismus at this time

•

Cause should be determined by history and explained to the patient so that she understands the mechanics of the muscle spasms.

•

Patient must be motivated to desire painless vaginal insertion for such reasons as pleasurable coitus, tampon insertion, or gynecologic examination.

•

Patient (and her partner) must be willing to patiently undergo the process of systematic desensitization and counseling.

DISPOSITION

A high percentage of successfully treated patients REFERRAL

To a gynecologist or sex therapist

PEARLS & CONSIDERATIONS COMMENTS

•

May uncover early sexual abuse or an aversion to sexuality in general.

•

To American Association of Sex Educators, Counselors and Therapists, 11 Dupont Circle, NW, Washington, DC, 20036.

•

To Sex Information and Education Council of the U.S. (SIECUS), 85th Avenue, New York, NY 10022.

SUGGESTED READINGS Heim LJ: Evaluation and differential diagnosis of dyspareunia. Am Fam Physician 2001; 63(8):1535. McGuire H, Hawton K: Interventions for vaginismus. [update of Cochrane Database Syst Rev 2001; 2:CD001760, ], 1:CD001760, 2003.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vaginosis, Bacterial ARUNDATHI G. PRASAD, M.D., RUBEN ALVERO, M.D. BASIC INFORMATION DEFINITION

Bacterial vaginosis (BV) is a thin, gray, homogenous, malodorous vaginal discharge that results from a shift in the vaginal flora from a predominance of lactobacilli to high concentrations of anaerobic bacteria. SYNONYMS

Before 1955: nonspecific vaginitis 1955: Haemophilus vaginalis vaginitis 1963: Corynebacterium vaginalis vaginitis 1980: Gardnerella vaginalis vaginitis 1990: Bacterial vaginosis

ICD-9CM CODES

616.10 Vaginitis, bacterial EPIDEMIOLOGY & DEMOGRAPHICS

•

Most common vaginal infection

•

Gardnerella, Mycoplasma, and Mobiluncus are harbored in the urethra of male partners; however, 1.

Male partners are asymptomatic.

2.

There is no improved cure rate or lower reinfection rate if the infected patient's male partner is treated.

3.

Abstinence from intercourse or condom use while the patient completes her treatment regimen may improve cure rates and lessen recurrences.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

50% of patients are asymptomatic

•

A thin, dark, or dull gray homogenous discharge that adheres to the vaginal walls

•

An offensive, “fishy” odor that is accentuated after intercourse or menses

•

Pruritus (only in 13%)

ETIOLOGY

•

Gardnerella vaginalis is detected in 40% to 50% of vaginal secretions. 1.

Increase in vaginal pH caused by decrease in hydrogen peroxide–producing lactobacilli

2.

Anaerobes predominate and produce amines

•

Amines, when alkalinized by semen, menstrual blood, the use of alkaline douches, or the addition of 10% KOH, volatilize and cause the unpleasant “fishy” odor.

•

In BV: 1.

Bacteroides (anaerobes) species are increased 1000 × the usual concentration.

2.

G. vaginalis are 100 × normal.

3.

Peptostreptococcus are 10 × normal.

4.

Mycoplasma hominis and Enterobacteriacea members are present in increased concentrations.

DIAGNOSIS WORKUP

Seattle Group Criteria:

•

Detecting three of the four following signs will diagnose 90% correctly, with 4.5

3.

Positive KOH whiff test

4.

Clue cells present on wet mount

•

Cultures are unnecessary.

•

Pap smear will not identify G. vaginalis.

•

Gram stain of vaginal secretions will reveal clue cells and abnormal mixed bacteria ( Fig. 1-287 ).

FIGURE 1-287 Clue cells characteristic of bacterial vaginosis, squamous epithelial cells whose borders are obscured by bacteria. (From Carlson K [ed]: Primary care of women, St Louis, 1995, Mosby.)

TREATMENT ACUTE GENERAL RX

recommended regimens (equal efficacy):

1.

Metronidazole 500 mg PO bid for 7 days

2.

0.75% metronidazole gel in vagina bid for 5 days

3.

2% clindamycin cream qd for 7 days

ALTERNATE REGIMENS (Lower efficacy for BV):

1.

Clindamycin ovules 100 g intravaginally qhs for 3 days

2.

Clindamycin 300 mg PO bid for 7 days (increased incidence of diarrhea)

3.

Metronidazole ER 750 mg PO qd for 7 days

4.

Metronidazole 2 g PO single dose (higher relapse rate)

Patients should be advised to avoid alcohol while taking metronidazole and for 24 hr thereafter.

TREATMENT IN PREGNANCY: All pregnant patients proven to have BV should be treated because of its association with preterm labor, chorioamnionitis, and PROM. RECOMMENDED REGIMENS: 1.

Metronidazole 250 mg PO tid for 7 days

2.

Clindamycin 300 mg PO bid for 7 days •

Existing data do not support the use of topical agents during pregnancy.

•

Multiple studies and meta-analysis have not demonstrated associations between metronidazole use during pregnancy and teratogenic effects in newborns.

RECURRENT BV:

•

Condom use may help reduce the risk of recurrence.

•

Concurrent treatment of male partner is controversial. Consider treating the male partner if there is recurrent vaginitis or any suspicion of associated upper genital tract infection.

PEARLS & CONSIDERATIONS

•

Bacterial vaginosis has been associated with PID, cystitis, posthysterectomy vaginal cuff cellulitis, postabortal infection, preterm delivery, premature rupture of membranes (PROM), amnionitis, chorioamnionitis, and postpartum endometritis. New evidence also shows BV increases women's risk of acquiring HIV.

•

Higher cumulative cure rates have been found at 3 to 4 weeks for a 7-day regimen of metronidazole (500 mg twice daily) than with a single dose (2 g).

EVIDENCE

See Section I, “Vulvovaginitis, Bacterial.” SUGGESTED READINGS Mitchell H: Vaginal discharge-causes, diagnosis, and treatment. BMJ 2004; 328(7451):1306.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Varicella ARUNDATHI G. PRASAD, M.D., RUBEN ALVERO, M.D. BASIC INFORMATION DEFINITION

Varicella is a common viral illness characterized by acute onset of generalized vesicular rash and fever. SYNONYMS

Chickenpox

ICD-9CM CODES

052.9 Varicella EPIDEMIOLOGY & DEMOGRAPHICS

•

Varicella is extremely contagious. More than 90% of unvaccinated contacts become infected.

•

The incubation period of chickenpox ranges from 9 to 21 days.

•

Peak incidence is in the springtime.

•

The predominant age is 5 to 10 yr.

•

Infectious period begins 2 days before onset of clinical symptoms and lasts until all lesions have crusted.

•

Most patients will have lifelong immunity following an attack of chickenpox; protection from chickenpox following varicella vaccine is approximately 6 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Findings vary with the clinical course. Initial symptoms consist of fever, chills, backache, generalized malaise, and headache.

•

Symptoms are generally more severe in adults.

•

Initial lesions generally occur on the trunk (centripetal distribution) and occasionally on the face; these lesions consist primarily of 3- to 4-mm red papules with an irregular outline and a clear vesicle on the surface (dew drops on a rose petal appearance).

•

Intense pruritus generally accompanies this stage.

•

New lesion development generally ceases by the fourth day with subsequent crusting by the sixth day.

•

Lesions generally spread to the face and the extremities (centrifugal spread).

•

Patients generally present with lesions at different stages at the same time.

•

Crusts generally fall off within 5 to 14 days.

•

Fever is usually highest during the eruption of the vesicles; temperature generally returns to normal following disappearance of vesicles.

•

Signs of potential complications (e.g., bacterial skin infections, neurologic complications, pneumonia, hepatitis) may be present on physical examination.

•

Mild constitutional symptoms (e.g., anorexia, myalgias, headaches, restlessness) may be present (most common in adults).

•

Excoriations may be present if scratching is prominent.

ETIOLOGY

Varicella-zoster virus (VZV) is a human herpes virus III that can manifest with either varicella or herpes zoster (i.e., shingles, which is a reactivation of varicella).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other viral infection

•

Impetigo

•

Scabies

•

Drug rash

•

Urticaria

•

Dermatitis herpetiformis

•

Smallpox

WORKUP

Diagnosis is usually made based on patient's history and clinical presentation. LABORATORY TESTS

•

Laboratory evaluation is generally not necessary.

•

CBC may reveal leukopenia and thrombocytopenia.

•

Serum varicella titers (significant rise in serum varicella IgG antibody level), skin biopsy, or Tzanck smear are used only when diagnosis is in question.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Use antipruritic lotions for symptomatic relief.

•

Avoid scratching to prevent excoriations and superficial skin infections.

•

Use a mild soap for bathing; hands should be washed often.

ACUTE GENERAL Rx

•

Use acetaminophen for fever and myalgias; aspirin should be avoided because of the increased risk of Reye's syndrome.

•

Oral acyclovir (20 mg/kg qid for 5 days) initiated at the earliest sign (within 24 hr of illness) is useful in healthy, nonpregnant individuals 13 yr of age or older to decrease the duration and severity of signs and symptoms. Immunocompromised hosts should be treated with IV acyclovir 500 mg/m2 or 10 mg/kg q8h IV for 7 to 10 days.

•

Varicella is most contagious from 2 days before to a few days after the onset of the rash. Varicella vaccine is available for children and adults; protection lasts at least 6 yr. Healthy, nonimmune adults and children exposed to varicella-zoster virus should receive prophylaxis with live attenuated varicella vaccine (Varivax). Patients with HIV or other immunocompromised patients should not receive the live attenuated vaccine.

•

Exposed patients with contraindications to varicella vaccine can be treated with varicella-zoster immunoglobulin (VariZIG). It is effective in preventing varicella in susceptible individuals. Dose is 12.5 U/kg IM (up to a maximum of 625 U). VZIG must be administered as early as possible after presumed exposure (within 4 days). If VariZIG cannot be obtained and administered within 4 days, providers should consider the use of intravenous immune globulin (IVIG) within 4 days of exposure.

•

Pruritus from chickenpox can be controlled with antihistamines (e.g., hydroxyzine 25 mg q6h) and oral antipruritic lotions (e.g., calamine).

•

Oral antibiotics are not routinely indicated and should be used only in patients with secondary infection and infected lesions (most common infective organisms are Streptococcus sp. and Staphylococcus sp.).

DISPOSITION

•

The course is generally benign in immunocompetent adults and children.

•

Infants who develop chickenpox are incapable of controlling the infection and should be given varicellazoster immunoglobulin or -globulin if VZIG is not available.

PEARLS & CONSIDERATIONS COMMENTS

•

VZIG can be obtained from the nearest regional Red Cross Blood Center or the Centers for Disease Control and Prevention in Atlanta, Georgia.

•

Varicella immunization is recommended for all who have not had chickenpox; dosage for adults and adolescents (>13 yr old) is two 0.5-ml doses 4 to 8 wk apart.

EVIDENCE

There is evidence that oral acyclovir reduces the symptoms of chickenpox in otherwise healthy people if started early, but its clinical importance in this area remains controversial. The reviewers note that the clinical importance of acyclovir in other-wise healthy children remains controversial.[[1]]

Evidence-Based Referencece 1. Klassen TP, et al: Acyclovir for treating varicella in otherwise healthy children and adolescents. Cochrane Database Syst Rev 2004; 2:CD002980,

AUTHOR: FRED F. FERRI, M.D. Varicose Veins BASIC INFORMATION DEFINITION

Varicose veins are dilated networks of the subcutaneous venous system that result from valvular incompetence. SYNONYMS

Chronic venous insufficiency Stasis skin changes

ICD-9CM CODES

454.9 Varicose veins EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE:

•

Approximately 30% of adults, with increasing incidence with age

•

Increased incidence during pregnancy, especially with advanced maternal age

PREDOMINANT SEX:Female > male GENETICS:

•

Familial tendency

•

Evidence for dominant, recessive, and multifactorial types of inheritance

RISK FACTORS:

•

Advancing age

•

Prolonged standing

•

Pregnancy

•

Obesity

•

Use of oral contraceptives

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Visible tortuous veins in the territory of either the long saphenous vein (most common), short saphenous vein, or both

•

Dull ache, burning, or cramping in leg muscles

•

Worsening discomfort with standing, warm temperatures, or menses

•

Blowouts-localized dilatations

•

Tortuous dilation of superficial veins

•

Dermatitis, hyper/hypopigmentation, edema, eczema

•

Varicose ulcer, sometimes with superficial infection

ETIOLOGY

•

Normally, blood flow directed from the superficial venous system to the deep venous system via communication of perforating vessels

•

Best thought of as “venous hypertension”

•

Valvular incompetence in perforator veins of lower extremity leading to reverse flow of fluid from highpressure deep venous system to low-pressure superficial venous system, resulting in dilation of superficial veins, leg edema, and pain

•

Rarely associated with deep vein thrombophlebitis

•

Exacerbated by restrictive clothing

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Conditions that can lead to superficial venous stasis other than primary valvular insufficiency include:

•

Arterial occlusive disease

•

Diabetes

•

Deep vein thrombophlebitis

•

Peripheral neuropathies

•

Unusual infections

•

Carcinoma

WORKUP

•

Mainly a clinical diagnosis—Trendelenburg test

•

Arterial studies to rule out arterial insufficiency before initiating therapy for venous insufficiency

LABORATORY TESTS

Not useful IMAGING STUDIES

Duplex ultrasound

•

Gold standard for evaluation of varicose veins

•

Quantitation of flow through venous valves under direct visualization

•

Allows precise anatomic identification of source of venous reflux

•

Rarely ascending venography and varicography for unusually located varices and recurrence after surgical treatment.

TREATMENT NONPHARMACOLOGIC THERAPY

•

Leg elevation and rest

•

Graded compression stockings: used early in morning before edema accumulates and removed before going to bed

•

Weight loss

•

Avoidance of occlusive clothing

ACUTE GENERAL Rx

•

For associated stasis dermatitis: topical corticosteroids

•

Treatment of secondary infection with appropriate antibiotics

CHRONIC Rx

•

Compression sclerotherapy: injection of 1% to 3% solution of sodium tetradecyl sulfate or 5% ethanolamine oleate

•

Surgery: indications include the following:

•

1.

Persistent varicosities with conservative treatment

2.

Failed sclerotherapy

3.

Previous or impending bleeding from ulcerated varicosities

4.

Disabling pain

5.

Cosmetic concerns

Surgical methods include (must be combined with compressive therapy): 1.

Saphenous vein ligation

2.

Ligation of incompetent perforating veins

3.

Saphenous vein stripping with or without avulsion of varicosities

4.

Ambulatory “miniphlebectomies”: avulsion of superficial varicosities with saphenous vein stripping

5.

New treatments: endovenous obliteration using radiofrequency (diathermy) or laser as an alternative to traditional stripping of the long saphenous vein and powered phlebectomy for avulsing calf varicosities.

COMPLICATIONS:

•

Hemorrhage

•

Thrombophlebitis

•

Atrophie blanche

•

Varicose eczema

•

Lipodermatosclerosis

•

Venous ulceration

DISPOSITION

A chronic condition in which a combination of compressive and surgical therapy can adequately control varicosities REFERRAL

•

To dermatologist for dermatitis complications

•

To surgeon for failed conservative management or varicose veins with complications

EVIDENCE

An RCT of endovenous radiofrequency obliteration vs. ligation and stripping demonstrated equivalent success rates, but significant advantages were demonstrated (e.g., shorter return to work and less pain experienced) in the radiofrequency obliteration group.[[1]] A systematic review found that compression was more effective than no compression for the healing of venous leg ulcers.[[2]]

Evidence-Based Referenceces 1. Lurie F, et al: Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected patient population (EVOLVeS Study). J Vasc Surg 2003; 38:207. 2. Cullum N, et al: Compression for venous leg ulcers (Cochrane Review). Cochrane Library 1, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Crane J, Cheshire N: Recent developments in vascular surgery. BMJ 2003; 327(7420):911. Hagen MD, Johnson ED: What treatments are effective for varicose veins?. J Fam Pract 2003; 52(4):329.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Varicocele ELIZABETH NOWAK, D.O.,, JANICE PATACSIL-TRULL, M.D.

BASIC INFORMATION DEFINITION

A varicocele is a collection of dilated and tortuous veins in the pampiniform plexus surrounding the spermatic cord in the scrotum. SYNONYM

Sometimes referred to as a “bag of worms”

ICD-9CM CODES 456.4 EPIDEMIOLOGY AND DEMOGRAPHICS

PREVALENCE: A varicocele is present in up to 20% of all males. It occurs in approximately 30% of infertile men. However, only 10% to 15% of males with varicoceles have fertility problems. RISK FACTORS: There is no reliable data on epidemiological risk factors for varicocele, such as a family history or environmental exposures. PHYSICAL FINDINGS & CLINICAL PRESENTATION

Patients may report a mass lying posterior to and above the testis. When the patient is supine, dilation of the veins is generally decreased. Dilation and tortuosity of the veins increases when the patient is upright and when the patient performs a Valsalva maneuver. The majority of cases occur more commonly on the left side because the left spermatic vein enters the left renal vein at a 90-degree angle, whereas the right testicular vein drains directly into the vena cava. ETIOLOGY

Varicoceles are caused by dysfunction of the valves in the spermatic vein, which allows pooling of blood in the pampiniform plexus.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hydrocele

•

Spermatocele

•

Epidydimal orchitis

•

Testicular tumor

WORKUP

Patient should be examined in an upright position and a supine position. LABORATORY TESTS

Semen analysis if a varicocele is detected and the patient is infertile. IMAGING STUDIES

Doppler ultrasound, with or without high-resolution color flow, is the most common and least invasive technique to confirm a varicocele and differentiate it from other scrotal abnormalities.

TREATMENT Once a varicocele is identified, providers must document bilateral testicular size at regular intervals. If the testicle on the affected side is small, spermatogenesis may have been adversely affected. SURGERY

•

Varicocelectomy is performed by ligation of the veins of the pampiniform plexus through an inguinal incision or by ligating the internal spermatic vein in the retroperitoneum. This is generally performed as an ambulatory surgery.

•

The goal of varicocelectomy is to maximize chances for fertility.

•

Surgical treatment is indicated when there is significant disparity in testicular size or pain. Also, surgery should be performed if the contralateral testis is diseased or absent. Surgery may be considered if the varicocele is large, even without a disparity in testicular size.

•

Postoperatively the involved testis typically enlarges and catches up to the uninvolved side in 1 to 2 yr. Semen parameters also improve significantly in 65% of patients.

•

The success rate of surgical repair is close to 98% and that of percutaneous repair is significantly lower.

PEARLS & CONSIDERATIONS COMMENTS

•

A varicocele in a boy less than 10 yr of age or on the right side may be indicative of an abdominal or retroperitoneal mass. Ultrasound should be performed.

•

The sudden occurrence of a left-sided varicocele in an older man indicates occlusion of the spermatic vein and should prompt evaluation for a renal tumor.

SUGGESTED READINGS Behrman R, et al: Nelson textbook of pediatrics, ed 16. Philadelphia: WB Saunders; 2000:1652-1654.

Diamond DA: Adolescent varicocele. Curr Opin Urol 2007; 17(b):263-267. Nseyo U, et al: Urology for primary care physicians, Philadelphia: WB Saunders; 1999:339-346.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Venous Ulcers KELLY BOSSENBROEK, M.D. BASIC INFORMATION DEFINITION

Venous ulcers are shallow wounds with irregular borders that usually occur on the lower extremities above or over the malleoli. These ulcerations develop due to high venous pressures caused by incompetent valves or obstructed veins. SYNONYMS

Stasis ulcers, peripheral venous insufficiency, venous leg ulcers

ICD-9CM CODES

459.3

Chronic venous hypertension, including stasis edema

459.81 Peripheral venous insufficiency 707.1

Ulcer of the lower limb

EPIDEMIOLOGY & DEMOGRAPHICS

Peak Prevalence: Occurs between 60 and 80 years of age, women > men. RISK FACTORS: Smoking, obesity, diabetes mellitus, phlebitis, increasing age, family history of varicose veins, history of DVT. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Patients with venous stasis often have chronic skin changes on their lower limbs, including hyperpigmentation, hyperkeratosis, and dependent edema. Skin color changes are due to the extravasation of red blood cells and the resultant deposition of hemosiderin.

•

Venous dermatitis or stasis dermatitis is common in these patients and is characterized by pruritic, red, and scaly eczematous changes.

•

Smooth white plaques of atrophic sclerosis are known as atrophie blanche and can be a clue that the patient has venous disease.

•

Venous ulcers are shallow, full-thickness ulcers, with irregular borders and areas of granulation tissue. Necrosis is extremely rare.

•

Patients often report a long history of dependent lower-extremity edema, and aching pain in the legs that is often worse after standing for long periods.

ETIOLOGY

Venous stasis develops from valvular incompetence or obstruction, resulting in venous hypertension. Some authors propose that venous hypertension leads to malformation of capillaries causing leakage of fluid and reduced blood flow to the skin. The resultant hypoxic tissue is prone to ulceration after minor trauma. The underlying vascular deficiency also impedes wound healing.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Peripheral arterial disease (with ischemia and necrosis)

•

Diabetic ulceration (often secondary to neuropathy)

•

Decubitus ulceration (due to pressure over a bony prominence)

•

Vasculitis (with erythema and bullae)

•

Necrotic ulceration from infection

•

Basal cell carcinoma or squamous cell carcinoma

WORKUP

•

The majority of patients can be diagnosed clinically from the physical exam; however up to 25% of patients have concomitant arterial disease. In these patients an ankle-brachial index should be performed. Arterial insufficiency is suggested by an ABI of f×5 cm) or long-standing wounds.

•

All patients should be evaluated after 1 month of therapy. If the wound shows little to no progress in healing, referral is also suggested.

SUGGESTED READINGS

Palfreyman SJ, et al: Dressings for healing venous leg ulcers (Cochrane Review). Cochrane Database of Syst Rev 2006; 3:CD001103

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Ventricular Septal Defect CRAIG J. MCMACKIN, M.D., WEN-CHIH WU, M.D.

BASIC INFORMATION DEFINITION

•

Ventricular septal defect (VSD) refers to an abnormal communication through the septum separating the right and left ventricles.

•

VSDs may be large or small, single or multiple.

•

VSDs are located at various anatomic regions of the septum and classified as: 1.

Membranous (75% to 80%): most common type, defect extends into the membranous portion of the interventricular septum.

2.

Muscular or trabecular (5% to 20%): defect entirely surrounded by muscular tissue.

3.

Canal or inlet (8%): defect commonly lies beneath the septal leaflet of the tricuspid valve; often seen in patients with Down's syndrome.

4.

Subarterial, outlet, infundibular, or supracristal (5% to 7%): least common type, defect usually found beneath the aortic valve and may lead to aortic regurgitation.

SYNONYMS

VSD

ICD-9CM CODES

745.4 Ventricular septal defect EPIDEMIOLOGY & DEMOGRAPHICS

•

VSD was first described by Dalrymple in 1847.

•

VSDs are some of the most common congenital heart abnormalities (along with bicuspid aortic valve and mitral valve prolapse), accounting for 30% of all congenital cardiac defects.

•

VSD accounts for about 25% of all congenital heart defects in children and 10% in adults (decrease due to spontaneous closure of many VSDs by adulthood).

•

Prevalence is 1.17 per 1000 live births and 0.5 per 1000 adults.

•

Found with equal frequency in males and females.

•

VSD may be associated with:

•

1.

Atrial septal defect (35%)

2.

Patent ductus arteriosus (22%)

3.

Coarctation of the aorta (17%)

4.

Subvalvular aortic stenosis (4%)

5.

Subpulmonic stenosis

Multiple VSDs are more prevalent in patients with tetralogy of Fallot and double outlet right ventricular defects.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Clinical presentation depends on the direction and volume of the VSD shunt, which is dictated by the size of the defect and the ratio of the pulmonary to systemic vascular resistance.

•

Infants may be asymptomatic at birth because of elevated pulmonary artery resistance. Over the first few weeks of life, pulmonary arterial resistance decreases, allowing more left-to-right shunting through the VSD, with subsequent increased flow into the lungs, left atrium, and left ventricle, causing left ventricular volume overload. Tachypnea, failure to thrive, and congestive heart failure will then ensue.

•

In adults with VSD, the shunt is left to right in the absence of pulmonary stenosis and pulmonary hypertension, and patients typically manifest with symptoms of heart failure (e.g., shortness of breath, orthopnea, and dyspnea on exertion).

•

A spectrum of physical findings may be seen including:

•

1.

Holosystolic murmur heard best along the left sternal border

2.

Systolic thrill

3.

Mid-diastolic rumble heard at the apex

4.

S3

5.

Rales

With the development of pulmonary hypertension: 1.

Augmented pulmonic component of S2

2.

Cyanosis, clubbing, right ventricular heave, and signs of right heart failure (seen in Eisenmenger's complex with reversal of the shunt in a right-to-left direction)

ETIOLOGY

•

Usually congenital (the focus of our review), but may occur post-myocardial infarction.

•

After acute myocardial infarction: rupture of the intraventricular septum typically occurs 3 to 5 days after the event, and occurs in up to 2% of the cases.

DIAGNOSIS The diagnosis of VSD is suspected by physical examination. Imaging studies, particularly transthoracic echocardiography with color Doppler, establish the diagnosis. DIFFERENTIAL DIAGNOSIS

Based on physical examination, the diagnosis of VSD may be confused with other causes of systolic murmurs such as mitral regurgitation, tricuspid regurgitation, aortic stenosis, pulmonary stenosis, and hypertrophic cardiomyopathy. WORKUP

Any person that is suspected of having a VSD should have an ECG, a chest x-ray, and an echocardiogram. LABORATORY TESTS

•

Laboratory tests are not specific, but may offer insight into the severity of the disease.

•

CBC may show polycythemia, especially in patients with Eisenmenger's complex.

•

Arterial blood gases may show hypoxemia.

IMAGING STUDIES

•

ECG findings vary according to the size of the VSD and whether pulmonary hypertension is present. In large VSDs with pulmonary hypertension, right axis deviation is seen along with evidence of right ventricular hypertrophy.

•

Chest x-ray findings in patients with VSD include:

•

1.

Cardiomegaly results from volume overload and directly relates to the magnitude of the shunt

2.

Enlargement of the proximal pulmonary arteries along with redistribution and pruning of the distal pulmonary vessels resulting from sustained pulmonary hypertension ( Fig. 1-288, A )

Echocardiography is the imaging modality of choice in the diagnosis of VSD. 1.

Two-dimensional echo and color Doppler displays the size and location of the VSD ( Fig. 1-288, B ).

2.

Continuous wave Doppler not only approximates the gradient between the left and right ventricle, but also estimates the pulmonary artery pressure.

3.

Magnitude of shunt can be determined by calculation of pulmonary to systemic flow ratio on echo.

•

Cardiac catheterization may confirm echocardiography findings in the measurement of right heart pressures and the calculation of the pulmonary to systemic flow ratio.

•

Ventriculography may help to locate the VSD.

FIGURE 1-288 A, Chest roentgenogram of a child with a large VSD, large pulmonary blood flow, and pulmonary hypertension, but only mild elevation of PVR. This is reflected in the evidence of left and right ventricular enlargement, enlargement of the main pulmonary artery, and marked increase in pulmonary blood flow. B, Apical four-chamber echocardiographic view of ventricular septal defect (large arrow). Small arrow points to interatrial septum. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. (A From Pacifico AD et al: Surgical treatment of ventricular septal defect. In Sabiston DC Jr, Spencer FC [eds]: Surgery of the chest, ed 5, Philadelphia, 1990, WB Saunders. B Courtesy Richard Humes, M.D., Associate Professor of Pediatrics, Director of Echocardiography Laboratory, Children's Hospital of Michigan, Detroit.)

TREATMENT The decision to close a VSD depends on its type, size, and shunt severity, as well as the patient's pulmonary vascular resistance, functional capacity, and associated valvular abnormalities. NONPHARMACOLOGIC THERAPY

•

In young children, small asymptomatic VSDs with a pulmonary to systemic blood flow ratio of =1.5:1 and no evidence of pulmonary hypertension can be observed.

•

Oxygen and low-salt diet is recommended in patients with congestive heart failure.

ACUTE GENERAL Rx

Surgery is indicated in:

•

Infants with congestive heart failure

•

Children between the ages of 1 and 6 with persistent VSD and a pulmonary to systemic blood flow ratio >2:1

•

Adults with VSD and flow ratios >1.5:1, pulmonary artery systolic pressure >50 mm Hg, increased LV and LA size, or deteriorating left ventricular function in the absence of irreversible pulmonary hypertension

•

Percutaneous transcatheter closure by Amplatzer occluder devices have been used with success for muscular VSD closure in small studies of congenital VSDs and anecdotally in postinfarct VSDs.

CHRONIC Rx

See “Acute General Rx.” DISPOSITION

•

The natural history of isolated VSD depends on the type of defect, its size, and associated abnormalities.

•

Approximately 75% to 80% of small VSDs close spontaneously by age 10 yr.

•

In patients with large VSDs, only 10% to 15% will close spontaneously.

•

Large VSDs left untreated may lead to arrhythmias, congestive heart failure, pulmonary hypertension, and Eisenmenger's complex.

•

Eisenmenger's complex carries a poor prognosis, with most patients dying before the age of 40 yr.

REFERRAL

All infants and children diagnosed with VSD should be referred to a pediatric cardiologist. Adults with VSD should be referred to an adult cardiologist. Cardiothoracic surgeons experienced in congenital heart disease surgery should be consulted if surgery is indicated.

PEARLS & CONSIDERATIONS COMMENTS

•

A loud murmur does not imply a large VSD. Small, hemodynamically insignificant VSDs can cause loud murmurs.

•

In Eisenmenger's complex, the right-to-left shunting across the VSD is usually not associated with an audible murmur.

•

Risk of patients with unrepaired VSD developing infective endocarditis is 4%. The risk is higher if aortic insufficiency is present.

•

Endocarditis prophylaxis is no longer indicated 6 months after a VSD repair without residual shunt, as per the updated 2007 AHA guidelines.

SUGGESTED READINGS Butera G, et al: Percutaneous closure of ventricular septal defects: state of the art. J Cardiovasc Med (Hagerstown) 2007; 8(1):39. Minette MS, Sahn DJ: Ventricular septal defects. Circulation 2006; 114(20):2190. Turner SW, et al: The natural history of ventricular septal defects. Arch Dis Child 1999; 81(5):413. Wilson W, et al: Prevention of infective endocarditis: guidelines from the American Heart Association.

Circulation 2007; 115:739.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vertebral Compression Fractures JEFFREY BORKAN, M.D., PH.D

BASIC INFORMATION DEFINITION

Vertebral compression fractures are defined as fractures of spinal vertebrae in which a bony surface is driven toward another bony surface. These fractures are classified as a radiographic reduction in vertebral body height of more than 15% to 20%. SYNONYMS

Thoracolumbar vertebral compression fractures Osteoporotic fractures

ICD9-CM CODES

805.8

Compression fracture, spine

805.4

Compression fracture, lumbar vertebra

805.2

Compression fracture, thoracic vertebra

733.13 Compression fracture, L2 vertebra EPIDEMIOLOGY & DEMOGRAPHICS

Approximately 700,000 vertebral compression fractures (VCFs) occur in the U.S. each year, affecting approximately 25% of postmenopausal women. The prevalence increases with age, reaching a peak of 40% in women greater than 80 years of age. Compression fractures are also a major concern among men, though VCF rates are lower. RISK FACTORS:

•

Modifiable: tobacco or alcohol use, osteoporosis, estrogen deficiency (early menopause, bilateral ovariectomy, premenopausal amenorrhea for more than 1 year), frailty, impaired vision, abusive situations, inadequate physical activity, low BMI, and dietary deficiency of vitamin D or calcium

•

Nonmodifiable: advanced age, female, dementia, Caucasian, history of fractures in adulthood and among first-degree relatives, falls

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Asymptomatic: most VCFs are asymptomatic, except for height loss or kyphosis (dowager hump). Kyphosis is often a sign of multiple VCF.

•

Symptomatic: often present as acute back pain after activity (e.g., bending, lifting) or coughing; neck strain and rib pain may also be present.

ETIOLOGY

•

Vertebral compression fractures take place when the combination of bending and axial loads on the spine exceed the strength of the vertebral body.

•

Primary etiology is osteoporosis.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hyperparathyroidism

•

Osteomalacia

•

Granulomatous diseases (e.g., tuberculosis)

•

Hematologic/oncologic diseases (e.g., multiple myeloma, malignancy)

WORKUP

•

Only one third of VCFs are diagnosed.

•

VCF can be clinical suspected from history and physical alone.

•

There may or may not be a specific injury or remembered event.

LABORATORY TESTS

Tests to rule out infection or cancer may be helpful, such as ESR, CBC, alkaline phosphatase, and C-reactive protein, but can be reserved for individuals for whom there is a clinical suspicion. IMAGING STUDIES

•

Plain frontal and lateral radiographs (x-rays) are the initial imaging method ( Fig. 1-289 ) and may be sufficient, particularly when no neurologic abnormalities are present. MRI and CT scans may be uncomfortable or painful for the patient, especially in the acute phase.

•

Computed tomography (CT scans), though not routinely necessary, can be helpful for visualizing fractures not seen on plain films, evaluating the integrity of the posterior vertebral wall, ruling out other causes of back pain, detecting spinal canal narrowing, and assessing instability.

•

Magnetic resonance imaging (MRI) may be useful when spinal cord compression is suspected, if neurologic symptoms are present, or to distinguish malignancy from osteoporosis (such as in patients younger than 55 years of age with a VCR after minimum or no trauma).

•

Bone density studies may be helpful in determining the severity of osteoporosis, a key risk fracture for predicting future fractures.

FIGURE 1-289 Dowager's hump. A, Marked thoracic kyphosis due to multiple osteoporotic fractures in an elderly woman with (B) corresponding radiograph. (From Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH [eds]: Rheumatology, ed 3, St. Louis, 2003, Mosby.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Physical therapy.

•

External back braces.

•

Exercise programs—getting the person active as soon as possible is extremely important both short and long term.

ACUTE GENERAL Rx

•

Analgesics for pain control, including acetaminophen and opioids (oral or parenteral). Prevention of constipation is important with opioids.

•

Nonsteroidal anti-inflammatory drugs are helpful but must be used with caution in the elderly or when contraindicated.

•

Muscle relaxants used judiciously.

•

Carefully selected patients who do not respond to conservative therapy or who have severe pain may be considered for percutaneous vertebroplasty (acrylic bone cement is injected into the affected vertebral body in an effort to stabilize the fracture and reduce pain) and kyphoplasty (a high-pressure inflatable bone tamp or balloon is expanded before injection of bone cement into the cavity in the fractured vertebral body). Although potentially useful procedures, prospective studies will need to be performed comparing long-term outcomes and risks to conventional treatment.

CHRONIC Rx

Osteoporosis should be treated: reduction of risk factors (e.g., smoking and alcohol), diet exercise, calcium and vitamin D supplements, and consideration of medications that treat osteoporosis (e.g., bisphosphonates). REFERRAL

Referral is indicated for neurologic abnormalities, unremitting pain, instability, continued disability, or when the investigation of the cause of the fracture reveals serious underlying pathology.

PEARLS & CONSIDERATIONS COMMENTS

•

Vertebral compression fractures should be suspected in anyone older than 50 years of age with the acute onset of low back pain.

•

Solitary vertebral fractures higher than T7 are unusual and may be suspicious for other pathologic etiologies.

•

Diagnosing and treating osteoporosis reduces the incidence of VCRs.

•

Getting people with VCF physically active as soon as possible will be efficacious both acutely and in the long term.

•

In general, VCF can perhaps be best managed through a partnership of the patient, the primary care physician, orthopedist, physical therapist, dietician, and social worker.

PREVENTION

Reducing the effects of modifiable risk factors is key. SUGGESTED READINGS Banerjee S, et al: Back stab: percutaneous vertebroplasty in severe back pain. Can Fam Physician 2007; 53(7):1169. Brunton S, et al: Vertebral compression fractures in primary care: recommendations from a consensus panel. J Fam Pract 2005; 54(b):781-788. Garfin SR, Reilley MA: Minimally invasive treatment of osteoporotic vertebral body compression fractures. Spine J 2002; 1:76-80.

Mazanec DJ, et al: Vertebral compression fractures: manage aggressively to prevent sequelae. Cleve Clin J Med 2003; 70(b):147-156. Old JL, Calvert M: Vertebral compression fractures in the elderly. Am Fam Physician 2004; 69:111-116.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vestibular Neuronitis JUDITH NUDELMAN, M.D.

BASIC INFORMATION DEFINITION

Vestibular neuronitis is a syndrome of sudden-onset, often severe, prolonged vertigo of peripheral origin. SYNONYMS

Labyrinthitis, vestibular neuronitis, acute neuritis

ICD-9CM CODES

078.81 Vestibular neuronitis 386.12 Neuronitis, vestibular EPIDEMIOLOGY & DEMOGRAPHICS

Viral origin supported by the fact that it occurs in epidemics, may affect several family members, and occurs more commonly in spring and early summer. Male-to-female ratio is similar. Thought to result from selective inflammation of the vestibular nerve; etiology presumed to be viral. There is selective damage to the superior part of the vestibular labyrinth, supplied by the superior division of the vestibular nerve. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Course: develops over period of hours, resolves over periods of days, though with frequent long-term sequela; may have viral prodrome.

•

Symptoms of vertigo, spontaneous peripheral nystagmus, positive head-thrust test, imbalance. Patient reports intense sensation of rotation, difficulty standing and walking, tends to veer toward affected side, autonomic symptoms with pallor, sweating, nausea and vomiting.

ETIOLOGY

Thought to be viral in origin, possibly thought to be due to herpes zoster, but trial of valacyclovir with and without methylprednisolone showed no efficacy for valacyclovir, but efficacy for the steroid.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Labyrinthitis: similar etiology, but includes hearing loss

•

Labyrinthine infarction

•

Perilymph fistula

•

Brainstem and cerebellar infarction

•

Migraine-associated vertigo

•

Multiple sclerosis

WORKUP

Head-thrust test: grasp patient's head, apply brief small-amplitude rapid head turn, first to one side and then the other; patient fixates on examiner's nose: positive test is lack of corrective eye movements “saccades” on affected side. LABORATORY TESTS

•

ENG: testing of the vestibular apparatus with physical challenges, unilateral lack of caloric response

•

Audiogram: normal

IMAGING STUDIES

Brain imaging: CT or MRI—normal

TREATMENT NONPHARMACOLOGIC THERAPY

Vestibular exercises, when tolerated, will accelerate recovery. ACUTE GENERAL Rx

•

Methylprednisolone: 100 mg days 1 to 3, 80 mg days 4 to 6, 60 mg days 7 to 9, 40 mg days 10 to 12, 20 mg days 13 to 15, 10 mg days 14 to 16, 5 mg days 18 to 20

•

Antihistamines: meclizine, dimenhydrinate, promethazine

•

Anticholinergics: scopolamine

•

Antidopaminergics: droperidol, prochlorperazine

•

AntiGABA agents: diazepam, valium

CHRONIC Rx

•

Vestibular rehabilitation exercises

•

AntiGABA agents

•

Antihistamines

DISPOSITION

Most patients able to be treated as outpatients, but if dehydrated due to severe vomiting may require brief parenteral therapy. REFERRAL

•

ENT: if diagnosis uncertain, additionally these patients are at risk for BPPV subsequently, also symptoms may linger.

•

Neurology: if question of central origin or migraine.

PEARLS & CONSIDERATIONS COMMENTS

Utility of steroids questioned until study reported in NEJM 7/04 demonstrated steroids improve recovery of vestibular function. Often damage to labyrinth is permanent, but compensated. These patients are at risk to develop BPPV due to damaged vestibular apparatus. Patients recover from dramatic acute symptoms, but subtle vestibular deficits may linger for prolonged period, if not indefinitely. PREVENTION

None PATIENT/FAMILY EDUCATION

Vestibular Disorders Association: http://www.vestibular.org SUGGESTED READINGS Baloh RW: Vestibular neuritis. N Eng J Med 2003; 348:1027-1032. Strupp M, et al: Methylprednisolone, valacyclovir or the combination for vestibular neuritis. N Eng J Med 2004; 351(b):354-361. Timothy Hain, M.D., director of Balance Center at Northwestern University, maintains http://www.tchain.com .

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vitiligo FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Vitiligo is the acquired loss of epidermal pigmentation characterized histologically by the absence of epidermal melanocytes.

ICD-9CM CODES

709.1 Vitiligo EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 1% of the population PREDOMINANT AGE: Can begin at any age, but age at onset is under 20 yr for half the patients GENETICS: Positive family history in 25%-30% PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Hypopigmented and depigmented lesions ( Fig. 1-290 ) favor sun-exposed regions, intertriginous areas, genitalia, and sites over bony prominences (type A vitiligo).

•

Areas around body orifices are also frequently involved.

•

The lesions tend to be symmetric.

•

Occasionally the lesions are linear or pseudodermatomal (type B vitiligo).

•

Vitiligo lesions may occur at trauma sites (Koebner's phenomenon).

•

The hair in affected areas may be white.

•

The margins of the lesions are usually well demarcated, and when a ring of hyperpigmentation is seen, the term trichrome vitiligo is used.

•

The term marginal inflammatory vitiligo is used to describe lesions with raised borders.

•

Initially the disease is limited, but the lesions tend to become more extensive over the years.

•

Type B vitiligo is more common in children.

•

Vitiligo may begin around pigmented nevi, producing a halo (Sutton's nevus); in such cases the central nevus often regresses and disappears over time.

FIGURE 1-290 Multiple, sharply demarcated, symmetric, depigmented areas of vitiligo. (From Behrman RE: Nelson textbook of pediatrics, Philadelphia, 2006, WB Saunders.)

ETIOLOGY & PATHOGENESIS

Three pathophysiologic theories:

•

Autoimmune theory (autoantibodies against melanocytes)

•

Neural theory (neurochemical mediator selectively destroys melanocytes)

•

Self-destructive process whereby melanocytes fail to protect themselves against cytotoxic melanin precursors

Although vitiligo is considered to be an acquired disease, 25% to 30% is familial; the mode of transmission is unknown (polygenic or autosomal dominant with incomplete penetrance and variable expression). Associated disorders:

•

Alopecia areata

•

Type 1 diabetes mellitus

•

Adrenal insufficiency

•

Hyper- and hypothyroidism

•

Mucocutaneous candidiasis

•

Pernicious anemia

•

Polyglandular autoimmune syndromes

•

Melanoma

DIAGNOSIS DIFFERENTIAL DIAGNOSIS (OTHER HYPOPIGMENTATION DISORDERS)

Acquired:

•

Chemical-induced

•

Halo nevus

•

Idiopathic guttate hypomelanosis

•

Leprosy

•

Leukoderma associated with melanoma

•

Pityriasis alba

•

Postinflammatory hypopigmentation

•

Tinea versicolor

•

Vogt-Koyanagi syndrome (vitiligo, uveitis, and deafness)

Congenital:

•

Albinism, partial (piebaldism)

•

Albinism, total

•

Nevus anemicus

•

Nevus depigmentosus

•

Tuberous sclerosis

WORKUP

•

Physical examination

•

Wood's light examination may enhance lesions in light-skinned individuals

TREATMENT

•

Treatment indicated primarily for cosmetic purposes when depigmentation causes emotional or social distress. Depigmentation is more noticeable in darker complexions.

•

Cosmetic masking agents (Dermablend, Covermark) or stains (Dy-O-Derm, Vita-Dye).

•

Sunless tanning lotions (dihydroxyacetone).

•

Repigmentation (achieved by activation and migration of melanocytes from hair follicles; therefore skin with little or no hair responds poorly to treatment).

•

PUVA (psoralen phototherapy): oral or topical psoralen administration followed by phototherapy with UVA (150 to 200 treatments required over 1 to 2 yr).

•

Psoralens and sunlight (Puvasol).

•

Topical midpotency steroids (e.g., triamcinolone 0.1% or desonide 0.05% cream qd for 3 to 4 mo).

•

Intralesional steroid injection.

•

Systemic steroids (betamethasone 5 mg qd on two consecutive days per wk for 2 to 4 mo).

•

Total depigmentation (in cases of extensive vitiligo) with 20% monobenzyl ether or hydroquinone. This is a permanent procedure, and patients will require lifelong protection from sun exposure.

•

Topical immunomodulators (tacrolimus, pimecromilus) can also induce repigmentation of vitiliginous skin lesions. Their potential for systemic immunosuppression or increased risk of skin or other malignancies remains to be defined.

•

Calcipotriol, a synthetic analog of vitamin D3, has also been used in combination with UV light or clobetasol, with limited results.

SUGGESTED READINGS Grimes PE: New insights and new therapies in vitiligo. JAMA 2005; 293:730.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Von Hippel-Lindau Disease WEN-Y. WU-CHEN, M.D.

BASIC INFORMATION DEFINITION

Von Hippel-Lindau disease (VHL) is a rare autosomal dominant inherited disease characterized by the formation of hemangioblastomas, cysts, and malignancies involving multiple organs and systems. SYNONYMS

Hippel-Lindau syndrome, cerebelloretinal hemangioblastomatosis, retinocerebellar angiomatosis

ICD-9CM CODES

759.6 von Hippel-Lindau disease EPIDEMIOLOGY & DEMOGRAPHICS

•

The incidence of VHL is 1 case/36,000 people.

•

Mean age at diagnosis is 26 years because of clinical manifestations, but it can occur from infancy to the seventh decade of life.

•

In the U.S. approximately 7000 people are affected.

•

Affected individuals are at risk of developing renal cell carcinoma, pheochromocytoma, pancreatic islet cell tumor, endolymphatic sac tumor, and hemangioblastomas of the cerebellum and retina.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

•

•

•

•

•

•

•

Retinal angiomas (60%) 1.

Usually occurs by age 25

2.

Often multifocal and bilateral

3.

Detached retina

4.

Glaucoma

5.

Blindness

CNS hemangioblastomas (59%) 1.

Cerebellum is the most common site followed by the spine and medulla

2.

Usually multiple, and mean age at diagnosis is 25 years

3.

Headache, ataxia, slurred speech, nystagmus, vertigo, nausea, and vomiting

Renal cysts (~60%) and clear cell renal cell carcinoma (25% to 45%) 1.

Usually occurs by the age of 40

2.

May be asymptomatic or cause abdominal and flank pain

3.

Renal cell carcinoma is bilateral in 75% of patients

Pancreatic cysts 1.

Usually asymptomatic

2.

Large cysts can cause biliary obstructive symptoms

3.

Diarrhea and diabetes may develop if enough of the pancreas is replaced by cysts

Pheochromocytoma (7% to 18%) 1.

Bilateral in 50% to 80% of cases

2.

Hypertension, palpitations, sweating, and headache

3.

Commonly occurs with pancreatic islet cell tumors

Papillary cystadenoma of the epididymis (10% to 25% of men with VHL) 1.

Palpable scrotal mass

2.

May be unilateral or bilateral

Papillary cystadenoma of the broad ligaments (unknown incidence) 1.

Usually asymptomatic

2.

Reported symptoms include pain, dyspareunia, menorrhagia

Endolymphatic sac tumors of the middle ear 1.

Ataxia

2.

Loss of hearing

3.

Facial paralysis

ETIOLOGY

VHL disease is primarily caused by a mutation of the von Hippel-Lindau gene located on the short arm of chromosome 3. The VHL disease gene codes for a cytoplasmic protein that functions in tumor suppression.

DIAGNOSIS

•

Established in presence of a positive family history, a single retinal or cerebellar hemangioblastoma, or a visceral lesion (e.g., renal cell carcinoma, pheochromocytoma, pancreatic cysts or tumor).

•

If no clear family history is present, two or more hemangioblastomas or one hemangioblastoma with a visceral lesion are required to make the diagnosis.

•

Screening family members is essential in the early detection of VHL disease.

WORKUP

Screening laboratory, ophthalmoscopic, and imaging studies to look for sites of involvement. LABORATORY TESTS

•

CBC may reveal erythrocytosis requiring periodic phlebotomies

•

Electrolytes, BUN, and creatinine

•

Urine for norepinephrine, epinephrine, and vanillylmandelic acid looking for pheochromocytoma

IMAGING STUDIES

•

Indirect and direct ophthalmoscopy, fluorescein angiography, and tonometry are studies used in screening for retinal angiomas and glaucoma.

•

CT scan of the abdomen is used in the screening, detection, and monitoring of patients with renal cysts or tumors, pheochromocytomas, pancreatic cysts, and tumors. 1.

Renal cysts grow on average 0.5 cm/yr.

2.

Renal tumors grow on average 1.5 cm/yr.

3.

CT scans are done every 6 mo for the first 2 yr and every yr for life in patients who have had surgery for renal cell carcinoma.

•

MRI with gadolinium is used for screening and evaluation of CNS and spinal hemangioblastomas, endolymphatic sac tumors, and pheochromocytomas.

•

Angiography may be done before CNS surgery.

TREATMENT NONPHARMACOLOGIC THERAPY

Genetic counseling ACUTE GENERAL Rx

•

Laser photocoagulation and cryotherapy is used in patients with retinal angiomas to prevent blindness.

•

For cerebellar hemangioblastomas the treatment is surgery. External-beam radiation and stereotactic radiosurgery can also be done.

•

For renal tumors, surgery is delayed until one of the renal tumors reaches 3 cm in diameter. Nephronsparing surgery is the preferred approach.

•

Nephrectomy is indicated in patients with end-stage renal disease requiring dialysis because of the malignant potential of the disease.

•

Pancreatic islet cell tumors usually require surgical removal.

•

Adrenalectomy for pheochromocytoma.

CHRONIC Rx

•

Dialysis has been delayed in many patients because of nephron-sparing surgery.

•

Renal transplantation is usually delayed for 1 yr after bilateral nephrectomy for renal tumors to ensure that no metastases have occurred.

DISPOSITION

Median life expectancy is 49 yr of age. REFERRAL

Geneticist, neurosurgeon, urologist, nephrologist, ophthalmologist, otolaryngologist, neurologist, endocrinologist, and radiation oncologist.

PEARLS & CONSIDERATIONS The most common cause of death is renal cell carcinoma. COMMENTS

More information for patients can be obtained at von Hippel-Lindau Family Alliance. SUGGESTED READINGS Couch V, et al: von Hippel-Lindau Disease. Mayo Clin Proc 2000; 75:265. Evans JP et al: von Hippel-Lindau disease, eMedcine, 2006. Lonser RR, et al: Von Hippel-Lindau disease. Lancet 2003; 361:2059.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Von Willebrand's Disease FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Von Willebrand's disease is a congenital disorder of hemostasis characterized by defective or deficient von Willebrand factor (vWF). There are several subtypes of von Willebrand's disease. The most common type (80% of cases) is type I, which is caused by a quantitative decrease in von Willebrand factor; type IIA and type IIB are results of qualitative protein abnormalities; type III is a rare autosomal recessive disorder characterized by a near complete quantitative deficiency of vWF. Acquired von Willebrand's disease (AvWD) is a rare disorder that usually occurs in elderly patients and usually presents with mucocutaneous bleeding abnormalities and no clinically meaningful family history. It is often accompanied by a hematoproliferative or autoimmune disorder. Successful treatment of the associated illness can reverse the clinical and laboratory manifestations. SYNONYMS

Pseudohemophilia

ICD-9CM CODES

286.4 von Willebrand's disease EPIDEMIOLOGY & DEMOGRAPHICS

•

Autosomal dominant disorder

•

Most common inherited bleeding disorder

•

Prevalence is 1% to 2 % in general population, according to screening studies; estimates based on referral for symptoms of bleeding suggest a prevalence of 30 to 100 cases per million

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Generally normal physical examination

•

Mucosal bleeding (gingival bleeding, epistaxis) and GI bleeding may occur

•

Easy bruising

•

Postpartum bleeding, bleeding after surgery or dental extraction, menorrhagia

ETIOLOGY

Quantitative or qualitative deficiency of vWF (see “Definition”)

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Platelet function disorders, clotting factor deficiencies WORKUP

•

Laboratory evaluation (see “Laboratory Tests”)

•

Initial testing includes PTT (increased), platelet count (normal), and bleeding time (prolonged)

•

Subsequent tests include vWF level (decreased), factor VIII:C (decreased), and ristocetin agglutination (increased in type II B) ( Table 1-52 )

TABLE 1-52 -- Genetic and Laboratory Findings in von Willebrand's Disease PARAMETER Type

BT VIII-c vw-Ag R-cof Ripa Multimer Structure Mode of Inheritance

I (classic) P

R

R

R

R

N

AD

II A

P

N/R

N/R

R

R

Abn

AD

B

P

N/R

N/R

N/R

I

Abn

AD

III

P

R

R

R

R

Variable

AR

From Behrman RE: Nelson textbook of pediatrics, ed 17, Philadelphia, 2004, WB Saunders. Abn, Abnormal; AD, autosomal dominant; AR, autosomal recessive; BT, bleeding time; I, increased; N, normal; N/R, normal or reduced; P, prolonged; R, reduced; R-Cof, ristocetin cofactor; RIPA, ristocetin-induced platelet aggregation (agglutination); vW-Aq, von Willebrand antigen (protein); VIII-C, factor VIII coagulant activity.

LABORATORY TESTS

•

Normal platelet number and morphology

•

Prolonged bleeding time

•

Decreased factor VIII coagulant activity

•

Decreased von Willebrand factor antigen or ristocetin cofactor

•

Normal platelet aggregation studies

•

Type II A von Willebrand can be distinguished from type I by absence of ristocetin cofactor activity and abnormal multimer

•

Type IIB von Willebrand is distinguished from type I by abnormal multimer

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoidance of aspirin and other NSAIDs.

•

Evaluation for likelihood of bleeding (with measurement of bleeding time) before surgical procedures. When a patient undergoes surgery or receives repeated therapeutic doses of concentrates, factor VIII activity should be assayed every 12 hr on the day a dose is administered and every 24 hr thereafter.

GENERAL Rx

•

The mainstay of treatment in von Willebrand's disease is the replacement of the deficient protein at the time of spontaneous bleeding, or before invasive procedures are performed.

•

Desmopressin acetate (DDAVP) is useful to release stored vWF from endothelial cells. It is used to cover minor procedures and traumatic bleeding in mild type I von Willebrand's disease. Dose is 0.3 g/kg in 100 ml of normal saline solution IV infused >20 min. DDAVP is also available as a nasal spray (dose of 150 g spray administered to each nostril) as a preparation for minor surgery and management of minor bleeding episodes. DDAVP is not effective in type IIA von Willebrand's disease and is potentially dangerous in type IIB (increased risk of bleeding and thrombocytopenia).

•

In patients with severe disease, replacement therapy in the form of cryoprecipitate is the method of choice. The standard dose is 1 bag of cryoprecipitate per 10 kg of body weight.

•

Factor VIII concentrate rich in vWF (Humate-P, Armour) is useful to correct bleeding abnormalities in type IIA, IIB and type III von Willebrand's disease without alloantibodies. Alloantibodies that inactivate von Willebrand factor and form circulating immune complexes develop in 15% of patients with type III von Willebrand's disease who have received multiple transfusions. In these patients, recombinant factor VIII is preferred because autoantibodies can elicit life-threatening anaphylactic reactions because of complement activation by immune complexes.

•

Life-threatening hemorrhage unresponsive to therapy with cryoprecipitate or factor VIII concentrate may require transfusion of normal platelets.

SUGGESTED READINGS Mannucci PM: Treatment of von Willebrand's disease. N Engl J Med 2004; 351:683.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vulvar Cancer GIL FARKASH, M.D., RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Vulvar cancer is an abnormal cell proliferation arising on the vulva and exhibiting malignant potential. The majority are of squamous cell origin; however, other types include adenocarcinoma, basal cell carcinoma, sarcoma, and melanoma. SYNONYMS

Squamous cell carcinoma of the vulva (90%) Basal cell carcinoma of the vulva Adenocarcinoma of the vulva Melanoma of the vulva Bartholin gland carcinoma Verrucous carcinoma of the vulva Vulvar sarcoma

ICD-9CM CODES

184.4 Vulvar neoplasm EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 1.8 cases/100,000 persons PREVALENCE: Vulvar cancer is uncommon. It comprises 4% of malignancies of the female genital tract. It is the fourth most common gynecologic malignancy. MEAN AGE AT DIAGNOSIS: Predominantly a disease of menopause. Mean age at diagnosis is 65 yr.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Vulvar pruritus or pain is present.

•

May produce a malodor or discharge or present as bleeding.

•

Raised lesion, may have fleshy, ulcerated, leukoplakic, or warty appearance; may have multifocal lesions.

•

Lesions are usually located on labia majora, but may be seen on labia minora, clitoris, and perineum.

•

The lymph nodes of groin may be palpable.

ETIOLOGY

•

The exact etiology is unknown.

•

Vulvar intraepithelial neoplasia has been reported in 20% to 30% of invasive squamous cell carcinoma of the vulva, but the malignant potential is unknown.

•

Human papillomavirus is found in 30% to 50% of vulvar carcinoma, but its exact role is unclear.

•

Chronic pruritus, wetness, industrial wastes, arsenicals, hygienic agents, and vulvar dystrophies have been implicated as causative agents.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Lymphogranuloma inguinale

•

Tuberculosis

•

Vulvar dystrophies

•

Vulvar atrophy

•

Paget's disease

WORKUP

•

Diagnosis is made histologically by biopsy

•

Thorough examination of the lesion and assessment of spread

•

Possible colposcopy of adjacent areas

•

Cytologic smear of vagina and cervix

•

Cystoscopy and proctosigmoidoscopy may be necessary

IMAGING STUDIES

•

Chest radiography

•

CT scan and MRI for assessing local tumor spread

TREATMENT NONPHARMACOLOGIC THERAPY

•

Treatment is individualized depending on the stage of the tumor.

•

Stage I tumors with 1 mm stromal invasion are treated with complete local excision with groin node dissection.

•

Stage II tumors require radical vulvectomy with bilateral groin node dissection.

•

Advanced-stage disease may require the addition of radiation and chemotherapy to the surgical regimen.

•

Section III describes a treatment algorithm for management of vulvar cancer.

DISPOSITION

Five-year survival ranges from 90% for stage I to 15% for stage IV. REFERRAL

Vulvar cancer should be managed by a gynecologic oncologist and radiation oncologist.

EVIDENCE

The relative rarity of vulvar malignancy means that randomized controlled trials of therapeutic modalities are uncommon; most studies are retrospective reviews and observational studies. Surgery remains the standard treatment for early vulval cancer. A systematic review that compared individualized treatment with standard extensive surgery in terms of effectiveness and safety identified two observational studies suitable for inclusion. Even so, on the basis of the available evidence, the reviewers felt able to draw a number of conclusions, as below.[[1]] Patients with T1-2 tumor can be safely treated with a radical local vulvar excision.[[1]] Patients with cT1-2N0M0 cancer can probably be safely treated by the triple incision technique rather than by en-bloc dissection, because the incidence of skin bridge recurrence is low after triple incision surgery.[[1]]

Patients with a lateral cT1N0M0 tumor can probably be treated safely with an ipsilateral groin lymph node dissection.[[1]] Femoral lymph node dissection should not be omitted, even in patients with a very favorable prognosis.[[1]]

In patients with early vulvar cancer, primary radiotherapy to the groin is associated with a greater risk of recurrence but lower morbidity than primary surgery to the groin. Recurrence of tumor after primary radiotherapy to the inguinofemoral lymph nodes appears to be more

common after primary radiotherapy than after surgery.[[1]] However, morbidity after radiotherapy is lower than after surgery, both in the short term and the long term.[[1]] Uncontrolled clinical trials suggest that primary radiotherapy in early vulvar cancer results in fewer recurrences in the groin than a wait-and-see policy.[[1]]

Evidence-Based Referencece 1. Ansink A, van der Velden J, Collingwood M: Surgical interventions for early squamous cell carcinoma of the vulva. Cochrane Database Syst Rev 1999; 4:

SUGGESTED READINGS Canavan TP, Cohen D: Vulvar cancer. Am Fam Physician 2002; 66(7):1269. Coleman RL, Santoso JT: Vulvar carcinoma. Curr Treat Opt Oncol 2000; 1(2):177. Grandys Jr EC, Aroris JV: Innovations in the management of vulvar carcinoma. Curr Opin Obstet Gynecol 2000; 12(1):15.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vulvovaginitis, Bacterial JULIE ANNE SZUMIGALA, D.O.,, RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Bacterial vulvovaginitis is inflammation affecting the vagina, only rarely affecting the vulva, caused by anaerobic and aerobic bacteria. SYNONYMS

Bacterial vaginosis Gardnerella vaginalis Haemophilus vaginalis Corynebacterium vaginalis

ICD-9CM CODES

616.10 Vulvovaginitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Most prevalent form of vaginal infection of reproductive age women in the U.S.

•

32% to 64% in patients visiting STD clinics

•

12% to 25% in other clinic populations

•

10% to 26% in patients visiting obstetric clinics

•

May be associated with adverse pregnancy outcomes: premature rupture of membranes, preterm labor, preterm birth

•

Organisms frequently found in postpartum or postcesarean endometritis

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

>50% of all women may be without symptoms.

•

Unpleasant, fishy, or musty vaginal odor in about 50% to 70% of all patients. Odor exacerbated immediately after intercourse or during menstruation.

•

Vaginal discharge is increased.

•

Vaginal itching and irritation occur.

ETIOLOGY

•

Synergistic polymicrobial infection characterized by an overgrowth of bacteria normally found in the vagina

•

Anaerobics: Bacteroides spp., Peptostreptococcus spp., Mobiluncus spp.

•

Facultative anaerobes: G. vaginalis, Mycoplasma hominis

•

Concentration of anaerobic bacteria increased to 100 to 1000 times normal

•

Lactobacilli are absent or greatly reduced

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Fungal vaginitis

•

Trichomonas vaginitis

•

Atrophic vaginitis

•

Cervicitis

WORKUP

•

Pelvic examination

•

Speculum examination

•

Normal saline and 10% KOH slide of discharge

•

Amsel criteria for diagnosis (three of four should be present):

•

1.

pH >4.5

2.

Clue cells (epithelial cells covered with bacteria) on saline solution slide

3.

Positive whiff test on 10% KOH

4.

Homogeneous, white, adherent discharge

Section III, “Vaginal Discharge,” describes the evaluation of discharge

TREATMENT ACUTE GENERAL Rx

•

Metronidazole 500 mg PO bid × 7 days, >90% cure rate

•

Metronidazole 2 g PO × 1 day, 67% to 92% cure rate

•

Metronidazole gel 5 g, intravaginal bid × 5 days

•

Clindamycin 2% cream 5 g, intravaginal qd × 7 days

•

Clindamycin 300 mg PO bid × 7 days in pregnancy

CHRONIC Rx

Clindamycin 300 mg PO bid × 7 days; cure rate similar to those achieved with metronidazole Related to adverse pregnancy outcomes

•

Metronidazole 250 mg PO bid × 7 days

•

Metronidazole zympoxidase

•

Clindamycin 300 mg PO bid × 7 days

•

Good hygiene: avoidance of douching, harsh shower gels, bubble baths; cotton underwear

DISPOSITION

•

Reevaluate if not cured with treatment

•

Recurrence fairly common

REFERRAL

Refer to obstetrician/gynecologist for recurrence or pregnant patient with bacterial vaginosis

PEARLS & CONSIDERATIONS COMMENTS

Treating sexual partners has failed to demonstrate a benefit.

EVIDENCE

Higher cumulative cure rates have been found at 3 to 4 weeks for a 7-day regimen of metronidazole (500 mg twice daily) than with a single dose (2 g).[[1]] The limited evidence comparing oral vs. intravaginal treatment and metronidazole vs. clindamycin concludes that there is little difference in outcome between the two agents.[[2]] Good-quality trials have shown that antibiotic therapy is effective at eradicating bacterial vaginosis during pregnancy. However, evidence does not support treating asymptomatic women to prevent preterm birth, but for women with previous preterm delivery, it may reduce the risk of preterm rupture of membranes and low birth weight.[[3]]

Evidence-Based Referenceces 1. Joesoef MR, Schmid GP: Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 1999; 28(suppl 1):S57.Reviewed in: Clin Evid 13:1968, 2005. 2. Joesoef MR, Schmid G: Bacterial vaginosis. Clin Evid, 13. London: BMJ Publishing Group; 2005:1968. 3. McDonald H, et al: Antibiotics for treating bacterial vaginosis in pregnancy (Cochrane Review). Cochrane Database Syst Rev 2005; 1:

SUGGESTED READINGS Centers for Disease Control and Prevention: 2002 Guidelines for treatment of sexually transmitted diseases. MMWR, Morb Mortal Wkly Rep 2002; 51(RR-6):

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vulvovaginitis, Estrogen-Deficient JULIE ANNE SZUMIGALA, D.O.,, RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Estrogen-deficient vulvovaginitis is the irritation and/or inflammation of the vulva and vagina because of progressive thinning and atrophic changes secondary to estrogen deficiency ( Fig. 1-291 ).

FIGURE 1-291 Advanced postmenopausal atrophy of the vulva in a 72-year-old woman. (From Symonds EM, Macpherson MBA: Color atlas of obstetrics and gynecology, St Louis, 1994, Mosby.)

SYNONYMS

Atrophic vaginitis

ICD-9CM CODES

616.10 Vulvovaginitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Seen most often in postmenopausal women

•

Average age of menopause is 52 yr

•

In 1990, there were 36 million women 50 yr of age or older

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Thinning of pubic hair, labia minora and majora

•

Decreased secretions from the vestibular glands, with vaginal dryness

•

Regression of subcutaneous fat

•

Vulvar and vaginal itching

•

Dyspaereunia

•

Dysuria and urinary frequency

•

Vaginal spotting

ETIOLOGY

Estrogen deficiency

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Infectious vulvovaginitis

•

Squamous cell hyperplasia

•

Lichen sclerosus

•

Vulvar malignancy

•

Vaginal malignancy

•

Cervical and endometrial malignancy

WORKUP

•

Pelvic examination

•

Speculum examination

•

Pap smear

•

Possible endometrial biopsy if bleeding

LABORATORY TESTS

FSH and estradiol: generally after menopause, estradiol 40 mIU/ml

TREATMENT ACUTE GENERAL Rx

•

Premarin 0.625 mg PO qd.

•

Estraderm patch 0.05 mg × 2 per week.

•

If uterus present: 1.

Estrogen + 2.5 mg PO Provera qd or

2.

Estrogen + 10 mg PO Provera × 10 days each mo

•

Conjugated estrogen vaginal cream intravaginally. Estradiol vaginal cream 0.01%. 2 to 4 g/day × 2 wk then 1 to 2 g/day × 2 wk then 1 to 2 g × 3 days/wk

•

Vagifen (estradiol vaginal tablets) 25 mg inserted intravaginally daily for 2 wk then twice weekly. May take up to 12 wk to feel the full benefits of the medication.

•

Conjugated estrogen vaginal cream: 2-4 g qd (3 wk on, 1 wk off) for 3 to 5 mo.

CHRONIC Rx

See “Acute General Rx.” May discontinue vaginal estrogen cream once symptoms alleviate. DISPOSITION

The symptoms should be improved with the therapy. Caution for vaginal bleeding if uterus present REFERRAL

To obstetrician/gynecologist if vaginal bleeding

EVIDENCE

A systematic review comparing intravaginal creams, pessaries/tablets, and the estradiol-releasing vaginal ring in postmenopausal women found significant differences favoring the cream, ring, and tablets compared with placebo or moisturizing gel. Creams, tablets, and the estradiol ring were equally effective. Some trials noted significant side effects with the cream (uterine bleeding, breast pain, perineal pain, endometrial overstimulation).[[1]] Estrogen therapy effectively decreases the frequency and severity of menopausal hot flashes as well as those symptoms related to vaginal and urethral atrophy. There is little to choose between the available estrogens now licensed, although some patients have ethical objections to conjugated equine estrogens, which are derived from the urine of pregnant mares. There is no evidence that estriol would be any safer in terms of risk of heart disease, heart attacks, strokes, or breast cancer.[[2]],[[3]]

Evidence-Based Referenceces 1. Suckling J, Lethaby A, Kennedy R: Local oestrogen for vaginal atrophy in postmenopausal women (Cochrane Review). Cochrane Database Syst Rev 2003; 4: 2. Grady D et al; HERS Research Group: Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:49. 3. Hulley S et al; HERS Research Group: Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:58.

AUTHORS: JULIE ANNE SZUMIGALA, M.D., and RUBEN ALVERO, M.D. Vulvovaginitis, Fungal

BASIC INFORMATION DEFINITION

Fungal vulvovaginitis is the inflammation of vulva and vagina caused by Candida spp. SYNONYMS

Monilial vulvovaginitis

ICD-9CM CODES

112.1 Vulvovaginitis, monilial EPIDEMIOLOGY & DEMOGRAPHICS

•

Second most common cause of vaginal infection.

•

Approximately 13 million people were affected in 1990.

•

75% of women will have at least one episode during their childbearing years, and approximately 40% to 50% of these will experience a second attack.

•

No symptoms in 20% to 40% of women who have positive cultures.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Intense vulvar and vaginal pruritus

•

Edema and erythema of vulva

•

Thick, curdlike vaginal discharge

•

Adherent, dry, white, curdy patches attached to vaginal mucosa

ETIOLOGY

•

Candida albicans is responsible for 80%-95% of vaginal fungal infections.

•

Candida tropicalis and Torulopsis glabrata (Candida glabrata) are the most common nonalbicans Candida species that can induce vaginitis.

PREDISPOSING HOST FACTORS

•

Pregnancy

•

Oral contraceptives (high-estrogen)

•

Diabetes mellitus

•

Antibiotics

•

Immunosuppression (e.g., HIV)

•

Tight, poorly ventilated, nylon underclothing, with increased local perineal moisture and temperature

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Bacterial vaginosis

•

Trichomonas vaginitis

•

Atrophic vaginitis

•

Section II describes the differential diagnosis of vaginal discharges and infections

WORKUP

•

Pelvic examination

•

Speculum examination

•

Hyphae or budding spores on 10% KOH preparation (positive in 50% to 70% of individuals with yeast infection)

•

Section III, “Vaginal Discharge,” describes the evaluation of discharge

LABORATORY TESTS

Culture, especially recurrence for identification

TREATMENT ACUTE GENERAL Rx

•

Cure rate of the various azole derivatives 85% to 90%; little evidence of superiority of one azole agent over another

•

No significant differences in persistent symptoms with oral or vaginal treatment

•

Fluconazole (oral) associated with increased frequency of mild nausea, headache, abdominal pain

•

Cure rate of polyene (Nystatin) cream and suppositories, 75% to 80%

•

Miconazole 200-mg suppository (Monistat 3), one suppository × 3 or 2% vaginal cream (Monistat 7), one applicator full intravaginally qhs × 7

•

Clotrimazole 200-mg vaginal tablet, one tablet intravaginally qhs × 3 or 100-mg vaginal tablet (GyneLotrimin, Mycelex-G) one tablet intravaginally qhs × 7, or 1% vaginal cream intravaginally qhs × 7

•

Butoconazole 2% cream (Femstat) one applicator intravaginally qhs × 3

•

Terconazole 80-mg suppository or 0.8% vaginal cream (Terazol 3), one suppository or one applicator intravaginally qhs × 3 or 0.4% vaginal cream (Terazol 7), one applicator intravaginally qhs × 7

•

Gynecazole-1 vaginal cream one applicator intravaginally × 1

•

Tioconazole 6.5% ointment (Vagi-stat), one applicator intravaginally × 1

•

Fluconazole (Diflucan) 150 mg PO × 1

CHRONIC Rx (FOUR OR MORE SYMPTOMATIC EPISODES/YR)

•

•

Resistance or recurrence 1.

14- to 21-day course of 7-day regimens mentioned in “Acute General Rx”

2.

Fluconazole (Diflucan) 150 mg PO × 1

3.

Ketoconazole (Nizoral) 200 mg PO bid × 5 to 14 days

4.

Itraconazole (Sporanox) 200 mg PO qd × 3 days

5.

Boric acid 600-mg capsule intravaginally bid × 14 days

Prophylactic regimens 1.

Clotrimazole one 500-mg vaginal tablet each month

2.

Ketoconazole 200 mg PO bid × 5 days each month

3.

Fluconazole 150 mg PO × 1 each month

4.

Miconazole 100-mg vaginal tablet × 2 weekly

DISPOSITION

•

If symptoms do not resolve completely with treatment, or if they recur within a 2- to 3-mo period, further evaluation is indicated.

•

Reexamination and possibly culture are necessary.

•

Positive culture in absence of symptoms should not lead to treatment. Approximately 30% of women harbor Candida spp. and other species in the vagina.

REFERRAL

To obstetrician/gynecologist for recurrence

PEARLS & CONSIDERATIONS COMMENTS

•

No evidence that treating a woman's male sexual partner significantly improves woman's infection or reduces their rate of relapse.

EVIDENCE

Vulvovaginal candidiasis Several randomized controlled trials (RCTs) found that topical imidazoles were more effective than placebo for the treatment of vulvovaginal candidiasis in nonpregnant women. [[1]] An RCT compared intravaginal nystatin vs. placebo in nonpregnant women with symptomatic vulvovaginal candidiasis. Nystatin significantly reduced the number of patients reporting a poor symptomatic response after 2 weeks.[[2]] A systematic review found that topical imidazole therapy was more effective than nystatin in the management of vaginal candidiasis in pregnancy. Treatment for 7 days may be necessary during pregnancy.[[3]] A systematic review compared oral vs. topical azoles in nonpregnant women with vulvovaginal candidiasis. Both routes of administration were found to be equally effective in terms of clinical and mycologic cure.[[4]]

Evidence-Based Referenceces 1. Spence D: Candidiasis (vulvovaginal). Clin Evid, 10. London: BMJ Publishing Group; 2003:2044. 2. Isaacs JH: Nystatin vaginal cream in monilial vaginitis. Illinois Med J 1973; 3:240.10:2044, 2003. 3. Young GL, Jewell D: Topical treatment for vaginal candidiasis (thrush) in pregnancy. Cochrane Library 1, Chichester, UK, John Wiley, 2004. 4. Watson MC, et al: Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Library 1, Chichester, UK, John Wiley, 2004.

AUTHORS: JULIE ANNE SZUMIGALA, M.D., and RUBEN ALVERO, M.D. Vulvovaginitis, Prepubescent

BASIC INFORMATION DEFINITION

Prepubescent vulvovaginitis is an inflammatory condition of vulva and vagina.

ICD-9CM CODES

616.10 Vulvovaginitis EPIDEMIOLOGY & DEMOGRAPHICS

•

Most common gynecologic problem of the premenarcheal female.

•

Prepubertal girl is susceptible to irritation and trauma because of the absence of protective hair and labial fat pads and the lack of estrogenization with atrophic vaginal mucosa.

•

Symptoms of vulvovaginitis and introital irritation and discharge account for 80% to 90% of gynecologic visits.

•

Nonspecific etiology in approximately 75% of children with vulvovaginitis.

•

Majority of vulvovaginitis in children involves a primary irritation of the vulva with secondary involvement of the lower one third of the vagina.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Vulvar pain, dysuria, pruritus 1.

Discharge is not a primary symptom.

2.

If present, vaginal discharge may be foul smelling or bloody.

ETIOLOGY

•

Infections 1.

Bacterial

2.

Protozoal

3.

Mycotic

4.

Viral

•

Endocrine disorders

•

Labial adhesions

•

Poor hygiene

•

Sexual abuse

•

Allergic substance

•

Trauma

•

Foreign body

•

Masturbation

•

Constipation

•

Section II describes the differential diagnosis of vaginal discharge in prepubertal girls

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Physiologic leukorrhea

•

Foreign body

•

Bacterial vaginosis

•

Gonorrhea

•

Fungal vulvovaginitis

•

Trichomonas vulvovaginitis

•

Sexual abuse

•

Pinworms

WORKUP

•

Pelvic, genital examination

•

Speculum examination

•

Rectal examination

•

KOH and normal saline preparation of discharge

•

Section III, “Vaginal Discharge,” describes the evaluation of discharge

LABORATORY TESTS

•

Urinalysis to rule out UTI and diabetes

•

Cultures including STDs

TREATMENT NONPHARMACOLOGIC THERAPY

•

Avoid tight clothing

•

Perineal hygiene

•

Avoid irritant chemicals

•

Reassurance

ACUTE GENERAL Rx

•

Group A ß Streptococcus and Streptococcus pneumoniae: penicillin V potassium 125 to 250 mg PO qid × 10 days

•

Chlamydia trachomatis: erythromycin 50 mg/kg/day PO × 10 days 1.

•

Children >8 yr of age, doxycycline 100 mg bid PO × 7 days

Neisseria gonorrhoeae: ceftriaxone 125 mg IM × 1 day 1.

Children >8 yr of age should also be given doxycycline 100 mg bid PO × 7 days

•

Staphylococcus aureus: amoxicillin-clavulanate 20 to 40 mg/kg/day PO × 7 to 10 days

•

Haemophilus influenzae: amoxicillin 20 to 40 mg/kg/day PO × 7 days

•

Trichomonas: metronidazole 125 mg (15 mg/kg/day) tid PO × 7 to 10 days

•

Pinworms: mebendazole 100-mg tablet chewable, repeat in 2 wk

•

Labial agglutination: spontaneous resolution or topical estrogen cream for 7 to 10 days

CHRONIC Rx

See “Referral.” DISPOSITION

Further education:

•

Young child: hygiene

•

Adolescent: pregnancy prevention and “safe sex”

REFERRAL

•

To obstetrician/gynecologist

•

To pediatrician

SUGGESTED READINGS Van Neer PA, Korver CR: Constipation presenting as recurrent vulvovaginitis in prepubertal children. J Am Acad Dermatol 2000; 43(4):718.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Vulvovaginitis, Trichomonas JULIE ANNE SZUMIGALA, D.O.,, RUBEN ALVERO, M.D.

BASIC INFORMATION DEFINITION

Trichomonas vulvovaginitis is the inflammation of vulva and vagina caused by Trichomonas spp. SYNONYMS

Trichomonas vaginalis

ICD-9CM CODES

131.01 Vulvovaginitis, trichomonal EPIDEMIOLOGY & DEMOGRAPHICS

•

Acquired through sexual contact

•

Diagnosed in: 1.

50% to 75% of prostitutes

2.

5% to 15% of women visiting gynecology clinics

3.

7% to 32% of women in STD clinics

4.

5% of women in family planning clinics

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Profuse, yellow, malodorous vaginal discharge and severe vaginal itching

•

Vulvar itching

•

Dysuria

•

Dyspareunia

•

Intense erythema of the vaginal mucosa

•

Cervical petechiae (“strawberry cervix”)

•

Asymptomatic in approximately 50% of women and 90% of men

ETIOLOGY

Single-cell parasite known as trichomonad

RISK FACTORS

•

Multiple sexual partners

•

History of previous STDs

DIAGNOSIS DIFFERENTIAL DIAGNOSIS ( Table 1-53 )

•

Bacterial vaginosis

•

Fungal vulvovaginitis

•

Cervicitis

•

Atrophic vulvovaginitis

TABLE 1-53 -- Differential Diagnosis of Vaginitis Characteristics of Vaginal Discharge C. Albicans Vaginitis T. Vaginalis Vaginitis Bacterial Vaginosis pH

4.5

>5.0

>5.0

Usually

No

No

Odor with KOH

No

Yes

Yes

Clue cells

No

No

Usually

Motile trichomonads

No

Usually

No

Yeast cells3

Yes

No

No

White curd

From Goldman L, Ausiello D (eds): Cecil textbook of medicine, ed 22, Philadelphia, 2004, WB Saunders. WORKUP

•

Pelvic examination

•

Speculum examination

•

Mobile trichomonads seen on normal saline preparation: 70% sensitivity

•

Elevated pH (>5) of vaginal discharge

•

Culture is most sensitive commercially available method

•

A large number of inflammatory cells on normal saline preparation

•

Section III describes the evaluation of vaginal discharge

LABORATORY TESTS

•

Culture (modified Diamond media): 90% sensitivity

•

Direct enzyme immunoassay

•

Fluorescein-conjugated monoclonal antibody test

•

Pap test 40% detected

TREATMENT

nonpharmacologic therapy

Condom use ACUTE GENERAL Rx

Metronidazole (Flagyl) 2 g PO × 1 or 500 mg PO bid × 7 days or Tindamax (tinidazole) single 2 g oral dose in both sexes CHRONIC Rx

•

Metronidazole gel: less likely to achieve therapeutic levels; therefore not recommended

•

Metronidazole (retreat): 500 mg PO bid × 7 days

•

Treatment of future recurrences: Metronidazole 2 g PO qd × 3 to 5 days

•

Allergy, intolerance, or adverse reactions: Alternatives to metronidazole are not available. Patients who are allergic to metronidazole can be managed by desensitization

•

Pregnancy 1.

Associated with adverse outcomes (i.e., PROM)

2.

Metronidazole 2 g PO × 1 day

DISPOSITION

Trichomonas infection is considered an STD; therefore treatment of the sexual partner is necessary. REFERRAL

To obstetrician/gynecologist for recurrence and pregnancy

EVIDENCE

A single oral dose of any nitroimidazole is effective in achieving parasitologic cure at short-term followup.[[1]] Treatment of sexual partners may significantly reduce reinfection rates of Trichomonas vaginalis.[[2]] The effects of metronidazole treatment on pregnancy outcomes remains uncertain and therefore treatment in pregnancy should be reserved for symptomatic infections only.[[3]]

Evidence-Based Referenceces 1. Forna F, Gülmezoglu AM: Interventions for treating trichomoniasis in women. Cochrane Library 3, Chichester, UK, John Wiley, 2004. 2. Lyng J, Christensen J: A double-blind study of the value of treatment with a single dose tinidazole of partners to females with trichomoniasis. Acta Obstet Gynecol Scand 1981; 60:199. 3. Gülmezoglu AM: Interventions for trichomoniasis in pregnancy. Cochrane Library 3, Chichester, UK, John Wiley, 2004.

SUGGESTED READINGS Workowski KA, Levine WC: Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2006; 55:11.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

W Waldenström's Macroglobulinemia RAMI ELTIBI, M.D.

BASIC INFORMATION DEFINITION

Waldenström's macroglobulinemia (WM) is a plasma cell dyscrasia characterized by the presence of immunoglobulin (IgM) monoclonal macroglobulins. SYNONYMS

WM Monoclonal macroglobulinemia

ICD-9CM CODES

273.3 Waldenström's macroglobulinemia EPIDEMIOLOGY & DEMOGRAPHICS

•

Accounts for 2% of all hematologic cancers

•

1500 people diagnosed each year in the U.S.

•

Overall incidence: 3 per million per year; 0.61/100,000 in men, 0.36/100,000 in women

•

Median age varies between 63 and 68 yr

•

More common among men than women and among whites than blacks

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Weakness

•

Fatigue

•

Weight loss

•

Headache, dizziness, vertigo, deafness, and seizures (hyperviscosity syndrome)

•

Easy bleeding (e.g., epistaxis)

•

Retinal vein link-sausage shaped

•

Lymphadenopathy (15%)

•

Hepatomegaly (20%)

•

Most commonly encountered neurological presentation is symmetric polyneuropathy

•

Splenomegaly (15%)

•

Purpura

•

Peripheral neuropathy (5%)

ETIOLOGY

•

The exact cause of WM is not known.

•

Multiple reports suggest familial clustering, which indicates a genetic defect. In one study, chromosomal deletions in 6q21-22.1 were confirmed in 42% of WM patients, regardless of family history. In another study, the strongest evidence of linkage was found on chromosomes 1q and 4q.

•

The main risk factor for development of WM is having IgM monoclonal gammopathy of unknown significance (MGUS).

•

Radiation exposure, occupational chemicals, and chronic inflammatory stimulation have been suggested but there is insufficient evidence to substantiate these hypotheses.

DIAGNOSIS The diagnosis of WM is usually established by laboratory blood tests and by bone marrow biopsy. DIFFERENTIAL DIAGNOSIS

•

MGUS

•

Multiple myeloma

•

Chronic lymphocytic leukemia

•

Hairy-cell leukemia

•

Lymphoma

WORKUP

In any patient suspected of having WM, specific blood tests (CBC, erythrocyte sedimentation rate [ESR], serum or urine protein electrophoresis [SPEP or UPEP, respectively], IgM level, beta 2-microglobulin, serum viscosity) should be ordered. Bone marrow biopsy will confirm the diagnosis. LABORATORY TESTS

•

CBC with differential: 1.

Anemia is a common finding, with a median hemoglobin value of approximately 10 g/dl. WBC count is usually normal; thrombocytopenia can occur.

2.

Peripheral smear may reveal malignant lymphoid cells in terminal patients.

•

Elevated ESR.

•

SPEP: homogeneous M spike

•

Immunoelectrophoresis: confirms IgM

•

Urine immunoelectrophoresis: monoclonal light chains are usually kappa chains. Bence Jones protein can be seen, but is not the typical finding in WM

•

IgM levels are high, generally >3 g/dl

•

Beta 2-microglobulin: elevated in 55%, high levels are associated with poor prognosis.

•

Serum viscosity: symptoms usually occur when the serum viscosity is four times the viscosity of normal serum; classical feature although present in only 15% of cases.

•

Cryoglobulins, rheumatoid factor, or cold agglutinins may be present

•

Bone marrow biopsy: lymphoplasmacytoid cells are characteristic.

IMAGING STUDIES

Chest x-ray can be obtained to rule out pulmonary involvement.

TREATMENT

•

Because of the incurable nature of WM, the aim of treatment is to relieve symptoms and reduce the risk of organ damage. Considerations for the initiation of treatment include the following: hemoglobin concentration less than 100 × 109/L, significant adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or evidence of disease transformation.

•

Treatment is directed at both hyperviscocity and the lymphoproliferative disorder itself.

NONPHARMACOLOGIC THERAPY

Asymptomatic patients do not require treatment, and these patients should be monitored periodically for the onset of symptoms or changes in blood tests (e.g., worsening anemia, thrombocytopenia, rising IgM, and serum viscosity). ACUTE GENERAL Rx

1.

Plasmapharesis is the treatment used to alleviate symptoms of hyperviscocity.

2.

Treatment of the lymphoproliferative disorder includes the age of combination therapy: a.

Rituximab, a monoclonal anti-CD 20 antibody, in combination with nucleoside analogs.

b.

Nucleoside analogs and alkylator agents (chlorambucil).

c.

Combination chemotherapy such as CHOP (cyclophosphamide, vincristine, prednisone, doxorubicin): studies suggest combination therapy is on par if not better than single-agent therapy.

CHRONIC Rx

•

Refractory patients can be retried on original therapy if length of response from initial therapy is greater than 2 yr. If the response from the initial therapy was 65, male gender, the presence of organomegaly and the presence of cytopenias.

REFERRAL

If WM is suspected, a hematology consultation is helpful in guiding future workup, treatment, and monitoring.

PEARLS & CONSIDERATIONS COMMENTS

•

WM was first described in 1944 by the Swedish physician Jan Gosta Waldenström.

•

Amyloidosis is rare, occurring in 5% of patients with WM.

SUGGESTED READINGS Dimopoulos MA, Anagnostopoulos A: WaldenstrÖm's macroglobulinemia. Best Pract Res Clin Haematol 2005; 18(4):747. Gertz MA: WaldenstrÖm macroglobulinemia: a review of therapy. Am J Hematol 2005; 79(2):147. Fonseca R, Hayman S: WaldenstrÖm macroglobulinaemia. Br J Haematol 2007; 138:700. Vijay A, Gertz MA: WaldenstrÖm macroglobulinemia. Blood 2007; 109(12):5096.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Warts FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Warts are benign epidermal neoplasms caused by human papillomavirus (HPV). SYNONYMS

Verruca vulgaris (common warts) Verruca plana (flat warts) Condyloma acuminatum (venereal warts) Verruca plantaris (plantar warts) Mosaic warts (cluster of many warts)

ICD-9CM CODES

078.10 Viral warts 0.78.19 Venereal wart (external genital organs) EPIDEMIOLOGY & DEMOGRAPHICS

•

Common warts occur most frequently in children and young adults.

•

Anogenital warts are most common in young, sexually active patients. Genital warts are the most common viral STD in the U.S., with up to 24 million Americans carrying the virus that causes them.

•

Common warts are longer lasting and more frequent in immunocompromised patients (e.g., lymphoma, AIDS, immunosuppressive drugs).

•

Plantar warts occur most frequently at points of maximal pressure (over the heads of the metatarsal bones or on the heels).

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Common warts ( Fig. 1-292 ) have an initial appearance of a flesh-colored papule with a rough surface; they subsequently develop a hyperkeratotic appearance with black dots on the surface (thrombosed capillaries); they may be single or multiple and are most common on the hands.

•

Warts obscure normal skin lines (important diagnostic feature). Cylindrical projections from the wart may become fused, forming a mosaic pattern.

•

Flat warts generally are pink or light yellow, slightly elevated, and often found on the forehead, back of hands, mouth, and beard area; they often occur in lines corresponding to trauma (e.g., a scratch); are often misdiagnosed (particularly when present on the face) and inappropriately treated with topical corticosteroids.

•

Filiform warts have a fingerlike appearance with various projections; they are generally found near the mouth, beard, or periorbital and paranasal regions.

•

Plantar warts are slightly raised and have a roughened surface; they may cause pain when walking; as they involute, small hemorrhages (caused by thrombosed capillaries) may be noted.

•

Genital warts are generally pale pink with several projections and a broad base. They may coalesce in the perineal area to form masses with a cauliflower-like appearance.

•

Genital warts on the cervical epithelium can produce subclinical changes that may be noted on Pap smear or colposcopy.

FIGURE 1-292 Verruca vulgaris or common viral warts. These papules often have verrucous surface changes. (From Callen JP: Color atlas of dermatology, ed 2, Philadelphia, 2000, WB Saunders.)

ETIOLOGY

•

Human papillomavirus (HPV) infection; .60 types of viral DNA have been identified. Transmission of warts is by direct contact.

•

Genital warts are usually caused by HPV types 6 or 11.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Molluscum contagiosum

•

Condyloma latum

•

Acrochordon (skin tags) or seborrheic keratosis

•

Epidermal nevi

•

Hypertrophic actinic keratosis

•

Squamous cell carcinomas

•

Acquired digital fibrokeratoma

•

Varicella zoster virus in patients with AIDS

•

Recurrent infantile digital fibroma

•

Plantar corns (may be mistaken for plantar warts)

WORKUP

•

Diagnosis is generally based on clinical findings.

•

Suspect lesions should be biopsied.

LABORATORY TESTS

Colposcopy with biopsy of patients with cervical squamous cell changes

TREATMENT NONPHARMACOLOGIC THERAPY

•

Importance of use of condoms to reduce transmission of genital warts should be emphasized.

•

Watchful waiting is an acceptable option in the treatment of warts, because many warts will disappear without intervention over time.

•

Plantar warts that are not painful do not need treatment.

GENERAL Rx

•

Common warts: 1.

Application of topical salicylic acid 17% (e.g., Duofilm). Soak area for 5 min in warm water and dry. Apply thin layer once or twice daily for up to 12 wk, avoiding normal skin. Bandage.

2.

Liquid nitrogen, electrocautery are also common methods of removal.

3.

Blunt dissection can be used in large lesions or resistant lesions.

4.

Duct tape occlusion is also effective for treating common warts. It is cut to cover warts and left in place for 6 days. It is removed after 6 days and the warts are soaked in water and then filed with pumice stones. New tape is applied 12 hr later. This treatment can be repeated until warts resolve.

•

Filiform warts: surgical removal is necessary.

•

Flat warts: generally more difficult to treat.

•

•

•

1.

Tretinoin cream applied at hs over the involved area for several weeks may be effective

2.

Application of liquid nitrogen

3.

Electrocautery

4.

5-Fluorouracil cream (Efudex 5%) applied once or twice a day for 3 to 5 wk is also effective. Persistent hyperpigmentation may occur following Efudex use

Plantar warts: 1.

Salicylic acid therapy (e.g., Occlusal-HP). Soak wart in warm water for 5 min, remove loose tissue, dry. Apply to area, allow to dry, reapply. Use once or twice daily; maximum 12 wk. Use of 40% salicylic acid plasters (Mediplast) is also a safe, nonscarring treatment; it is particularly useful in treating mosaic warts covering a large area.

2.

Blunt dissection is also a fast and effective treatment modality.

3.

Laser therapy can be used for plantar warts and recurrent warts; however, it leaves open wounds that require 4 to 6 wk to fill with granulation tissue.

4.

Interlesional bleomycin is also effective but generally used when all other treatments fail.

Genital warts: 1.

Can be effectively treated with 20% podophyllin resin in compound tincture of benzoin applied with a cotton tip applicator by the treating physician and allowed to air dry. The treatment can be repeated weekly if necessary.

2.

Podofilox (Condylox 0.5% gel) is now available for application by the patient. Local adverse effects include pain, burning, and inflammation at the site.

3.

Cryosurgery with liquid nitrogen delivered with a probe or as a spray is effective for treating smaller genital warts.

4.

Carbon dioxide laser can also be used for treating primary or recurrent genital warts (cure rate .90%).

5.

Imiquimod (Aldara) cream, 5% is a patient-applied immune response modifier effective in the treatment of external genital and perianal warts (complete clearing of genital warts in .70% of females and .30% of males in 4 to 16 wk). Sexual contact should be avoided while the cream is on the skin. It is applied three times/wk before normal sleeping hours and is left on the skin for 6 to 10 hr.

Application of trichloroacetic acid (TCA) or bichloracetic acid (BCA) 80% to 90% is also effective for external genital warts. A small amount should be applied only to warts and allowed to dry, at which time a white “frosting” develops. This treatment can be repeated weekly if necessary.

DISPOSITION

•

Warts can be effectively treated with the previous modalities, with complete resolution in the majority of patients; however, recurrence rate is high.

•

Cervical carcinomas and precancerous lesions in women are associated with genital papillomavirus infection.

•

Squamous cell anal cancer is also associated with a history of genital warts.

REFERRAL

•

Dermatology referral for warts resistant to conservative therapy

•

Surgical referral in selected cases

•

STD counseling for patients with anogenital warts

PEARLS & CONSIDERATIONS COMMENTS

•

Subungual and periungual warts are generally more resistant to treatment. Dermatology referral for cryosurgery is recommended in resistant cases.

•

Examination of sex partners is not necessary for the management of genital warts because no data indicate that reinfection plays a role.

EVIDENCE

Genital Podofilox has been shown to be more effective than placebo after 16 weeks of treatment.[[1]] No significant difference has been found between podofilox and podophyllin resin in terms of genital wart clearance.[[1]] Imiquimod is more effective than placebo in clearing genital warts and reducing recurrences in non-HIVinfected patients.[[2]] Palmar-Plantar Salicylic acid is an effective treatment for cutaneous warts. Topical treatments containing salicylic acid are clearly better than placebo for the treatment of cutaneous warts.[[3]] The reviewers note that there is some evidence that cryotherapy is of only equivalent efficacy to simpler, safer treatments, including topical salicylic acid.[[3]] Cryotherapy is significantly less effective than treatment with duct tape at producing complete resolution.[[4]]

There is no significant difference between cryotherapy at intervals of 2 weeks, 3 weeks, or 4 weeks in terms of wart clearance.[[3]] There is no significant difference between no further treatment vs. prolonging cryotherapy for a further 3 months (after 6 months of therapy) in terms of the proportion of patients with clearance of warts.[[3]]

Evidence-Based Reference 1. Wiley DJ: Genital warts. Clin Evid 9, web version only, London, BMJ Publishing Group, 2003. 2. Moore RA, et al: Imiquimod for the treatment of genital warts: a quantitative systematic review. BMC Infect Dis 2001; 1:3.Reviewed in: Clin Evid 10, 2003, web version only. 3. Gibbs S, et al: Local treatments for cutaneous warts (Cochrane Review). The Cochrane Library 2, Oxford, Update Software, 2003. Reviewed In: Clin Evid 9:1868, 2003. 4. Focht DR, Spicer C, Fairchok MP: The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart). Arch Pediatr Adolesc Med 2002; 156:971.

SUGGESTED READINGS Bacelieri R, Johnson SM: Cutaneous warts: an evidence-based approach to therapy. Am Fam Physician 2005; 72:647.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Wegener Granulomatosis FRED F. FERRI, M.D.

BASIC INFORMATION DEFINITION

Wegener granulomatosis is a multisystem disease generally consisting of the classic triad of:

1.

Necrotizing granulomatous lesions in the upper or lower respiratory tract

2.

Generalized focal necrotizing vasculitis involving both arteries and veins

3.

Focal glomerulonephritis of the kidneys

“Limited forms” of the disease can also occur and may evolve into the classic triad; Wegener granulomatosis can be classified using the “ELK” classification, which identifies the three major sites of involvement: E, ears, nose, and throat or respiratory tract; L, lungs; K, kidneys.

ICD-9CM CODES

446.4 Wegener's granulomatosis EPIDEMIOLOGY & DEMOGRAPHICS

INCIDENCE: 3/100,000 persons, equal in men and women MEAN AGE AT ONSET: 41 yr PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Clinical manifestations often vary with the stage of the disease and degree of organ involvement. 90% of patients present with symptoms involving the upper or lower airways or both.

•

Frequent manifestations are: 1.

Upper respiratory tract: chronic sinusitis, chronic otitis media, mastoiditis, nasal crusting, obstruction and epistaxis, nasal septal perforation, nasal lacrimal duct stenosis, saddle nose deformities (resulting from cartilage destruction)

2.

Lung: hemoptysis, multiple nodules, diffuse alveolar pattern

3.

Kidney: renal insufficiency, glomerulonephritis

4.

Skin: necrotizing skin lesions

5.

Nervous system: mononeuritis multiplex, cranial nerve involvement

6.

Joints: monarthritis or polyarthritis (nondeforming), usually affecting large joints

7.

Mouth: chronic ulcerative lesions of the oral mucosa, “mulberry” gingivitis

8.

Eye: proptosis, uveitis, episcleritis, retinal and optic nerve vasculitis

ETIOLOGY

Unknown

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Other granulomatous lung diseases (e.g., sarcoidosis, lymphomatoid granulomatosis, Churg-Strauss syndrome, necrotizing sarcoid granulomatosis, bronchocentric granulomatosis, sarcoidosis); the differential diagnosis of granulomatous lung disease is described in Section II

•

Neoplasms (especially lymphoproliferative disease)

•

Goodpasture's syndrome

•

Bacterial or fungal sinusitis

•

Midline granuloma

•

Viral infections

•

Other causes of glomerulonephritis (e.g., poststreptococcal nephritis)

WORKUP

•

Wegener granulomatosis should be suspected in anyone presenting with sinus disease that does not respond to conventional treatment, pulmonary hemorrhage, glomerulonephritis, mononeuritis multiplex resulting in wrist or foot drop, progressive migratory arthralgias or arthritis, and unexplained multisystem disease.

•

Chest x-ray, laboratory evaluation, PFTs, and tissue biopsy.

LABORATORY TESTS

•

Positive test for cytoplasmic pattern of ANCA (c-ANCA).

•

Anemia, leukocytosis.

•

Urinalysis: may reveal hematuria, RBC casts, and proteinuria.

•

Elevated serum creatinine, decreased creatinine clearance.

•

Increased ESR, positive rheumatoid factor, and elevated C-reactive protein may be found.

IMAGING STUDIES

•

Chest x-ray: may reveal bilateral multiple nodules, cavitated mass lesions, pleural effusion (20%). Up to one third of patients without pulmonary signs or symptoms have an abnormal chest x-ray.

•

PFTs: useful in detecting stenosis of the airways.

•

Biopsy of one or more affected organs should be attempted; the most reliable source for tissue diagnosis is the lung. Lesions in the nasopharynx (if present) can be easily biopsied but biopsy is positive in only 20%. Biopsy of radiographically abnormal pulmonary parenchyma provides the highest yield (90%).

TREATMENT NONPHARMACOLOGIC THERAPY

•

Ensure proper airway drainage.

•

Give nutritional counseling.

ACUTE GENERAL Rx

•

Prednisone 60 to 80 mg/day and cyclophosphamide 2 mg/kg are generally effective and are used to control clinical manifestations; once the disease comes under control, prednisone is tapered and cyclophosphamide is continued. Other potentially useful agents in patients intolerant to cyclophosphamide are methotrexate, azathioprine, and mycophenolate mofetil.

•

TMP-SMX therapy may represent a useful alternative in patients with lesions limited to the upper or lower respiratory tracts in absence of vasculitis or nephritis. Treatment with TMP-SMX (160 mg/800 mg bid) also reduces the incidence of relapses in patients with Wegener granulomatosis in remission. It is also useful in preventing Pneumocystis carinii pneumonia, which occurs in 10% of patients receiving induction therapy. When used for prophylaxis, dose of TMP-SMX (160 mg/800 mg) is 1 tablet three times/wk.

DISPOSITION

Five-year survival with aggressive treatment is approximately 80%; without treatment 2-yr survival is 20%. REFERRAL

Surgical referral for biopsy

PEARLS & CONSIDERATIONS COMMENTS

•

Methotrexate (20 mg/wk) represents an alternative to cyclophosphamide in patients who do not have immediately life-threatening disease.

•

C-ANCA levels should not dictate changes in therapy, because they correlate erratically with disease activity.

•

The incidence of venous thrombotic events in Wegener granulomatosis is significantly higher than the general population. Clinicians should maintain a heightened awareness of the risks of venous thrombosis and a lower threshold for evaluating patients for possible DVT or pulmonary embolism.

SUGGESTED READINGS Finkielman JD et al: Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis Ann Intern Med, 147(9): 611–619. Langford CA: Update on Wegener granulomatosis. Cleve Clin J Med 2005; 72:689-697. Merkel PA, et al: Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) study. Ann Intern Med 2005; 142:620-626.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Wernicke's Encephalopathy DANIEL MATTSON, M.D., M.SC.(MED.)

BASIC INFORMATION DEFINITION

Wernicke's encephalopathy is the syndrome of acute extraocular muscle dysfunction, confusion, and ataxia, resulting from thiamine deficiency. SYNONYMS

Korsakoff's syndrome Wernicke-Korsakoff syndrome Alcoholic polyneuritic psychosis

ICD-9CM CODES

265.1 Wernicke's encephalopathy, disease, or syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

Most commonly associated with alcohol abuse; consider in other conditions where malabsorption or altered metabolism may occur (e.g., hyperemesis gravidarum, gastric bypass)

•

Slightly more common in males

•

Age of onset evenly distributed between ages 30 and 70

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Disturbance of extraocular motility, including nystagmus, abducens nerve palsy, and disorders of conjugate gaze.

•

Encephalopathy.

•

Ataxia of gait.

•

Peripheral neuropathy may be seen in addition to the typical findings described previously.

ETIOLOGY

Thiamine deficiency from alcohol abuse or other malnourished state. It may be iatrogenic from prolonged dextrose infusion without thiamine supplementation.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Thiamine deficiency, including alcohol abuse, malnutrition, or iatrogenic cause

•

Stroke, mass lesion, or trauma affecting upper brainstem, thalamus, and associated structures

WORKUP

Patients must be evaluated with a high index of suspicion, and treated rapidly, even in advance of laboratory results. LABORATORY TESTS

•

CBC.

•

Serum chemistries.

•

Serum pyruvate is elevated.

•

Whole-blood or erythrocyte transketolase are decreased; rapid resolution to normal in 24 hr with thiamine repletion.

IMAGING STUDIES

•

MRI may show T2 hyperintense diencephalic and mesencephalic lesions acutely, but there is no definitive radiologic study for diagnosis.

•

CT scan may show cerebral atrophy from chronic alcoholism.

TREATMENT NONPHARMACOLOGIC THERAPY

Alcoholics Anonymous ACUTE GENERAL Rx

•

100 mg thiamine IV or IM immediately; typically thiamine IV for 3 to 5 days, then oral.

•

Avoid dextrose-containing fluids until thiamine repleted.

•

Prophylactic treatment for delirium tremens if alcoholic.

CHRONIC Rx

•

Attempt to treat alcoholism or underlying malnourished state.

•

Chronic oral thiamine repletion; typical dose 5 mg/day.

•

Case reports suggest donepezil may help chronic memory problems.

•

Inadequately treated disease may progress to Korsakoff's psychosis (see relevant entry).

DISPOSITION

Enter substance abuse program after acute phase. Long-term care is determined by level of recovery. REFERRAL

Neurology should be consulted if symptoms do not resolve after thiamine therapy.

PEARLS & CONSIDERATIONS COMMENTS

•

Give thiamine if the disease is even suspected.

•

Prognosis is generally poor, with 10%-20% mortality even with treatment. Most patients will be left with impaired learning and memory, which may be subtle.

•

A preventable cause is prolonged dextrose-containing IV fluids without supplemental thiamine.

EVIDENCE

Thiamine has been established as the treatment of choice for over 50 years. The evidence for its benefit is based on case reports and clinical experience. No randomized controlled trials (RCTs) are available to guide clinicians in the dosage, route, or duration of therapy in the acute presentation of the syndrome. A recent RCT that looked at alcoholics without frank clinical evidence of Korsakoff's psychosis showed that those treated with the highest dose of thiamine showed neuropsychologic evidence of improvement in working memory, suggesting that even “asymptomatic” alcoholics may benefit from thiamine supplementation. [13] [14]

Evidence-Based References 1. Ambrose ML, et al: Thiamine treatment and working memory function of alcohol-dependent people: preliminary findings. Alcohol Clin Exp Res 2001; 25(b):112-116. 2. Day E, et al: Thiamine for Wernicke-Korsakoff syndrome in people at risk from alcohol abuse. Cochrane Database Syst Rev 2004; 1:CD004033

SUGGESTED READINGS Cochrane , et al: Acetylcholinesterase inhibitors for the treatment of Wernicke-Korsakoff syndrome—three further cases show response to donepezil. Alcohol Alcohol 2005; 40(b):151-154. Cook CC: Prevention and treatment of Wernicke-Korsakoff syndrome. Alcohol Alcohol Suppl 2000; 35(suppl 1):19. Harper C: Thiamine (vitamin B1) deficiency and associated brain damage is still common throughout the world and prevention is simple and safe!. Eur J Neurol 2006; 13(10):1078. Martin PR, et al: The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health 2003; 27(b):134-142.

Sechi G, Serra A: Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007; 6(5):442. Zubaran C, Fernandes JG, Rodnight R: Wernicke-Korsakoff syndrome. Postgrad Med J 1997; 73(855):27.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

West Nile Virus Infection GLENN G. FORT, M.D., M.P.H., DENNIS J. MIKOLICH, M.D., JOSEPH R. MASCI, M.D.

BASIC INFORMATION DEFINITION

West Nile virus infection is an illness affecting the central nervous system (CNS) caused by the mosquito-borne West Nile virus. SYNONYMS

West Nile virus fever West Nile virus encephalitis Neuroinvasive West Nile virus infection Nonneuroinvasive West Nile virus infection

ICD-9CM CODES

066.4 West Nile virus infection EPIDEMIOLOGY & DEMOGRAPHICS

•

Before 1999, West Nile virus (WNV) infection was confined to areas in the Middle East, with occasional outbreaks in Europe. The infection began being diagnosed in the Western hemisphere in 1999. First seen in the northeast and mid-Atlantic states, West Nile virus infection has spread steadily, each year, to new regions of the U.S., with a general westward migration pattern. In the year 2003, a record number of cases were reported from the U.S., with over 7000 cases reported resulting in several hundred deaths. Most deaths occur in elderly patients with WNV encephalitis. In 2003, the midwestern states of Illinois, Ohio, Michigan, and Louisiana were hardest hit. In 2004 and 2005, the incidence of WNV infection diminished gradually as it spread to the western states. Human cases of WNV infection have now been reported across all the contiguous continental U.S. (sparing only Hawaii and Alaska). More than 4200 neuroinvasive and nonneuroinvasive cases were reported in the U.S. in 2006.

•

The virus is carried by a number of species of birds, as well as horses and several other animals. It is transmitted to humans through the bite of an infected mosquito. For this reason, West Nile virus infection is seen primarily from mid-summer to mid-autumn, the period of maximum mosquito intensity.

•

The majority of severe cases have been reported among individuals 50 yr of age. There is no gender predilection.

•

Person-to-person transmission is fortunately rare but has been reported to occur by blood transfusion, organ transplantation, breastfeeding, and perhaps by perinatal transmission; the blood supply is now routinely tested by nucleic acid testing methods to reduce the risk of transmission-acquired WNV in the U.S.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Less than 20% of infected individuals develop symptomatic disease. The initial phase of illness is nonspecific, with abrupt onset of fever accompanied by malaise, eye pain, anorexia, headache, and, occasionally, rash and lymphadenopathy. Less commonly, myocarditis, hepatitis, or pancreatitis may occur.

•

In approximately 1 in 150 cases, especially among elderly patients, severe neurologic sequelae will occur. Most common among these are ataxia, cranial nerve palsies, optic neuritis, seizures, myelitis, and polyradiculitis.

ETIOLOGY

The West Nile virus is a member of the flavivirus group, along with the yellow fever, dengue, St. Louis, and Japanese encephalitis viruses. It has a large reservoir in nature, infecting many species of birds, as well as certain mammals, and is thought to be spread to humans exclusively by various species of mosquito. Neurologic disease is caused by direct invasion of the CNS.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Meningitis or encephalitis caused by more common viruses (e.g., enteroviruses, herpes simplex)

•

Bacterial meningitis

•

Vasculitis

•

Fungal meningitis (e.g., cryptococcal infection)

•

Tuberculous meningitis

LABORATORY TESTS

•

CBC, electrolytes (hyponatremia common)

•

Spinal tap and CSF examination: typically demonstrates lymphocytic pleocytosis with normal level of glucose and elevated level of protein

•

CSF West Nile virus IgM antibody level: rare false-positive results in persons recently vaccinated to Japanese encephalitis or yellow fever viruses

IMAGING STUDIES

CT or MRI studies of the brain to exclude mass lesions; cerebral edema

TREATMENT NONPHARMACOLOGIC THERAPY

Hospitalization, intravenous hydration, ventilator support may be necessary. ACUTE GENERAL Rx

No specific therapy has been established in clinical trials. Ribavirin and interferon alpha-2b have been shown to have in vitro activity against the virus. Intravenous immune globulin from convalescent patient plasma is under study but no controlled trials have been reported as yet. CHRONIC Rx

Chronic rehabilitation therapy usually necessary for patients with severe neurologic impairment. Mental status defects following WNV neuroinvasive disease appear to be more common and severe than initially recognized. DISPOSITION

Chronic rehabilitation as needed following recovery from acute infection REFERRAL

•

Infectious disease consultant

•

Public health authorities

PEARLS & CONSIDERATIONS COMMENTS

•

Diagnosis requires a high index of suspicion, because disease course may be nonspecific and may mimic other, more common disorders.

•

Specific laboratory diagnostic studies are available only through public health laboratories.

•

Best means of prevention is reduction in mosquito population by draining of stagnant water deposits and, if necessary, insecticide spraying.

•

Individuals may reduce risk by covering arms and legs in areas where mosquitoes are likely to be found and using insect repellent containing DEET.

EVIDENCE

We are unable to cite evidence that meets our criteria. SUGGESTED READINGS Carson PJ, et al: Long-term clinical and neuropsychological outcomes of West Nile virus infection. Clin Infect Dis 2006; 43(6):723. CDC: Update: West Nile virus activity—United States, 2005. MMWR 2005; 54(b):851-852. Gottfried K, Quinn R, Jones T: Clinical description and follow-up investigation of human West Nile Virus cases. South Med J 2005; 98(b):603-606. Haaland KY, et al: Mental status after West Nile virus infection. Emerg Infect Dis 2006; 12(8):1260. Higgs S, et al: Nonviremic transmission of West Nile virus. Proc Natl Acad Sci U S A 2005; 102(b):8871-8874. Stramer SL, et al: West Nile virus among blood donors in the United States, 2003 and 2004. N Engl J Med 2005; 353(b):451-459.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Whiplash JORGE VILLAFUERTE, M.D.

BASIC INFORMATION DEFINITION

Whiplash refers to a hyperextension injury to the neck, often the result of being struck from behind by a fastmoving vehicle. SYNONYMS

Acceleration flexion-extension neck injury

ICD-9CM CODES

847.0 Whiplash injury or syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

Whiplash occurs in more than 1 million people each year.

•

Most injuries (40%) are the result of rear-end motor vehicle accidents.

•

Whiplash occurs at all ages, in both sexes, and at all socioeconomic levels.

•

Incidence is 4 per 1000 persons and is higher in women than men.

•

Nearly 50% of patients with whiplash seek legal advice.

•

Whiplash is also seen in shaken baby syndrome.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most present with a history of being involved in a motor vehicle accident and rear-ended by another vehicle

•

Pain not present initially but usually develops hours to a few days later

•

Neck tightness and stiffness

•

Occipital headache

•

Shoulder, arm, and back pain

•

Numbness in the arms

•

Tinnitus

•

TMJ pain

•

Dysphagia (retropharyngeal hematoma)

•

Decreased range of motion of the neck

•

Depressive symptoms

ETIOLOGY

•

The mechanism of injury is due to the sudden acceleration of the body forward, forcing the neck to hyperextend backward, causing injury to ligaments, muscles, bone, and/or intervertebral disk. At the end of the accident the head is thrust forward in a flexion position, sometimes causing injury to C5-C6-C7.

•

Motor vehicle accidents, trauma from falls, contact sports, physical abuse, and altercations are all possible causes of whiplash.

•

The incidence of whiplash injury following polytrauma is low.

•

Low-velocity crashes constitute a major cause of whiplash injury.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Osteoarthritis

•

Cervical disk disease

•

Fibrositis

•

Neuritis

•

Torticollis

•

Spinal cord tumor

•

TMJ syndrome

•

Tension headache

•

Migraine headache

WORKUP

Any patient who presents with symptoms of whiplash and musculoskeletal or neurologic signs merits a workup to exclude cervical spine fractures or herniated disk disease. LABORATORY TESTS

Laboratory studies are not helpful. IMAGING STUDIES

•

Plain C-spine films (AP, lateral, and odontoid views)

•

Flexion/extension x-rays

•

CT scan to exclude fracture

•

MRI

TREATMENT NONPHARMACOLOGIC THERAPY

•

Soft cervical collar for no longer than 72 hr

•

Moist heat 15 to 20 min 4 to 6 times per day

•

Continue with usual activities

ACUTE GENERAL Rx

•

•

Analgesics 1.

Ibuprofen 800 mg PO tid

2.

Naproxen 500 mg PO bid

3.

Acetaminophen 1 g PO qid

Muscle relaxants (short-term use) 1.

Cyclobenzaprine 10 mg PO tid

2.

Methocarbamol 1 g PO qid

3.

Carisoprodol 350 mg PO qid

CHRONIC Rx

NSAIDs can be used long term. DISPOSITION

•

Most patients recover from the acute whiplash injury within weeks.

•

20% to 40% may develop chronic whiplash syndrome (symptoms of headache, neck pain, and psychiatric complaints that persist for 6 mo).

•

Older age, female gender, lawyer involvement, and being at work before entry to the clinic were found to be prognostic factors associated with a negative outcome.

REFERRAL

Orthopedic

PEARLS & CONSIDERATIONS

COMMENTS

•

Nearly one third of all personal injury cases involve cervical injuries.

•

There is no dose-response relationship between trauma severity and incidence of whiplash injury.

•

The entity of chronic whiplash syndrome remains elusive. Some authorities argue that financial motivation is a factor leading to persistent neck symptoms. Other studies do not substantiate this, countering a true chronic injury to the soft tissues of the neck.

EVIDENCE

High-dose methylprednisolone has been shown to be effective in improving outcomes after acute spinal cord injury, provided that it can be administered within 8 hours of injury and continued for 23 hours.[[1]] Two systematic reviews found a general lack of evidence supporting treatments used in acute whiplash injury. [28] [29] One of the reviews found that early mobilization resulted in better pain relief and improved range of motion at 4 and 8 weeks compared with immobilization, analgesics, rest, and education.[[2]] The other review found a trend toward active interventions being more effective than passive.[[3]] Active mobilization was shown to be significantly more effective than rest plus a collar in one randomized controlled trial, but only when commenced immediately after the injury.[[4]] A meta-analysis in people with chronic neck or back pain with acute spasm found cyclobenzaprine significantly improved symptoms compared with placebo after 2 weeks.[[5]] A randomized, parallel-group trial showed that immobilization, “act-as-usual,” and mobilization had similar effects regarding prevention of pain, disability, and work capability 1 year after a whiplash injury.[[6]]

Evidence-Based References 1. Bracken MB: Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002; 2: 2. Spitzer WO, et al: Scientific monograph of the Quebec Task Force on whiplash-associated disorders: redefining ‘whiplash’ and its management. Spine 1995; 20(suppl 8):1.Reviewed in: Clin Evid 13:2005.

3. Verhagen AP, et al: Conservative treatments for whiplash. Cochrane Database Syst Rev 2004; 1: 4. Rosenfeld M, Gunnarsson R, Borenstein P: Early intervention in whiplash-associated disorders: a comparison of two treatment protocols. Spine 2000; 25:1782.Reviewed in: Clin Evid 10:1377, 2003. 5. Aker PD, et al: Conservative management of mechanical neck pain: systematic overview and metaanalysis. BMJ 1996; 313:1291.Reviewed in: Clin Evid 10:1377, 2003. 6. Kongsted A, et al: Neck collar, “act-as-usual” or active mobilization for whiplash injury? A randomized parallel-group trial. Spine 2007; 32(6):618.

SUGGESTED READINGS Carroll LJ, et al: Frequency, timing, and course of depressive symptomatology after whiplash. Spine 2006; 31(16):E551. Dufton JA, et al: Prognostic factors associated with minimal improvement following acute whiplash-associated disorders. Spine 2006; 31(20):E759. Giannoudis PV, et al: Incidence and outcome of whiplash injury after multiple trauma. Spine 2007; 32(7):776. Rodriquez AA, Barr KP, Burns SP: Whiplash: pathophysiology, diagnosis, treatment, and prognosis. Muscle Nerve 2004; 29(6):768. Sterner Y, Gerdle B: Acute and chronic whiplash disorders—a review. J Rehabil Med 2004; 36(5):193.

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Whipple's Disease FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Whipple's disease is a multisystem illness characterized by malabsorption and its consequences, lymphadenopathy, arthritis, cardiac involvement, ocular symptoms and neurologic problems, caused by the gram-positive bacillus Tropheryma whippeli. SYNONYMS

Intestinal lipodystrophy (name used by Dr. Whipple in 1907)

ICD-9CM CODES

040.2 Whipple's disease EPIDEMIOLOGY & DEMOGRAPHICS

•

Uncommon illness (only about 1000 cases have been reported to date)

•

Peak age: 30 to 60 yr of age; mean age at diagnosis is 50

•

More frequent in men than women and in Caucasians

•

Specific environmental factors have not been associated with Whipple's disease.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

PHYSICAL FINDINGS:

•

Abdominal distention, sometimes with tenderness and less commonly fullness or mass, which represents enlarged mesenteric lymph

•

Signs of weight loss, cachexia

•

Clubbing

•

Lymphadenopathy

•

Inflamed joints

•

Heart murmur or rub

•

Sensory loss or motor weakness related to peripheral neuropathy

•

Abnormal mental status examination

•

Pallor

CLINICAL PRESENTATION:

Whipple's disease is characterized by 2 stages: a prodromal stage and a much later steady-state stage. The prodromal stage is marked by protean symptoms and chronic arthralgias and arthritis. The steady-state stage, which follows the prodromal stage by an average time of 6 years, is manifested with weight loss, diarrhea, or both. When the disease presents with extraintestinal symptoms (e.g., arthralgia), few clinicians will suspect the diagnosis unless or until GI symptoms are present. Weight loss, diarrhea, and arthropathies are found together in 75% of patients at time of diagnosis. The GI manifestations are those seen in malabsorption of any cause:

•

Diarrhea: 5 to 10 semiformed, malodorous steatorrheic stools per day

•

Abdominal bloating and cramps

•

Anorexia

Extraintestinal manifestations of malabsorption:

•

Weight loss, fatigue

•

Anemia

•

Bleeding diathesis

•

Edema and ascites

•

Osteomalacia

Extraintestinal involvement:

•

Arthritis (intermittent, migratory, affecting small, large, and axial joints)

•

Pleuritic chest pain and cough

•

Pericarditis, endocarditis

•

Dementia, ophthalmoplegia, myoclonus, and many other symptoms, because any portion of the central nervous system may be a disease site

•

Fever

ETIOLOGY & PATHOGENESIS

•

Infectious disease caused by Tropheryma whippeli, an actinobacter.

•

The bacillus has never been cultured, nor has direct transmission from patient to patient ever been documented; however, the agent can be seen in tissue samples by electron microscopy and identified by polymerase chain reaction (PCR).

•

Predictable response to appropriate antibiotic therapy confirms the pathogenic role of the infection.

•

Tissue infiltration by macrophages is believed to be the mechanism of specific organ dysfunction and symptoms.

•

Subtle defects of the cell-mediated immunity exist in active and inactive Whipple's disease that may predispose certain individuals to clinical manifestations. HLA-B27 positivity is found in 26% of patients (four times higher than expected).

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Malabsorption/maldigestion:

•

Celiac disease

•

Mycobacterium avium-intracellulare intestinal infection in patients with AIDS

•

Intestinal lymphoma

•

Abetalipoproteinemia

•

Amyloidosis

•

Systemic mastocytosis

•

Radiation enteritis

•

Crohn's disease

•

Short bowel syndrome

•

Pancreatic insufficiency

•

Intestinal bacterial overgrowth

•

Lactose deficiency

•

Postgastrectomy syndrome

•

Other cause of diarrhea (see Section III, “Diarrhea, Acute” and “Diarrhea, Chronic”)

•

Seronegative inflammatory arthritis (see Section II for differential diagnosis)

•

Pericarditis and pleuritis

•

Lymphadenitis

•

Neurologic disorders

WORKUP

Laboratory tests and imaging studies are useful; however, the diagnosis of Whipple's disease is usually made by upper endoscopy and biopsy. Endoscopic findings reveal a pale yellow shaggy mucosa alternating with an erythematous, erosive, or friable mucosa in the duodenum or jejunum. LABORATORY TESTS

•

Anemia (iron, folate, or vitamin B12 deficiency)

•

Hypokalemia

•

Hypocalcemia

•

Hypomagnesemia

•

Hypoalbuminemia

•

Prolonged prothrombin time

•

Low serum carotene

•

Low cholesterol

•

Leukocytosis

•

Steatorrhea demonstrated by a Sudan fecal fat stain

•

72-Hr stool collection demonstrating more than 7 g/24 hr of fat in the stool is impractical to perform, especially in ambulatory patients

•

Defective d-xylose absorption

IMAGING STUDIES

Small bowel x-rays after barium ingestion often show thickening of mucosal folds. BIOPSY

Infiltration of the intestinal lamina propria by PAS-positive macrophages containing gram-positive, acid-fast negative bacilli, associated with lymphatic dilation (diagnostic); PCR of the involved tissue in uncertain cases. If PAS staining of the small bowel biopsy specimen is positive and the PCR assay is negative, the diagnosis of Whipple's disease must be confirmed; this can be done by immunohistochemical testing with an antibody to T. whippeli. If this test is positive, Whipple's disease is confirmed.

TREATMENT

•

Antibiotics: TMP/SMX DS bid for 12 to 24 months, usually preceded by parenteral administration of streptomycin (1 g/day) together with penicillin G (1.2 million U/day) or ceftriaxone (2 g/day) for 2 weeks.

•

Alternative regimen consists of doxycycline (200 mg/day) plus hydroxychloroquine (200 mg tid).

•

Treat specific vitamin, mineral, and nutrient deficiencies.

•

Patients with a neurologic recurrence of Whipple's disease have a poor prognosis. Interferon gamma has been proposed for treatment of recurrent CNS disease.

SUGGESTED READINGS Fenollar F, et al: Whipple's disease. N Engl J Med 2007; 356:55.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Wilson's Disease FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Wilson's disease is a disorder of copper transport with inadequate biliary copper excretion, leading to an accumulation of the metal in liver, brain, kidneys, and corneas. SYNONYMS

Progressive hepatolenticular degeneration

ICD-9CM CODES

275.1 Wilson's disease EPIDEMIOLOGY & DEMOGRAPHICS

PREVALENCE: 1 in 30,000 PREDOMINANT SEX: Affects men and women equally (autosomal recessive gene) Onset of symptoms: 3 to 40 yr of age PHYSICAL FINDINGS & CLINICAL PRESENTATION

Hepatic presentation: •

Acute hepatitis with malaise, anorexia, nausea, jaundice, elevated transaminase, prolonged prothrombin time; rarely fulminant hepatic failure

•

Chronic active (or autoimmune) hepatitis with fatigue, malaise, rashes, arthralgia, elevated transaminase, elevated serum IgG, positive ANA and anti–smooth muscle antibody

•

Chronic liver disease/cirrhosis with hepatosplenomegaly, ascites, low serum albumin, prolonged prothrombin time, portal hypertension

Neurologic presentation:

•

Movement disorder: tremors, ataxia

•

Spastic dystonia: masklike facies, rigidity, gait disturbance, dysarthria, drooling, dysphagia

Ophthalmic:

•

Kaiser-Fleisher ring

•

Sunflower cataracts

Psychiatric presentation:

•

Depression, obsessive-compulsive disorder, psychopathic behaviors, neuroses

Other organs:

•

Hemolytic anemia

•

Renal disease (i.e., Fanconi's syndrome with hematuria, phosphaturia, renal tubular acidosis, vitamin D–resistant rickets)

•

Cardiomyopathy

•

Arthritis

•

Hypoparathyroidism

•

Hypogonadism

PHYSICAL FINDINGS: •

Ocular: the Kayser-Fleischer ring is a gold-yellow ring seen at the periphery of the iris ( Fig. 1-293 ); these should be sought using slit-lamp examination by a skilled examiner

•

Stigmata of acute or chronic liver disease

•

Neurologic abnormalities: see previous

FIGURE 1-293 Wilson's disease. A Kayser-Fleisher ring, which is a gold-yellow ring, extends to the limbus without a clear interval. (From Palay D [ed]: Ophthalmology for the primary care physician, St Louis, 1997, Mosby.)

ETIOLOGY & PATHOGENESIS

•

Dietary copper is transported from the intestine to the liver where normally it is metabolized into ceruloplasmin. In Wilson's disease, defective incorporation of copper into ceruloplasmin and a decrease of biliary copper excretion lead to accumulation of this mineral.

•

The gene for Wilson's disease is located in chromosome 13.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Hereditary hypoceruloplasminemia

•

Menkes' disease

•

Consider the diagnosis of Wilson's disease in all cases of acute or chronic liver disease where another cause has not been established

•

Consider Wilson's disease in patients with movement disorders or dystonia even without symptomatic liver disease

LABORATORY TESTS

•

Abnormal LFTs (note that AST may be higher than ALT)

•

Low serum ceruloplasmin level (,200 mg/L)

•

Low serum copper (,65 mg/L)

•

24-hr urinary copper excretion greater than 100 mg (normal, 30 mg); increases to greater than 1200 mg/24 hr after 500 mg of d-penicillamine (normal, 500 mg/24 hr)

•

Low serum uric acid and phosphorus

•

Abnormal urinalysis (hematuria)

BIOPSY

•

Early: Steatosis, focal necrosis, glycogenated hepatocyte nuclei May reveal inflammation and piecemeal necrosis

•

Late: cirrhosis

•

Hepatic copper content (.250 mg/g of dry weight) (normal is 20 to 50 mg)

•

Histochemical confirmation of excess copper can be helpful in diagnosis, but if absent, does not exclude Wilson's disease. The lack of immunoreactivity to copper-binding protein can occur because of the diffuse presence of copper in the cytoplasm and because of the assay's low sensitivity. Rhodamine and rubeanic acid stains can show dense granular lysosomal copper deposition in hepatocytes at the stage of cirrhotic nodular regeneration.

TREATMENT

•

Penicillamine: (chelator therapy) 0.75 to 1.5 g/day divided bid (with pyridoxine 25 mg/day) Monitor CBC and urinalysis weekly

•

Trientine: (triethylene tetramine) (chelator therapy) 1 to 2 g/day divided tid Monitor CBC

•

Zinc: (inhibits intestinal copper absorption) 50 mg tid Monitor zinc level

•

Ammonium tetrathiomolybdate for neurologic symptoms

•

Antioxidants

•

Liver transplant (for severe hepatic failure unresponsive to chelation); liver transplantation corrects the underlying pathophysiology and can be lifesaving

PROGNOSIS

Good with early chelation treatment REFERRAL

To gastroenterologist, neurologist COMMENTS

Family screening of first-degree relatives must be undertaken. Genetic diagnosis is also useful in patients with indeterminate clinical and biochemical features. SUGGESTED READINGS Ala A, et al: Wilson's disease. Lancet 2007; 369:397.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Wolff-Parkinson-White Syndrome FRED F. FERRI, M.D., TOM J. WACHTEL, M.D.

BASIC INFORMATION DEFINITION

Wolff-Parkinson-White syndrome is an electrocardiographic abnormality associated with earlier than normal ventricular depolarization following the atrial impulse and predisposing the affected person to tachyarrhythmias. SYNONYMS

Preexcitation syndrome

ICD-9CM CODES

426.7

Wolff-Parkinson-White syndrome

426.81 Lown-Ganong-Levine syndrome EPIDEMIOLOGY & DEMOGRAPHICS

•

Prevalence: 1.5 cases/1000 persons

•

Prevalence higher in males and decreases with age

•

Most patients with WPW syndrome have normal hearts, but associations with mitral valve prolapse, cardiomyopathies, and Ebstein's anomaly have been reported

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Paroxysmal tachycardias

•

10% of WPW patients aged 20 to 40 yr

•

35% of WPW patients aged .60 yr

The type of tachycardia is:

•

Reciprocating tachycardia at 150 to 250 beats per minute (80%)

•

Atrial fibrillation (15%)

•

Atrial flutter (5%)

•

Ventricular tachycardia: rare

•

Sudden death is rare (,1/1000 cases)

ETIOLOGY & PATHOGENESIS

•

Existence of accessory pathways (Kent bundles).

•

If the accessory pathway is capable of anterograde conduction, two parallel routes of AV conduction are possible, one subject to delay through the AV mode, the other without delay through the accessory pathway. The resulting QRS complex is a fusion beat with the “delta” wave representing ventricular activation through the accessory pathway ( Fig. 1-294 ).

•

Tachycardias occur when, because of different refractory periods, conduction is anterograde in one pathway (usually the normal AV pathway) and retrograde in the other (usually the accessory pathway). Some patients (5% to 10%) with WPW syndrome have multiple accessory pathways.

•

In patients with WPW, development of atrial fibrillation may be associated with very rapid ventricular rates due to atrial ventricular conduction over the anomalous AV pathway.

FIGURE 1-294 With Wolff-Parkinson-White syndrome an abnormal accessory conduction pathway called a bypass tract (BT) connects the atria and ventricles. (From Goldberger AL [ed]: Clinical electrocardiography: a simplified approach, ed 6, St Louis, 1999, Mosby.)

DIAGNOSIS Three basic features characterize the ECG abnormalities in WPW syndrome ( Fig. 1-295 ):

FIGURE 1-295 A, SVT in a child with Wolff-Parkinson-White (WPW) syndrome. Note the normal QRS complexes during the tachycardia. B, Later the typical features of WPW syndrome are apparent (short P-R interval, delta wave, and wide QRS). (From Behrman RE: Nelson textbook of pediatrics, ed 17, Philadelphia, 2004, WB Saunders.)

•

PR interval, 120 msec

•

QRS complex .120 msec with a slurred, slowly rising onset of QRS in some lead (delta wave)

•

ST-T wave changes

Variants

•

Lown-Ganong-Levine syndrome: atriohisian pathway with short PR interval and normal QRS complex on ECG (no delta wave)

•

Atriofascicular accessory pathways: duplication of the AV node, with normal baseline ECG

TREATMENT

•

No treatment in the absence of tachyarrhythmias.

•

Symptomatic tachyarrhythmias.

•

Acute episode: adenosine, verapamil, or diltiazem can be used to terminate an episode of reciprocal tachycardia.

•

Digitalis should not be used because it can reduce refractoriness in the accessory pathway and accelerate the tachycardia. Cardioversion should be used in the presence of hemodynamic impairment.

•

Treatment of atrial fibrillation: in patients with WPW, administration of AV nodal-blocking agents will not slow the ventricular rate because AV bypass tracts capable of rapid conduction do not respond to AV blocking agents. Procainamide is the drug of choice to control ventricular rate and restore sinus rhythm in patients with WPW who have atrial fibrillation.

•

Prevention: Empiric trials or serial electrophysiologic drug testing of:

•

1.

Quinidine and propranolol

2.

Procainamide and verapamil

3.

Amiodarone

4.

Sotalol

Electrical or surgical ablation of the accessory pathway (see below)

EVIDENCE

In a literature review of studies of children receiving hospital treatment in the U.S. for Wolff-ParkinsonWhite (WPW) syndrome, catheter ablation was found to have lower cost, mortality, and morbidity than either medical management or surgery. The authors concluded that it is the treatment of choice for the child aged 5 years or older with WPW and supraventricular tachycardia. [40] [41]

Evidence-Based References 1. Garson A, Kanter RJ: Management of the child with Wolff-Parkinson-White syndrome and supraventricular tachycardia: model for cost effectiveness. J Cardiovasc Electrophysiol 1997; 8(11):1320.Reviewed in: The NHS Economic Evaluation Database, 1997. 2. Pappone C, et al: Radiofrequency ablation in children with asymptomatic WPW. N Engl J Med 2004; 351:1197.

SUGGESTED READINGS Pappone C, et al: A randomized study of prophylactic catheter ablation in asymptomatic patients with the WPW syndrome. N Engl J Med 2003; 349:1803.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Y Yellow Fever STEVEN M. OPAL, M.D., MARILYN FABBRI, M.D.

BASIC INFORMATION DEFINITION

Yellow fever is an infection, primarily of the liver, with systemic manifestations caused by the yellow fever virus (YFV). The clinical spectrum ranges from asymptomatic infection to life-threatening disease. SYNONYMS

Tropical hemorrhagic fever from Yellow Fever Virus

ICD-9CM CODES

060.9 Yellow fever EPIDEMIOLOGY & DEMOGRAPHICS

GEOGRAPHIC DISTRIBUTION •

South America and Africa, in countries between +15 and -15 degrees latitude.

•

From 1985 to 1999, more than 20,000 cases and 7000 deaths were reported to the World Health Organization, with more than 90% of cases in Africa.

INCIDENCE: Approximate attack rates of 3% in Africa and Amazon. PREVALENCE: Endemic areas: 20% of population. PREDOMINANT SEX: In Africa and Amazon, male agricultural workers. PHYSICAL FINDINGS & CLINICAL PRESENTATION

•

Most subclinical.

•

Onset sudden after incubation period of 3 to 6 days.

•

Viremic (early) phase:

•

•

1.

Fever, chills

2.

Severe headache

3.

Lumbosacral pain

4.

Myalgias, nausea, malaise

5.

Conjunctivitis

6.

Relative bradycardia (Faget's sign)

After brief recovery, toxic phase: 1.

Jaundice

2.

Oliguria

3.

Albuminuria

4.

Hemorrhage

5.

Encephalopathy

6.

Shock

7.

Acidosis

Case fatality rate 25% to 50%.

ETIOLOGY

•

•

Yellow fever virus (L. flavus) 1.

Flavivirus infects hepatic cells.

2.

Late in infection, cytopathic effects (antibody- and cell-mediated) produce pathology.

Vector 1.

Aedes aegypti (urban).

2.

Aedes spp., Haemagogus (especially in Amazon) mosquitos (sylvan).

3.

Primary hosts humans and simian species.

4.

Exists in two transmission cycles: a.

Sylvatic or jungle cycle involving mosquitos and nonhuman primates.

b.

Urban cycle involving mosquitos and humans.

PATHOGENESIS & PATHOLOGY

•

Virus replication begins at site of mosquito bite, spreading to lymphatic channels and regional lymph nodes. Viremic spread to other organs, especially liver, spleen, and bone marrow.

•

Shock and fatal illness result from direct damage to organs and vasoactive cytokines.

•

Viral antigen found in hepatocytes, kidneys, and myocardium.

•

Midzone of liver lobules primarily affected.

•

Hemorrhages of mucosal surfaces of gastrointestinal tract.

DIAGNOSIS DIFFERENTIAL DIAGNOSIS

•

Viral hepatitis

•

Leptospirosis

•

Malaria

•

Typhoid fever

•

1.

Typhus

2.

Relapsing fever

Other hemorrhagic fevers

LABORATORY TESTS

•

•

CBC 1.

Mild leukopenia

2.

Thrombocytopenia

3.

Anemia

LFTs 1.

AST levels exceed ALT levels.

2.

Alkaline phosphatase normal or slightly elevated.

3.

Elevated bilirubin levels.

•

Elevated BUN and creatinine

•

Proteinuria

•

Coagulation studies

1.

Demonstrate abnormal prothrombin time or 2.

Reveal DIC

•

Terminal hypoglycemia

•

CSF

•

1.

Pleocytosis

2.

Elevated protein count

Specific diagnosis confirmed by: 1.

Viral isolation from blood

2.

Viral antigen in serum (ELISA)

3.

Viral RNA by PCR

4.

IgM-capture ELISA

5.

a.

Preferred serologic test.

b.

Appears within 5 to 7 days.

c.

Rising Ab confirmed by paired sera.

d.

Cross-reactivity with other flavivirus infections.

Immunohistochemical staining of postmortem liver biopsy specimens

TREATMENT ACUTE GENERAL Rx

•

Acetaminophen (for headache and fever) and H2 blockers (GI bleeding)

•

Blood transfusion, volume replacement for hemorrhage and shock

•

Dialysis for renal failure

•

Avoidance of sedatives and drugs dependent on hepatic metabolism

DISPOSITION

Follow up until hepatic, renal, CNS disease resolved REFERRAL

To infectious diseases expert for accurate diagnosis and management

PEARLS & CONSIDERATIONS PREVENTION

•

Yellow fever is preventable.

•

Recovery from yellow fever confers lasting immunity.

•

Live, attenuated yellow fever vaccine provides protective immunity in 95% of vaccinees within 10 days of vaccination. Reimmunization at 10-yr intervals for travelers.

•

Vaccine contraindicated in:

•

1.

Infants < 6 months (postvaccinal encephalitis)

2.

Immunosuppressed patients

3.

Pregnant women and nursing mothers

4.

Patients with egg hypersensitivity

Adverse effects of vaccine: 1.

b.

3.

General a.

Mild headaches, myalgias, low-grade fevers (25% vaccinees in clinical trials).

b.

Immediate hypersensitivity reaction (history of egg allergy).

Vaccine-associated neurotropic disease (postvaccine encephalitis) a.

Primarily among infants.

b.

Adult cases only in first-time vaccine recipients.

Vaccine-associated viscerotropic disease a.

Disease syndrome resembling wild-type yellow fever, often fatal.

b.

All cases in first-time vaccinees.

SUGGESTED READINGS Doblas A, et al: Yellow fever vaccine–associated viscerotropic disease and death in Spain. J Clin Virol 2006; 36(2):156. Gerasimon G, Lowry K: Rare case of fatal yellow fever vaccine-associated viscerotropic disease. South Med J 2005; 98(6):653. Lourenco-de-Oliveira R, et al: Ades aegypti in Brazil: genetically differentiated populations with high susceptibility to dengue and yellow fever viruses. Trans R Soc Trop Med Hyg 2004; 98(1):43. Massad E, et al: Yellow fever vaccination: how much is enough?. Vaccine 2005; 23(30):3908. Monath TP: Yellow fever vaccine. Expert Rev Vaccines 2005; 4(4):553. Pugachev KV, Guirakhoo F, Monath TP: New developments in flavivirus vaccines with special attention to yellow fever. Curr Opin Infect Dis 2005; 18(5):387.

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

Z Zenker's (Pharyngoesophageal) Diverticulum ABDULBAKI ABDULRAHMAN, M.D.

BASIC INFORMATION DEFINITION

Zenker's diverticulum refers to the acquired physiologic obstruction of the esophageal introitus that results from mucosal herniation posteriorly between the cricopharyngeus muscle and the inferior pharyngeal constrictor muscle ( Fig. 1-296 ).

FIGURE 1-296 Formation of pharyngoesophageal (Zenker's) diverticulum. Left, Herniation of the pharyngeal mucosa and submucosa occurs at the point of transition between the oblique fibers of the thyropharyngeus muscle and the more horizontal fibers of the cricopharyngeus muscle. Center and right, As the diverticulum enlarges, it dissects toward the left side and downward into the superior mediastinum in the prevertebral space. (From Sabiston D: Textbook of surgery, ed 15, Philadelphia, 1997, WB Saunders.)

SYNONYMS

Pharyngoesophageal diverticulum Pulsion diverticulum

ICD-9CM CODES

530.6 Zenker's diverticulum (esophagus) EPIDEMIOLOGY & DEMOGRAPHICS

•

Rare disease: 1% of all barium swallows

•

Commonly seen in people over 50 yr of age (most common in women and elderly)

•

Peak incidence is seventh to ninth decades

•

Associated with gastroesophageal reflux disease (GERD) and hiatal hernia

PHYSICAL FINDINGS & CLINICAL PRESENTATION

Small Zenker's diverticulum may be asymptomatic. As they become larger, symptoms include:

•

Dysphagia to solids and liquids

•

Regurgitation of undigested food

•

Sensation of globus or fullness in the neck

•

Cough

•

Halitosis

•

Aspiration pneumonia

•

Weight loss

•

Voice changes

•

Sialorrhea (excessive drooling)

ETIOLOGY

•

The specific cause is not known. The leading hypothesis suggests a discoordination of the swallowing muscles (specifically, incomplete relaxation of the cricopharyngeus muscle) that leads to an increased pressure on the mucosa of the hypopharynx, resulting in a progressive distention of that mucosa in its weakest area (posterior wall in “Killian's triangle,” the point between the oblique fibers of the inferior pharyngeal muscle and the horizontal fibers of the cricopharyngeus muscle). The end result is the formation of a false diverticulum where food elements and secretions may be lodged, causing the symptoms listed previously.

•

Zenker's diverticulum may also occur after anterior spinal surgery or cervical spine injury.

DIAGNOSIS

•

Clinical presentation and barium swallow typically make the diagnosis of Zenker's diverticulum.

•

Neck ultrasound can also be used.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis is similar to anyone presenting with dysphagia:

•

Achalasia

•

Esophageal spasm

•

Esophageal carcinoma

•

Esophageal webs

•

Peptic stricture

•

Lower esophageal (Schatzki) ring

•

Foreign bodies

•

Central nervous system disorders (stroke, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, myasthenia gravis, muscular dystrophies)

•

Dermatomyositis

•

Infection

WORKUP

Barium swallow is the test of choice. Upper endoscopy runs the risk of perforation. Manometry motility studies are usually not indicated. LABORATORY TESTS

Not specific. IMAGING STUDIES

•

Barium swallow: demonstrates a herniated sac with a narrow diverticular neck that typically originates proximal to the cricopharyngeus at the level of C5-C6 ( Fig. 1-297 ).

•

Endoscopy is only indicated if barium studies show mucosal irregularities to rule out neoplasia.

•

Oropharyngeal-esophageal scintigraphy has recently been shown to be an effective, sensitive, and simple diagnostic study for both qualitative and quantitative analyses.

•

A chest x-ray is performed in cases of suspected aspiration pneumonia.

FIGURE 1-297 Posteroanterior (left) and oblique (right) views from barium esophagogram showing both a typical diverticulum of the junction of the mid-esophagus and distal esophagus and a small traction diverticulum (arrow) of the mid-esophagus. (From Sabiston D: Textbook of surgery, ed 15, Philadelphia, 1997, Saunders.)

TREATMENT NONPHARMACOLOGIC THERAPY

•

Soft mechanical diet can be tried in patients with symptoms of dysphagia.

•

Avoid seeds, skins, and nuts.

ACUTE GENERAL Rx

•

•

Surgical repair is the conventional treatment for symptomatic patients (dysphagia, cough, aspiration) with excellent relief of symptoms in nearly all patients and low procedural mortality (1.5%). Procedures include: 1.

Cervical diverticulectomy with cricopharyngeal myotomy (most common approach)

2.

Diverticulopexy or diverticular inversion with cricopharyngeal myotomy

3.

Diverticulectomy alone

4.

Cricopharyngeal myotomy alone

Endoscopic techniques (esophagodiverticulotomy) have largely replaced conventional surgery and include: 1.

Endoscopic stapler diverticulotomy (may be the initial treatment of choice)

2.

Microendoscopic carbon dioxide laser surgical diverticulotomy

3.

Diverticula 4 Infection. Hypocalcemia. Hyperphosphatemia. Hyponatremia. Developmental malformation. Drug withdrawal. Inborn error of metabolism. 1 TO 6 MONTHS As above. 6 MONTHS TO 3 YEARS Febrile seizures. Birth injury. Infection. Toxin. Trauma. Metabolic disorder. Cerebral degenerative disease. >3 YEARS Idiopathic. Infection. Trauma.

Cerebral degenerative disease.

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SEXUALLY TRANSMITTED DISEASES, ANORECTAL REGION 23

ICD-9CM # 569.49 INFECTION AND REGION ULCERATIVE Lymphogranuloma venereum. Herpes simplex virus. Early (primary) syphilis. Chancroid (Haemophilus ducreyi). Cytomegalovirus. Idiopathic (usually HIV positive). NONULCERATIVE Condyloma acuminatum. Gonorrhea. Chlamydia (Chlamydia trachomitis). Syphilis.

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SEXUAL PRECOCITY 36

ICD-9CM # 259.1 TRUE PRECOCIOUS PUBERTY Premature reactivation of LHRH pulse generator. INCOMPLETE SEXUAL PRECOCITY (Pituitary Gonadotropin Independent). Males Chorionic gonadotropin-secreting tumor. Leydig cell tumor. Familial testotoxicosis. Virilizing congenital adrenal hyperplasia. Virilizing adrenal tumor. Premature adrenarche. Females Granulosa cell tumor (follicular cysts may be manifested similarly). Follicular cyst. Feminizing adrenal tumor. Premature thelarche. Premature adrenarche. Late-onset virilizing congenital adrenal hyperplasia. In both sexes

McCune-Albright syndrome. Primary hypothyroidism.

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SHOULDER PAIN

ICD-9CM # 952.2

SHOULDER INJURY

718.81 SHOULDER INSTABILITY 726.19 SHOULDER LIGAMENT OR MUSCLE INSTABILITY 840.9

SHOULDER STRAIN, SITE UNSPECIFIED

WITH LOCAL FINDINGS IN SHOULDER Trauma: contusion, fracture, muscle strain, trauma to spinal cord. Arthrosis, arthritis, RA, ankylosing spondylitis. Bursitis, synovitis, tendinitis, tenosynovitis. Aseptic (avascular) necrosis. Local infection: septic arthritis, osteomyelitis, abscess, herpes zoster, TB. WITHOUT LOCAL FINDINGS IN SHOULDER Cardiovascular disorders: ischemic heart disease, pericarditis, aortic aneurysm. Subdiaphragmatic abscess, liver abscess. Cholelithiasis, cholecystitis. Pulmonary lesions: apical bronchial carcinoma, pleurisy, pneumothorax, pneumonia. GI lesions: PUD, gastric neoplasm, peptic esophagitis. Pancreatic lesions: carcinoma, calculi, pancreatitis. CNS abnormalities: neoplasm, vascular abnormalities. Multiple sclerosis. Syringomyelia.

Polymyositis/dermatomyositis. Psychogenic. Polymyalgia rheumatica. Ectopic pregnancy.

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SHOULDER PAIN BY LOCATION

ICD-9CM # 952.2

SHOULDER INJURY

726.19 SHOULDER LIGAMENT OR MUSCLE INSTABILITY 840.8

SHOULDER SEPARATION

TOP OF SHOULDER (C4) Cervical source. Acromioclavicular. Sternoclavicular. Diaphragmatic. SUPEROLATERAL (C5) Rotator cuff tendinitis. Impingement. Adhesive capsulitis. Glenohumeral arthritis. ANTERIOR Bicipital tendinitis and rupture. Glenoid labral tear. Adhesive capsulitis. Glenohumeral arthritis. Osteonecrosis. AXILLARY Neoplasm (Pancoast's, mediastinal).

Herpes zoster.

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SMALL BOWEL OBSTRUCTION 23

ICD-9CM # 751.1

SMALL INTESTINE OBSTRUCTION, CONGENITAL

560.81 SMALL INTESTINE OBSTRUCTION DUE TO ADHESION INTRINSIC Congenital (atresia, stenosis). Inflammatory (Crohn's, radiation enteritis). Neoplasms (metastatic or primary). Intussusception. Traumatic (hematoma). EXTRINSIC Hernias (internal and external). Adhesions. Volvulus. Compressing masses (tumors, abscesses, hematomas). INTRALUMINAL Foreign body. Gallstones. Bezoars. Barium. Ascaris infestation.

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SMALL INTESTINE ULCERATION

ICD-9CM # 569.82

Inflammatory bowel disease. Celiac disease. Vasculitis, systemic lupus erythematosus (SLE), Behçet's syndrome. Uremia. Infections (Campylobacter, tuberculosis [TB], Yersinia, parasites, typhoid, cytomegalovirus [CMV], Clostridium). Mesenteric insufficiency. Neoplasms. Radiation. Drugs (salicylates, potassium, indomethacin, antimetabolites). Meckel diverticulum. Zollinger-Ellison syndrome. Lymphocytic enterocolitis. Stomal ulceration.

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SMELL DISTURBANCE

ICD-9CM # CODE VARIES WITH SPECIFIC DISORDER

Upper respiratory tract infection. Nasal or paranasal sinus disease. Exposure to noxious vapors. Head trauma. Idiopathic. Dental caries, periodontal disease. Medications.

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SORE THROAT 30

ICD-9CM # 426 075

PHARYNGITIS MONONUCLEOSIS

472.1 CHRONIC PHARYNGITIS 487.1 PHARYNGITIS, INFLUENZAL 074.0 COXSACKIE VIRUS PHARYNGITIS WITHOUT PHARYNGEAL ULCERS Viral pharyngitis. Allergic pharyngitis. Infectious mononucleosis. Streptococcal pharyngitis. Gonococcal pharyngitis. Sinusitis with postnasal drip. WITH PHARYNGEAL ULCERS Herpangina. Herpes simplex. Candidiasis. Fusospirochetal infection (Vincent's angina).

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SPASTIC PARAPLEGIAS

ICD-9CM # 344.1

Cervical spondylosis. Friedreich's ataxia. Multiple sclerosis. Spinal cord tumor. HIV. Tertiary syphilis. Vitamin B12 deficiency. Spinocerebellar ataxias. Syringomyelia. Spinal cord AV malformations. Adrenoleukodystrophy.

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SPINAL CORD COMPRESSION, EPIDURAL

ICD-9CM # CODE VARIES WITH SPECIFIC DISORDER

Osteoarthritis. Meningioma. Spinal epidural abscess. Spinal epidural hematoma. Spinal epidural vascular malformations. Rheumatoid arthritis. Metastatic cancer (vertebral, intramedullary, leptomeninges). Radiation myelopathy. Neurofibroma. Sarcoidosis. Paraneoplastic myelopathy. Histiocytosis.

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SPINAL CORD DYSFUNCTION

ICD-9CM # 336.9

SPINAL CORD COMPRESSION

336.9

SPINAL CORD DISEASE NOS

742.9

SPINAL CORD DISEASE, CONGENITAL

281.1

SPINAL CORD DEGENERATION, B12 DEFICIENCY ANEMIA

336.8

SPINAL CORD ATROPHY, ACUTE

336.10 SPINAL CORD ATROPHY, ADULT

Trauma. Multiple sclerosis. Transverse myelitis. Neoplasm (primary, metastatic). Syringomyelia. Spinal epidural abscess. HIV myelopathy. Diskitis. Spinal epidural hematoma. Spinal cord infarction. Spinal AV malformation. Subarachnoid hemorrhage.

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SPINAL CORD ISCHEMIC SYNDROMES

ICD-9CM # CODE VARIES WITH SPECIFIC DISORDER

Systemic hypotension. Venous or arterial occlusion. Arterial dissection. Thromboembolism. Endovascular procedures. Vasculitis. Fibrocartilaginous embolism. Regional hemodynamic compromise.

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SPINAL TUMORS 12

ICD-9CM # 299.7 EXTRADURAL Metastases. Primary bone tumors arising in spine. INTRADURAL EXTRAMEDULLARY Meningiomas. Neurofibromas. Schwannomas. Lipomas. Arachnoid cysts. Epidermoid cysts. Metastasis. INTRAMEDULLARY Ependymoma. Glioma. Hemangioblastoma. Lipoma. Metastases.

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SPLENOMEGALY

ICD-9CM # 789.2

SPLENOMEGALY UNSPECIFIED

289.51 CHRONIC CONGESTIVE 759.0

CONGENITAL

789.2

UNKNOWN ORIGIN

Hepatic cirrhosis. Neoplastic involvement: CML, CLL, lymphoma, multiple myeloma. Bacterial infections: TB, infectious endocarditis, typhoid fever, splenic abscess. Viral infections: infectious mononucleosis, viral hepatitis, HIV. Gaucher's disease and other lipid storage diseases. Sarcoidosis. Parasitic infections (malaria, kala-azar, histoplasmosis). Hereditary and acquired hemolytic anemias. Idiopathic thrombocytopenic purpura (ITP). Collagen vascular disorders: SLE, RA (Felty's syndrome), polyarteritis nodosa. Serum sickness, drug hypersensitivity reaction. Splenic cysts and benign tumors: hemangioma, lymphangioma. Thrombosis of splenic or portal vein. Polycythemia vera, myeloid metaplasia.

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STEATOHEPATITIS

ICD-9CM # 571.8

Alcohol abuse. Obesity. Diabetes mellitus. Parenteral nutrition. Medications (high-dose estrogen, amiodarone, corticosteroids, methotrexate, nifedipine). Jejunoileal bypass. Abetalipoproteinemia. Wilson's disease, Weber-Christian disease.

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STOMATITIS, BULLOUS

ICD-9CM # 528.0

Erythema multiforme. Erosive lichen planus. Bullous pemphigoid. SLE. Pemphigus vulgaris. Mucous membrane pemphigoid.

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STRIDOR, PEDIATRIC AGE 4

ICD-9CM # 786.1 STRIDOR 748.3 STRIDOR LARYNGEAL CONGENITAL RECURRENT Allergic (spasmodic) croup. Respiratory infections in a child with otherwise asymptomatic anatomic narrowing of the large airways. Laryngomalacia. PERSISTENT Laryngeal obstruction: Laryngomalacia. Papillomas, other tumors. Cysts and laryngoceles. Laryngeal webs. Bilateral abductor paralysis of the cords. Foreign body. Tracheobronchial disease: Tracheomalacia. Subglottic tracheal webs. Endotracheal, endobronchial tumors. Subglottic tracheal stenosis. Congenital. Acquired. Extrinsic masses. Mediastinal masses.

Vascular ring. Lobar emphysema. Bronchogenic cysts. Thyroid enlargement. Esophageal foreign body. Tracheoesophageal fistulas. Other. Gastroesophageal reflux. Macroglossia, Pierre Robin syndrome. Cri du chat syndrome. Hysterical stridor. Hypocalcemia.

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STROKE 33

ICD-9CM # 436 ACUTE STROKE

Hypoglycemia. Drug overdose or intoxication. Hysterical conversion reaction. Hyperventilation. Metabolic encephalopathy. Migraine. Syncope. Transient global amnesia. Seizures. Vestibular vertigo.

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STROKE, PEDIATRIC AGE 20

ICD-9CM # 436 STROKE, ACUTE CARDIAC DISEASE Congenital: Aortic stenosis. Mitral stenosis; mitral prolapse. Ventricular septal defects. Patent ductus arteriosus. Cyanotic congenital heart disease involving right-to-left shunt. Acquired: Endocarditis (bacterial, SLE). Kawasaki disease. Cardiomyopathy. Atrial myxoma. Arrhythmia. Paradoxical emboli through patent foramen ovale. Rheumatic fever. Prosthetic heart valve. HEMATOLOGIC ABNORMALITIES Hemoglobinopathies: Sickle cell (SS) disease. Sickle (SC) disease. Polycythemia. Leukemia/lymphoma. Thrombocytopenia. Thrombocytosis. Disorders of coagulation:

Protein C deficiency. Protein S deficiency. Factor V Leiden. Antithrombin III deficiency. Lupus anticoagulant. Oral contraceptive pill use. Pregnancy and the postpartum state. Disseminated intravascular coagulation. Paroxysmal nocturnal hemoglobinuria. Inflammatory bowel disease (thrombosis). INFLAMMATORY DISORDERS Meningitis: Viral. Bacterial. Tuberculosis. Systemic infection: Viremia. Bacteremia. Local head and neck infections. Drug-induced inflammation: Amphetamine. Cocaine. Autoimmune disease: Systemic lupus erythematosus. Juvenile rheumatoid arthritis. Takayasu's arteritis. Mixed connective tissue disease. Polyarteritis nodosum. Primary CNS vasculitis. Sarcoidosis. Behçet's syndrome. Wegener's granulomatosis. METABOLIC DISEASE ASSOCIATED WITH STROKE Homocystinuria.

Pseudoxanthoma elasticum. Fabry's disease. Sulfite oxidase deficiency. Mitochondrial disorders: MELAS. Leigh syndrome. Ornithine transcarbamylase deficiency. INTRACEREBRAL VASCULAR PROCESSES Ruptured aneurysm. Arteriovenous malformation. Fibromuscular dysplasia. Moyamoya disease. Migraine headache. Postsubarachnoid hemorrhage vasospasm. Hereditary hemorrhagic telangiectasia. Sturge-Weber syndrome. Carotid artery dissection. Postvaricella. TRAUMA AND OTHER EXTERNAL CAUSES Child abuse. Head trauma/neck trauma. Oral trauma. Placental embolism.

ECMO therapy. CNS, Central nervous system; ECMO, extracorporeal membrane oxygenation; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke.

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STROKE, YOUNG ADULT, CAUSES 1

ICD-9CM # 436

Cardiac factors (ASD, MVP, patent foramen ovale). Inflammatory factors (SLE, polyarteritis nodosa). Infections (endocarditis, neurosyphilis). Drugs (cocaine, heroin, oral contraceptives, decongestants). Arterial dissection. Hematolic factors (DIC, TTP, deficiency of protein S, protein C, antithrombin III). Migraine. Postpartum angiopathy. Others: premature atherosclerosis, fibromuscular dysplasia.

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ST SEGMENT ELEVATIONS, NONISCHEMIC

ICD-9CM #794.31

Early repolarization. Acute pericarditis. LVH. Normal pattern variant. LBBB. Pulmonary embolism. Hyperkalemia. Postcardioversion.

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SUDDEN DEATH, PEDIATRIC AGE 4

ICD-9CM # 336.9

SPINAL CORD COMPRESSION

336.9

SPINAL CORD DISEASE NOS

742.9

SPINAL CORD DISEASE, CONGENITAL

281.1

SPINAL CORD DEGENERATION, B12 DEFICIENCY ANEMIA

336.8

SPINAL CORD ATROPHY, ACUTE

336.10 SPINAL CORD ATROPHY, ADULT SIDS AND SIDS “MIMICS” SIDS. Long Q-T syndromes. Inborn errors of metabolism. Child abuse. Myocarditis. Duct-dependent congenital heart disease. CORRECTED OR UNOPERATED CONGENITAL HEART DISEASE Aortic stenosis. Tetralogy of Fallot. Transposition of great vessels (postoperative atrial switch). Mitral valve prolapse. Hypoplastic left heart syndrome. Eisenmenger's syndrome. CORONARY ARTERIAL DISEASE Anomalous origin.

Anomalous tract. Kawasaki disease. Periarteritis. Arterial dissection. Marfan's syndrome. Myocardial infarction. MYOCARDIAL DISEASE Myocarditis. Hypertrophic cardiomyopathy. Dilated cardiomyopathy. Arrhythmogenic right ventricular dysplasia. CONDUCTION SYSTEM ABNORMALITY/ARRHYTHMIA Long Q-T syndromes. Proarrhythmic drugs. Preexcitation syndromes. Heart block. Commotio cordis. Idiopathic ventricular fibrillation. Heart tumor. MISCELLANEOUS Pulmonary hypertension. Pulmonary embolism.

Heat stroke. Cocaine. Anorexia nervosa. Electrolyte disturbances. SIDS, Sudden infant death syndrome.

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SUDDEN DEATH, YOUNG ATHLETE

ICD-9CM # CODE VARIES WITH SPECIFIC DIAGNOSIS

Hyperthrophic cardiomyopathy. Coronary artery anomalies. Myocarditis. Ruptured aortic aneurysm (Marfan's syndrome). Arrhythmias. Aortic valve stenosis. Asthma. Trauma (cerebral, cardiac). Drug and alcohol abuse. Heat stroke. Cardiac sarcoidosis. Atherosclerotic coronary artery disease. Dilated cardiomyopathy.

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SWOLLEN LIMB

ICD-9CM # 729.81 SWOLLEN ARM OR HAND 729.81 SWOLLEN LEG OR FOOT

Trauma. Insect bite. Abscess. Lymphedema. Thrombophlebitis. Lipoma. Neurofibroma. Postphlebitic syndrome. Myositis ossificans. Nephrosis, cirrhosis, CHF. Hypoalbuminemia. Varicose veins.

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T TALL STATURE 24

ICD-9CM # 253.0 GROWTH HORMONE OVER-PRODUCTION, GIGANTISM CONSTITUTIONAL (FAMILIAL OR GENETIC)—MOST COMMON CAUSE

ENDOCRINE CAUSES Growth hormone excess—gigantism. Sexual precocity (tall as children, short as adults): True sexual precocity. Pseudosexual precocity. Androgen deficiency: Klinefelter's syndrome. Bilateral anorchism. GENETIC CAUSES Klinefelter's syndrome. Syndromes of XYY, XXYY. MISCELLANEOUS SYNDROMES AND DISORDERS Cerebral gigantism or Sotos' syndrome: prominent forehead, hypertelorism, high arched palate, dolichocephaly, mental retardation, large hands and feet, and premature eruption of teeth. Large at birth, with most rapid growth in first 4 years of life. Marfan's syndrome: disorder of mesodermal tissues, subluxation of the lenses, arachnodactyly, and aortic aneurysm. Homocystinuria: same phenotype as Marfan's syndrome. Obesity: tall as infants, children, and adolescents. Total lipodystrophy: large hands and feet, generalized loss of subcutaneous fat, insulin-resistant diabetes mellitus, and hepatomegaly.

Beckwith-Wiedemann syndrome: neonatal tallness, omphalocele, macroglossia, and neonatal hypoglycemia. Weaver-Smith syndrome: excessive intrauterine growth, mental retardation, megalocephaly, widened bifrontal diameter, hypertelorism, large ears, micrognathia, camptodactyly, broad thumbs, and limited extension of elbows and knees. Marshall-Smith syndrome: excessive intrauterine growth, mental retardation, blue sclerae, failure to thrive, and early death.

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TARDIVE DYSKINESIA 11

ICD-9CM # 781.3

DYSKINESIA

300.11 HYSTERICAL DYSKINESIA 333.82 OROFACIAL DYSKINESIA 307.9

PSYCHOGENIC DYSKINESIA

DIFFERENTIAL DIAGNOSIS: Medications (antidepressants, anticholinergics, amphetamines, lithium, l-dopa, phenytoin). Brain neoplasms. Ill-fitting dentures. Huntington's disease. Idiopathic dystonias (tics, blepharospasm, aging). Wilson's disease. Extrapyramidal syndrome (postanoxic or postencephalitic). Torsion dystonia.

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TASTE AND SMELL LOSS 1

ICD-9CM # 781.1 SMELL AND TASTE DISTURBANCE OF SENSATION TASTE Local: radiation therapy. Systemic: cancer, renal failure, hepatic failure, nutritional deficiency (vitamin B12, zinc), Cushing's syndrome, hypothyroidism, DM, infection (influenza), drugs (antirheumatic and antiproliferative). Neurologic: Bell's palsy, familial dysautonomia, multiple sclerosis. SMELL Local: allergic rhinitis, sinusitis, nasal polyposis, bronchial asthma. Systemic: renal failure, hepatic failure, nutritional deficiency (vitamin B12), Cushing's syndrome, hypothyroidism, DM, infection (viral hepatitis, influenza), drugs (nasal sprays, antibiotics). Neurologic: head trauma, multiple sclerosis, Parkinson's disease, frontal brain tumor.

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TELANGIECTASIA

ICD-9CM # 448.9

Oral contraceptive agents. Pregnancy. Rosacea. Varicose veins. Trauma. Drug induced (corticosteroids, systemic or topical). Spider telangiectases. Hepatic cirrhosis. Mastocytosis. SLE, dermatomyositis, systemic sclerosis.

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TENDINOPATHY 23

ICD-9CM # 727.9 INTRINSIC FACTORS Anatomic factors Malalignment. Muscle weakness or imbalance. Muscle inflexibility. Decreased vascularity. Systemic factors Inflammatory conditions (e.g., SLE). Pregnancy. Quinolone-induced tendinopathy. Age-related factors Tendon degeneration. Increased tendon stiffness. Tendon calcification. Decreased vascularity. EXTRINSIC FACTORS Repetitive mechanical load Excessive duration. Excessive frequency.

Excessive intensity. Poor technique. Workplace factors. Equipment problems Footwear. Athletic field surface. Equipment factors (e.g., racquet size). Protective gear.

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TESTICULAR FAILURE 9

ICD-9CM # 257.1 TESTICULAR FAILURE PRIMARY Klinefelter's syndrome (XXY). XYY. Vanishing testes syndrome (in utero or early postnatal torsion). Noonan's syndrome. Varicocele. Myotonic dystrophy. Orchitis (mumps, gonorrhea). Cryptorchidism. Chemical exposure. Irradiation to testes. Spinal cord injury. Polyglandular failure. Idiopathic oligospermia or azoospermia. Germinal cell aplasia (Sertoli cell–only syndrome). Idiopathic testicular failure. Testicular torsion. Testicular trauma.

Diethylstilbestrol (maternal use during pregnancy resulting in in utero estrogen exposure). Testicular tumor with subsequent irradiation therapy, chemotherapy, or surgery (retroperitoneal lymph node dissection or orchiectomy). SECONDARY Delayed puberty. Kallmann's syndrome. Isolated gonadotropin deficiency. Prader-Labhart-Willi syndrome. Lawrence-Moon-Biedl syndrome. Central nervous system irradiation. Prepubertal panhypopituitarism. Postpubertal panhypopituitarism. Hypogonadism secondary to hyperprolactinemia. Adrenogenital syndrome. Chronic liver disease. Chronic renal failure/uremia. Hemochromatosis. Cushing's syndrome. Malnutrition. Massive obesity. Sickle cell anemia. Hyper/hypothyroidism. Anabolic steroid use.

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TESTICULAR PAIN

ICD-9CM # 608.9

Testicular torsion. Trauma. Epididymitis. Orchitis. Neoplasm. Urolithiasis. Inguinal hernia. Infection (cellulitis, abscess, folliculitis). Anxiety.

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TESTICULAR SIZE VARIATIONS 9

ICD-9CM # 608.3

TESTICULAR ATROPHY

608.89 TESTICULAR MASS 257.2

HYPOGONADISM

SMALL TESTES Hypothalamic-pituitary dysfunction. Gonadotropin deficiency. Growth hormone deficiency. Normal variant. Primary hypogonadism. Autoimmune destruction, chemotherapy, cryptorchidism, irradiation, Klinefelter's syndrome, orchiditis, testicular regression syndrome, torsion, trauma. LARGE TESTES Adrenal rest tissue. Compensatory. Fragile X syndrome. Idiopathic. Tumor.

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TETANUS 23

ICD-9CM # 037

Acute abdomen. Black widow spider bite. Dental abscess. Dislocated mandible. Dystonic reaction. Encephalitis. Head trauma. Hyperventilation syndrome. Hypocalcemia. Meningitis. Peritonsillar abscess. Progressive fluctuating muscular rigidity (stiff-man syndrome). Psychogenic. Rabies. Sepsis. Subarachnoid hemorrhage. Status epilepticus. Strychnine poisoning.

Temporomandibular joint syndrome.

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THROMBOCYTOPENIA

ICD-9CM # 287.3 CONGENITAL OR PRIMARY 287.4 SECONDARY 287.5 THROMBOCYTOPENIA NOS INCREASED DESTRUCTION Immunologic Drugs: quinine, quinidine, digitalis, procainamide, thiazide diuretics, sulfonamides, phenytoin, aspirin, penicillin, heparin, gold, meprobamate, sulfa drugs, phenylbutazone, nonsteroidal anti-inflammatory drugs (NSAIDs), methyldopa, cimetidine, furosemide, INH, cephalosporins, chlorpropamide, organic arsenicals, chloroquine, platelet glycoprotein IIb/IIIa receptor inhibitors, ranitidine, indomethacin, carboplatin, ticlopidine, clopidogrel. Idiopathic thrombocytopenic purpura (ITP). Transfusion reaction: transfusion of platelets with plasminogen activator (PLA) in recipients without PLA-1. Fetal/maternal incompatibility. Collagen vascular diseases (e.g., systemic lupus erythematosus [SLE]). Autoimmune hemolytic anemia. Lymphoreticular disorders (e.g., CLL). Nonimmunologic Prosthetic heart valves. Thrombotic thrombocytopenic purpura (TTP). Sepsis. DIC. Hemolytic-uremic syndrome (HUS). Giant cavernous hemangioma.

DECREASED PRODUCTION Abnormal marrow. Marrow infiltration (e.g., leukemia, lymphoma, fibrosis). Marrow suppression (e.g., chemotherapy, alcohol, radiation). Hereditary disorders. Wiskott-Aldrich syndrome: X-linked disorder characterized by thrombocytopenia, eczema, and repeated infections. May-Hegglin anomaly: increased megakaryocytes but ineffective thrombopoiesis. Vitamin deficiencies (e.g., vitamin B12, folic acid). SPLENIC SEQUESTRATION, HYPERSPLENISM

DILUTIONAL, AS A RESULT OF MASSIVE TRANSFUSION

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THROMBOCYTOSIS

ICD-9CM # 289.9 THROMBOCY-TOSIS, ESSENTIAL

Iron deficiency. Posthemorrhage. Neoplasms (GI tract). CML. Polycythemia vera. Myelofibrosis with myeloid metaplasia. Infections. After splenectomy. Postpartum. Hemophilia. Pancreatitis. Cirrhosis. Idiopathic.

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THYROMEGALY

ICD-9CM # CODE VARIES WITH SPECIFIC DIAGNOSIS

Goiter. Graves' disease. Thyroiditis (lymphocytic, granulomatous, suppurative). Toxic adenoma. Neoplasm (primary, metastatic).

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TICK-RELATED INFECTIONS

ICD-9CM # 082.0 066.1

ROCKY MOUNTAIN SPOTTED FEVER COLORADO TICK FEVER

088.82 BABESIOSIS 082.8

EHRLICHIOSIS

088.81 LYME DISEASE

Lyme disease. Rocky Mountain spotted fever. Babesiosis. Tularemia. Q fever. Colorado tick fever. Ehrlichiosis. Relapsing fever.

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TICS

ICD-9CM # 307.20

Tourette's syndrome. Physiologic tic. Anxiety disorder. Huntington's disease. Medications (e.g., antipsychotics, carbamazepine, phenytoin, phenobarbital). Encephalitis. Head trauma. Schizophrenia. Carbon monoxide poisoning. Stroke. Sydenham's chorea. Creutzfeldt-Jakob disease.

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TORSADES DE POINTES 19

ICD-9CM # CODE NOT AVAILABLE

Antiarrhythmics known to increase the QT interval (e.g., quinidine, procainamide, amiodarone, disopyramide, sotalol). Tricyclic antidepressants and phenothiazines. Histamine (H1) antagonists (e.g., astemizole, terfenadine). Antiviral and antifungal agents and antibiotics. Hypokinemia. Hypomagnesemia. Insecticide poisoning. Bradyarrhythmias. Congenital long QT syndrome. Subarachnoid hemorrhage. Chloroquinine, pentamidine. Cocaine abuse.

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TREMOR

ICD-9CM # 781.0 TREMOR NOS 333.1 BENIGN ESSENTIAL TREMOR 333.1 FAMILIAL TREMOR Tremor present at rest Parkinsonism. CNS neoplasms. Tardive dyskinesia. POSTURAL TREMOR (PRESENT DURING MAINTENANCE OF A POSTURE) Essential senile tremor. ACTION TREMOR (PRESENT WITH MOVEMENT) Anxiety. Medications (bronchodilators, caffeine, corticosteroids, lithium, etc.). Endocrine disorders (hyperthyroidism, pheochromocytoma, carcinoid). Withdrawal from substance abuse.

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TUBULOINTERSTITIAL DISEASE, ACUTE 12

ICD-9CM # 584.5 DRUGS Antibiotics, penicillins, cephalosporins, rifampin. Sulfonamides: cotrimoxazole, sulfamethoxazole. NSAIDs: propionic acid derivatives. Miscellaneous: phenytoin, thiazides, allopurinol, cimetidine, ifosfamide. INFECTIONS Invasion of renal parenchyma. Reaction to systemic infections: streptococcal, diphtheria, hantavirus. SYSTEMIC DISEASES Immune mediated: lupus, transplanted kidney, cryoglobulinemias. Metabolic: urate, oxalate. Neoplastic: lymphoproliferative diseases. IDIOPATHIC

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TUBULOINTERSTITIAL KIDNEY DISEASE 12

ICD-9CM # 584.5

Ischemic and toxic acute tubular necrosis. Allergic interstitial nephritis. Interstitial nephritis secondary to immune complex-related collagen vascular disease (e.g., SLE, Sjögren's). Granulomatous diseases (sarcoidosis, uveitis). Pigment-related tubular injury (myoglobinuria, hemoglobinuria). Hypercalcemia with nephrocalcinosis. Tubular obstruction (drugs such as indinavir, uric acid in tumor lysis syndrome). Myeloma kidney or cast nephropathy. Infection-related interstitial nephritis: legionella, leptospira. Infiltrative diseases (e.g., lymphoma).

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U URETHRAL DISCHARGE AND DYSURIA

ICD-9CM # 788.7 URETHRAL DISCHARGE 599.9 URETHRAL DISCHARGE BLOODY 788.1 DYSURIA

Urethritis (gonococcal, chlamydial, trichomonal). Cystitis. Prostatitis. Vaginitis (candidiasis, chemical). Meatal stenosis. Interstitial cystitis. Trauma (foreign body, masturbation, horseback or bike riding).

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URIC ACID STONES

ICD-9CM # 792.9

Hyperuricemia. Excessive dietary purine. Medications (salicylates, allopurinol, probenecid). Urine pH 55°/o)

From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders. * Left-sided symptoms of pulmonary congestion: dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea. Right-sided symptoms of systemic venous congestion: discomfort on bending, hepatic and abdominal distention, peripheral edema.

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CARDIOMYOPATHY, HYPERTROPHIC

ICD-9CM # 425.1

FIGURE 3-61 Suggested management of symptoms and risk in patients who have hypertrophic cardiomyopathy. ECG, Electrocardiogram. (From Crawford MH, DiMarco JP, Paulus WJ [eds]: Cardiology, ed 2, St Louis, 2004, Mosby.)

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CARDIOMYOPATHY, ISCHEMIC

ICD-9CM # 414.8

FIGURE 3-62 Choice of revascularization procedures in heart failure. Approaches should be dictated by the degree of left ventricular dysfunction, the presence of significant amounts of viable myocardium, the severity of valvular regurgitation, the amount of resectable myocardial scar, and suitability for ventriular assist device of heart transplant “bail out.” Targets for revascularization must also be present. These considerations will dictate, in large part, which patients may be candidates for percutaneous revascularization strategies as well. All patients regardless of procedure require appropriate medication treatments and atherosclerotic cardiovascular risk factor prevention. CABG, Coronary artery bypass graft; LVEF, left ventricular ejection fraction; PTCA, percutaneous transluminal coronary angioplasty. (From Crawford MH, DiMarco JP, Paulus WJ [eds]: Cardiology, ed 2, St Louis, 2004, Mosby.)

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CEREBRAL ISCHEMIA

ICD-9CM # 437.1 Cerebral ischemia (chronic) 435.9 Cerebral ischemia intermittent (transient)

FIGURE 3-63 Evaluation of patients with cerebral ischemia for a cardioembolic source. CT, Computed tomography; CXR, chest radiograph; ECG, electrocardiogram; MRI, magnetic resonance imaging; TIA, transient ischemic attack. (Modified from Johnson R [ed]: Current therapy in neurologic disease, ed 5, St Louis, 1997, Mosby.)

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CERVICAL DISK SYNDROME

ICD-9CM # 722.4

Degenerative intervertebral cervical disk

722.71 Degenerative cervical disk with myelopathy

FIGURE 3-64 Algorithm for suspected cervical disk syndrome. NSAID, Nonsteroidal anti-inflammatory drug; PT, physical therapy. (From Mercier LR [ed]: Practical orthopaedics, ed 6, St Louis, 2004, Mosby.)

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE

ICD-9CM # 496

COPD

492.8 Emphysema

FIGURE 3-65 Managed care guide: pharmacotherapy and general management approaches for chronic obstructive pulmonary disease (COPD). DNase, Deoxyribonuclease; Hct, hematocrit; prn, as needed; qid, four times a day; qod, every other day. (Modified from Noble J: Primary care medicine, ed 3, St Louis, 2001, Mosby.)

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CONSTIPATION

ICD-9CM # 564.0

FIGURE 3-66 Constipation. BE, Barium enema; CNS, central nervous system; CVA, cerebral vascular accident; TSH, thyroid-stimulating hormone. (From Healey PM: Common medical diagnosis, ed 3, Philadelphia, 2000, WB Saunders.)

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CONTRACEPTIVE METHOD SELECTION

ICD-9CM # V25.09

FIGURE 3-67 Helping couples select a contraceptive method. COC, Combination estrogen-progestin oral contraceptive; DMPA, depot medroxyprogesterone acetate; IUCD, intrauterine contraceptive device; P-only OC, progestin-only oral contraceptive; STD, sexually transmitted disease. (From Copeland LJ: Textbook of gynecology, ed 2, Philadelphia, 2000, WB Saunders.)

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CONTRACEPTIVE USE, ORAL

ICD-9CM # V25.01 Prescription or use, oral contraceptive

FIGURE 3-68 Contraceptive use. BP, Blood pressure; BTB, breakthrough bleeding; COC, combination oral contraceptives; CVA, cerebrovascular accident; OC, oral contraceptive. BP, Blood pressure; BTB, breakthrough bleeding; COC, combination oral contraceptives; CVA, cerebrovascular accident; OC, oral contraceptive. (From Robles TA: Use of oral contraceptives. In Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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CONVULSIVE DISORDER, PEDIATRIC AGE

ICD-9CM # 780.39

FIGURE 3-69 An approach to the child with a suspected convulsive disorder. CBC, Complete blood count; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; MRI, magnetic resonance imaging. (From Behrman RE: Nelson textbook of pediatrics, ed 18, Philadelphia, 2007, WB Saunders.)

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CORNEAL DISORDERS

ICD-9CM # 918.1 Corneal abrasion 743.9 Corneal anomalies NOS

FIGURE 3-70 Approach to the patient with corneal disorders. (From Noble J [ed]: Primary care medicine, ed 3, St Louis, 2001, Mosby.)

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CORONARY ARTERY DISEASE, UNSTABLE

ICD-9CM # 414.00

FIGURE 3-71 Recommended treatment strategy for unstable coronary artery disease. ACE, Angiotensin-converting enzyme; BNP, brain natriuretic peptide; CABG, coronary artery bypass grafting; CRP, C-reactive protein; ECG, electrocardiogram; PCI, percutaneous coronary intervention. (From Crawford MH, DiMarco JP, Paulus WJ [eds]: Cardiology, ed 2, St Louis, 2004, Mosby.)

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COUGH, CHRONIC

ICD-9CM # 786.2

FIGURE 3-72 Diagnostic approach to chronic cough. ECG, Electrocardiogram; GERD, gastroesophageal reflux disease; PND, paroxysmal nocturnal dyspnea; UGI, upper gastrointestinal tract; URI, upper respiratory infection. (From Carlson KJ et al: Primary care of women, ed 2, St Louis, 2002, Mosby.)

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CREATINE KINASE ELEVATION

ICD-9CM # V72.6

FIGURE 3-73 Evaluation of creatine kinase elevation. CBC, Complete blood count; CK, creatine kinase; CT, computed tomography; EMG, electromyography; MRI, magnetic resonance imaging. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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CUSHING'S SYNDROME

ICD-9CM #255.0

FIGURE 3-74 Cushing's syndrome. ACTH, Adrenocorticotropic hormone; CT, computed tomography; MRI, magnetic resonance imaging; PO, by mouth. (From Ferri F: Practical guide to the care of the medical patient, ed 7, St Louis, 2007, Mosby.)

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CUTANEOUS MICROVASCULAR OCCLUSION SYNDROMES

ICD-9CM #variable with specific disorder

FIGURE 3-75 Cutaneous microvascular occlusion syndromes. APL, Antiphospholipid; CBC, complete blood count; DIC, disseminated intravascular coagulation; PNH, paroxysmal nocturnal hemoglobinuria; SLE, systemic lupus erythematosus. (From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G [eds]: Dermatology, ed 2, St Louis, 2008, Mosby.)

TABLE 3-5 -- Differential Diagnosis of Cutaneous Microvascular Occlusion Based on Pathophysiology

Platelet plugging •

Heparin necrosis

•

Myeloproliferative thrombocytosis

•

Paroxysmal nocturnal hemoglobinuria

•

Thrombotic thrombocytopenic purpura

Cold-related gelling or agglutination •

Cryoglobulinemia

•

Cryofibrinogenemia

•

Cold agglutinins

Vessel-invasive organisms •

Ecthyma gangrenosum

•

Opportunistic fungi

•

Disseminated strongyloidiasis

•

Lucio phenomenon of leprosy

Embolization •

Cholesterol embolus

•

Oxalate embolus

•

Atrial myxoma

•

Marantic endocarditis

•

Libman—Sacks/antiphospholipid antibody

•

Crystal globulin vasculopathy

•

Hypereosinophilic syndrome

Systemic coagulopathies •

Neonatal purpura fulminans

•

Coumadin (warfarin) necrosis

•

Purpura fulminans of sepsis/DIC

•

Postinfectious purpura fulminans

•

Antiphospholipid antibody/lupus anticoagulant syndrome

Vascular coagulopathies •

Sneddon's syndrome

•

Livedoid vasculopathy

•

Malignant atrophic papulosis/Degos' disease

Miscellaneous •

Stress reticulocyte adhesion

•

Cutaneous calciphylaxis

From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G [eds]: Dermatology, ed 2, St Louis,

2008, Mosby. DIC, Disseminated intravascular coagulation.

TABLE 3-6 -- Basic Screening Tests for Occlusive Syndrome Complete blood count with differential, platelet count, and blood smear •

Polycythemia or anemia, granulocytosis, thrombocytosis, poikilocytosis –

•

•

•

May be sign of myeloproliferative or myelodysplastic diseases

Evidence of red cell fragmentation (schistocytes) and micro-angiopathy, consider: –

TTP/HUS

–

Purpura fulminans with DIC, occasionally

–

Antiphospholipid antibody syndrome, occasionally

Thrombocytopenia, consider: –

Heparin necrosis, some patients

–

Purpura fulminans with DIC

–

TTP/HUS

–

Antiphospholipid antibody syndrome, some patients

Severe neutropenia –

Immunocompromised; opportunistic infections very likely

Partial thromboplastin time (PTT) •

Minimally prolonged in TTP/HUS

•

Prolonged in purpura fulminans and DIC

•

Prolonged if lupus anticoagulant activity present, and assay sensitive

Cryoglobulins (occasionally cryofibrinogen and cold agglutinins) when location and history suggest cold occlusion syndrome Biopsy •

Confirms occlusion versus other mechanisms of vessel injury

•

May suggest platelet plugs instead of fibrin thrombi

•

May suggest cryoglobulin gelling

•

May suggest cholesterol, oxalate, or crystal globulin occlusion

•

Special stains for organisms in immunocompromised hosts, when appropriate

Basic hepatic and renal function screens •

Hepatic function can affect vitamin K-dependent factors and coumadin metabolism

•

Renal disease moves cutaneous calciphylaxis higher in the differen-tial diagnosis

ANCA To reduce the likelihood of the uncommon noninflammatory retiform purpura presentation of Wegener's granulomatosis or microscopic polyangiitis. ANCA may be available before permanent histology sections. From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G [eds]: Dermatology, ed 2, St Louis, 2008, Mosby.

ANCA, Antineutrophil cytoplasmic antibody; HUS, hemolytioc uremic syndrome; TTP, thrombotic thrombocytopenic purpura.

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CYANOSIS

ICD-9CM #782.5 Cyanosis NOS

FIGURE 3-76 Cyanosis. A-V, Arteriovenous; CXR, chest x-ray; V/Q, ventilation-perfusion. (From Healey PM: Common medical diagnosis: an algorithmic approach, ed 3, Philadelphia, 2000, WB Saunders.)

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CYSTITIS, ACUTE

ICD-9CM #595.0

FIGURE 3-77 Algorithm for management of acute cystitis. (From Feehally J, Floege J, Johnson RJ: Comprehensive clinical nephrology, ed 3, St Louis, 2007, Mosby.)

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D DEEP VEIN THROMBOSIS

ICD-9CM # 451.1

Thrombosis of deep veins of lower extremities

451.83 Thrombosis of deep veins of upper extremities

FIGURE 3-78 Diagnostic approach to deep vein thrombosis. CUS, Compressive ultrasound; DVT, deep vein thrombosis.

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DELIRIUM

ICD-9CM #293.0

FIGURE 3-79 Delirium. ABG, Arterial blood gas; BUN, blood urea nitrogen; CBC, complete blood count; CNS, central nervous system; C&S, culture and sensitivity; CSF, cerebrospinal fluid; CT, computed tomography; TSH, thyroid-stimulating hormone.

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DELIRIUM, GERIATRIC PATIENT

ICD-9CM # 293.0

Delirium, acute

292.81 Delirium, drug induced 293.1

Delirium, subacute

293.81 Delirium, transient organic with delusions 293.82 Delirium, transient organic with hallucinations

FIGURE 3-80 Algorithm for evaluation of suspected mental status change in an older patient. IM, Intramuscular; NG, nasogastric; PO, by mouth; PRNs, as needed; TFTs, thyroid function tests. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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DEMENTIA

ICD-9CM # 290.10 Dementia, presenile 290.0

Dementia, senile

437.0

Dementia, arteriosclerotic

FIGURE 3-81 Management of dementia. VA, Ventriculoatrial; VP, ventriculoperitoneal.

TABLE 3-7 -- Screening Tests for Diagnosis of Dementia Test Rationale Blood Test Complete blood Assess general nutritional status count

Remarks

Test

Rationale

Serum B12 level Exclude vitamin B12 deficiency TSH + free T 4 or TSH + FTI

Exclude primary and secondary hypothyroidism

HIV serology

Exclude HIV infection

Remarks Consider Schilling's test if B12 level is low

Perform only if indicated; consent from patient required

Cerebrospinal Fluid Cell count/protein level

Exclude chronic meningitis

Perform only if indicated

Cytology

Exclude carcinomatous meningitis

Perform only if indicated

VDRL

Exclude neurosyphilis

Perform only if indicated; check serum TPHA and HIV serology if CSF VDRL is positive

CT Scan/MRI/PET Scan of the Brain Identify infarcts and white matter changes; exclude presence of neoplasm, demyelinating disease, and hydrocephalus: location of atrophy may suggest the diagnosis (e.g., para-hippocampal atrophy in Alzheimer's disease, frontotemporal atrophy in Pick's disease) Electroencephalogram Exclude metabolic encephalopathies; useful if Creutzfeldt-Jakob disease or status epilepticus is suspected

Perform only if indicated

Neuropsychologic Evaluation Help to characterize pattern of cognitive impairment, which may aid in the classification of dementia; rule out pseudo-dementia from depression Modified from Johnson RT, Griffin JW: Current therapy in neurologic disease, ed 5, St Louis, 1997, Mosby. CSF, Cerebrospinal fluid; CT, computed tomography; FTI, free thyroxine index; HTV, human immunodeficiency virus; MRI, magnetic resonance imaging; PET, positron emission tomography; T 4, thyroxine; TPHA, Treponema pallidum hemagglutination assay; TSH, thyroid-stimulating hormone; VDRL, Venereal Disease Research Laboratory test.

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DEPRESSION

ICD-9CM #296.2 Major depressive disorder, single episode

FIGURE 3-82 Guidelines for the treatment of depression in the primary care setting. SSRI, Selective serotonin reuptake inhibitor. note: Time of assessment (weeks 6 and 12) rests on very modest data. It may be necessary to revise the treatment plan earlier for patients who fail to respond. (From AHCPR Quick Reference Guide of Clinicians, No. 5: Depression in primary care: Detection, diagnosis and treatment, 1993; and American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 4, Washington, DC, 1994, American Psychiatric Association.)

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DEVELOPMENTAL DELAY

ICD-9CM #783.4 Developmental delay, physiological

FIGURE 3-83 Workup for developmental delay. ALD, Adrenoleukodystrophy; CTX, cerebrotendinous xanthomatosis; MLD, metachromatic leukodystrophy; MPS, mucopolysaccharidosis; MRI, magnetic resonance imaging. (From Johnson RT, Griffin JW: Current therapy in neurologic disease, ed 5, St Louis, 1997, Mosby.)

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DIABETES INSIPIDUS

ICD-9CM #253.5

FIGURE 3-84 Diagnostic flowchart for diabetes insipidus. (From Ferri F: Practical guide to the care of the medical patient, ed 7, St Louis, 2007, Mosby.)

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DIABETIC AUTONOMIC NEUROPATHY

ICD-9CM #250.6

FIGURE 3-85 Diagnosis and treatment algorithm of diabetic autonomic neuropathy. ACE, Angiotensin-converting enzyme; ARI, aldose reductase inhibitor; BP, blood pressure; DM, diabetes mellitus; GI, gastrointestinal; HRV, heart rate variability; PGE1, prostaglandin E 1; SSR, sympathetic skin response. (Modified from Larsen PR, Kronenberg HM, Memlmed S, Polansky, KS [eds]: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders.)

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DIABETIC KETOACIDOSIS/HYPEROSMOLAR HYPERGLYCEMIC STATE

ICD-9CM # 250.1 Diabetic ketoacidosis 250.2 Hyperosmolar hyperglycemic state

FIGURE 3-86 Management of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). ABG, Arterial blood gas; DKA, diabetic ketoacidosis; ECG, electrocardiograph; HHS, hyperosmolar hyperglycemic state. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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DIARRHEA, ACUTE

ICD-9CM #787.91

FIGURE 3-87 Diagnostic steps in the assessment of acute diarrhea. IBD, Inflammatory bowel disease; IBS, irritable bowel syndrome. (Modified from Stein JH [ed]: Internal medicine, ed 5, St Louis, 1998, Mosby.)

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DIARRHEA, ACUTE

ICD-9CM #787.91

FIGURE 3-88 Diagnostic approach to the patient with chronic diarrhea (patients who are HIV negative). 5-HIAA, 5Hydroxyindoleacetic acid; VIP, vasoactive intestinal polypeptide. (Modified from Stein JH [ed]: Internal medicine, ed 5, St Louis, 1998, Mosby.)

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DIARRHEA, CHRONIC WITH HIV INFECTION

ICD-9CM #787.1 Diarrhea, chronic

FIGURE 3-89 Approach to evaluating chronic diarrhea in patients with HIV infection. WBC, White blood cell count. (Modified from Wilcox CM: Gastrointest Dis Today 5:9, 1996.)

TABLE 3-8 -- Common Gastrointestinal Pathogens Associated with HIV Infection

CD4+ Cells/µI

Stool Volume and Frequency

Abdominal Pain

Weight Loss

Fever

Fecal Leukocytes

Cytomegalovirus[*]

55 yr

Age >55 yr

Enlargement

WBC >16,000/µL

WBC >15,000/µL

Pancreatic inflammation

AST >250 U/L

LDH >600 U/L

Single fluid collection

LDH >350 U/L

Glucose >180 mg/dl

Multiple fluid collection

Glucose >200 mg/dl

Albumin 10%

Ca2+ 5 mg/dl

Arterial Po2 6 L From Goldman L, Ausiello D (eds): Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders. AST, Aspartate aminotransferase; BUN, blood urea nitrogen; LDH, lactate dehydrogenase; WBC, white blood cells.

* Three or more Ranson's criteria predict a complicated clinical course. Data from Ranson JH, Rifkind KM, Turner JW: Prognostic signs and nonoperative peritoneal lavage in acute pancreatitis. Surg Gynecol Obstet 1976:143:209-219. † Data from Blarney SL et al: Prognostic factors in acute pancreatitis, Gut 25:1340, 1984. ‡ Grades A and B represent mild disease with no risk of infection or death. Grade C represents moderately severe disease with a minimal likelihood of infection and essentially no risk of mortality. Grades D and E represent severe pancreatitis with an infection rate of 30% to 50% and mortality rate of 15%. Data from Balthazar EJ et al: Acute pancreatitis value of CT in establishing prognosis, Radiology 174:331, 1990.

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PANCREATITIS, CHRONIC

ICD-9CM # 577.1

FIGURE 3-213 Approach to the patient with painful chronic pancreatitis. ERCP, Endoscopic retrograde cholangiopancreatography; ETOH, alcohol. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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PARKINSON'S DISEASE

ICD-9CM # 332.0 Idiopathic Parkinson's desease 332.1 Parkinson's desease, secondary

FIGURE 3-214 Diagrammatic representation of a therapeutic approach to patients with parkinsonism. COMT, Catechol-O-methyl transferase; CR, controlled release; DA, dopamine. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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PATIENT WITH ILL-DEFINED PHYSICAL COMPLAINTS

ICD-9CM # 301.9

Personality disorder NOS

301.51 Munchausen syndrome

FIGURE 3-215 Patient with ill-defined physical complaints. Previous or recent evaluations are noncontributory. SSRIs, Selective serotonin reuptake inhibitors. (From Greene H, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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PELVIC MASS

ICD-9CM # 789.39

FIGURE 3-216 Approach to the patient with a pelvic mass. CT, Computed tomography; MRI, magnetic resonance imaging; US, ultrasound. (Modified from Carlson KJ et al: Primary care of women, ed 2, St Louis, 2002, Mosby.)

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PELVIC PAIN, REPRODUCTIVE-AGE WOMAN

ICD-9CM # 625.9

FIGURE 3-217 Evaluation and management of reproductive-age women with acute pelvic pain. CBC, Complete blood count; GI, gastrointestinal; GU, genitourinary; Hct, hematocrit; PID, pelvic inflammatory disease; UA/micro, urinalysis with microscopy. (From Marx JA (ed): Rosen's emergency medicine, ed 6, St Louis, 2006, Mosby.)

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PERICARDIAL EFFUSION, MALIGNANT

ICD-9CM # 420.90

FIGURE 3-218 Treatment approach to patient with known malignant pericardial effusion. CT, Computed tomography. (From Abeloff MD: Clinical oncology, ed 3, Philadelphia, 2004, Elsevier.)

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PERIPHERAL NEUROPATHY

ICD-9CM # 356.9

Peripheral nerve neuropathy

355.10 Lower extremity neuropathy 354.11 Upper extremity neuropathy

FIGURE 3-219 Approach to the patient with peripheral neuropathy. CIDP, Chronic inflammatory demyelinating polyradioneuropathy; EMG, electromyogram; NCS, nerve conduction studies. (From Greene HL, Johnson WP, Lemcke DL: Decision making in medicine, ed 2, St Louis, 1988, Mosby.)

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PHEOCHROMOCYTOMA

ICD-9CM # 194.0

FIGURE 3-220 Pheochromocytoma. IMIBG, Iodine metaiodobenzyl guanidine; MRI, magnetic resonance imaging; PET, positron emission tomography.

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PHOTOSENSITIVITY

ICD-9CM # 692.72

FIGURE 3-221 Guide to the diagnosis of cutaneous photosensitivity. The diagnosis can generally be made from patient history and clinical findings, provided the lupus titers are normal. PUVA, Photochemotherapy with psoralens. (From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G [eds]: Dermatology, ed 2, St Louis, 2008, Mosby.)

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PITUITARY TUMOR

ICD-9CM # 253

Pituitary adenoma

253.0 Acromegaly 253.1 Prolactinoma

FIGURE 3-222 Evaluation of suspected pituitary tumor. CT, Computed tomography; GH, growth hormone; IGF-I, one of the insulin-like growth factors; MRI, magnetic resonance imaging; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone. (From Greene HL, Johnson WP, Lemcke D: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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PLEURAL EFFUSION, MALIGNANT

ICD-9CM #197.2

FIGURE 3-223 Treatment approach to patient with known malignant effusion. RT, Radiation therapy; VATS, video-assisted thoracic surgery. (From Abeloff MD: Clinical oncology, ed 3, Philadelphia, 2004, Elsevier.)

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PLEURAL SPACE FLUID

ICD-9CM #511.9 Pleural effusion, unspecified

FIGURE 3-224 Evaluation, common etiologies, and management of pleural effusion and empyema. LDH, Lactate dehydrogenase; RBC, red blood cells; SLE, systemic lupus erythematosus; WBC, white blood cells. (From Kassirer J [ed]: Current therapy in adult medicine, ed 4, St Louis, 1998, Mosby.)

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POISONING, ACUTE

ICD-9CM #977.9

FIGURE 3-225 Algorithm for the management of acute poisoning. See also Table 3-16 . AC, activated charcoal; BARAs, betaadrenergic receptor antagonists; CCAs, L-type calcium channel antagonists; HF, hydrolluoric acid; MDAC, multidose activated charcoal; NS, 0.9% saline solution; PEG, nonabsorbable polyethylene glycol solution. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

TABLE 3-17 -- Common Toxicants Removed by Hemodialysis/Hemoperfusion

Toxicant

Indications

Technique Comments

Ethylene glycol

Serum level =50 ml/dl, or lower levels with concomitant metabolic acidosis and evidence of end-organ toxicity

HD

May not be required in patient with normal creatinine clearance and acid-base status who is receiving fomepizole

Lithium[*]

Clinical indications

HD

Clinical indication is CNS toxicity (e.g., decreased mental status, ataxia, coma, seizures)

Methanol

Serum level =50 ml/dl, or lower levels with concomitant metabolic acidosis and evidence of end-organ toxicity

HD

Usually required owing to slow elimination half-life in presence of fomepizole or ethanol (30.3 to 54.4 hr), even in patients with no metabolic acidosis or evidence of end-organ toxicity

Phenobarbital Clinical indications

HP/HD

Rarely necessary except when the patient is hemodynami-cally unstable despite aggressive support; clearance rates are better with HD than HP

Salicylates

HD

Serum protein binding decreases with increasing toxic levels, increasing amount of free salicylate available for HD removal; clinical indications are one or more of the following: altered mental status, seizures, pulmonary edema, intractable acidosis, renal failure

Acute toxicity: serum level >100 ml/dl or 90 µg/ml or 40 µg/dl and not declining despite MDAC; any clinical indication

Clinical indications: seizures, hypotension, ventricular arrhythmias; clearance rates better with HD than HP

From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders. CNS, Central nervous system; HD, hemodialysis; HP, hemoperfusion; MDAC, multidose activated charcoal.

* Hemodiafiltration removes lithium; clinical benefit with this technique is unknown.

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POLYCYTHEMIA

ICD-9CM #776.4

FIGURE 3-226 Diagnostic algorithm for polycythemia. JAK2V617F, JAK-2 mutation; PFCP, primary familial and congenital polycythemia; PRV-1, polycythemia rubra vera 1. (From Young NS, Gerson SL, High KA [eds]: Clinical hematology, St Louis, 2006, Mosby.)

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PREOPERATIVE EVALUATION, PATIENT WITH CORONARY HEART DISEASE

ICD-9CM # 411.89 Coronary insufficiency, acute 411.8

Coronary insufficiency, chronic

411.1

Coronary insufficiency or intermediate syndrome

FIGURE 3-227 Preoperative evaluation of patients with known or suspected coronary artery disease. (From Goldman L, Braunwald E [eds]: Primary cardiology, ed 2, Philadelphia, 2003, WB Saunders.)

TABLE 3-18 -- New York Heart Association Functional Classification Class I

No limitation

Class II Slight limitation

Ordinary physical activity does not cause symptoms Comfortable at rest Ordinary physical activity causes symptoms

Class III Marked limitation

Comfortable at rest Less than ordinary activity causes symptoms

Class IV Inability to carry on any physical activity Symptoms present at rest

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PROLACTINOMA, MANAGEMENT

ICD-9CM #253.1

FIGURE 3-228 Prolactinoma management. After secondary causes of hyperprolactinemia have been excluded, subsequent management decisions are based on clinical imaging and biochemical criteria. MRI, Magnetic resonance imaging; PRL, prolactin. (From Larsen PR, Kronenberg HM, Memlmed S, Polansky KS: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders.)

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PROSTATE CANCER

ICD-9CM #185

FIGURE 3-229 Assessment and treatment of a patient with prostate cancer suspected on the grounds of a digital rectal exam and PSA. DRE, Digital rectal examination; HM, hormonal manipulation; PSA, prostate specific antigen; TUR(P), transurethral resection (prostate); WW, watchful waiting. (Modified from Tallis RC, Fillit HM [eds]: Brocklehurst's textbook of geriatric medicine and gerontology, ed 6, London, 2003, Churchill Livingstone.)

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PROSTATIC HYPERPLASIA, BENIGN

ICD-9CM #600 Benign prostatic hyperplasia

FIGURE 3-230 Critical pathway for patients with benign prostatic hypertrophy. AUA, American Urological Association; DRE, digital rectal examination; GU, genitourinary; PSA, prostate-specific antigen; TUIP, transurethral incision of the prostate; TURP, transurethral resection of the prostate. (From Nseyo UO [ed]: Urology for primary care physicians, Philadelphia, 1999, WB Saunders.)

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PROTEINURIA

ICD-9CM #791.0

FIGURE 3-231 Proteinuria. AIDS, Acquired immunodeficiency syndrome; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic autoantibody; anti-GBM, anti–glomerular basement membrane; GN, glomerulonephritis. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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PRURITUS, GENERALIZED

ICD-9CM #698.9 Pruritus NOS

FIGURE 3-232 Evaluation of generalized pruritus. BUN, Blood urea nitrogen; CBC, complete blood count; FBS, fasting blood sugar; HBA1c, hemoglobin A1c; T4, thyroxine; TSH, thyroid-stimulating hormone. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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PRURITUS, PREGNANT PATIENT

ICD-9CM #698.9

FIGURE 3-233 An algorithmic approach to the pregnant woman presenting with pruritus. (From Black M, McKay M: Obstetrics and gynecological dermatology, ed 2, St. Louis, 2002, Mosby.)

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PRURITUS, VULVA

ICD-9CM #698.1

FIGURE 3-234 The diagnosis of vulvar pruritus. (From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G [eds]: Dermatology, ed 2, St Louis, 2008, Mosby.)

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PSEUDOGOUT

ICD-9CM #275.49

FIGURE 3-235 Algorithm for evaluation and treatment of calcium pyrophosphate dihydrate deposition disease. ACTH, Adrenocorticotropic hormone; AP, anteroposterior; CPPD, calcium pyrophosphate deposition; OA, osteoarthritis; TIBC, total iron-binding capacity; TSH, thyroid-stimulating hormone. (From Harris ED, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, et al: Kelley's textbook of rheumatology, ed 7, Philadelphia, 2005, Saunders.)

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PSEUDOHERMAPHRODITISM

ICD-9CM #752.7

FIGURE 3-236 Steps in the differential diagnosis of male pseudohermaphroditism. 3ß-HSD 11, 3ß-hydroxysteroid dehydrogenase/ 5isomerase; 17ß-HSD 3, 17ß-hydroxysteroid dehydrogenase (oxido-reductase) type 3; ACTH, adrenocorticotropic hormone; AMH, antimüllerian hormone; CYP17, 17a-hydroxylase/17,20-lyase; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; MRI, magnetic resonance imaging; SHBG, sex hormone-binding globulin; SF1, steroidogenic factor-1; T, testosterone; WAGR, Wilms tumor, aniridia, genital anomalies, and mental retardation. (From Larsen PR, Kronenberg HM, Memlmed S, Polansky KS: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders.)

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PSYCHOTIC PATIENT

ICD-9CM #301.9 Psychosomatic personality disorder

FIGURE 3-237 Evaluation of psychotic patient. ECT, Electroconvulsive therapy. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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PUBERTY, DELAYED

ICD-9CM #259.0

FIGURE 3-238 Evaluation of patient with delayed puberty. CT, Computed tomography; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; MRI, magnetic resonance imaging. (From Moore WT, Eastman RC: Diagnostic endocrinology, ed 2, St Louis, 1996, Mosby.)

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PUBERTY, PRECOCIOUS

ICD-9CM #259.1 Puberty precocious NOS

FIGURE 3-239 Evaluation of precocious puberty, excluding factitious and iatrogenic causes. CT, Computed tomography; DHEAS, dehydroepiandrosterone sulfate; FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; LH, luteinizing hormone; MRI, magnetic resonance imaging. (Modified from Odell WD: The physiology of puberty: disorders of the pubertal process. In DeGroot LJ et al [eds]: Endocrinology, vol 3, New York, 1979, Grune & Stratton.)

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PULMONARY EMBOLISM

ICD-9CM #415.1

FIGURE 3-240 Diagnostic approach to pulmonary embolism. CT, Computed tomography; CUS, compressive ultrasound of lower extremities; PE, pulmonary embolism; V/Q, ventilation/perfusion.

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PULMONARY NODULE

ICD-9CM #518.89

FIGURE 3-241 Pulmonary nodule. CT, Computed tomography; PET, positron emission tomography.

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PURPURA, PALPABLE

ICD-9CM #287.2 Purpura, NOS

FIGURE 3-242 Diagnostic algorithm for palpable purpura. AIDS, Acquired immunodeficiency syndrome; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody test; BUN, blood urea nitrogen; CBC, complete blood cell count; DIC, disseminated intravascular coagulation; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; MCV, mean corpuscular volume; RF, rheumatoid factor; U/A, urinalysis. (From Stevens GL, Adelman HM, Wallach PM: Am Fam Physician 52:1355, 1995.)

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R RED EYE, ACUTE

ICD-9CM #379.93

FIGURE 3-243 Algorithm showing diagnostic procedure for the acute red eye. HSV, Herpes simplex virus; UV, ultraviolet. (From Auerbach PS: Wilderness medicine, ed 5, St Louis, 2007, Mosby.)

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RENAL ARTERY STENOSIS

ICD-9CM #440.1

FIGURE 3-244 Approach to the anatomical evaluation of renal artery stenosis. Once stenosis is suspected, if the patient is to have another invasive arterial procedure, noninvasive imaging is deferred and a low-volume digital substraction aortogram (DSA) is done at the time of that procedure. In other cases, the clinician should assess whether a negative noninvasive test would be sufficient evidence to acquit the renal arteries. If so, noninvasive testing should be performed. If not, consideration should be given to DSA and selective angiography. Cath, Catherization; CT, computed tomography; MRA, magnetic resonance angiography. (From Zipes DP, Libby P, Bonow RO, Braunwauld E [eds]: Braunwald's heart disease, ed 7, Philadelphia, 2005, Elsevier.)

FIGURE 3-245 Approach to the angiographic evaluation and treatment of renal artery stenosis. Once a digital substraction aortogram (DSA) is performed, confirming the presence of renovascular disease, quantitative angiography and objective evaluation of the severity of stenosis should be performed. Very severe (70% diameter stenosis) lesions are subjected to revascularization, and mild lesions (50% diameter stenosis) are not. It is believed that the intermediate lesion should be assessed with physiological evaluation and/or an additional anatomical documentation of severity, such as intravascular ultrasound (IVUS). The absence of tranlesional flow acceleration or a pressure gradient should mitigate the desire to intervene. (From Zipes DP, Libby P, Bonow RO, Braunwauld E [eds]: Braunwald's heart disease, ed 7, Philadelphia, 2005, Elsevier.)

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RENAL DISEASE, ISCHEMIC

ICD-9CM #593.81

FIGURE 3-246 Clinical presentation suggestive of ischemic renal disease. ARF, acute renal failure; CTA, computed tomography angiography; CRF, chronic renal failure; DSA, digital substraction angiogram; IRD, ischemic renal disease; MRA, magnetic resonance angiography; PTRA, percutaneuos transluminal renal angioplasty; RAS, renal artery stenosis; RDS, respiratory distress syndrome. (Modified from Feehally J, Floege J, Johnson RJ: Comprehensive clinical nephrology, ed 3, St Louis, 2007, Mosby.)

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RENAL FAILURE, ACUTE

ICD-9CM #584.9 Acute renal failure, unspecified

FIGURE 3-247 Causes of acute renal failure. (From Andreoli TE [ed]: Cecil essentials of medicine, ed 7, Philadelphia, 2008, WB Saunders.)

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RENAL MASS

ICD-9CM #593.9

FIGURE 3-248 Evaluation of a patient with a renal mass. CT, Computed tomography; MRI, magnetic resonance imaging. (Modified from Williams RD: Tumors of the kidney, ureter, and bladder. In Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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RESPIRATORY DISTRESS

ICD-9CM # 786.09 Respiratory distress NOS 518.82 Respiratory distress, acute

FIGURE 3-249 Respiratory distress pediatric patient. ABG, Arterial blood gas; Abn, abnormal; CF, cystic fibrosis; CHF, congestive heart failure; WNL, within normal limits. (From Barkin RM, Rosen P: Emergency pediatrics, St Louis, 1999, Mosby.)

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RETICULOCYTE COUNT, ELEVATED

ICD-9CM #790.99

FIGURE 3-250 Differential diagnosis of elevated reticulocyte count. DIC, Disseminated intravascular coagulation; G6PD, glucose-6phosphate dehydrogenase; HIV, human immunodeficiency virus; LDH, lactic dehydrogenase; TTP, thrombotic thrombocytopenic purpura. (From Rakel RE [ed]: Principles of family practice, ed 7, Philadelphia, 2007, WB Saunders.)

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RHINORRHEA

ICD-9CM #478.1

FIGURE 3-251 Approach to a patient with rhinorrhea. CT, Computed tomography; MRI, magnetic resonance imaging. (From Noble J [ed]: Primary care medicine, ed 3, St Louis, 2001, Mosby.)

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S SCHILLING TEST

ICD-9CM #281.0

FIGURE 3-252 Schilling test. IM, Intramuscular. (From Ferri FF: Practical guide to the care of the medical patient, ed 7, St Louis, 2007, Mosby.)

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SCOLIOSIS

ICD-9CM # 737.30 Idiopathic scoliosis 737.39 Paralytic scoliosis 754.2

Congenital scoliosis

724.3

Sciatic scoliosis

737.43 Associated with neurofibromatosis

FIGURE 3-253 Scoliosis screening and follow-up. AP, Anteroposterior. (From Driscoll C [ed]: The family practice desk reference, ed 3, St Louis, 1996, Mosby.)

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SCROTAL MASS

ICD-9CM #608.89

FIGURE 3-254 Evaluation of scrotal mass. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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SEPSIS AND SEPTIC SHOCK

ICD-9CM #038.9

FIGURE 3-255 Diagnostic evaluation and management of sepsis and septic shock. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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SEPTIC ARTHRITIS

ICD-9CM #711.0

FIGURE 3-256 Algorithm for synovial fluid analysis in septic arthritis. OA, Osteoarthritis; RA, rheumatoid arthritis. (From Harris ED, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, Sledge CB [eds]: Kelley's textbook of rheumatology, ed 7, Philadelphia, 2005, Saunders.)

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SEXUAL DYSFUNCTION

ICD-9CM # 309.2 Sexual disorder (psychosexual) V41.7 Sexual function problem

FIGURE 3-257 Evaluation of sexual dysfunction. FSH, Follicle-stimulating hormone; LH, luteinizing hormone; SSRI, selective serotonin reuptake inhibitor. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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SEXUAL PRECOCITY, FEMALE BREAST DEVELOPMENT

ICD-9CM #259.1

FIGURE 3-258 The diagnosis of sexual precocity in girls. LH, Luteinizing hormone; LHRH, luteinizing hormone-releasing hormone; MRI, magnetic resonance imaging; T4, thyroxine; TSH, thyroid-stimulating hormone; yrs, years. (From Larsen PR, Kronenberg HM, Memlmed S, Polansky, KS [eds]: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders.)

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SEXUAL PRECOCITY, FEMALE PUBIC HAIR DEVELOPMENT

ICD-9CM #259.1

FIGURE 3-259 The evaluation of pubic hair in normal phenotypic girls before 7 years. DHEA, Dehydroepiandrosterone; 17-OH-P, 17hydroxy progesterone. (From Larsen PR, Kronenberg HM, Memlmed S, Polansky, KS [eds]: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders.)

TABLE 3-19 -- Differential Diagnosis of Sexual Precocity

Plasma Gonadotropins

LH Response to berum bex bteroid LHRH Concentration Gonadal Size

Miscellaneous

In Both Sexes McCune-Albright Suppressed syndrome

Suppressed

Sex steroids pubertal or higher

Ovarian (on ultrasound); slight testicular enlargement

Skeletal survey for polyostotic fibrous dysplasia and skin examination for cafe au lait spots

Primary hypothyroidism

Prepubertal FSH may be increased

Estradiol may be pubertal

Testicular enlargement; ovaries cystic

TSH and prolactin elevated; T4 low

Granulosa cell Suppressed tumor (follicular cysts may present similarly)

Prepubertal LH response

Very high estradiol Ovarian enlargement on physical examination, CT, or ultrasonography

Tumor often palpable on abdominal examination

Follicular cyst

Suppressed

Prepubertal LH response

Prepubertal to very Ovarian high estradiol enlargement on physical examination, CT, or ultrasonography

Single or recurrent episodes of menses and/or breast development; exclude McCuneAlbright syndrome

Feminizing adrenal tumor

Suppressed

Prepubertal LH response

High estradiol and DHEAS values

Ovaries prepubertal

Unilateral adrenal mass

Premature thelarche

Prepubertal

Prepubertal LH, pubertal estradiol response

Prepubertal or early

Ovaries prepubertal

Onset usually before 3 years of age

Premature adrenarche

Prepubertal

Prepubertal LH response

Prepubertal estradiol; DHEAS or urinary 17ketosteroid values appropriate for pubic hair stage 2

Ovaries prepubertal

Onset usually after 6 years of age; more frequent in brain-injured children

Late-onset viril izing congenital adrenal hyperplasia

Prepubertal

Prepubertal LH response

Elevated 17-OHP in basal or corticotropinstimulated state

Ovaries prepubertal

Autosomal recessive

LH prepubertal: FSH may be slightly elevated

Females

From Larson PR, Kronenberg HM, Memlmed S, Polansky, KS [eds]: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders. CNS, Central nervous system; CT, computed tomography; DHEAS, dehydroepiandrosterone sulfate; hCG, human chorionic gonadotropin; LH, luteinizing hormone; MRI, magnetic resonance imaging; 17-OHP, 17hydroxyprog-esterone; T 4, thyroxine; TSH, thyrotropin.

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SEXUAL PRECOCITY, MALE

ICD-9CM #259.1

FIGURE 3-260 The diagnosis of sexual precocity in a phenotypic male. CAH, Congenital adrenal hyperplasia; DHEA, dehydroepiandrosterone; hCG, human chorionic gonadotropin; LH, luteinizing hormone; LHRH, luteinizing hormone-releasing hormone; 17OH-P, 17-hydroxyprogesterone. (From Larsen PR, Kronenberg HM, Memlmed S, Polansky, KS [eds]: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders.)

TABLE 3-20 -- Differential Diagnosis of Sexual Precocity

LH Plasma Response Gonadotropins to LHRH True Precocious Puberty (premature reactivation of LHRH pulse generator)

Prominent LH pulses, initially during sleep

Serum Sex Steroid Concentration

Gonadal Size

Miscellaneous

Pubertal LH Pubertal values of Normal pubertal response testosterone or testicular estradiol enlargement or ovarian and uterine enlargement (by ultrasonography)

MRI of brain to rule out CNS tumor or other abnormality; skeletal survey for McCune-Albright syndrome

Chorionic High hCG, low gonadotropinsecreting LH tumor in males

Prepubertal Pubertal value of LH testosterone response

Slight to moderate uniform enlargement of testes

Hepatomegaly suggests hepatoblastoma: CT scan of brain if chorionic gonadotropinsecreting CNS tumor suspected

Leydig cell tumor in males

Suppressed

No LH response

Very high testosterone

Irregular assymmetrical enlargement of testes

Familial testotoxicosis

Suppressed

No LH response

Pubertal values of Testes testosterone symmetrical and larger than 2.5 cm but smaller than expected for pubertal development; spermato-genesis occurs

Virilizing congenital adrenal hyperplasia

Prepubertal

Prepubertal Elevated 17-OHP Testes LH in CYP21 prepubertal response deficiency or elevated 11deoxycortisol in CYP11B1 deficiency

Autosomal recessive, may be congenital or lateonset form, may have salt loss in CYP21 deficiency or hypertension in CYP11B1 deficiency

Virilizing adrenal tumor Prepubertal

Prepubertal High DHEAS and Testes LH androstenedione prepubertal response values

CT, MRI, or ultrasonography of abdomen

Premature adrenarche Prepubertal

Prepubertal Prepubertal LH testosterone, response DHEAS, or urinary 17-

Onset usually after 6 years of age; more frequent in CNS-injured

Incomplete Sexual Precocity (pituitary gonadotropinindependent) Males

Testes prepubertal

Familial; probably sex-limited, autosomal dominant trait

LH Plasma Response Gonadotropins to LHRH

Serum Sex Steroid Concentration Gonadal Size urinary 17ketosteroid values appropriate for pubic hair stage 2

Miscellaneous CNS-injured children

In Both Sexes McCune-Albright syndrome

Suppressed

Suppressed Sex steroids Ovarian (on pubertal or higher ultrasound); slight testicular enlargement

Primary hypothyroidism

LH prepubertal: Prepubertal Estradiol may be FSH may be FSH may pubertal slightly elevated be increased

Testicular enlargement; ovaries cystic

Skeletal survey for polyostotic fibrous dysplasia and skin examination for cafe au lait spots TSH and prolactin elevated; T4 low

From Larson PR, Kronenberg HM, Memlmed S, Polansky, KS [eds]: Williams textbook of endocrinology, ed 11, Philadelphia, 2008, Saunders. CNS, Central nervous system; CT, computed tomography; DHEAS, dehydroepiandrosterone sulfate; hCG, human chorionic gonadotropin; LH, luteinizing hormone; MRI, magnetic resonance imaging; 17-OHP, 17hydroxyprog-esterone; T 4, thyroxine; TSH, thyrotropin.

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SHIN SPLINTS

ICD-9CM #844.9

FIGURE 3-261 Evaluation and management of shin splints. MRI, Magnetic resonance imaging. (Modified from Scudieri G [ed]: Sports medicine, principles of primary care, St Louis, 1997, Mosby.)

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SHOCK

ICD-9CM # 785.50 ShockNOS 995.0

Shock anaphylactic

785.51 Shock cardiogenic 785.59 Shock septic Hypotension 958.4

Shock traumatic Tachycardia

977.9

Shock due to drug, Peripheral hypoperfusion medicine incorrectly administered

FIGURE 3-262 An approach to the diagnosis and treatment of shock. BUN, Blood urea nitrogen; CT, computed tomography; LV, left ventricular; MAP, mean arterial pressure; MRI, magnetic resonance imaging; PA, pulmonary arterial; PCWP, pulmonary capillary wedge pressure, PT, prothrombin time; PTT, partial thromboplastin time; RV, right ventricular; WBC, white blood cell count. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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SHOULDER PAIN

ICD-9CM # variable with specific disorder

FIGURE 3-263 Algorithmic evaluation of shoulder pain. AC, Acromioclavicular; AP, anteroposterior; GH, glenohumeral; Hx, history; MRI, magnetic resonance imaging; NSAID, nonsteroidal anti-inflammatory drug; PRN, as required; PT, physical therapy; R/O, rule out; ROM, range of motion; Sx, symptoms; trx, traction; Tx, therapy. Algorithmic evaluation of shoulder pain. AC, Acromioclavicular; AP, anteroposterior; GH, glenohumeral; Hx, history; MRI, magnetic resonance imaging; NSAID, nonsteroidal anti-inflammatory drug; PRN, as required; PT, physical therapy; R/O, rule out; ROM, range of motion; Sx, symptoms; trx, traction; Tx, therapy. (From Harris ED, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, Sledge CB [eds]: Kelley's textbook of rheumatology, ed 7, Philadelphia, Saunders.)

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SJÖGREN'S SYNDROME

ICD-9CM # 710.2

FIGURE 3-264 Algorithm for the diagnosis of Sjögren's syndrome. (From Tzoufas AG, Moutsopoulos HM: Sjögren's syndrome. In Klippel JH, Dieppe P [eds]: Rheumatology, ed 2, London, 1998, Mosby, with permission.)

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SKIN BLISTERS

ICD-9CM # 709.8

FIGURE 3-265 An approach to the patient with blistering of the skin. BP, Bullous pemphigoid; CRF, chronic renal failure; EBA, epidermolysis bullosa acquisita. (From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G [eds]: Dermatology, ed 2, St Louis, 2008, Mosby.)

TABLE 3-21 -- Investigative Tests Used in the Diagnosis of Porphyria Porphyria Enzyme Urine Stool Porphyria cutanea tarda

Uroporphyrinogen decarboxylase

URO + + + ISOCOPRO+ +

Plasma

RBC

+

-

COPRO + 7COOH 7COOH III>I Erythropoietic protoporphyria

Ferrochelatase

Congenital erythropoietic porphyria Uroporphyrinogen III synthase

Normal

PROTO +

+

free PROTO+ +

URO 1 +

COPRO 1+

+

URO 1+

COPRO 1 +

COPRO 1+ PROTO +

Porphyria

Enzyme

Urine

Acute intermittent porphyria

Porphobilinogen deaminase

[*]ALA+

+

Stool

Plasma

RBC

[*]ALA +

-

-

+ [*]PBG

++

[*]PBG

+

+ Variegate porphyria

Protoporphyrinogen oxidase

[*]ALA+

[*]PBG

+

COPRO +

625—7 nm peak

+ + PROTO+ +

URO +

PORPHX+ + +

COPRO+ + Heriditary coproporphyria

Coproporphyrinogen oxidase

[*]ALA+

[*]PBG

+

COPRO +

+

-

-

Zn PROTO +

+

Zn and free

++

COPRO+ + URO + Aminolevulinic acid (ALA) dehydratase-deficient porphyria

ALA dehydratase

Hepatoerythropoietic porphyria

Uroporphyrinogen decarboxylase

AIA + + + COPROIII

URO + + + ISOCOPRO+ + COPRO + 7COOH

PROTO+ +

7COOH III>I Tyrosinemia

ALA dehydratase

ALA

-

-

-

Iron deficiency

Ferrochelatase

-

-

-

Zn PROTO+ +

Lead poisoning

ALA dehydratase

AIA + + +

Coproporphyrinogen oxidase

COPRO ±

-

-

Zn PROTO +

Ferrochelatase From Bolognia JL, Mascaro JM, Mancini AJ, Salasche SJ, Saurat JH, Stingl G (eds): Dermatology, ed 2, St Louis, 2008, Mosby. COPRO, Coproporphyrin; ISO-COPRO, isoco pro porphyrin; PROTO, protoporphyrin; RBC, red blood cells; URO, uroporphyrin; +, positive; —, negative;

* during acute attack.

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SLEEP DISORDERS

ICD-9CM # 780.50 Sleep disorder, unspecified cause

FIGURE 3-266 A, Patient with sleep disturbance. MSLT, Multiple sleep latency tests; PSG, polysomnography. B, Hypersomnia. CNS, Central nervous system; EMG, electromyelogram; MSLTs, multiple sleep latency tests; PSG, polysomnography; SDC, sleep disorders clinic. C, Sleep-associated affective and behavioral disturbance. EEG, Electroencephalogram; PSG, polysomnography. (From Greene HL, Johnson WP, Lemcke D [eds]: Decision making in medicine, ed 2, St Louis, 1998, Mosby.)

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SPINE TUMOR

ICD-9CM # 192.2

FIGURE 3-267 Diagnostic and therapeutic approach to tumors of the spine. CT, Computed tomography; IV, intravenous; MRI, magnetic resonance imaging. (From Abeloff MD: Clinical oncology, ed 3, Philadelphia, 2004, Elsevier.)

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SPLENOMEGALY

ICD-9CM # 789.2

Splenomegaly, unspecified

289.51 Splenomegaly, chronic congestive 759.0

Splenomegaly, congenital

789.2

Splenomegaly, unknown etiology

FIGURE 3-268 Clinical approach to patient with splenomegaly. CT, Computed tomography. (Modified from Stein JH [ed]: Internal medicine, ed 5, St Louis, 1998, Mosby.)

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SPONDYLOARTHROPATHY, DIAGNOSIS

ICD-9CM # 720.7

FIGURE 3-269 Algorithm for diagnosis of the spondyloarthropathies. (From Goldman L, Ausiello D: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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SPONDYLOARTHROPATHY, TREATMENT

ICD-9CM # 720.7

FIGURE 3-270 Treatment algorithm for patients with a spondyloarthropathy. FDA, Food and Drug Administration; NSAID, nonsteroidal anti-inflammatory drug. (From Goldman L, Ausiello D: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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SPONDYLOSIS, CERVICAL

ICD-9CM # 721.0

FIGURE 3-271 Algorithm for the treatment of cervical spondylosis. MRI, Magnetic resonance imaging. (From Ronthal M, Rachlin JR: Cervical spondylosis. In Johnson RT, Griffin JW [eds]: Current therapy in neurologic disease, ed 5, St Louis, 1997, Mosby.)

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STRABISMUS

ICD-9CM # 378.9

FIGURE 3-272 Diagnostic tests that help differentiate between common causes of strabismus. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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STROKE

ICD-9CM # 436

FIGURE 3-273 Algorithm for the emergency evaluation of a patient with suspected stroke. BP, Blood pressure; CBC, complete blood count; CT, computed tomography; RBCs, red blood cells; tPA, tissue plasminogen activator. (From Goldman L, Ausiello D [eds]: Cecil textbook of medicine, ed 23, Philadelphia, 2008, WB Saunders.)

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SYNCOPE

ICD-9CM # 720.2

FIGURE 3-274 Syncope evaluation. CNS, Central nervous system; CT, computed tomography; ECG, electrocardiograph; EEG, electroencephalograph; EPS, electrophysiologic. (From Ferri FF: Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009, Elsevier Mosby.)

BOX 3-12

Syncope Diagnostic imaging

Best test None. Diagnostic imaging should be guided by history and physical exam

Ancillary tests Echocardiography is useful in patients with a heart murmur to r/o aortic stenosis, hypertrophic cardiomyopathy, or atrial myxoma If seizure is suspected, CT of head and EEG are indicated Spiral CT of chest or ventilation/perfusion scan if PE is suspected Lab evaluation

Best test None

Ancillary tests Routine blood tests rarely yield diagnostically useful information and should be done only when specifically suggested by history and physical exam Serum pregnancy test should be considered in women of childbearing age CBC, lytes, BUN, creatinine Serum calcium, magnesium ABGs ECG Cardiac troponins, isoenzymes if history of chest pain before syncope Toxicology screen in selected patients Cardiac stress test Electrophysiologic (EPS) studies From Ferri FF: Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009, Elsevier Mosby.ABG, Arterial blood gas; BUN, blood urea nitrogen; CBC, complete blood count; CT, computed tomography; ECG, electrocardiograph; EEG, electroencephalograph.

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SYPHILIS TESTING

ICD-9CM # 097.9

FIGURE 3-275 Interpretation of reactive serologic tests for syphilis. CSF, cerebrospinal fluid; FTA-ABS, fluorescent treponemal antibody absorption; RPR, rapid plasma reagent; STD, sexually transmitted disease. (From Habif TA: Clinical dermatology, ed 4, St Louis, 2004, Mosby.)

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SYSTEMIC SCLEROSIS

ICD-9CM # 710.1

FIGURE 3-276 Management strategies in systemic sclerosis. (From Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH: Rheumatology, ed 3, St Louis, 2003, Mosby.)

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T TACHYCARDIA

ICD-9CM # 785.0

FIGURE 3-277 Stepwise approach to the diagnosis of type of tachycardia based on 12-lead electrocardiogram during the episode. The initial step is to determine whether the tachycardia has a wide or narrow QRS complex. For wide-complex tachycardia, see Figure 3-265 ; the remainder of the algorithm is helpful in diagnosiing the type of narrow-complex tachycardia. AP, Accessory pathway; AT, atrial tachycardia; AV, atrioventricular; AVNRT, AV nodal reentrant tachycardia; AVRT, AV reciprocating tachycardia; CSM, carotid sinus massage; SANRT, sinoatrial nodal reentry tachycardia; SVT, supraventricular tachycardia. (From Zipes DP, Libby P, Bonow RO, Braunwald E [eds]: Braunwald's heart disease, ed 7, Philadelphia, 2005, Elsevier.)

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TACHYCARDIA, NARROW COMPLEX

ICD-9CM # 427.2 427.0

Paroxysmal tachycardia Supraventricular paroxysmal tachycardia

427.42 Ventricular flutter 427.1

Ventricular paroxysmal tachycardia

427.89 Atrial tachycardia

FIGURE 3-278 Evaluation and management of narrow complex tachycardia. AV, Atrioventricular; COPD, chronic obstructive pulmonary disease; EPS, electrophysiologic studies; IV, intravenous; IVP, intravenous push; PSVT, paroxysmal supraventricular tachycardia; RF, radiofrequency.

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TACHYCARDIA, WIDE COMPLEX

ICD-9CM # 427.2 427.0

Paroxysmal tachycardia Supraventricular paroxysmal tachycardia

427.42 Ventricular flutter 427.1

Ventricular paroxysmal tachycardia

427.89 Atrial tachycardia

FIGURE 3-279 Evaluation and management of wide complex tachycardia. AV, Atrioventricular; EP, electrophysiologic; IV, intravenous; SVT, supraventricular tachycardia; VT, ventricular tachycardia. (From Driscoll CE et al: The family practice desk reference, ed 3, St Louis, 1996, Mosby.)

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TESTICULAR MASS

ICD-9CM # 186.9 M906/3

Testicular neoplasm (seminoma)

M9101/3 (embryonal carcinoma or teratoma) M9100/3 (choriocarcinoma)

FIGURE 3-280 Diagnosis, staging, and risk assessment of patients with testicular germ cell tumor. AFP, Alpha-fetoprotein; CT, computed tomography; hCG, human chorionic gonadotropin; LDH, lactic dehydrogenase; NSGCT, nonseminoma germ cell tumor. (From Abeloff MD: Clinical oncology, ed 3, New York, 2004, Churchill Livingstone.)

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THORACIC OUTLET SYNDROME

ICD-9CM # 353.0

FIGURE 3-281 Thoracic outlet syndrome. EMG, Electromyogram; MRI, magnetic resonance imaging.

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THROMBOCYTOPENIA

ICD-9CM # 287.3 Congenital or primary 287.4 Secondary 287.5 Thrombocytopenia NOS

FIGURE 3-282 Evaluation of thrombocytopenia. DIC, Disseminated intravascular coagulation; ITP, idiopathic thrombocytopenic purpura; LDH, lactic dehydrogenase; PPT, partial thromboplastin time; TTP, thrombotic thrombocytopenic purpura. (From Ferri FF: Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009, Elsevier Mosby.)

BOX 3-13

Thrombocytopenia Diagnostic imaging

Best Test None

Ancillary test CT of abdomen if splenomegaly is present Lab evaluation

Best Test Bone marrow exam

Ancillary tests CBC, PT, PTT LDH HIV, ANA Antiplatelet Ab D-dimer

Coombs' tests From Ferri FF: Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009, Elsevier Mosby.ANA, Antibody to nuclear antigens; CBC, complete blood count; CT, computed tomography; HIV, human immunodeficiency virus; LDH, lactic dehydrogenase; PT, prothrombin time; PTT, partial thromboplastin time.

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THROMBOCYTOSIS

ICD-9CM # 289.9

FIGURE 3-283 Thrombocytosis diagnosis. CBC, Complete blood count; CML, chronic myelogenous leukemia; CT, computed tomography; Fe, iron; Hb/Hct, hemoglobin/hematocrit; TIBC, total iron-binding capacity. (From Ferri FF: Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009, Elsevier Mosby.)

BOX 3-14

Thrombocytosis Diagnostic imaging

Best Test None

Ancillary test CT of chest and abdomen Lab evaluation

Best Test Bone marrow exam

Ancillary tests CBC Reticulocyte count Stool for OB ×3 Serum ferritin, TIBC, iron From Ferri FF: Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009, Elsevier Mosby.CBC, Complete blood count; CT, computed tomography; OB, occult blood; TIBC, total iron-binding capacity.

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THROMBOTIC MICROANGIOPATHIES

ICD-9CM # 453.9

FIGURE 3-284 Algorithm for the differential diagnosis of thrombotic microangiopathies. Patients with suggestive symptoms should be investigated for specific signs of microangiopathic hemolysis. In adults, secondary forms of the disease must be ruled out. Early diagnosis may help establish the most appropriate therapy. In children with Shiga toxin–associated hemolytic-uremic syndrome (HUS), supportive treatment is mandatory. Specific therapies should be considered only in adults and in atypical forms. In secondary forms, treating and/or removing the underlying disease is fundamental. LDH, Lactate dehydrogenase. (From Feehally J, Floege J, Johnson RJ: Comprehensive clinical nephrology, ed 3, St. Louis, 2007, Mosby.)

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THROMBOTIC THROMBOCYTOPENIC PURPURA AND HEMOLYTIC-UREMIC SYNDROME

ICD-9CM # 446.6

Thrombotic thrombocytic purpura

ICD-9CM # 283.11 Hemolytic-uremic syndrome

FIGURE 3-285 Algorithm for diagnosis of thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). MCP, Membrane cofactor protein; PT, prothrombin time; PTT, partial thromboplastin time; RBC, red blood cell count. (From Young NS, Gerson SL, High KA [eds]: Clinical hematology, St Louis, 2006, Mosby.)

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THYROID NODULE

ICD-9CM # 241.0 Nodule, thyroid

FIGURE 3-286 Diagnostic evaluation of solitary thyroid nodule. High risk for malignancy: nodule >2 cm, age 670 nkat/L [CF: 16.67; SMI: 10 nkat/L]) Elevated in: Sarcoidosis, primary biliary cirrhosis, alcoholic liver disease, hyperthyroidism, hyperparathyroidism, diabetes mellitus, amyloidosis, multiple myeloma, lung disease (asbestosis, silicosis, berylliosis, allergic alveolitis, coccidioidomycosis), Gaucher's disease, leprosy ANION GAP Normal range: 9-14 mEq/L Elevated in: Lactic acidosis, ketoacidosis (diabetes, alcoholic starvation), uremia (chronic renal failure), ingestion of toxins (paraldehyde, methanol, salicylates, ethylene glycol), hyperosmolar nonketotic coma, antibiotics (carbenicillin)

Decreased in: Hypoalbuminemia, severe hypermagnesemia, IgG myeloma, lithium toxicity, laboratory error (falsely decreased sodium or overestimation of bicarbonate or chloride), hypercalcemia of parathyroid origin, antibiotics (e.g., polymyxin) ANTICARDIOLIPIN ANTIBODY (ACA) Normal range: Negative: Test includes detection of IgG, IgM, and IgA antibody to phospholipid, cardiolipin Present in: Antiphospholipid antibody syndrome, chronic hepatitis C ANTICOAGULANT; see CIRCULATING ANTICOAGULANT ANTI-DNA Normal range: Absent Present in: Systemic lupus erythematosus, chronic active hepatitis, infectious mononucleosis, biliary cirrhosis ANTIGLOMERULAR BASEMENT ANTIBODY; see GLOMERULAR BASEMENT MEMBRANE ANTIBODY ANTIMITOCHONDRIAL ANTIBODY Normal range: >1:20 titer Elevated in: Primary biliary cirrhosis (85% to 95%), chronic active hepatitis (25% to 30%), cryptogenic cirrhosis (25% to 30%) ANTINEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA) Positive test: Cytoplasmic pattern (cANCA): positive in Wegener's granulomatosis Perinuclear pattern (pANCA): positive in inflammatory bowel disease, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune chronic active hepatitis, crescenteric glomerulonephritis ANTINUCLEAR ANTIBODY (ANA) Normal range: >1:20 titer Positive test: Systemic lupus erythematosus (more significant if titer >1:160), drugs (phenytoin, ethosuximide, primidone, methyldopa, hydralazine, carbamazepine, penicillin, procainamide, chlorpromazine, griseofulvin, thiazides), chronic active hepatitis, age over 60 years (particularly age over 80 years), rheumatoid arthritis, scleroderma, mixed connective tissue disease, necrotizing vasculitis, Sjögren's syndrome, tuberculosis, pulmonary interstitial fibrosis. Table 4-3 describes diseases associated with ANA subtypes. Fig. 4-1 illustrates various fluorescent ANA test patterns.

TABLE 4-3 -- Disease-Associated ANA Subtypes

Nuclear Location

Disease(s)

“Native” DNA (dsDNA, or dsDNA/ssDNA complex)

SLE (60%-70%; range, 35%-75%)

sNP

SLE (50%)

—also PSS (5%-55%), MCTD (ll%-25%), RA (5%-40%), DM (5%-25%), SS (5%)

—also other collagen diseases DNP (DNA-histone complex)

SLE (52%) —also MCTD (8%), RA (3%)

Histones

Drug-induced SLE (95%) —also SLE (30%), RA (15%-24%)

ENA Sm

SLE (30%-40%; range, 28%-40%) —also MCTD (0%-8%)

RNP (Ul-RNP)

MCTD (in high titer without any other ANA subtype present: 95%-100%) —also SLE (26%-50%), PSS (ll%-22%), RA (10%), SS (3%)

SS-A (Ro)[*]

SS without RA (60%-70%) —also SLE (26%-50%), neonatal SLE (over 95%), PSS (30%), MCTD (50%), SS with RA (9%), PBC (15%-19%)

SS-B (La)

SS without RA (40%-60%) —also SLE (5%-15%), SS with RA (5%)

Scl-70[*]

PSS (15%-43%)

Centromere[*]

CREST syndrome (7O%-90%; range 57%-96%) —also PSS (4%-20%), PBC (12%)

Nucleolar

PSS (scleroderma) (54%-90%) —also SLE (25%-26%), RA (9%)

RAP (RANA)

SS with RA (60%-76%) —also SS without RA (5%)

Jo-1

Polymyositis (30%)

PM-1

Polymyositis or PMS/PSS overlap syndrome (6O%-90%) —also DM (17%)

ssDNA

SLE (60%-70%) —also CAH, infectious mononucleosis, RA, chronic GN, chronic infections, PBC

Cytoplasmic Location

Disease(s)

Mitochondrial

Primary biliary cirrhosis (90%-100%) —also CAH (7%-30%), cryptogenic cirrhosis (30%), acute hepatitis, viral hepatitis (3%), other liver diseases (0%-20%), SLE (5%), SS and PSS (8%)

Microsomal [†]

Chronic active hepatitis (60%-8O%), Hashimoto's thyroiditis (97%)

Ribosomal

SLE (5%-12%)

From Ravel R: Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby.

Nuclear Location

Disease(s)

Smooth muscle[‡]

Chronic active hepatitis (60%-91%) —also cryptogenic cirrhosis (28%), acute hepatitis, viral hepatitis (5%-87%), infectious mononucleosis (81%), MS (40%-50%), malignancy (67%), PBC (10%50%)

From Ravel R: Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby. CAH, Chronic active hepatitis; DM, dermatomyositis; GN, glomerulonephritis; MS, multiple sclerosis; PBC, primary biliary cirrhosis; SS, Sjögren's syndrome.

* Not detected using rat or mouse liver or kidney tissue method. † Not detected by cultured cell method. ‡ Detected by cultured cells but better with rat or mouse tissue.

FIGURE 4-1 Fluorescent antinuclear antibody test patterns (HEP-2 cells). A, Solid (homogeneous). B, Peripheral (rim). C, Speckled. D, Nucleolar. E, Anticentromere. F, Antimitochondrial. G, Normal (nonreactive). (From Ravel R [ed]: Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby.)

ANTI-RNP ANTIBODY; see EXTRACTABLE NUCLEAR ANTIGEN ANTI-Sm (ANTI-SMITH) ANTIBODY; see EXTRACTABLE NUCLEAR ANTIGEN ANTI-SMOOTH MUSCLE ANTIBODY; see SMOOTH MUSCLE ANTIBODY ANTISTREPTOLYSIN O TITER (Streptozyme, ASLO titer) Normal range for adults: >160 Todd units Elevated in: Streptococcal upper airway infection, acute rheumatic fever, acute glomerulonephritis, increased levels of ß-lipoprotein

note: A fourfold increase in titer between acute and convalescent specimens is diagnostic of streptococcal upper airway infection regardless of the initial titer. ANTITHROMBIN III Normal range: 81% to 120% of normal activity; 17-30 mg/dl Decreased in: Hereditary deficiency of antithrombin III, disseminated intravascular coagulation, pulmonary embolism, cirrhosis, thrombolytic therapy, chronic liver failure, postsurgery, third trimester of pregnancy, oral contraceptives, nephrotic syndrome, IV heparin >3 days, sepsis, acute leukemia, carcinoma, thrombophlebitis Elevated in: Warfarin drugs, post–myocardial infarction ARTERIAL BLOOD GASES Normal range: Po2: 75-100 mm Hg Pco2: 35-45 mm Hg HCO3: 24-28 mEq/L pH: 7.35-7.45 Abnormal values: Acid-base disturbances (see the following) METABOLIC ACIDOSIS Metabolic acidosis with increased AG (AG acidosis) Lactic acidosis Ketoacidosis (diabetes mellitus, alcoholic ketoacidosis) Uremia (chronic renal failure) Ingestion of toxins (paraldehyde, methanol, salicylate, ethylene glycol) High-fat diet (mild acidosis) Metabolic acidosis with normal AG (hyperchloremic acidosis) Renal tubular acidosis (including acidosis of aldosterone deficiency) Intestinal loss of HCO3- (diarrhea, pancreatic fistula)

Carbonic anhydrase inhibitors (e.g., acetazolamide) Dilutional acidosis (as a result of rapid infusion of bicarbonate-free isotonic saline) Ingestion of exogenous acids (ammonium chloride, methionine, cystine, calcium chloride) Ileostomy Ureterosigmoidostomy Drugs: amiloride, triamterene, spironolactone, ß-blockers RESPIRATORY ACIDOSIS Pulmonary disease (COPD, severe pneumonia, pulmonary edema, interstitial fibrosis) Airway obstruction (foreign body, severe bronchospasm, laryngospasm) Thoracic cage disorders (pneumothorax, flail chest, kyphoscoliosis) Defects in muscles of respiration (myasthenia gravis, hypokalemia, muscular dystrophy) Defects in peripheral nervous system (amyotrophic lateral sclerosis, poliomyelitis, Guillain-Barrè syndrome, botulism, tetanus, organophosphate poisoning, spinal cord injury) Depression of respiratory center (anesthesia, narcotics, sedatives, vertebral artery embolism or thrombosis, increased intracranial pressure) Failure of mechanical ventilator METABOLIC ALKALOSIS Intestinal loss of HCO It is divided into chloride-responsive (urinary chloride >15 mEq/L) and chloride-resistant forms (urinary chloride level >15 mEq/L) Chloride-responsive Vomiting Nasogastric (NG) suction Diuretics Posthypercapnic alkalosis

Stool losses (laxative abuse, cystic fibrosis, villous adenoma) Massive blood transfusion Exogenous alkali administration Chloride-resistant Hyperadrenocorticoid states (Cushing's syndrome, primary hyperaldosteronism, secondary mineralocorticoidism [licorice, chewing tobacco]) Hypomagnesemia Hypokalemia Bartter's syndrome RESPIRATORY ALKALOSIS Hypoxemia (pneumonia, pulmonary embolism, atelectasis, high-altitude living) Drugs (salicylates, xanthines, progesterone, epinephrine, thyroxine, nicotine) Central nervous system (CNS) disorders (tumor, cerebrovascular accident [CVA], trauma, infections) Psychogenic hyperventilation (anxiety, hysteria) Hepatic encephalopathy Gram-negative sepsis Hyponatremia Sudden recovery from metabolic acidosis Assisted ventilation ARTHROCENTESIS FLUID Interpretation of results:

1.

Color: Normally it is clear or pale yellow; cloudiness indicates inflammatory process or presence of crystals, cell debris, fibrin, or triglycerides.

2.

Viscosity: Normally it has a high viscosity because of hyaluronate; when fluid is placed on a slide, it can be stretched to a string >2 cm in length before separating (low viscosity indicates breakdown of hyaluronate [lysosomal enzymes from leukocytes] or the presence of edema fluid).

3.

Mucin clot: Add 1 ml of fluid to 5 ml of a 5% acetic acid solution and allow 1 minute for the clot to form; a firm clot (does not fragment on shaking) is normal and indicates the presence of large molecules of hyaluronic acid (this test is nonspecific and infrequently done).

4.

Glucose: Normally it approximately equals serum glucose level; a difference of more than 40 mg/dl is suggestive of infection.

5.

Protein: Total protein concentration is >2.5 g/dl in the normal synovial fluid; it is elevated in inflammatory and septic arthritis.

6.

Microscopic examination for crystals a.

Gout: Monosodium urate crystals

b.

Pseudogout: Calcium pyrophosphate dihydrate crystals

ASLO TITER; see ANTISTREPTOLYSIN O TITER ASPARTATE AMINOTRANSFERASE (AST, SGOT) Normal range: 0-35 U/L (0-0.58 µkat/L [CF: 0.01667, SMI: 0.01 µkat/L]) Elevated in: HEART Acute myocardial infarction Pericarditis (active: some cases) LIVER Hepatitis virus, Epstein-Barr, or cytomegalovirus infection Active cirrhosis Liver passive congestion or hypoxia Alcohol or drug-induced liver dysfunction Space-occupying lesions (active) Fatty liver (severe) Extrahepatic biliary obstruction (early)

Drug-induced SKELETAL MUSCLE Acute skeletal muscle injury Muscle inflammation (infectious or noninfectious) Muscular dystrophy (active) Recent surgery Delirium tremens KIDNEY Acute injury or damage Renal infarct OTHER Intestinal infarction Shock Cholecystitis Acute pancreatitis Hypothyroidism Heparin therapy (60%-80% of cases)

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B BASOPHIL COUNT Normal range: 0.4% to 1% of total WBC; 40-100/mm 3 Elevated in: Leukemia, inflammatory processes, polycythemia vera, Hodgkin's lymphoma, hemolytic anemia, after splenectomy, myeloid metaplasia, myxedema Decreased in: Stress, hypersensitivity reaction, steroids, pregnancy, hyperthyroidism, postirradiation BILE, URINE; see URINE BILE BILIRUBIN, DIRECT (conjugated bilirubin) Normal range: 0-0.2 mg/dl (0-4 µmol/L [CF: 17.10; SMI: 2 µmol/L]) Elevated in: Hepatocellular disease, biliary obstruction, drug-induced cholestasis, hereditary disorders (DubinJohnson syndrome, Rotor's syndrome) BILIRUBIN, INDIRECT (unconjugated bilirubin) Normal range: 0-1.0 mg/dl (2-18 µmol/L [CF: 17.10; SMI: 2 µmol/L]) Elevated in: A. Increased bilirubin production (if normal liver, serum unconjugated bilirubin is usually less than 4 mg/100 ml) 1.

2.

3.

Hemolytic anemia a.

Acquired

b.

Congenital

Resorption from extravascular sources a.

Hematomas

b.

Pulmonary infarcts

Excessive ineffective erythropoiesis a.

Congenital (congenital dyserythropoietic anemias)

b.

Acquired (pernicious anemia, severe lead poisoning; if present, bilirubinemia is usually mild)

B.

Defective hepatic unconjugated bilirubin clearance (defective uptake or conjugation) 1.

Severe liver disease

2.

Gilbert's syndrome

3.

Crigler-Najjar type I or II

4.

Drug-induced inhibition

5.

Portacaval shunt

6.

Congestive heart failure

7.

Hyperthyroidism (uncommon)

BILIRUBIN, TOTAL Normal range: 0-1.0 mg/dl (2-18 µmol/L [CF: 17.10, SMI: 2 µmol/L]) Elevated in: Liver disease (hepatitis, cirrhosis, cholangitis, neoplasm, biliary obstruction, infectious mononucleosis), hereditary disorders (Gilbert's disease, Dubin-Johnson syndrome), drugs (steroids, diphenylhydantoin, phenothiazines, penicillin, erythromycin, clindamycin, captopril, amphotericin B, sulfonamides, azathioprine, isoniazid, 5-aminosalicylic acid, allopurinol, methyldopa, indomethacin, halothane, oral contraceptives, procainamide, tolbutamide, labetalol), hemolysis, pulmonary embolism or infarct, hepatic congestion secondary to congestive heart failure BILIRUBIN, URINE; see URINE BILE BLEEDING TIME (modified Ivy method) Normal range: 2 to 9½ min Elevated in: Thrombocytopenia, capillary wall abnormalities, platelet abnormalities (Bernard-Soulier disease, Glanzmann's disease), drugs (aspirin, warfarin, anti-inflammatory medications, streptokinase, urokinase, dextran, ß-lactam antibiotics, moxalactam), disseminated intravascular coagulation, cirrhosis, uremia, myeloproliferative disorders, von Willebrand's disease BRCA ANALYSIS Description of analysis Comprehensive BRCA analysis: BRCA1: Full sequence determination in both forward and reverse directions of approximately 5500 base pairs comprising 22 coding exons and one noncoding exon (exon 4) and approximately 800 adjacent base pairs in the noncoding intervening sequence (intron). Exon 1, which is noncoding, is not analyzed. The wild-type BRCA1 gene encodes a protein comprising 1863 amino acids. BRCA2: Full sequence determination in both forward and reverse directions of approximately 10,200 base pairs comprising 26 coding exons and approximately 900 adjacent base pairs in the noncoding intervening sequence (intron). Exon 1, which is noncoding, is not analyzed. The wild-type BRCA2 gene encodes a protein comprising 3418 amino acids.

The noncoding intronic regions of BRCA1 and BRCA2 that are analyzed do not extend more than 20 base pairs proximal to the 5' end and 10 base pairs distal to the 3' end of each exon. SINGLE-SITE BRACANALYSIS: DNA sequence analysis for a specified mutation in BRCA1 and/or BRCA2. MULTISITE 3 BRACANALYSIS: DNA sequence analysis of specific portions of BRCA1 exon 2, BRCA1 exon 20 and BRCA2 exon 11 designed to detect only mutations 187delAG and 5385insC in BRCA1 and 6174delT in BRCA2. Interpretive Criteria “POSITIVE FOR A DELETERIOUS MUTATION”: Includes all mutations (nonsense, insertions, deletions) that prematurely terminate (“truncate”) the protein product of BRCA1 at least 10 amino acids form the C-terminus, or the protein product of BRCA2 at least 110 amino acids from the C-terminus (based on documentation of deleterious mutations in BRCA1 and BRCA2). In addition, specific missense mutations and noncoding intervening sequence (IVS) mutations are recognized as deleterious on the basis of data derived from linkage analysis of high-risk families, functional assays, biochemical evidence and/or demonstration of abnormal mRNA transcript processing. “GENETIC VARIANT, SUSPECTED DELETERIOUS”: Includes genetic variants for which the available evidence indicates a likelihood, but not proof, that the mutation is deleterious. The specific evidence supporting such an interpretation will be summarized for individual variants on each such report. “GENETIC VARIANT, FAVOR POLYMORPHISM”: Includes genetic variants for which available evidence indicates that the variant is highly unlikely to contribute substantially to cancer risk. The specific evidence supporting such an interpretation will be summarized for individual variants on each such report. “GENETIC VARIANT OF UNCERTAIN SIGNIFICANCE”: Includes missense mutations and mutations that occur in analyzed intronic regions whose clinical significance has not yet been determined, as well as chainterminating mutations that truncate BRCA1 and BRCA2 distal to amino acid positions 1853 and 3308, respectively. “NO DELETERIOUS MUTATION DETECTED”: Includes nontruncating genetic variants observed at an allele frequency of approximately 1% of a suitable control population (providing that no data suggest clinical significance), as well as all genetic variants for which published data demonstrate absence of substantial clinical significance. Also includes mutations in the protein-coding region that neither alter the amino acid sequence nor are predicted to significantly affect exon splicing, and base pair alterations in noncoding portions of the gene that have been demonstrated to have no deleterious effect on the length or stability of the mRNA transcript. There may be uncommon genetic abnormalities in BRCA1 and BRCA2 that will not be detected by BRCA Analysis. This analysis, however, is believed to rule out the majority of abnormalities in these genes, which are believed responsible for most hereditary susceptibility to breast and ovarian cancer. “SPECIFIC VARIANT/MUTATION NOT IDENTIFIED”: Specific and designated deleterious mutations or variants of uncertain clinical significance are not present in the individual being tested. If one (or rarely two) specific deleterious mutations have been identified in a family member, a negative analysis for the specific mutation(s) indicates that the tested individual is at the general population risk of developing breast or ovarian cancer.

B-type NATRIURETIC PEPTIDE Normal range: Up to 100 pg/ml Elevated in: Heart failure. This test is useful to differentiate patients with heart failure from those with chronic obstructive pulmonary disease presenting with dyspnea. BUN; see UREA NITROGEN

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C C282Y AND H63D MUTATION ANALYSIS PROCEDURE: Detection of the C282Y and H63D mutations is accomplished by amplification of exons 2 and 4 of the HFE gene on chromosome 6 by polymerase chain reaction (PCR) followed by allele-specific hybridization and chemiluminescent detection of hybridized probes. H63D is viewed by some as a polymorphism rather than a mutation because of its prevalence in the population, because 15% of the individuals affected with hereditary hemochromatosis (HH) are compound heterozygotes for C282Y and H63D and about 1% of patients are H63D homozygotes, which suggests that H63D may be causative in the development of the disorder at reduced penetrance. The test is performed by Quest diagnostics pursuant to a license agreement with Roche Molecular systems, Inc. INTERPRETATION: Homozygosity for the C282Y mutation has been associated with an increased risk of being affected with hereditary hemochromatosis (HH) compared with the general population. The genotype is observed in 60% to 90% of individuals affected with HH and occurs in less than 1% of the general population. However, approximately 25% of asymptomatic individuals with this genotype do not develop the disorder. C3; see COMPLEMENT C3 C4; see COMPLEMENT C4 CALCITONIN (serum) Normal range: >100 pg/ml (>100 ng/L [CF: 1; SMI: 10 ng/L]) Elevated in: Medullary carcinoma of the thyroid (particularly if level >1500 pg/ml), carcinoma of the breast, apudomas, carcinoids, renal failure, thyroiditis CALCIUM (serum) Normal range: 8.8-10.3 mg/dl (2.2-2.58 mmol/L [CF: 0.2495; SMI: 0.02 mmol/L]) Elevated in: Relatively Common Neoplasia (noncutaneous) Bone primary Myeloma Acute leukemia Nonbone solid tumors Breast Lung Squamous nonpulmonary Kidney Neoplasm secretion of parathyroid hormone-related protein (PTHrP, “ectopic PTH”) Primary hyperparathyroidism

Thiazide diuretics Tertiary (renal) hyperparathyroidism Idiopathic Spurious (artifactual) hypercalcemia Dehydration Serum protein elevation Laboratory technical problem RELATIVELY UNCOMMON Neoplasia (less common tumors) Sarcoidosis Hyperthyroidism Immobilization (mostly seen in children and adolescents) Diuretic phase of acute renal tubular necrosis Vitamin D intoxication Milk-alkali syndrome Addison's disease Lithium therapy Idiopathic hypercalcemia of infancy Acromegaly Theophylline toxicity • Table 4-4 describes the laboratory differential diagnosis of hypercalcemia.

TABLE 4-4 -- Laboratory Differential Diagnosis of Hypercalcemia Primary hyperparathyroidism N/ N N/

Parathyroid adenoma most common MEN I

Parathyroid hyperplasia; also includes pituitary and pancreatic neoplasms MEN Ha

Parathyroid hyperplasia; also includes medullary thyroid carcinoma and pheochromocytoma MEN lib

Parathyroid disease uncommon, primarily medullary thyroid carcinoma and pheochromocytoma FHH N N/ N N N/ N/ Autosomal dominant inheritance; hypercalcemia present within first decade; benign Malignancy

Solid tumor—humoral N/ N N

Primarily epidermoid tumors: PTH-related protein(s) is mediator Solid tumor—osteolytic

N/ N N

Lymphoma N/ N/

Granulomatous disease N/ N/

Sarcoid most common etiology Vitamin D intoxication N/

N

Hyperthyroidism N N N N N Plasma concentrations of T4 and/or T3 are elevated PLASMA TESTS

URINE TESTS

Diagnosis Ca PO4 PTH 25(OH)D 1,25(OH)2 D cAMP TmP/GFR Ca Comments From Moore WT, Eastman RC: Diagnostic endocrinology, ed 2, St Louis, 1996, Mosby. Ca, Calcium; cAMP, cyclic adenosine monophosphate; FHH, familial hypocalciuric hypercalcemia; GFR, glomerular nitration rate; MEN, multiple endocrine neoplasia; N, normal; 25(0H)D, 25 hydroxyvitamin D; P04 , phosphate; PTH, parathormone; T3 , triiodothyronine; T4 , thyroxine; TmP, renal threshold for phosphorus.

DECREASED Artifactual Hypoalbuminemia Hemodilution Primary hypoparathyroidism Pseudohypoparathyroidism Vitamin D–related Vitamin D deficiency Malabsorption Renal failure Magnesium deficiency Sepsis Chronic alcoholism Tumor lysis syndrome Rhabdomyolysis Alkalosis (respiratory or metabolic) Acute pancreatitis Drug-induced hypocalcemia Large doses of magnesium sulfate Anticonvulsants Mithramycin Gentamicin Cimetidine • Table 4-5 describes the laboratory differential diagnosis of hypocalcemia.

TABLE 4-5 -- Laboratory Differential Diagnosis of Hypocalcemia Hypoparathyroidism

N/ N

N/ Deficiency of PTH Pseudohypo-parathyroidism

Type I

N

NC

N/ Resistance to PTH; patients may have Albright's hereditary osteodystrophy and resistance to multiple hormones Type II N N

N/ Renal resistance to cAMP Vitamin D deficiency N/

N/

Deficient supply (e.g., nutrition) or absorption (e.g., pancreatic insufficiency) of vitamin D Vitamin D-dependent rickets

Type I N/ N

Deficient activity of renal 25(OH)D-la-hydroxylase Type II N/ N

Resistance to l,25(OH)2D PLASMA TESTS

URINE TESTS

cAMP 1,25(OH) 2 AFTER TmP/GFR DIAGNOSIS Ca PO4 PTH 25(OH)D D cAMP PTH TmP/GFR AFTER PTH Ca COMMENTS From Moore WT, Eastman RC: Diagnostic endocrinology, ed 2, St Louis, 1996, Mosby. Ca, Calcium; cAMP, cyclic adenosine monophosphate; GFR, glomerular nitration rate; NC, no change or small increase; (OH)D, hydroxycalciferol D; P04 , phosphate; PTH, parathyroid hormone; T4) thyroxine; TmP, renal threshold for phosphorus.

CALCIUM, URINE; see URINE CALCIUM CANCER ANTIGEN 125 Normal range: Less than 1.4% The cancer antigen 125 (CA 125) test uses an antibody against antigen from tissue culture of an ovarian tumor cell line. Various published evaluations report sensitivity of about 75%-80% in patients with ovarian carcinoma. There is also an appreciable incidence of elevated values in nonovarian malignancies and in certain benign conditions (see below). Test values may transiently increase during chemotherapy. MALIGNANT

Epithelial ovarian carcinoma, 75%-80% (range 25%-92%, better in serous than mucinous cystadenocarcinoma) Endometrial carcinoma, 25%-48% (2%-90%) Pancreatic carcinoma, 59% Colorectal carcinoma, 20% (15%-56%) Endocervical adenocarcinoma, 83% Squamous cervical or vaginal carcinoma, 7%-14% Lung carcinoma, 32% Breast carcinoma, 12%-40% Lymphoma, 35% BENIGN Cirrhosis, 40%-80% Acute pancreatitis, 38% Acute peritonitis, 75% Endometriosis, 88% Acute pelvic inflammation disease, 33% Pregnancy first trimester, 2%-24% During menstruation (occasionally) Renal failure (?frequency) Normal persons, 0.6%-1.4% CARBAMAZEPINE (Tegretol) Normal therapeutic range: 4-12 mcg/ml CARBON MONOXIDE; see CARBOXYHEMOGLOBIN CARBOXYHEMOGLOBIN Normal range: Saturation of hemoglobin > 2%; smokers >9% (coma: 50%; death: 80%) Elevated in: Smoking, exposure to smoking, exposure to automobile exhaust fumes, malfunctioning gasburning appliances CARCINOEMBRYONIC ANTIGEN (CEA) Normal range: Nonsmokers: 0-2.5 ng/ml (0-2.5 µg/L [CF: 1; SMI: 0.1 µg/L]) Smokers: 0-5 ng/ml (0-5 µg/L [CF: 1; SMI: 0.1 µg/L]) Elevated in: Colorectal carcinomas, pancreatic carcinomas, and metastatic disease (usually produce higher elevations: >20 ng/ml) Carcinomas of the esophagus, stomach, small intestine, liver, breast, ovary, lung, and

thyroid (usually produce lesser elevations) Benign conditions (smoking, inflammatory bowel disease, hypothyroidism, cirrhosis, pancreatitis, infections) (usually produce levels >10 ng/ml) CAROTENE (serum) Normal range: 50-250 µg/dl (0.9-4.6 µmol/L [CF: 0.01863; SMI: 0.1 µmol/L]) Elevated in: Carotenemia, chronic nephritis, diabetes mellitus, hypothyroidism, nephrotic syndrome, hyperlipidemia Decreased in: Fat malabsorption, steatorrhea, pancreatic insufficiency, lack of carotenoids in diet, high fever, liver disease CATECHOLAMINES, URINE; see URINE CATECHOLAMINES CBC; see COMPLETE BLOOD COUNT CD4+ T-LYMPHOCYTE COUNT (CD4+ T-cells) Calculated as total WBC × % lymphocytes × % lymphocytes stained with CD4. This test is used primarily to evaluate immune dysfunction in HIV infection and should be done every 3-6 months in all HIV-infected persons. It is useful as a prognostic indicator and as a criterion for initiating prophylaxis for several opportunistic infections that are sequelae of HIV infection. Progressive depletion of CD4+ T-lymphocytes is associated with an increased likelihood of clinical complications ( Table 4-6 . Adolescents and adults with HIV are classified as having AIDS if their CD4+ lymphocyte count is under 200/µL and/or if their CD4+ T-lymphocyte percentage is less than 14%. HIV-infected patients whose CD4+ count is less than 200/µL and who acquire certain infectious diseases or malignancies are also classified as having AIDS. Corticosteroids decrease CD4+ T-cell percentage and absolute number.

TABLE 4-6 -- Relation of CD4 Lymphocyte Counts to the Onset of Certain HIV-Associated Infections and Neoplasms in North America >500 Herpes zoster, polydermatomal 5-10 200-500 Mycobacterium tuberculosis infection, pulmonary and extrapulmonary 2-20 Oral hairy leukoplakia 40-70 Candida pharyngitis (thrush) 40-70 Recurrent Candida vaginitis 15-30 09 Kaposi's sarcoma, mucocutaneous 15-30 (M) Bacterial pneumonia, recurrent 15-20 Cervical neoplasia 1-2 (F) 100-200

Pneumocystis carinii pneumonia 15-60 Herpes simplex, chronic, ulcerative 5-10 Histoplasma capsulatum infection, disseminated 0-20 Kaposi's sarcoma, visceral 3-8 (M) Progressive multifocal leukoencephalopathy 2-3 Lymphoma, non-Hodgkin's 2-5 1:10 or positive indicates current or recent infection Anti-EBNA =1.5 or positive indicates previous infection Table 4-11 and Fig. 4-3 describe test interpretation

TABLE 4-11 -- Antibody Tests in Epstein-Barr Viral Infection Appearance Peak

Disappears

Heterophil Ab

3-5 days after onset of Sx (range, 0- During second wk after 21 days) onset of Sx (1-4 wk)

2-3 mo after onset of Sx (still found at 1 yr in 20% of cases)

VCA-IgM

Beginning of Sx (1 wk before to 1 wk after Sx begins)

During first wk after onset of Sx (0-21 days)

2-3 mo after onset of Sx (1-6 mo)

VCA-IgG

3 days after onset of Sx (0-2 wk)

During second wk after onset of Sx (1-3 wk)

Decline to lower level, then persists for life

EBNA-IgG

3 wk after onset of Sx (1-4 wk)

8 mo after appearance (312 mo)

Lifelong

EA-D

5 days after onset of Sx (during first 14-21 days after onset of 1-2 wk after onset of Sx) Sx (1-4 wk)

9 wk after appearance (2-6 mo)

(EBNAIgM)

(Same as VCA-IgM)

(Same as VCA-IgM)

(Same as VCA-IgM)

From Ravel R: Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby. Ab, Antibody; EA, early antigen; EBNA, Epstein-Barr virus nuclear antigen; Sx, symptoms; VGA, viral capsid antigen.

FIGURE 4-3 Tests in Epstein-Barr viral infection. See Table 4-11 for abbreviations. (From Ravel R: Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby.)

ERYTHROCYTE SEDIMENTATION RATE (ESR; Westergren) Normal range: Male: 0-15 mm/hr Female: 0-20 mm/hr Elevated in: Collagen-vascular diseases, infections, myocardial infarction, neoplasms, inflammatory states (acute phase reactant), hyperthyroidism, hypothyroidism, rouleaux formation Decreased in: Sickle cell disease, polycythemia, corticosteroids, spherocytosis, anisocytosis, hypofibrinogenemia, increased serum viscosity ERYTHROPOIETIN (EP) Normal: 3.7-16.0 IU/L by radioimmunoassay Erythropoietin is a glycoprotein secreted by the kidneys that stimulates RBC production by acting on erythroidcommitted stem cells. Increased in: Extremely high: generally seen in patients with severe anemia (Hct 1000 ng/ml), germinal neoplasms (testis, ovary, mediastinum, retroperitoneum), liver disease (alcoholic cirrhosis, acute hepatitis, chronic active hepatitis), fetal anencephaly, spina bifida, basal cell carcinoma, breast carcinoma, pancreatic carcinoma, gastric carcinoma, retinoblastoma, esophageal atresia FIBRIN DEGRADATION PRODUCT (FDP) Normal range: 59 years: 5.8-11.9 micromol/L Increased: Thrombophilic states, B6, B12, folic acid, riboflavin deficiency, pregnancy, homocystinuria note: An increased homocysteine level is an independent risk factor for atherosclerosis.

HUMAN CHORIONIC GONADOTROPIN (hCG) Normal range: Varies with gestational stage 1st week: 5-50 mU/ml 1-2 wk: 50-550 mU/ml 2-3 wk: up to 5000 mU/ml 3-4 wk: up to 10,000 mU/ml 4-5 wk: up to 50,000 mU/ml 2-3 mo: 10,000-100,000 mU/ml Elevated in: Normal pregnancy, hydatidiform mole, choriocarcinoma, germ cell tumors of testicle, some nontrophoblastic neoplasms (e.g., neoplasms of cervix, gastrointestinal tract, ovary, lung, breast) HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY, type 1 (HIV-1) Normal range: Not detected Abnormal result: HIV antibodies usually appear in the blood 1-4 mo after infection. Testing sequence: 1.

ELISA is the recommended initial screening test. Sensitivity and specificity are >99%. False-positive ELISA may occur with autoimmune disorders, administration of immune globulin manufactured before 1985 within 6 wk of testing, presence of rheumatoid factor, presence of DLA-DR antibodies in multigravida female, administration of influenza vaccine within 3 mo of testing, hemodialysis, positive plasma reagin test, certain medical disorders (hemophilia, hypergammaglobulinemia, alcoholic hepatitis)

2.

A positive ELISA is confirmed with Western blot. False-positive Western blot may result from connective tissue disorders, human leukocyte antigen antibodies, polyclonal gammopathies, hyperbilirubinemia, presence of antibody to another human retrovirus, or cross reaction with other non-virus-derived proteins in healthy persons. Undetermined Western blot may occur in AIDS patients with advanced immunodeficiency (caused by loss of antibodies), and in recent HIV infections.

3.

Polymerase chain reaction is used to confirm indeterminate Western blot results or negative results in persons with suspected HIV infection.

Fig. 4-10 describes tests in HIV infection.

FIGURE 4-10 Tests in HIV-1 infection. HIV, Human immunodeficiency virus; IgG, immunoglobulin G; IgM, immunoglobulin M; PCR, polymerase chain reaction. (From Ravel R: Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby.)

Indications for plasma HIV RNA testing are described in Table 4-13 .

TABLE 4-13 -- Indications for Plasma HIV RNA Testing [*] Clinical Indication Information

Use

Syndrome consistent with acute HIV infection

Establishes diagnosis when HIV antibody test is negative or indeterminate

Diagnosis[†]

Initial evaluation of newly diagnosed HIV infection

Baseline viral load “set point”

Decision to start or defer therapy

Every 3-4 mo in patients not on therapy

Changes in viral load

Decision to start therapy

4-8 wk after initiation of antiretroviral therapy

Initial assessment of drug efficacy

Decision to continue or change therapy

3-4 mo after start of therapy

Maximal effect of therapy

Decision to continue or change therapy

Every 3-4 mo in patients on therapy

Durability of antiretroviral effect

Decision to continue or change therapy

Clinical event or significant decline in CD41 T cells

Association with changing or stable

Decision to continue, initiate, or change

From MMWR, vol 47, no RR-5, Apr 24, 1998.

* Acute illness (e.g., bacterial pneumonia, tuberculosis, HSV, PCP) and immunizations can cause increase in plasma HIV RNA for 2-4 wk; viral load testing should not be performed during this time. Plasma HIV RNA results should usually be verified with a repeat determination before starting or making changes in therapy. HIV RNA should be measured using the same laboratory and the same assay. † Diagnosis of HIV infection determined by HIV RNA testing should be confirmed by standard methods (e.g., Western blot serology) performed 2-4 mo after the initial indeterminate or negative test.

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) ANTIGEN (p24), QUALITATIVe (p24 antigen) Normal range: Negative This test detects uncomplexed HIV-1 p24 antigen. The core protein p24 is the first detectable protein encoded by the group-specific antigen (gag) gene. This protein is a marker for viremia. This test should not be used in place of HIV-1 antibody testing as a screen for HIV-1 infection. HIV-1 p24 may be detectable in the first month of acute HIV-1 infection and generally falls to undetectable levels during the asymptomatic stage of HIV-1 infection. A negative result does not exclude the possibility of infection or exposure to HIV-1. It is recommended that a negative result be followed with repeat testing at least 8 weeks after the original test. This test is used primarily for screening of donated blood and plasma and as an aid for the prognosis of HIV-1 infection. HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) VIRAL LOAD Normal range: HIV-1 RNA, quant. bDNA 3: less than 50 copies/ml or less than 1.7 log copies/ml This test should be used only in individuals with documented HIV-1 infection for monitoring the progression of infection, response to antiretroviral therapy, and disease prognosis. It is not indicated for diagnosis of HIV infection. 5-HYDROXYINDOLE-ACETIC ACID, URINE; see URINE 5-HYDROXYINDOLE-ACETIC ACID

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Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright © 2009 Mosby, An Imprint of Elsevier

I IMMUNE COMPLEX ASSAY Normal: Negative Detected in: Collagen-vascular disorders, glomerulonephritis, neoplastic diseases, malaria, primary biliary cirrhosis, chronic acute hepatitis, bacterial endocarditis, vasculitis IMMUNOGLOBULINS Normal range: IgA: 50-350 mg/dl (0.5-3.5 g/L [CF: 0.01; SMI: 0.01 g/L]) IgD: 60 in RAEB and RARS Unexplained 25 (22.5-27) — Normal newborn

Less common 60% motile 40% to >70%)

% Normal sperm >60% (literature range, >60% to >70%) Viscosity

Can be poured from a pipet in droplets rather than a thick strand

From Ravel R (ed): Clinical laboratory medicine, ed 6, St Louis, 1995, Mosby.

SGOT; see ASPARTATE AMINOTRANSFERASE SGPT; see ALANINE AMINOTRANSFERASE SMOOTH MUSCLE ANTIBODY Normal: Negative Present in: Chronic acute hepatitis (=1:80), primary biliary cirrhosis (=1:80), infectious mononucleosis SODIUM (serum) Normal range: 135-147 mEq/L (135-147 mmol/L [CF: 1; SMI: 1 mmol/L]) HYPONATREMIA

A.

Sodium and water depletion (deficit hyponatremia) 1.

2.

3.

4.

5.

6.

Loss of gastrointestinal secretions with replacement of fluid but not electrolytes a.

Vomiting

b.

Diarrhea

c.

Tube drainage

Loss from skin with replacement of fluids but not electrolytes a.

Excessive sweating

b.

Extensive burns

Loss from kidney a.

Diuretics

b.

Chronic renal insufficiency (uremia) with acidosis

Metabolic loss a.

Starvation with acidosis

b.

Diabetic acidosis

Endocrine loss a.

Addison's disease

b.

Sudden withdrawal of long-term steroid therapy

Iatrogenic loss from serous cavities a.

B.

Paracentesis or thoracentesis

Excessive water (dilution hyponatremia) 1.

Excessive water administration

2.

Congestive heart failure

3.

Cirrhosis

4.

Nephrotic syndrome

5.

Hypoalbuminemia (severe)

6.

Acute renal failure with oliguria

C.

Inappropriate antidiuretic hormone (IADH) syndrome

D.

Intracellular loss (reset osmostat syndrome)

E.

False hyponatremia (actually a dilutional effect) 1.

Marked hypertriglyceridemia*

2.

Marked hyperproteinemia*

3.

Severe hyperglycemia

HYPERNATREMIA Dehydration is the most frequent overall clinical finding in hypernatremia.

1.

Deficient water intake (either orally or intravenously)

2.

Excess kidney water output (diabetes insipidus, osmotic diuresis)

3.

Excess skin water output (excess sweating, loss from burns)

4.

Excess gastrointestinal tract output (severe protracted vomiting or diarrhea without fluid therapy)

5.

Accidental sodium overdose

6.

High-protein tube feedings

STREPTOZYME; see ANTI-STREPTOLYSIN O TITER SUCROSE HEMOLYSIS TEST (sugar water test) Normal: Absence of hemolysis Positive in: Paroxysmal nocturnal hemoglobinuria False positive: autoimmune hemolytic anemia, megaloblastic anemias False negative: may occur with use of heparin or EDTA SUDAN III STAIN (qualitative screening for fecal fat) Normal: Negative. Test should be preceded by diet containing 100-150 g of dietary fat/day for 1 week, avoidance of high-fiber diet, and avoidance of suppositories or oily material before specimen collection. Positive in: Steatorrhea, use of castor oil or mineral oil droplets SYNOVIAL FLUID ANALYSIS Table 4-23 describes the classification and interpretation of synovial fluid analysis.

TABLE 4-23 -- Classification and Interpretation of Synovial Fluid Analysis Glucose (mg/dl) (BloodMucin Synovia Protein Viscosity Clot WBC/mm3 %PMN 1 Fluid) (g/dl)

Group

Diseases

Appearance

Normal

—

Clear

Firm

I Osteoarthritis, (noninflammatory) aseptic necrosis, traumatic arthritis, erythema nodosum, osteochondritis dissecans

Clear, yellow (may be xanthochromic if traumatic arthritis)

Firm

II (inflammatory)

Clear, yellow, turbid

Friable

Crystal-induced arthritis,

115 mg/dl. (2). Pseudochylous effusion: often seen with chronic inflammation of the pleural space (e.g., TB, connective tissue diseases).

4. 5.

If transudate, consider CHF, cirrhosis, chronic renal failure, and other hypoproteinemic states and perform subsequent workup accordingly.

If exudate, consider ordering these tests on the pleural fluid: a.

Cytologic examination for malignant cells (for suspected neoplasm).

b.

Gram stain, cultures (aerobic and anaerobic), and sensitivities (for suspected infectious process).

c.

AFB stain and cultures (for suspected TB).

d.

pH: a value < 7.0 suggests parapneumonic effusion or empyema; a pleural fluid pH must be drawn anaerobically and iced immediately; the syringe should be prerinsed with 0.2 ml of 1:1000 heparin.

e.

Glucose: a low glucose level suggests parapneumonic effusions and rheumatoid arthritis.

f.

Amylase: a high amylase level suggests pancreatitis or ruptured esophagus.

g.

Perplexing pleural effusions are often a result of malignancy (e.g., lymphoma, malignant mesothelioma, ovarian carcinoma), TB, subdiaphragmatic processes, prior asbestos exposure, and postcardiac injury syndrome.

THROMBIN TIME (TT) Normal range: 11.3-18.5 sec Elevated in: Thrombolytic and heparin therapy, disseminated intravascular coagulation, hypofibrinogenemia, dysfibrinogenemia THYROID-STIMULATING HORMONE (TSH)

Normal range: 2-11 µU/ml (2-11 mU/L [CF: 1; SMI: 1 mU/L]) Conditions That Increase Serum Thyroid-Stimulating Hormone Values Laboratory error Primary hypothyroidism Synthroid therapy with insufficient dose Lithium or amiodarone; some patients Hashimoto's thyroiditis in later stage Large doses of inorganic iodide (e.g., SSKI) Severe nonthyroid illness in recovery phase Iodine deficiency (moderate or severe) Addison's disease TSH specimen drawn in evening (peak of diurnal variation) Pituitary TSH-secreting tumor Therapy of hypothyroidism (3-6 wk after beginning therapy [range, 1-8 wk]; sometimes longer when pretherapy TSH is over 100 µU/ml) Acute psychiatric illness Peripheral resistance to T 4 syndrome Antibodies (e.g., HAMA) interfering with monoclonal sandwich method of TSH assay Telepaque (iopanoic acid) and Oragrafin (ipodate) x-ray contrast media Amphetamines High altitudes Conditions That Decrease Serum Thyroid-Stimulating Hormone Values Laboratory error

T4/T3 toxicosis (diffuse or nodular etiology) Excessive therapy for hypothyroidism Active thyroiditis (subacute, painless, or early active Hashimoto's disease) Multinodular goiter containing areas of autonomy Severe nonthyroid illness (especially acute trauma, dopamine, or glucocorticoid) T3 toxicosis Pituitary insufficiency Cushing's syndrome (and some patients on high-dose glucocorticoid) Jod-Basedow (iodine-induced) hyperthyroidism Thyroid-stimulating hormone drawn 2-4 hr after levothyroxine dose Postpartum transient toxicosis Factitious hyperthyroidism Struma ovarii Radioimmunoassay, surgery, or antithyroid drug therapy for hyperthyroidism 4-6 wk (range 2 wk–2 yr) after the treatment Interleukin-2 drugs (3%-6% of cases) or a-interferon therapy (1% of cases) Hyperemesis gravidarum Amiodarone therapy THYROXINE (T4) Normal range: 4-11 µg/dl (51-142 nmol/L [CF: 12.87; SMI: 1 nmol/L]) TIBC; see IRON-BINDING CAPACITY TRANSFERRIN Normal range: 170-370 mg/dl (1.7-3.7 g/L [CF: 0.01; SMI: 0.01 g/L])

Elevated in: Iron deficiency anemia, oral contraceptive administration, viral hepatitis, late pregnancy Decreased in: Nephrotic syndrome, liver disease, hereditary deficiency, protein malnutrition, neoplasms, chronic inflammatory states, chronic illness, thalassemia, hemochromatosis, hemolytic anemia TRIGLYCERIDES Normal range: 12 years will exist who did not have the opportun age 11 to 12 years. Catch-up vaccination is recommended for females aged 13 to 26 years who have not yet been vaccin

The recommendation for routine vaccination of females aged 11 to 12 years is based on several considerations, includin quadrivalent HPV vaccine among adolescents will be safe and effective, high antibody titers achieved after vaccination a on HPV epidemiology and age of sexual debut in the United States, and the high probability of HPV acquisition within se debut. Ideally, HPV vaccine should be administered before sexual debut, and duration of protection should extend for ma protection when exposure through sexual activity might occur. The vaccine has been demonstrated to provide protection evidence of waning protection. Long-term follow-up studies are under way to determine duration of protection. The recom considered cost-effectiveness evaluations and the established young adolescent health care visit at age 11 to 12 years re professional organizations, when other vaccines are also recommended.

Although routine vaccination is recommended at age 11 to 12 years, the majority of females aged 13 to 26 years also ca Females not yet sexually active can be expected to receive the full benefit of vaccination. Although sexually active femal have been infected with one or more vaccine HPV types, type-specific prevalence studies in the United States suggest th sexually active females have been infected with all four of the HPV vaccine types. These data, available from North Ame 24 years who participated in the quadrivalent vaccine trials, are from women who were more likely to have ever had sex females in the general U.S. population. Among those sexually active females, the median number of lifetime sex partner participants and females in the general U.S. population. The vaccine does not appear to protect against persistent infect precursor lesions, or genital warts caused by an HPV type that females are infected with at the time of vaccination. Howe infected with one or more vaccine HPV types before vaccination would be protected against disease caused by the other Therefore, although overall vaccine effectiveness would be lower when administered to a population of females who are decrease with older age and likelihood of HPV exposure with increasing number of sex partners, the majority of females derive at least partial benefit from vaccination. RECOMMENDATIONS FOR USE OF HPV VACCINE Recommendations for Routine Use and Catch-Up Routine Vaccination of Females Aged 11-12 Years

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of females aged 11 to 12 y quadrivalent HPV vaccine. The vaccination series can be started as young as age 9 years. Catch-Up Vaccination of Females Aged 13-26 Years

Vaccination also is recommended for females aged 13 to 26 years who have not been previously vaccinated or who hav series. Ideally, vaccine should be administered before potential exposure to HPV through sexual contact; however, fema already been exposed to HPV should be vaccinated. Sexually active females who have not been infected with any of the receive full benefit from vaccination. Vaccination would provide less benefit to females if they have already been infected four vaccine HPV types. However, it is not possible for a clinician to assess the extent to which sexually active persons w vaccination, and the risk for HPV infection might continue as long as persons are sexually active. Pap testing and screen antibody are not needed before vaccination at any age. Dosage and Administration

The vaccine should be shaken well before administration. The dose of quadrivalent HPV vaccine is 0.5 ml, administered preferably in the deltoid muscle.

Recommended Schedule

Quadrivalent HPV vaccine is administered in a 3-dose schedule. The second and third doses should be administered 2 a dose. Minimum Dosing Intervals and Management of Persons Who Were Incorrectly Vaccinated

The minimum interval between the first and second doses of vaccine is 4 weeks. The minimum recommended interval b third doses of vaccine is 12 weeks. Inadequate doses of quadrivalent HPV vaccine or vaccine doses received after a sho dosing interval should be readministered. Interrupted Vaccine Schedules

If the quadrivalent HPV vaccine schedule is interrupted, the vaccine series does not need to be restarted. If the series is dose, the second dose should be administered as soon as possible and the second and third doses should be separated 12 weeks. If only the third dose is delayed, it should be administered as soon as possible. Simultaneous Administration with Other Vaccines

Although no data exist on administration of quadrivalent HPV vaccine with vaccines other than hepatitis B vaccine, quad a live vaccine and has no components that adversely impact safety or efficacy of other vaccinations. Quadrivalent HPV v administered at the same visit as other age-appropriate vaccines, such as the tetanus, diphtheria, pertussis (Tdap) and q meningococcal conjugate (MCV4) vaccines. Administering all indicated vaccines together at a single visit increases the l and young adults will receive each of the vaccines on schedule. Each vaccine should be administered using a separate s anatomic site. Cervical Cancer Screening among Vaccinated Females

Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. HPV types in the for approximately 70% of cervical cancers; females who are vaccinated could subsequently be infected with a carcinoge quadrivalent vaccine does not provide protection. Furthermore, those who were sexually active before vaccination could vaccine type HPV before vaccination. Health care providers administering quadrivalent HPV vaccine should educate wo of cervical cancer screening. Groups for Which Vaccine is Not Licensed Vaccination of Females Aged 26 Years

Quadrivalent HPV vaccine is not licensed for use among females aged 26 years. Studies are on aged >26 years. No studies are under way among children aged 13 weeks, a shorter deferral interval should be used to ensure the first dose of RV is administered no later than age 13 weeks.

TABLE 5-14 -- Dose and Route of Administration for Selected Vaccines Vaccines

Dose

Ro

Diphtheria, tetanus, pertussis (DTaP, DT, Td, Tdap)

0.5 ml

Intr

Diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B vaccine (DTaP-IPV-HepB) 0.5 ml

IM

Diphtheria, tetanus, acellular pertussis, haemophilus influenza type b vaccine (DTaP-Hib)

0.5 ml

IM

Haemophilus influenzae type b (Hib)

0.5 ml

IM

Haemophilus influenzae type b-Hepatitis B (Hib-HepB)

0.5 ml

IM

Hepatitis A (HepA)

=18 years: 0.5 ml

IM

=19 years: 1.0 ml HepB

=19 years: 0.5 ml[*] =20 years: 1.0 ml

IM

HepA/HepB

>18 years: 1.0 ml

IM

Influenza, live attenuated

0.5 ml

Intr

Influenza, trivalent inactivated

6-35 months: 0.25 ml IM =3 years: 0.5 ml

Measles, mumps, rubella

0.5 ml

Su

Measles, mumps, rubella, varicella

0.5 ml

SC

Vaccines

Dose

Ro

Meningococcal conjugate

0.5 ml

IM

Meningococcal polysaccharide

0.5 ml

SC

Pneumococcal conjugate

0.5 ml

IM

Pneumococcal polysaccharide

0.5 ml

IM

Human papillomavirus

0.5 ml

IM

Polio, inactivated

0.5 ml

IM

Rotavirus

2.0 ml

Ora

Varicella

0.5 ml

SC

Zoster

0.7 ml

SC

From CDC: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Pra 55CRR-15), 2006. Adapted from Immunization Action Coalition (http://wvAV.immunize.org ). * persons aged 11-15 years can be administered Recombivax HB (Merck) 1.0 ml (adult formulation) on a 2-dose schedule.

VACCINE ADMINISTRATION[*]

* From CDC: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 55(RR-15)

INFECTION CONTROL AND STERILE TECHNIQUE

Persons administering vaccines should follow appropriate precautions to minimize risk for spread of disease. Hands sho alcohol-based, waterless antiseptic hand rub or washed with soap and water between each patient contact. Occupationa Administration (OSHA) regulations do not require that gloves be worn when administering vaccinations unless persons a are likely to come into contact with potentially infectious body fluids or have open lesions on their hands. Needles used fo and disposable to minimize the risk for contamination. A separate needle and syringe should be used for each injection. C drawing vaccine from a vial and injecting it into a recipient is not necessary. Different vaccines should never be mixed in specifically licensed for such use, and no attempt should be made to transfer between syringes.

For all intramuscular injections, the needle should be long enough to reach the muscle mass and prevent vaccine from s tissue but not so long as to involve underlying nerves, blood vessels, or bone. Vaccinators should be familiar with the an which they are injecting vaccine. Intramuscular injections are administered at a 90-degree angle to the skin, preferably in of the thigh or the deltoid muscle of the upper arm depending on the age of the patient.

Decision on needle size and site of injection must be made for each person on the basis of the size of the muscle, the thi at the injection site, the volume of the material to be administered, injection technique, and the depth below the muscle s material is to be injected ( Fig. 5-1 ). Aspiration before injection of vaccines or toxoids (i.e., pulling back on the syringe pl insertion before injection) is not required because no large blood vessel exists at the recommended injection sites.

FIGURE 5-1 Intramuscular needle insertion. (Adapted from California Immunization Branch. In CDC: General recommendations on immunization: recomm Committee on Immunization Practices [ACIP], MMWR 55[RR-15]:16 2006.)

Infants (Aged 118 kg), a 1½-inch needle is required.

† If the gluteal muscle is chosen, injection should be administered lateral and superior to a line between the posterior superior iliac spine and the greater trochante of a triangle bounded by the anterior superior iliac spine, the tubercle of the iliac crest, and the upper border of the greater trochanter.

SUBCUTANEOUS INJECTIONS

Subcutaneous injections are administered at a 45-degree angle usually into the thigh for infants aged 15%.

TABLE 5-17 -- Approaches to the Evaluation and Vaccination of Internationally Adopted Children with No or Ques Records Vaccine Recommended Approach Alternative Approach Measles, mumps, and rubella (MMR)

Revaccinate with MMR

Serologie testing for immunoglobulin G (IgG) antibody rubella

Haemophilus influenzae Age-appropriate revaccination type b CHib)

—

Hepatitis A

Age-appropriate revaccination

Serologie testing for IgG antibody to hepatitis A virus

Hepatitis B (Hep B)

Age-appropriate revaccination and Serologie testing for HBsAg[*]

Poliovirus

Revaccinate with inactivated poliovirus vaccine (IPV)

Serologie testing for neutralizing antibody to polioviru availability)

Diphtheria and tetanus toxoids and acellular pertussis (DTaP)

Revaccination with DTaP, with Serologie testing for specific IgG antibody to tetanus and diphtheria toxins in the event of a severe local reaction

Children whose records indicate receipt of >3 doses: IgG antibody to diphtheria and tetanus toxins before a doses or administer a single booster dose of DTaP, fo testing after 1 month for specific IgG antibody to dipht with revaccination as appropriate

Varicella

Age-appropriate vaccination of children who lack evidence of varicella immunity

—

Pneumococcal conjugate

Age-appropriate vaccination

—

—

From CDC: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Pra 55CRR-15), 2006.

* Very rarely, Hep B vaccine can give a false-positive HBsAg result up to 18 days following vaccination; therefore, blood should be drawn to test for HBsAg befo

comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee Part I: immunization in infants, children, and adolescents, MMWR 54[RR-l6], 20050

TABLE 5-18 -- Recommended Adult Immunization Schedule—United States

TABLE 5-19 -- Recommended Adult Immunization Schedule for Adults with Medical Conditions—United States

TABLE 5-20 -- Immunizations Risk from Disease to Immunobiologic Pregnant Agent Woman

during Pregnancy

Risk from Risk from Immunizing Indications for Disease to Fetus Type of Agent to Immunization or Neonate Immunizing Agent Fetus during Pregnancy Dose Sched

Live Virus Vaccines Measles

Significant morbidity, low mortality; not

Significant increase in abortion rate; may cause

Live attenuated virus vaccine

None confirmed

Contraindicated (see immune globulins)

Single dose S preferably as measlesmum rubella[*]

Risk from Disease to Immunobiologic Pregnant Agent Woman mortality; not altered by pregnancy

Risk from Risk from Immunizing Indications for Disease to Fetus Type of Agent to Immunization or Neonate Immunizing Agent Fetus during Pregnancy Dose may cause rubellaSched [*] malformations

Mumps

Low morbidity and mortality; not altered by pregnancy

Probable increased rate of abortion in first trimester

Live attenuated virus vaccine

Poliomyelitis

No increased incidence in pregnancy, but may be more severe if it does occur

Anoxic fetal damage reported; 50% mortality in neonatal disease

Live attenuated None virus (oral polio confirmed vaccine [OPV]) and enhanced, potency inactivated virus (e-IPV) vaccine[†]

Rubella

Low morbidity and mortality; not altered by pregnancy

High rate of Live attenuated abortion and virus vaccine congenital rubella syndrome

Yellow fever

Significant Unknown morbidity and mortality; not altered by pregnancy

None confirmed

Contraindicated

Single dose S preferably as measlesmum rubella

Not routinely recommended for women in U.S., except persons at increased risk of exposure

Primary: Two of e-IPV SC a wk intervals a third dose 6-1 after the seco dose

Immediate protection: O dose OPV or out-break set None confirmed

Contraindicated

Single dose S preferably as measlesmum rubella

Live attenuated virus vaccine

Unknown

Contraindicated except if exposure is unavoidable

Single dose S

Inactivated virus vaccine

None confirmed

Women with One dose IM serious underlying year diseases; public health authorities to be consulted for current recommendation

Inactivated Virus Vaccines Influenza

Possible increase in morbidity and mortality during epidemic of new antigenic strain

Possible increased abortion rate; no malformations confirmed

Rabies

Near 100% fatality; not altered by pregnancy

Determined by Killed virus vaccine Unknown maternal disease

Indications for prophylaxis not altered by pregnancy; each case considered individually

Public health authorities to consulted for indications, d and route of administratio

Hepatitis B

Possible

Possible increase Recombinant

Preexposure and

Threeor four-

None

Risk from Disease to Immunobiologic Pregnant Agent Woman Hepatitis B Possible increased severity during third trimester

Risk from Risk from Immunizing Disease to Fetus Type of Agent to or Neonate Immunizing Agent Fetus Possible increase Recombinant None in abortion rate vaccine reported and prematurity; neonatal hepatitis can occur; high risk of newborn carrier state

Indications for Immunization during Pregnancy Dose Sched Preexposure and Threeor fourpost-exposure for series IM women at risk of infection

Inactivated Bacterial Vaccines Cholera

Significant morbidity and mortality; more severe during third trimester

Plague

Increased risk of Killed bacterial fetal death during vaccine third-trimester maternal illness

None confirmed

Indications not altered by pregnancy; vaccination recommended only in unusual outbreak situations

Single dose S IM, dependin manufacturer reconmendat when indicate

Significant Determined by Killed bacterial morbidity maternal disease vaccine and mortality; not altered by pregnancy

None reported

Selective vaccination of exposed persons

Public health authorities to consulted for indications, d and route of administratio

Pneumococcus

No Unknown increased risk during pregnancy; no increase in severity of disease

Polyvalent polysaccharide vaccine

No data available on use during pregnancy

Indications not altered by pregnancy; vaccine used only for highrisk individuals

In adults, one IM dose only consider repe dose in 6 yr f high-risk indi

Typhoid

Significant Unknown morbidity and mortality; not altered by pregnancy

Killed or live attenuated oral bacterial vaccine

None confirmed

Not recommended Killed; Prima routinely except for injections SC close, continued least 4 wk ap exposure or travel to endemic areas

Booster: Sing dose SC or ID (depending o of product us every 3 yr

Oral; Primary doses on alte days

Booster: Sch not yet determ Toxoids Tetanus, diphtheria

Severe morbidity; tetanus mortality

Neonatal tetanus mortality 60%

Combined tetanusdiphtheria toxoids preferred: adult

None confirmed

Lack of primary series, or no booster within past 10 yr

Primary: Two IM at 1-2 mo interval with a dose 6-12 mo

Risk from Disease to Risk from Immunobiologic Pregnant Disease to Fetus Agent Woman or Neonate mortality 30%, diphtheria mortality 10%; unaltered by pregnancy

Risk from Immunizing Type of Agent to Immunizing Agent Fetus adult tetanusdiphtheria formulation

Indications for Immunization during Sched 10 yr Pregnancy Dose dose 6-12 mo the second

Booster: Sing dose IM ever yr, after comp of primary se

Specific Immune Globulins Hepatitis B

Possible increased severity during third trimester

Possible increase Hepatitis B in abortion rate immune globulin and prematurity; neonatal hepatitis can occur; high risk of carriage in newborn

None reported

Postexposure prophylaxis

Depends on exposure; co Immunization Practices Ad Committee recommenda

Rabies

Near 100% fatality; not altered by pregnancy

Determined by Rabies immune maternal disease globulin

None reported

Postexposure prophylaxis

Half dose at site, half dos deltoid

Tetanus

Severe morbidity; mortality 21%

Neonatal tetanus mortality 60%

Tetanus immune globulin

None reported

Postexposure prophylaxis

One dose IM

Varicella

Possible increase in severe varicella pneumonia

Can cause congenital varicella with increased mortality in neonatal period; very rarely causes congenital defects

Varicella-zoster immune globulin (obtained from the American Red Cross)

None reported

Can be considered One dose IM for healthy 96 hr of expo pregnant women exposed to varicella to protect against maternal, not congenital, infection

Standard Immune Globulins Hepatitis A

Possible increased severity during third trimester

Probable Standard immune increase in globulin abortion rate and prematurity; possible transmission to neonate at delivery if mother is incubating the virus or is acutely ill at that time

Postexposure prophylaxis

0.02 ml/kg IM one dose of immune glob

Risk from Disease to Immunobiologic Pregnant Agent Woman

Risk from Risk from Immunizing Indications for Disease to Fetus Type of Agent to Immunization or Neonate Immunizing Agent Fetus during Pregnancy Dose Sched

Measles

Significant increase in abortion rate; may cause malformations

Significant morbidity, low mortality; not altered by pregnancy

Standard immune globulin

Postexposure prophylaxis

0.25 ml/kg IM one dose of immune glob up to 15 ml

From ACOG Technical Bulletin, No 160, Oct 1991. ID, Intradermally; IM, intramuscularly; PO, orally; SC, subcutaneously.

* Two doses necessary for adequate vaccination of students entering institutions of higher education, newly hired medical personnel, and international travelers. † Inactivated polio vaccine recommended for nonimmunized adults at increased risk.

TABLE 5-21 -- Immunizing Agents and Immunization Schedules for Health Care Workers (HCWs) [*] Primary Schedule and Major Precautions and Generic Name Booster(s) Indications Contraindications

Sp

Immunizing Agents Strongly Recommended for Health Care Workers Hepatitis B (HB) Two doses IM 4 wk apart; third Preexposure: HCWs at recombinant dose 5 mo after second: risk for exposure to blood vaccine booster doses not necessary. or body fluids.

Based on limited data no risk of adverse effects to developing fetuses is apparent. Pregnancy should not be considered a contraindication to vaccination of women. Previous anaphylactic reaction to common baker's yeast is a vaccination.contraindication to

Hepatitis B 0.06 ml/kg IM as soon as immune globulin possible after exposure. A (HBIG) second dose of HBIG should be administered 1 mo later if the HB vaccine series has not been started.

Postexposure prophylaxis: For persons exposed to blood or body fluids containing HBsAg and who are not immune to HBV infection—0.06 ml/kg IM as soon as possible (but no later than 7 days after exposure).

Influenza vaccine (inactivated whole-virus and split-virus

HCWs who have contact History of anaphylactic with patients at high risk hypersensitivity to egg ingestion. for influenza or its complications: HCWs who work in chronic care

Annual vaccination with current vaccine. Administered IM.

Th the on Pre scr pe be HC pa tes to res

No mo vac pre un

Generic split-virusName vaccines)

Primary Schedule and Booster(s)

Indications work in chronic care facilities: HCWs with highrisk medical conditions or who are aged =65 yr.

Major Precautions and Contraindications

Sp un Inf rec an pre inc ho

Measles livevirus vaccine

One dose SC; second dose at least 1 mo later.

HCWs[†] born during or after 1957 who do not have documentation of having received two doses of live vaccine on or after the first birthday or a history of physiciandiagnosed measles or serologic evidence of immunity. Vaccination should be considered for all HCWs who lack proof of immunity, including those born before 1957.

Pregnancy; immunocompromised persons[‡], including HrV-infected persons who have evidence of severe immunosuppression; anaphylaxis after gelatin ingestion or administration of neomycin; recent administration of immune globulin.

MM rec sus mu Pe 19 me vac vac un rev live

Mumps livevirus vaccine

One dose SC; second dose at least 1 mo later

HCWsf believed to be susceptible can be vaccinated. Adults born before 1957 can be considered immune.

Pregnancy; immunocompromised persons[‡]; history of anaphylactic reaction after gelatin ingestion or administration of neomycin

MM rec sus rub

Hepatitis A vaccine

Two doses of vaccine either 6- Not routinely indicated for 12 mo apart (HAVRTX), or 6 HCWs in the United mo apart (VAQTA) States. Persons who work with HAV-infected primates or with HAV in a research laboratory setting should be vaccinated.

History of anaphylactic hypersensitivity to alum or, for HAVRIX, the preservative 2phenoxyethanol. The safety of the vaccine in pregnant women has not been determined: the risk associated with vaccination should be weighed against the risk for hepatitis A in women who may be at high risk for exposure to HAV.

Meningococcal polysaccharide vaccine (tetravalent A, C. W135, and Y)

One dose in volume and by route specified by manufacturer: need for boosters unknown

Not routinely indicated for HCWs in the United States.

The safety of the vaccine in pregnant women has not been evaluated; it should not be administered during pregnancy unless the risk for infection is high.

Typhoid vaccine. IM vaccine: One 0.5-ml dose, IM, SC, and oral booster 0.5 ml every 2 yr. SC vaccine: two 0.5 ml doses, >4 wk apart, booster 0.5 ml SC or 0.1 ID every 3 yr if exposure continues Oral vaccine: Four doses on alternate days. The manufacturer recommends re vaccination with the entire four-dose series every 5 yr

Workers in microbiology laboratories who frequently work with Salmonella typhi

Severe local or systemic reaction to a previous dose. Ty21a (oral) vaccine should not be administered to immunocompromised personsf or to persons receiving antimicrobial agents.

Va con use ha cul

Vaccinia vaccine One dose administered with a

Laboratory workers who

The vaccine is contraindicated in

Va

Primary Schedule and Generic Vaccinia Name vaccine Booster(s) One dose administered with a (smallpox) bifurcated needle; boosters administered every 10 yr

Major Precautions and Indications Contraindications Laboratory workers who The vaccine is contraindicated in directly handle cultures pregnancy, in persons with eczema or with vaccinia, recombinant a history of eczema, and in vaccinia viruses, or immunocompromised personsf and orthopox viruses that their household contacts. infect humans

Sp Va for con dre ma clin rec

Other Vaccine-Preventable Diseases Tetanus and diphtheria (toxoids [TdD

Two IM doses 4 wk apart; third All adults dose 6-12 mo after second dose; booster every 10 yr

Except in the first trimester, Te pregnancy is not a precaution. History ma of a neurologic reaction or immediate hypersensitivity reaction after a previous dose. History of severe local (Arthus-type) reaction after a previous dose. Such persons should not receive further routine or emergency doses of Td for 10 yr.

Pneumococcal polysaccharide vaccine (23 valent)

One dose, 0.5 ml, IM or SC; revaccination recommended for those at highest risk =5 yr after the first dose

Adults who are at increased risk of pneumococcal disease and its complications because of underlying health conditions: older adults, especially those age >65 who are healthy

The safety of vaccine in pregnant women has not been evaluated; it should not be administered during pregnancy unless the risk for infection is high. Previous recipients of any type of pneumococcal polysaccharide vaccine who are at highest risk for fatal infection or antibody loss may be revaccinated =5 yr after the first dose.

Rubella livevirus vaccine

One dose SC; second dose at least 1 mo later

Indicated for HCWs,f both men and women, who do not have documentation of having received live vaccine on or after their first birthday or laboratory evidence of immunity. Adults born before 1957, except women who can become pregnant, can be considered immune.

Pregnancy; immunocompromised personsf: history of anaphylactic reaction after administration of neomycin

Th vac ma of vac pre vac wo reg con the rec sus mu

Varicella zoster live-virus vaccine

Two 0.5-ml doses SC 4-8 wk apart if =13 yr of age

Indicated for HCWs[†] who do not have either a reliable history of varicella or serologic evidence of immunity

Pregnancy, immunocompromised persons, i history of anaphylactic reaction following receipt of neomycin or gelatin. Avoid salicylate use for 6 wk after vaccination.

Va ma pa leu Be wit are be be

Varicella-zoster Persons 18 years who are at increased risk for both hepatitis B virus and hepatitis A vi d Recombinant hepatitis B surface-antigen protein dose. e Dialysis formulation administered on a 3-dose schedule at 0, 1, and 6 months f

Two 1.0-ml doses administered in 1 or 2 injections on a 4-dose schedule at 0, 1, 2, and 6 months.

g Not applicable.

TABLE 5-25 -- Recommended HIV/AIDS, Sexually Transmitted Disease (STD), and Viral Hepatitis Prevention Servi Risk Population[a] Recommended Services High-Risk Heterosexuals Persons seeking STD evaluation or treatment

Hepatitis B vaccination

Testing for human immunodeficiency virus (HIV) infectio

Testing for syphilis, gonorrhea, and chlamydia, as clinica Sexually active men not in a long-term. mutually monogamous relationship

Hepatitis B vaccination

Sexually active women not in a long-term. mutually monogamous relationship

Hepatitis B vaccination[e]

Annual testing for HIV infection[b],[d]

Annual testing for HIV infection[b],[d]

Annual testing for chlamydia (NOTE: Also recommended females aged 10 mIU/ml after vaccine series completion; hepatitis B immune globulin administration

From CDC: A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United Sta Advisory Committee on Immunization Practices (ACIP), MMWR 55(RR-l6):4, 2006. a Hepatitis B surface antigen. b Antibody to hepatitis B core antigen. c Immunoglobulin M. d Antibody to HbsAg e Negative test result. f

Positive test result

g To ensure that an HBsAg-positive test result is not a false-positive, samples with reactive HBsAg results should be tested with a licensed neutralizing confirma manufacturer's package insert.

h Persons positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they are the source for direct percutaneous expos quantities of virus (e.g., blood transfusion or organ transplant). 'Milliinternational units per milliliter.

Hepatitis A Prophylaxis

TABLE 5-28 -- Recommended Dosages of Hepatitis A Immune Globulin

Setting

Duration of Coverage

Dose (ml per kg)

Preexposure prophylaxis Short term (i.e., less than 3 months) 0.02 Long term (i.e., 3-5 months)[*] Postexposure prophylaxis —

0.06 0.02

Adapted from CDC: Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Com Practices (ACIP). MMWR 55CRR-07):9, 2006.

NOTE: Immune globulin should be administered intramuscularly into the deltoid or gluteal muscle in children younger tha administered in the anterolateral thigh muscle.

* Repeat every 5 months if continued exposure to hepatitis A virus occurs.

TABLE 5-29 -- Licensed Dosages of Hepatitis A Vaccines

Num Dos

Vaccine

Patient's Age

Hepatitis A vaccine, inactivated (Havrix)

12 months to 18 720 EL.U. years

0.5

2

19 years or older

1.0

2

12 months to 18 25 U years

0.5

2

19 years or older

50 U

1.0

2

720 EL.U. of hepatitis A antigen and 20 meg of hepatitis B surface antigen protein

1.0

3

Hepatitis A vaccine, inactivated (Vaqta)

Combined hepatitis A and hepatitis 18 years or B vaccine (Twinrix) older

Dose

Volume (ml)

1,440 EL.U.

Adapted from CDC: Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Com Practices (ACIP). MMW55(RR-07):10, 2006. * Zero represents the timing of the initial dose, subsequent numbers represent months after the initial dose.

Influenza Treatment and Prophylaxis

TABLE 5-30 -- Recommended Daily Dosage of Influenza Antiviral Medications for Treatment and Prophylaxis AGE GROUP (YRS) Antiviral Agent

1-6

7-9

10-12

13-64

Zanamivir * Treatment, influenza A and B

-

10 mg (2 inhalations) twice daily

1-4

5-9

Chemoprophylaxis influenza _ A and B

10 mg (2 inhalations) once daily

10 mg (2 inhalations) twice daily

10 mg (2 inhalatio twice daily

10 mg (2 inhalations) once daily

10 mg (2 inhalatio once daily

AGE GROUP (YRS) Antiviral Agent

1-6

7-9

10-12

13-64

Oseltamivir Treatment[§] influenza A and Dose varies by B child's Weight[¶]

Dose varies by child's Dose varies by child's weight[¶] weightweighty

75 mg twice daily

Chemoprophylaxis influenza Dose varies by A and B child's weight[**]

Dose varies by child's Dose varies by child's weight[**] weight[**]

75 mg once daily

Modified from MMWR 56CRR-6), 2007.

NOTE: Zanamivir is manufactured by GlaxoSmithKline (Relenza—inhaled powder). Zanamivir is approved for treatment approved for chemoprophylaxis of persons aged =5 years. Oseltamivir is manufactured by Roche Pharmaceuticals (Tam is approved for treatment or chemoprophylaxis of persons aged =1 year. No antiviral medications are approved for treat of influenza among children 40 kg, the dose is 75 mg once a day.

BOX 5-3 Persons for Whom Annual Vaccination Is Recommended Annual vaccination against influenza is recommended for •

All persons, including school-aged children, who want to reduce the risk of becoming ill with influenza or of transm others

•

All children aged 6-59 months (i.e., 6 months-4 years)

•

All persons aged =50 years

•

Children and adolescents (aged 6 months-18 years) receiving long-term aspirin therapy who therefore might be a Reye's syndrome after influenza virus infection

•

Women who will become pregnant during the influenza season

•

Adults and children who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal metabolic disorders (including diabetes mellitus)

•

Adults and children who have immunosuppression (including immunosuppression caused by medications or by h immunodeficiency virus)

•

Adults and children who have any conditions (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, o disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase

•

Residents of nursing homes and other chronic-care facilities

•

Health care personnel

•

Healthy household contacts (including children) and caregivers of children aged 60 kg (132 lb) body weight: 200 mg twice daily or 400 mg daily; if with tenofovir, 250 mg/daily

260

Pancreatitis peripheral n

60 kg (132 lb) body weight: 40 mg twice daily

320

Pancreatitis rapidly prog neuromuscu