THE 2002 OFFICIAL PATIENT’S SOURCEBOOK
on
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The 2002 Official Patient’s Sourcebook on Lupus: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83378-8 1. Lupus-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail:
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Dedication To the healthcare professionals dedicating their time and efforts to the study of lupus.
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to lupus. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.
Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.
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About ICON Health Publications In addition to lupus, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Arthritis of the Knee
·
The Official Patient's Sourcebook on Arthritis of the Shoulder
·
The Official Patient's Sourcebook on Ehlers-danlos Syndrome
·
The Official Patient's Sourcebook on Epidermolysis Bullosa
·
The Official Patient's Sourcebook on Fibromyalgia
·
The Official Patient's Sourcebook on Gout
·
The Official Patient's Sourcebook on Juvenile Rheumatoid Arthritis
·
The Official Patient's Sourcebook on Marfan Syndrome
·
The Official Patient's Sourcebook on Osteoarthritis
·
The Official Patient's Sourcebook on Osteogenesis Imperfecta
·
The Official Patient's Sourcebook on Polymyalgia Rheumatica
·
The Official Patient's Sourcebook on Raynaud's Phenomenon
·
The Official Patient's Sourcebook on Reiter's Syndrome
·
The Official Patient's Sourcebook on Rheumatoid Arthritis
·
The Official Patient's Sourcebook on Scleroderma
To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
Contents vii
Table of Contents INTRODUCTION...................................................................................... 1
Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4
PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON LUPUS: GUIDELINES ........................ 9
Overview............................................................................................................... 9 What Is Lupus? .................................................................................................. 10 Understanding What Causes Lupus .................................................................. 12 Symptoms of Lupus ............................................................................................ 13 Diagnosing Lupus .............................................................................................. 15 Treating Lupus ................................................................................................... 16 Lupus and Quality of Life................................................................................... 20 Tips for Working with Your Doctor ................................................................... 22 Pregnancy For Women With Lupus................................................................... 22 Current Research ................................................................................................ 23 Additional Resources .......................................................................................... 26 More Guideline Sources ..................................................................................... 28 Vocabulary Builder............................................................................................. 41
CHAPTER 2. SEEKING GUIDANCE ....................................................... 51
Overview............................................................................................................. 51 Associations and Lupus...................................................................................... 51 Finding More Associations................................................................................. 57 Finding Doctors.................................................................................................. 59 Finding a Rheumatologist .................................................................................. 60 Selecting Your Doctor ........................................................................................ 60 Working with Your Doctor ................................................................................ 61 Broader Health-Related Resources ..................................................................... 62 Vocabulary Builder............................................................................................. 63
CHAPTER 3. CLINICAL TRIALS AND LUPUS ........................................ 65
Overview............................................................................................................. 65 Recent Trials on Lupus....................................................................................... 68 Benefits and Risks............................................................................................... 92 Keeping Current on Clinical Trials.................................................................... 95 General References.............................................................................................. 96 Vocabulary Builder............................................................................................. 97
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL................................................ 101
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CHAPTER 4. STUDIES ON LUPUS ....................................................... 103
Overview........................................................................................................... 103 The Combined Health Information Database ................................................... 103 Federally-Funded Research on Lupus .............................................................. 112 E-Journals: PubMed Central ............................................................................ 128 The National Library of Medicine: PubMed .................................................... 133 Vocabulary Builder........................................................................................... 140
CHAPTER 5. PATENTS ON LUPUS ...................................................... 147
Overview........................................................................................................... 147 Patents on Lupus .............................................................................................. 148 Patent Applications on Lupus .......................................................................... 164 Keeping Current ............................................................................................... 168 Vocabulary Builder........................................................................................... 169
CHAPTER 6. BOOKS ON LUPUS .......................................................... 173
Overview........................................................................................................... 173 Book Summaries: Federal Agencies .................................................................. 173 Book Summaries: Online Booksellers ............................................................... 181 The National Library of Medicine Book Index ................................................. 185 Chapters on Lupus............................................................................................ 188 Directories......................................................................................................... 192 General Home References ................................................................................. 194 Vocabulary Builder........................................................................................... 194
CHAPTER 7. MULTIMEDIA ON LUPUS ............................................... 199
Overview........................................................................................................... 199 Video Recordings .............................................................................................. 199 Bibliography: Multimedia on Lupus ................................................................ 201 Vocabulary Builder........................................................................................... 203
CHAPTER 8. PERIODICALS AND NEWS ON LUPUS ............................ 205
Overview........................................................................................................... 205 News Services & Press Releases ....................................................................... 205 Newsletters on Lupus ....................................................................................... 215 Newsletter Articles ........................................................................................... 216 Academic Periodicals covering Lupus .............................................................. 225 Vocabulary Builder........................................................................................... 227
CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 229
Overview........................................................................................................... 229 NIH Guidelines................................................................................................. 229 NIH Databases.................................................................................................. 230 Other Commercial Databases ........................................................................... 237 The Genome Project and Lupus........................................................................ 238 Specialized References....................................................................................... 242 Vocabulary Builder........................................................................................... 243
CHAPTER 10. DISSERTATIONS ON LUPUS ......................................... 245
Contents
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Overview........................................................................................................... 245 Dissertations on Lupus..................................................................................... 245 Keeping Current ............................................................................................... 247
PART III. APPENDICES .................................................. 249 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 251
Overview........................................................................................................... 251 Your Medications: The Basics .......................................................................... 252 Learning More about Your Medications .......................................................... 253 Commercial Databases...................................................................................... 255 Contraindications and Interactions (Hidden Dangers) ................................... 259 A Final Warning .............................................................................................. 260 General References............................................................................................ 261 Vocabulary Builder........................................................................................... 262
APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 265
Overview........................................................................................................... 265 What Is CAM? ................................................................................................. 265 What Are the Domains of Alternative Medicine?............................................ 266 Can Alternatives Affect My Treatment? ......................................................... 269 Finding CAM References on Lupus ................................................................. 270 Additional Web Resources................................................................................ 280 General References............................................................................................ 289 Vocabulary Builder........................................................................................... 290
APPENDIX C. RESEARCHING NUTRITION ......................................... 293
Overview........................................................................................................... 293 Food and Nutrition: General Principles........................................................... 294 Finding Studies on Lupus ................................................................................ 298 Federal Resources on Nutrition........................................................................ 302 Additional Web Resources................................................................................ 303 Vocabulary Builder........................................................................................... 307
APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 309
Overview........................................................................................................... 309 Preparation ....................................................................................................... 309 Finding a Local Medical Library ...................................................................... 310 Medical Libraries Open to the Public............................................................... 310
APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 317
Overview........................................................................................................... 317 Your Rights as a Patient................................................................................... 317 Patient Responsibilities .................................................................................... 321 Choosing an Insurance Plan............................................................................. 322 Medicare and Medicaid .................................................................................... 324 NORD’s Medication Assistance Programs ..................................................... 327 Additional Resources ........................................................................................ 328
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Contents
APPENDIX F. NEUROLOGICAL SEQUELAE OF LUPUS........................ 329
Overview........................................................................................................... 329 Is There Any Treatment? ................................................................................. 329 What Is the Prognosis?..................................................................................... 330 What Research Is Being Done? ........................................................................ 330 For More Information....................................................................................... 330 Vocabulary Builder........................................................................................... 331
ONLINE GLOSSARIES.................................................... 332 Online Dictionary Directories.......................................................................... 338
LUPUS GLOSSARY........................................................... 339 General Dictionaries and Glossaries ................................................................ 368
INDEX................................................................................... 370
Introduction
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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don't know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3
Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2
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Lupus
Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor's offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The 2002 Official Patient’s Sourcebook on Lupus has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to lupus, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on lupus. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on lupus should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate options is always up to the patient in consultation with their physician and healthcare providers.
Introduction
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Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching lupus (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to lupus. It also gives you sources of information that can help you find a doctor in your local area specializing in treating lupus. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with lupus. Part II moves on to advanced research dedicated to lupus. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on lupus. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with lupus or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with lupus. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with lupus.
Scope While this sourcebook covers lupus, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that lupus is often considered a synonym or a condition closely related to the following: ·
Chronic Cutaneous Lupus Erythematosus
·
Disseminated Lupus Erythematosus
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Focal Glomerulonephritis
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Lupus Erythematosus
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Lupus Glomerular Disease
·
Lupus Glomerulonephritis
·
Lupus Nephritis
4
Lupus
In addition to synonyms and related conditions, physicians may refer to lupus using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world's illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for lupus:4 ·
695.4 lupus erythematosus
·
710.0 systemic lupus erythematosus
For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to lupus. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.
Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson's approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with lupus will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with lupus is even indexed in 4 This list is based on the official version of the World Health Organization's 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”
Introduction
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search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of lupus, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors
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PART I: THE ESSENTIALS
ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on lupus. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of lupus to you or even given you a pamphlet or brochure describing lupus. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.
Guidelines
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CHAPTER 1. THE ESSENTIALS ON LUPUS: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on lupus. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on lupus can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.
The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on lupus. Originally founded in 1887, the NIH is one of the world's foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world's most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.
5
Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.
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There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with lupus and associated conditions: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
·
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc. ) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html
·
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines at http://www.nih.gov/niams/healthinfo/
Among those listed above, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is especially noteworthy. The mission of NIAMS, a part of the National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. The NIAMS provides the following guideline concerning lupus.6
What Is Lupus?7 Lupus is a disorder of the immune system known as an autoimmune disease. In autoimmune diseases, the body harms its own healthy cells and tissues. This leads to inflammation and damage to various body tissues. Lupus can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain. Although people with the disease may have many different symptoms, some of the most common ones include 6 This and other passages are adapted from the NIH and NIAMS (http://www.niams.nih.gov/hi/index.htm). “Adapted” signifies that the text is reproduced with attribution, with some or no editorial adjustments. 7 Adapted from The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): http://www.niams.nih.gov/hi/topics/lupus/slehandout/index.htm.
Guidelines 11
extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes, and kidney problems. At present, there is no cure for lupus. However, lupus can be very successfully treated with appropriate drugs, and most people with the disease can lead active, healthy lives. Lupus is characterized by periods of illness, called flares, and periods of wellness, or remission. Understanding how to prevent flares and how to treat them when they do occur helps people with lupus maintain better health. Intense research is underway and scientists funded by the NIH are continuing to make great strides in understanding the disease, which may ultimately lead to a cure. Two of the questions researchers are studying are who gets lupus and why. We know that many more women than men have lupus. Lupus is three times more common in African American women than in Caucasian women and is also more common in women of Hispanic, Asian, and Native American descent. In addition, lupus can run in families, but the risk that a child or a brother or sister of a patient will also have lupus is still quite low. It is difficult to estimate how many people in the United States have the disease because its symptoms vary widely and its onset is often hard to pinpoint. Although “lupus” is used as a broad term, there actually are several kinds of lupus: ·
Systemic lupus erythematosus (SLE) is the form of the disease that most people are referring to when they say “lupus.” The word “systemic” means the disease can affect many parts of the body. The symptoms of SLE may be mild or serious. Although SLE usually first affects people between the ages of 15 and 45 years, it can occur in childhood or later in life as well. This booklet focuses on SLE.
·
Discoid lupus erythematosus refers to a skin disorder in which a red, raised rash appears on the face, scalp, or elsewhere. The raised areas may become thick and scaly and may cause scarring. The rash may last for days or years and may recur. A small percentage of people with discoid lupus have or develop SLE.
·
Drug-induced lupus refers to a form of lupus caused by specific medications. Symptoms are similar to those of SLE (arthritis, rash, fever, and chest pain) that typically go away when the drug is stopped.
·
Neonatal lupus is a rare form of lupus affecting newborn babies of women with SLE or certain other immune system disorders. At birth, the babies have a skin rash, liver abnormalities, or low blood counts, which
12 Lupus
entirely go away over several months. However, babies with neonatal lupus may have a serious heart defect. Physicians can now identify most at-risk mothers, allowing for prompt treatment of the infant at or before birth. Neonatal lupus is very rare, and most infants of mothers with SLE are entirely healthy.
Understanding What Causes Lupus Lupus is a complex disease whose cause is unknown. It is likely that there is no single cause but rather a combination of genetic, environmental, and possibly hormonal factors that work together to cause the disease. The exact cause may differ from one person to another. Scientists are making progress in understanding the processes leading to lupus, as described here and in the Current Research section. Research suggests that genetics plays an important role; however, no specific “lupus gene” has been identified. Instead, it appears that several genes may increase a person's susceptibility to the disease. The fact that lupus can run in families indicates that its development has a genetic basis. In addition, studies of identical twins have shown that lupus is much more likely to affect both members of a pair of identical twins, who share the exact same set of genes, than two nonidentical twins or other siblings. However, scientists think that genes alone cannot account for who gets lupus. Other factors must also play a role. Some of the factors that scientists are studying include sunlight, stress, certain drugs, and infectious agents such as viruses. Even though a virus might trigger the disease in susceptible individuals, a person cannot “catch” lupus from someone else. In lupus, the body's immune system does not work as it should. A healthy immune system produces substances called antibodies that help fight and destroy viruses, bacteria, and other foreign substances that invade the body. In lupus, the immune system produces antibodies against the body’s healthy cells and tissues. These antibodies, called autoantibodies (“auto” means self), contribute to the inflammation of various parts of the body, causing damage and altering the function of target organs and tissues. In addition, some autoantibodies join with substances from the body’s own cells or tissues to form molecules called immune complexes. A buildup of these immune complexes in the body also contributes to inflammation and tissue injury in people with lupus. Researchers do not yet understand all of the factors that cause inflammation and tissue damage in lupus, and this is an active area of research.
Guidelines 13
Symptoms of Lupus Each person’s experience with lupus is different, although there are patterns that permit accurate diagnosis. Symptoms can range from mild to severe and may come and go over time. Common symptoms of lupus include painful or swollen joints, unexplained fever, and skin rashes, along with extreme fatigue. A characteristic skin rash may appear across the nose and cheeks-the so-called butterfly or malar rash. Other rashes occur elsewhere on the face and ears, upper arms, shoulders, chest, and hands. Other symptoms of lupus include chest pain, hair loss, sensitivity to the sun, anemia (a decrease in red blood cells), and pale or purple fingers and toes from cold and stress. Some people also experience headaches, dizziness, depression, or seizures. New symptoms may continue to appear years after the initial diagnosis, and different symptoms can occur at different times. Common symptoms of lupus include: ·
Painful or swollen joints and muscle pain
·
Unexplained fever
·
Red rashes, most commonly on the face.
·
Chest pain upon deep breathing
·
Unusual loss of hair
·
Pale or purple fingers or toes from cold or stress (Raynaud's phenomenon)
·
Sensitivity to the sun
·
Swelling (edema) in legs or around eyes
·
Swollen glands
·
Extreme fatigue
In some people with lupus, only one system of the body such as the skin or joints is affected. Other people experience symptoms in many parts of their body. Just how seriously a body system is affected also varies from person to person. Most commonly, joints and muscles are affected, causing arthritis and muscle pain. Skin rashes are quite common. The following systems in the body also can be affected by lupus.
14 Lupus
Kidneys Inflammation of the kidneys (nephritis) can impair their ability to get rid of waste products and other toxins from the body effectively. Because the kidneys are so important to overall health, lupus affecting the kidneys generally requires intensive drug treatment to prevent permanent damage. There is usually no pain associated with kidney involvement, although some patients may notice that their ankles swell. Most often the only indication of kidney disease is an abnormal urine or blood test.
Lungs Some people with lupus develop pleuritis, an inflammation of the lining of the chest cavity that causes chest pain, particularly with breathing. Patients with lupus also may get pneumonia. Central Nervous System In some patients, lupus affects the brain or central nervous system. This can cause headaches, dizziness, memory disturbances, vision problems, stroke, or changes in behavior.
Blood Vessels Blood vessels may become inflamed (vasculitis), affecting the way blood circulates through the body. The inflammation may be mild and may not require treatment or may be severe and require immediate attention.
Blood People with lupus may develop anemia, leukopenia (a decreased number of white blood cells), or a decrease in the number of platelets (thrombocytopenia). Some people with lupus may have abnormalities that cause an increased risk for blood clots.
Guidelines 15
Heart In some people with lupus, inflammation can occur in the heart itself (myocarditis and endocarditis) or the membrane that surrounds it (pericarditis), causing chest pains or other symptoms. Lupus can also increase the risk of atherosclerosis.
Diagnosing Lupus Diagnosing lupus can be difficult. It may take months or even years for doctors to piece together the symptoms to diagnose this complex disease accurately. Making a correct diagnosis of lupus requires knowledge and awareness on the part of the doctor and good communication on the part of the patient. Giving the doctor a complete, accurate medical history (for example, what health problems you have had and for how long) is critical to the process of diagnosis. This information, along with a physical examination and the results of laboratory tests, helps the doctor consider other diseases that may mimic lupus, or determine if the patient truly has the disease. Reaching a diagnosis may take time and occur gradually as new symptoms appear. No single test can determine whether a person has lupus, but several laboratory tests may help the doctor to make a diagnosis. The most useful tests identify certain autoantibodies often present in the blood of people with lupus. For example, the antinuclear antibody (ANA) test is commonly used to look for autoantibodies that react against components of the nucleus, or “command center,” of the patient’s own cells. Most people with lupus test positive for ANA; however, there are a number of other causes of a positive ANA besides lupus, including infections, other rheumatic or immune diseases, and occasionally as a finding in normal healthy adults. The ANA test simply provides another clue for the doctor to consider in making a diagnosis. In addition, there are blood tests for individual types of autoantibodies that are more specific to people with lupus, although not all people with lupus test positive for these and not all people with these antibodies have lupus. These antibodies include anti-DNA, anti-Sm, antiRNP, anti-Ro (SSA), and anti-La (SSB). The doctor may use these antibody tests to help make a diagnosis of lupus. Some tests are used less frequently but may be helpful if the cause of a person’s symptoms remains unclear. The doctor may order a biopsy of the skin or kidneys if those body systems are affected. Some doctors may order a syphilis test or a test for anticardiolipin antibody. A positive test does not
16 Lupus
mean that a patient has syphilis; however, the presence of this antibody may increase the risk of blood clotting and can increase the risk of miscarriages in pregnant women with lupus. Again, all these tests merely serve as tools to give the doctor clues and information in making a diagnosis. The doctor will look at the entire picture--medical history, symptoms, and test results--to determine if a person has lupus. Other laboratory tests are used to monitor the progress of the disease once it has been diagnosed. A complete blood count, urinalysis, blood chemistries, and erythrocyte sedimentation rate (ESR) test can provide valuable information. Another common test measures the blood level of a group of substances called complement. People with lupus often have increased ESRs and low complement levels, especially during flares of the disease. Diagnostic tools used for diagnosing lupus: ·
Medical history
·
Complete physical examination
·
Laboratory tests:
·
Complete blood count
·
Erythrocyte sedimentation rate (ESR)
·
Urinalysis
·
Blood chemistries
·
Complement levels
·
Antinuclear antibody test (ANA)
·
Other autoantibody tests (anti-DNA, anti-Sm, anti-RNP, anti-Ro [SSA], anti- La [SSB])
·
Syphilis test or anticardiolipin antibody
·
Skin or kidney biopsy
Treating Lupus Diagnosing and treating lupus is often a team effort between the patient and several types of health care professionals. A person with lupus can go to his or her family doctor or internist, or can visit a rheumatologist. A rheumatologist is a doctor who specializes in rheumatic diseases (arthritis and other diseases of the joints, bones, and muscles). Clinical immunologists
Guidelines 17
(doctors specializing in immune system disorders) may also treat people with lupus. As treatment progresses, other professionals often help. These may include nurses, psychologists, social workers, and specialists such as nephrologists (doctors who treat kidney disease), hematologists (doctors specializing in blood disorders), dermatologists (doctors who treat skin disease), and neurologists (doctors specializing in disorders of the nervous system). The range and effectiveness of treatments for lupus have increased dramatically, giving doctors more choices in how to treat the disease. It is important for the patient to work closely with the doctor and take an active role in treatment. Once lupus has been diagnosed, the doctor will develop a treatment plan based on the patient’s age, sex, health, symptoms, and lifestyle. Treatment plans are tailored to the individual’s needs and may change over time. In developing a treatment plan, the doctor has several goals: to prevent flares, to treat them when they do occur, and to minimize organ damage and complications. The doctor and patient should reevaluate the plan regularly to ensure that it is as effective as possible. Several types of drugs are used to treat lupus. The treatment the doctor chooses is based on the patient’s individual symptoms and needs. For people with joint or chest pain or fever, drugs that decrease inflammation, referred to as nonsteroidal anti-inflammatory drugs (NSAIDs), are often used. While some NSAIDs are available over the counter, a doctor’s prescription is necessary for others. NSAIDs may be used alone or in combination with other types of drugs to control pain, swelling, and fever. Even though some NSAIDs may be purchased without a prescription, it is important that they be taken under a doctor’s direction. Common side effects of NSAIDs, including those available over the counter, can include stomach upset, heartburn, diarrhea, and fluid retention. Some patients with lupus also develop liver and kidney inflammation while taking NSAIDs, making it especially important to stay in close contact with the doctor while taking these medications. A new class of anti-inflammatory drugs called COX-2 inhibitors (celecoxib [Celebrex]; rofecoxib [Vioxx]; mobic [Meloxicam]) have all of the same effects as NSAIDs on pain and inflammation but have a much lower risk of significant gastrointestinal side effects. These agents have not been extensively studied in patients with lupus and have not been approved by the Food and Drug Administration for use specifically in lupus. However, they might provide benefits similar to NSAIDs.
18 Lupus
NSAIDs Used to Treat Lupus8 Generic Name Ibuprofen Naproxen Sulindac Diclofenac Piroxicam Ketoprofen Diflunisal Nabumetone Etodolac Oxaprozin Indomethacin
Brand Name Motrin, Advil Naprosyn, Aleve Clinoril Voltaren Feldene Orudis Dolobid Relafen Lodine Daypro Indocin
Antimalarials Antimalarials are another type of drug commonly used to treat lupus. These drugs were originally used to treat malaria, but doctors have found that they also are useful for lupus. Exactly how antimalarials work in lupus is unclear, but scientists think that they may work by suppressing parts of the immune response. A common antimalarial used to treat lupus is hydroxychloroquine (Plaquenil). It may be used alone or in combination with other drugs and generally is used to treat fatigue, joint pain, skin rashes, and inflammation of the lungs. Clinical studies have found that continuous treatment with antimalarials may prevent flares from recurring. Side effects of antimalarials can include stomach upset and, extremely rarely, damage to the retina of the eye. Corticosteroids The mainstay of lupus treatment involves the use of corticosteroid hormones, such as prednisone (Deltasone), hydrocortisone, methylprednisolone (Medrol), and dexamethasone (Decadron, Hexadrol). Corticosteroids are related to cortisol, which is a natural anti-inflammatory Brand names included in this publication are provided as examples only and their inclusion does not mean that these products are endorsed by the National Institutes of Health or any other Government agency. Also, if a particular brand name is not mentioned, this does not mean or imply that the product is unsatisfactory. 8
Guidelines 19
hormone. They work by rapidly suppressing inflammation. Corticosteroids can be given by mouth, in creams applied to the skin, or by injection. Because they are potent drugs, the doctor will seek the lowest dose with the greatest benefit. Short-term side effects of corticosteroids include swelling, increased appetite, weight gain, and emotional ups and downs. These side effects generally stop when the drug is stopped. It can be dangerous to stop taking corticosteroids suddenly, so it is very important that the doctor and patient work together in changing the corticosteroid dose. Sometimes doctors give very large amounts of corticosteroid by vein over a brief period of time (days) (“bolus” or “pulse” therapy). With this treatment, the typical side effects are less likely and slow withdrawal is unnecessary. Long-term side effects of corticosteroids can include stretch marks on the skin, excessive hair growth, weakened or damaged bones (osteoporosis and osteonecrosis), high blood pressure, damage to the arteries, high blood sugar, infections, and cataracts. Typically, the higher the dose of prolonged corticosteroids, the more severe the side effects. Also, the longer they are taken, the greater the risk of side effects. Researchers are working to develop alternative strategies to limit or offset the use of corticosteroids. For example, corticosteroids may be used in combination with other, less potent drugs, or the doctor may try to slowly decrease the dose once the disease is under control. People with lupus who are using corticosteroids should talk to their doctors about taking supplemental calcium and vitamin D or other drugs to reduce the risk of osteoporosis (weakened, fragile bones). In special circumstances, patients may require stronger drugs to combat lupus symptoms. In some patients, methotrexate (Folex, Mexate, Rheumatrex) may be used to help control the disease. Patients who have many body systems affected by the disease may receive intravenous gamma globulin (Gammagard S/D), a blood protein that increases immunity and helps fight infection. Gamma globulin also may be used to control acute bleeding in patients with thrombocytopenia or to prepare a person with lupus for surgery. For patients whose kidneys or central nervous systems are affected by lupus, a type of drug called an immunosuppressive may be used. Immunosuppressives, such as azathioprine (Imuran) and cyclophosphamide (Cytoxan), restrain the overactive immune system by blocking the production of some immune cells and curbing the action of others. These drugs may be given by mouth or by infusion (dripping the drug into the vein through a small tube). Side effects may include nausea, vomiting, hair loss, bladder problems, decreased fertility, and increased risk of cancer and infection. The risk for side effects increases with the length of treatment. As
20 Lupus
with other treatments for lupus, there is a risk of relapse after the immunosuppressives have been stopped.
Side Effects Working closely with the doctor helps ensure that treatments for lupus are as successful as possible. Because some treatments may cause harmful side effects, it is important to report any new symptoms to the doctor promptly. It is also important not to stop or change treatments without talking to the doctor first.
Alternative Therapies Because of the nature and cost of the medications used to treat lupus, their potentially serious side effects, and the lack of a cure, many patients seek other ways of treating the disease. Some alternative approaches that have been suggested include special diets, nutritional supplements, fish oils, ointments and creams, chiropractic treatment, and homeopathy. Although these methods may not be harmful in and of themselves, and they may be associated with symptomatic or psychosocial benefit, no research to date shows that they affect the disease process or prevent organ damage. Some alternative or complementary approaches may help the patient cope or reduce some of the stress associated with living with a chronic illness. If the doctor feels the approach has value and will not be harmful, it can be incorporated into the patient’s treatment plan. However, it is important not to neglect regular health care or treatment of serious symptoms. An open dialogue between the patient and the physician about the relative values of complementary and alternative and more traditional therapy is essential in permitting the patient to make an informed choice about treatment options.
Lupus and Quality of Life Despite the symptoms of lupus and the potential side effects of treatment, people with lupus can maintain a high quality of life overall. One key to managing lupus is to understand the disease and its impact. Learning to recognize the warning signs of a flare can help the patient take steps to ward it off or reduce its intensity. Many people with lupus experience increased fatigue, pain, a rash, fever, abdominal discomfort, headache, or dizziness just before a flare. Developing strategies to prevent flares can also be helpful,
Guidelines 21
such as learning to recognize your warning signals and maintaining good communication with your doctor. It is also important for people with lupus to receive regular health care, instead of seeking help only when symptoms worsen. Having a medical exam and laboratory work on a regular basis allows the doctor to note any changes and may help predict flares. The treatment plan, which is tailored to the individual's specific needs and circumstances, can be adjusted accordingly. If new symptoms are identified early, treatments may be more effective. Other concerns also can be addressed at regular checkups. The doctor can provide guidance about such issues as the use of sunscreens, stress reduction, and the importance of structured exercise and rest, as well as birth control and family planning. Because people with lupus can be more susceptible to infections, the doctor may recommend yearly influenza vaccinations or pneumococcal vaccination for some patients. Warning signs of a flare-up: ·
Increased fatigue
·
Pain
·
Rash
·
Fever
·
Abdominal discomfort
·
Headache
· Dizziness Preventing a flare: ·
Learn to recognize your warning signals
·
Maintain good communication with your doctor
People with lupus should receive regular preventive health care, such as gynecological and breast examinations. Regular dental care will help avoid potentially dangerous infections. If a person is taking corticosteroids or antimalarial medications, a yearly eye exam should be done to screen for and treat eye problems. Staying healthy requires extra effort and care for people with lupus, so it becomes especially important to develop strategies for maintaining wellness. Wellness involves close attention to the body, mind, and spirit. One of the primary goals of wellness for people with lupus is coping with the stress of having a chronic disorder. Effective stress management varies from person
22 Lupus
to person. Some approaches that may help include exercise, relaxation techniques such as meditation, and setting priorities for spending time and energy. Developing and maintaining a good support system is also important. A support system may include family, friends, medical professionals, community organizations, and organized support groups. Participating in a support group can provide emotional help, boost self-esteem and morale, and help develop or improve coping skills. (For more information on support groups, see the Additional Resources section). Learning more about lupus may also help. Studies have shown that patients who are well informed and participate actively in their own care experience less pain, make fewer visits to the doctor, build self-confidence, and remain more active.
Tips for Working with Your Doctor ·
Seek a health care provider who will listen to and address your concerns.
·
Provide complete, accurate medical information.
·
Make a list of your questions and concerns in advance.
·
Be honest and share your point of view with the health care provider.
·
Ask for clarification or further explanation if you need it.
·
Talk to other members of the health care team, such as nurses, therapists, or pharmacists.
·
Do not hesitate to discuss sensitive subjects (for example, birth control, intimacy) with your doctor.
·
Discuss any treatment changes with your doctor before making them.
Pregnancy For Women With Lupus Although a lupus pregnancy is considered high risk, most women with lupus carry their babies safely to the end of their pregnancy. Experts disagree on the exact numbers, but 20 to 25 percent of lupus pregnancies end in miscarriage, compared to 10 to 15 percent of pregnancies in women without the disease. Pregnancy counseling and planning before pregnancy are important. Ideally, a woman should have no signs or symptoms of lupus
Guidelines 23
and be taking no medications for at least 6 months before she becomes pregnant. Some women may experience a mild to moderate flare during or after their pregnancy; others do not. Pregnant women with lupus, especially those taking corticosteroids, also are more likely to develop high blood pressure, diabetes, hyperglycemia (high blood sugar), and kidney complications, so regular care and good nutrition during pregnancy are essential. It is also advisable to have access to a neonatal (newborn) intensive care unit at the time of delivery in case the baby requires special medical attention. About 25 percent (one in four) of babies of women with lupus are born prematurely, but do not suffer from birth defects.
Current Research Lupus is the focus of intense research as scientists try to determine what causes the disease and how it can best be treated. Some of the questions they are working to answer include: Exactly who gets lupus, and why? Why are women more likely than men to have the disease? Why are there more cases of lupus in some racial and ethnic groups? What goes wrong in the immune system, and why? How can we correct the way the immune system functions once something goes wrong? What treatment approaches will work best to lessen or cure lupus symptoms? To help answer these questions, scientists are developing new and better ways to study the disease. They are doing laboratory studies that compare various aspects of the immune systems of people with lupus with those of other people both with and without lupus. They also use mice with disorders resembling lupus to better understand the abnormalities of the immune system that occur in lupus and to identify possible new therapies. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a component of the National Institutes of Health (NIH), has a major program of lupus research in its intramural program in Bethesda, Maryland, and funds many individual researchers across the United States who are studying lupus. To help scientists gain new knowledge, the NIAMS also has established Specialized Centers of Research devoted specifically to lupus research. In addition, the NIAMS is funding several lupus registries that will gather medical information as well as blood and tissue samples from patients and their relatives. This will give researchers across the
24 Lupus
country access to information and materials they can use to help identify genes that determine susceptibility to the disease. Identifying genes that play a role in the development of lupus is an active area of research. For example, researchers suspect a genetic defect in a cellular process called apoptosis, or “programmed cell death,” in people with lupus. Apoptosis is similar to the process that causes leaves to turn color in autumn and fall from trees; it allows the body to eliminate cells that have fulfilled their function and typically need to be replaced. If there is a problem in the apoptosis process, harmful cells may stay around and do damage to the body’s own tissues. For example, in a mutant mouse strain that develops a lupus-like illness, one of the genes that controls apoptosis is defective. When it is replaced by a normal gene, the mice no longer develop signs of the disease. Scientists are studying what role genes involved in apoptosis may play in human disease development. Studying genes for complement, a series of proteins in the blood that play an important part in the immune system, is another active area of lupus research. Complement acts as a backup for antibodies, helping them destroy foreign substances that invade the body. If there is a decrease in complement, the body is less able to fight or destroy foreign substances. If these substances are not removed from the body, the immune system may become overactive and begin to make autoantibodies. Recent large studies of families with lupus have identified a number of genetic regions that appear to confer risk of SLE. Although the specific genes and their function remain unknown, intensive work in delineating the entire human genome offers promise that these genes will be identified in the near future. This should provide knowledge of the fundamental nature of the risk factors that can lead to lupus and new insights into how these risks can be modified. It is thought that autoimmune diseases, such as lupus, occur when a genetically susceptible individual encounters an unknown environmental agent or trigger. In this circumstance, an abnormal immune response can be initiated that leads to the signs and symptoms of lupus. Research has focused on both the genetic susceptibility and the environmental trigger. Although the environmental trigger remains unknown, microbial agents such as Epstein-Barr virus and others have been considered. Researchers also are studying other factors that may affect a person’s susceptibility to lupus. For example, because lupus is more common in women than in men, some researchers are investigating the role of hormones and other male-female differences in the development and course of the disease.
Guidelines 25
A current study funded by the NIH is focusing on the safety and effectiveness of oral contraceptives (birth-control pills) and hormone replacement therapy in women with lupus. Doctors have worried about the wisdom of prescribing oral contraceptives or estrogen replacement therapy for women with lupus because of a widely held view that estrogens can make the disease worse. However, recent limited data suggest these drugs may be safe for some women with lupus. Researchers hope this study will yield options for safe, effective methods of birth control for young women with lupus and enable postmenopausal women with lupus to benefit from estrogen replacement therapy. Promising areas of research: ·
Identifying lupus susceptibility genes
·
Searching for environmental agents that cause lupus
·
Developing drugs or biologic agents that cure lupus
Researchers are also focusing on finding better treatments for lupus. A primary goal of this research is to develop treatments that can effectively minimize the use of corticosteroids. Scientists are trying to identify combination therapies that may be more effective than single-treatment approaches. Researchers are also interested in using male hormones, called androgens, as a possible treatment for the disease. Another goal is to improve the treatment and management of lupus in the kidneys and central nervous system. For example, a 20-year study supported by the NIAMS and the NIH found that combining cyclophosphamide with prednisone helped delay or prevent kidney failure, a serious complication of lupus. On the basis of new information about the disease process, scientists are using novel “biologic agents” to selectively block parts of the immune system. Development and testing of these new drugs, which are based on compounds that occur naturally in the body, comprise an exciting and promising new area of lupus research. The hope is that these treatments not only will be effective, but also will have fewer side effects. Other treatment options currently being explored include reconstructing the immune system by bone marrow transplantation. In the future, gene therapy also may play an important role in lupus treatment.
Hope for the Future With research advances and a better understanding of lupus, the prognosis for people with lupus today is far brighter than it was even 20 years ago. It is
26 Lupus
possible to have lupus and remain active and involved with life, family, and work. As current research efforts unfold, there is continued hope for new treatments; improvements in quality of life; and, ultimately, a way to prevent or cure the disease. The research efforts of today may yield the answers of tomorrow, as scientists continue to unravel the mysteries of lupus.
Additional Resources For more information on lupus, contact: National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse NIAMS/National Institutes of Health 1 AMS Circle Bethesda, MD 20892-3675 (301) 495-4484 or (877) 22-NIAMS (toll free) TTY: (301) 565-2966 Fax: (301) 718-6366 http://www.niams.nih.gov/ The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. The clearinghouse provides information on lupus. Fact sheets, additional information, and research updates can also be found on the NIAMS Web site at http://www.niams.nih.gov/. Association of Rheumatology Health Professionals, American College of Rheumatology 1800 Century Place, Suite 250 Atlanta, GA 30345 (404) 633-3777 Fax: (404) 633-1870 http://www.rheumatology.org/ The American College of Rheumatology (ACR) is an organization of doctors and associated health professionals who specialize in arthritis and related diseases of the bones, joints, and muscles. The Association of Rheumatology Health Professionals, a division of ACR, aims to enhance the knowledge and skills of rheumatology health professionals and to promote their involvement in rheumatology research, education, and quality patient care. The association also works to advance and promote basic and continuing education in rheumatology for health professionals who provide care to people with rheumatic diseases.
Guidelines 27
Lupus Foundation of America (LFA), Inc. 1300 Piccard Drive, Suite 200 Rockville, MD 20850 (301) 670-9292 (800) 558-0121 or your local chapter, listed in the telephone directory http://www.lupus.org/ This is the main voluntary organization devoted to lupus. The LFA assists local chapters in providing services to people with lupus, works to educate the public about lupus, and supports lupus research. Through a network of more than 500 branches and support groups, the chapters provide education through information and referral services, health fairs, newsletters, publications, and seminars. Chapters provide support to people with lupus, their families, and friends through support group meetings, hospital visits, and telephone help lines. SLE Foundation, Inc. 149 Madison Avenue, Suite 205 New York, NY 10016 (212) 685-4118 http://www.lupusny.org/ The foundation supports and encourages medical research to find the cause and cure of lupus and improve its diagnosis and treatment. It also provides a wide variety of services to help patients with lupus and their families. In addition, this voluntary organization conducts a broad-based public education program to raise awareness of lupus and increase understanding of this serious, chronic, autoimmune disease. Arthritis Foundation 1330 West Peachtree Street Atlanta, GA 30309 (404) 872-7100 (800) 283-7800, or call your local chapter (listed in the telephone directory) http://www.arthritis.org/ The Arthritis Foundation is the major voluntary organization devoted to supporting arthritis research and providing educational and other services to individuals with arthritis. It publishes free pamphlets and a magazine for members on all types of arthritis. It also provides up-todate information on research and treatment, nutrition, alternative therapies, and self-management strategies. Chapters nationwide offer exercise programs, classes, support groups, physician referral services, and free literature. For more information, call your local chapter, listed in
28 Lupus
the white pages of the phone book, or contact the Arthritis Foundation at the above address. Alliance for Lupus Research, Inc. 1270 Avenue of the Americas, Suite 609 New York, NY 10020 (212) 218-2840 The Alliance for Lupus Research, Inc. (ALR), is a nonprofit organization devoted exclusively to the support of promising research for the prevention, treatment, and cure of lupus. Through accelerated, focused, goal-oriented research programs, the ALR aims to promote basic and clinical sciences to achieve major advances leading to a better understanding of the cause of lupus.
More Guideline Sources The guideline above on lupus is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to lupus. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with lupus. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.
Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is
Guidelines 29
similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.
The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on lupus and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·
Steroids in the Treatment of Lupus Source: Rockville, MD: Lupus Foundation of America. 1999. 6 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus related brochures for $3.95 plus shipping and handling. Summary: This pamphlet provides people who have lupus with information on using steroids to treat the symptoms resulting from inflammation in various tissues. People should take the lowest possible effective dose of steroids and should never suddenly stop taking them after more than 4 weeks. Cortisone, which is manufactured by the body's adrenal glands and is also made synthetically, has been found to reduce inflammation. Steroids produced by the outer part of the adrenal gland are called corticosteroids. Prednisone is the synthetic corticosteroid most often used to treat lupus. The pamphlet discusses dosage, mode of administration, and common side effects, such as a change in appearance, psychological effects, and an increase in susceptibility to infections. In addition, side effects of long-term use include avascular necrosis of bone, osteoporosis, cataracts, and muscle weakness. The pamphlet also provides information on the Lupus Foundation of America. 1 table.
30 Lupus
·
Depression in Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 1998. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus-related brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus uses a question and answer format to examine the occurrence of depression during the course of lupus. It presents the physical and psychological symptoms of clinical depression, identifies the symptoms that indicate the depth and degree of depression, and highlights the most common psychological signs of clinical depression. The pamphlet discusses the occurrence and underdiagnosis of clinical depression in people with a chronic medical illness such as lupus. Other topics include the causes of depression in lupus, the treatment of depression with psychotropic medication or psychotherapy, the prognosis for depression in lupus, and cognitive changes in lupus. The pamphlet also provides information on the Lupus Foundation of America.
·
The Many Shades of Lupus: Information for Multicultural Communities Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2001. 36 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 toll-free or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. Price: One to 10 copies available free. Order Number: AR-231 (booklet). Summary: This booklet uses a question and answer format to provide people who have lupus with information on this autoimmune disease. Lupus can affect many parts of the body and can affect different people in different ways. The cause of lupus is unknown, but genetic and environmental factors are believed to be involved. The main types are systemic lupus erythematosus, discoid lupus erythematosus, and drug induced lupus. The booklet outlines the signs and symptoms of lupus, explains what a flare is, identifies the population most commonly affected by lupus, and discusses its diagnosis and management. In addition, the booklet highlights research on lupus and presents
Guidelines 31
government and nongovernment organizations that can provide additional information about lupus. ·
Childhood Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 2000. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. Price: $0.25 each plus shipping and handling; brochures must be ordered in quantities of 100. Summary: This pamphlet provides parents who have a child with lupus with information on some of the medical considerations involved. The first step for every family is to be sure the diagnosis is correct. Next, the family should comply with physician instructions, because compliance has been shown to be one of the most important factors in determining outcome for people with systemic lupus erythematosus. The most important issue for parents of children with lupus is dealing with the side effects of drugs such as corticosteroids. Cytotoxic immunosuppressive drugs are an alternative to high doses of corticosteroids; however, they may increase a child's risk of developing certain forms of cancer. The pamphlet also addresses the social and psychological concerns that can have an impact on the outcome for children who have lupus and their families. These issues include dealing with activities where a child may be away overnight, educating a child about his or her condition and its treatment, educating others about a child's lupus, and coping with a child's anger or depression. The pamphlet also includes a brief discussion on the genetic component of lupus. The pamphlet concludes with information on the Lupus Foundation of America.
·
Joint and Muscle Pain in Systemic Lupus Erythematosus (SLE) Source: Rockville, MD: Lupus Foundation of America, Inc. 2000. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. Price: $0.25 each plus shipping and handling; brochures must be ordered in quantities of 100. Summary: This pamphlet provides people who have lupus with information on joint and muscle pain. More than 80 percent of people with lupus will experience joint or muscle pain at some time during the course of their illness. The major cause of joint pain in lupus is inflammation. Pain in and around the joints is not always due to lupus arthritis but can be due to other medical disorders, including fibromyalgia, avascular necrosis of the bone, tendinitis and bursitis, and
32 Lupus
other types of arthritis. Inflammation of skeletal muscle, known as myositis, may develop in people with lupus. The pamphlet discusses these disorders in terms of their diagnosis and treatment. In addition, the pamphlet provides information on the Lupus Foundation of America. ·
Introduction to Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 2000. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. Price: $0.25 each plus shipping and handling; brochures must be ordered in quantities of 100. Summary: This pamphlet provides people who have lupus with information on its types, cause, prevalence, symptoms, diagnosis, and treatment. Lupus is a chronic inflammatory disease that can affect various parts of the body. Types include cutaneous or discoid lupus, systemic lupus erythematosus (SLE), and drug induced lupus. Although the cause of lupus is unknown, both genetic and environmental factors may have a role in its development. Data indicate that lupus affects 1 out of every 185 Americans. Lupus can affect any part of the body, but most people have symptoms in only a few organs. Many people have mild disease affecting only a few organs, but others may experience serious and life threatening problems. Diagnosis is based on a person's having 4 or more of 11 symptoms that distinguish lupus from other diseases. Although there is no cure, early diagnosis and proper treatment can help to control the disease. Management involves resting when the disease is active, using sunscreen, and taking appropriate medications. Most people who have lupus have a normal lifespan. The pamphlet includes information on the Lupus Foundation of America. 1 table.
·
Lupus Erythematosus: A Patient's Guide Source: Rockville, MD: Lupus Foundation of America. 2000. 40 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. Price: 3.95 plus shipping and handling. Summary: This booklet provides people who have lupus erythematosus (LE) with information on the types, frequency, cause, diagnosis, symptoms, and treatment of this autoimmune disease. LE involves changes in the immune system so that it attacks the body's own tissues. LE usually appears in one of two forms: cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE). Other variants include
Guidelines 33
drug induced lupus, neonatal lupus, mixed connective tissue disease, and undifferentiated connective tissue disease. Most patients with CLE and SLE are women. The severity of lupus varies from mild to life threatening. The cause of CLE and SLE is unknown, but genetic and environmental factors are believed to be involved. Although CLE can be diagnosed by the history and appearance of the skin rash, diagnosing SLE is more difficult. A complete medical history, a physical examination, and laboratory tests are important components of the diagnostic workup. A diagnosis of SLE can be made if 4 of 11 diagnostic criteria are met. Special tests for SLE may be performed to confirm the diagnosis. Symptoms are varied, and any part of the body may be involved. The booklet presents the cutaneous, musculoskeletal, cardiovascular, gastrointestinal, urogenital, lymphatic, and neurological symptoms of SLE. Other considerations addressed include flares, employment, pregnancy, contraception, and hormone replacement therapy. The booklet also discusses drugs available to treat SLE, including aspirin and nonsteroidal antiinflammatory drugs, antimalarial drugs, corticosteroids, and immunosuppressives. Another topic is self care, focusing on physical measures and preventive coping strategies. The booklet includes a glossary of terms and information on the Lupus Foundation of America. 1 table. ·
Sjogren's Syndrome and Systemic Lupus Erythematosus Source: Rockville, MD: Lupus Foundation of America. 1999. 6 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus related brochures for $3.95 plus shipping and handling. Summary: This pamphlet provides people who have Sjogren's syndrome with information on this chronic autoimmune disorder in which the glands that produce tears and saliva do not function correctly. Sjogren's syndrome can occur alone or in association with other autoimmune diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. The disorder is termed primary Sjogren's syndrome when it occurs by itself and secondary Sjogren's syndrome when it is associated with another disease. The pamphlet discusses symptoms, including dryness of the mouth, eyes, and vagina. Other topics are the various laboratory tests and procedures used for diagnosis, as well as laboratory abnormalities associated with the disorder, including the presence of antinuclear antibodies and histocompatibility antigens, elevated erythrocyte sedimentation rate, mild anemia, and low albumin levels. In
34 Lupus
addition, the pamphlet examines the association between Sjogren's syndrome and SLE, discusses treatment with local and systemic agents that increase lubrication and moisture and with various drugs, comments on the prognosis for people who have Sjogren's syndrome, and provides information on the Lupus Foundation of America. ·
Drug-Induced Lupus Erythematosus Source: Rockville, MD: Lupus Foundation of America. 1999. 6 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus related brochures for $3.95 plus shipping and handling. Summary: This pamphlet uses a question and answer format to provide people who have lupus with information on drug-induced lupus erythematosus (DILE). This form of lupus is a side-effect of long-term use of certain medications used to treat chronic diseases (especially procainamide, hydralazine, and quinidine). The only well-defined genetic risk factor in DILE is the slow drug acetylation phenotype. Circumstantial evidence suggests that the metabolic change a drug undergoes in the body, rather than the drug itself, makes the drug able to react with the immune system. People with DILE may experience flu-like symptoms. The features are the same regardless of the medication. Tests that can help with diagnosis include the antinuclear antibody test and the antihistone test. The most important aspect of treating DILE is to identify the medication that is likely to be causing the problem and then discontinue it. Although most people recover once they stop using the medication, they may develop the syndrome if they take the medication again. The pamphlet explains the difference between DILE and systemic lupus erythematosus, lists drugs reported to induce lupus-like disease, and provides information on the Lupus Foundation of America.
·
What is Lupus? Source: Rockville, MD: Lupus Foundation of America, Inc. 1998. 12 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus-related brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus provides an overview of this chronic inflammatory disease that can affect various parts of the
Guidelines 35
body. It describes the discoid, systemic, and drug-induced forms of lupus and discusses the cause of lupus. Although the cause is unknown, scientists believe that there is a genetic predisposition to the disease and that certain environmental factors may trigger the disease. The pamphlet outlines the symptoms of lupus and discusses its diagnosis. Lupus is diagnosed through information obtained from the medical history, a physical examination, and diagnostic testing. There are 11 symptoms that help physicians distinguish lupus from other diseases, and various laboratory tests may help diagnosis this disease. Tests include the lupus erythematosus cell test, the immunofluorescent antinuclear antibody test, and tests that measure complement levels in the blood and individual antigen antibody reactions. Skin and kidney biopsies may also be performed. The pamphlet describes the commonly prescribed medications for lupus, including nonsteroidal anti-inflammatory drugs, acetaminophen, corticosteroids, antimalarials, immunomodulating drugs, and anticoagulants. Other topics discussed include nutrition and diet, pregnancy, and the prognosis for people with lupus. The pamphlet also provides information on the Lupus Foundation of America. 2 tables. ·
Skin Disease in Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 1998. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus-related brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus focuses on skin disease in lupus. It describes the skin lesions seen only in people with lupus erythematosus (LE), including chronic cutaneous LE (CCLE), subacute cutaneous LE (SCLE), and acute cutaneous LE (ACLE). Discoid LE (DLE) is the most common form of CCLE. DLE may be localized or generalized. DLE lesions are often red, scaly, and thickened; however, they are usually painless and not itchy. There are two clinical forms of SCLE lesions. The papulosquamous variety of SCLE is characterized by red plaques occurring on sun-exposed areas of the body. The other form of SCLE consists of red annular lesions occurring on the same parts of the body. The most common form of ACLE consists of flattened areas of red skin on the face that resemble a sunburn. These lesions tend to be photosensitive. The pamphlet also identifies other skin lesions in LE, including vasculitis and hair loss. Other topics discussed include photosensitivity, sun protection, and treatment for LE skin disease. The pamphlet also provides information on the Lupus Foundation of America.
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·
Lupus: Basics for Better Living Source: Rockville, MD: Lupus Foundation of America, Inc. 1998. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus-related brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus presents lifestyle adjustments that they can make to help fight the disease and improve well-being. It stresses the need for people who have been told that they have lupus to have their diagnosis confirmed by a board certified rheumatologist or other recognized lupus specialist. The pamphlet describes various forms of lupus, including chronic cutaneous, druginduced, and systemic lupus erythematosus. It outlines ways patients can help themselves. Physical measures include being careful in the sun, eating a well-balanced diet, applying heat to painful joints, engaging in general conditioning exercises, consulting a rehabilitation specialist, and avoiding smoking. Preventive coping strategies include dealing with changes in barometric pressure, controlling fatigue, developing a good doctor-patient relationship, obtaining genetic and prognosis counseling, having a successful pregnancy, taking care of fevers or infections promptly, asking about cognitive therapy, discussing alternative therapies with a lupus specialist, and asking for help. The pamphlet also provides information on the Lupus Foundation of America.
·
Handout on Health: Systemic Lupus Erythematosus Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1997. 35 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. Price: Single copy free. Order Number: AR-96HH (booklet), or AR-96L HH (large print). Summary: This booklet is for people with systemic lupus erythematosus (SLE), family members, friends, and others and focuses on the causes, symptoms, diagnosis, and treatment of SLE. It explains who is more likely to get SLE, what parts of the body it can affect, the characteristic cycles of illness and remission, and the several kinds of lupus. Also discussed are the factors that may influence getting this disease, common symptoms, how a doctor makes a diagnosis, the goals of treatment, and
Guidelines 37
the various medications used to treat lupus. The booklet presents some alternative therapies that may help patients cope with the stress of living with a chronic illness, emphasizing the importance of understanding the disease and its impact, receiving regular health care, developing strategies for maintaining wellness, and establishing a good support system. Also included are issues on the impact of lupus for women considering pregnancy. The booklet also describes current research on the causes and treatments for lupus by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other components of the National Institutes of Health. It then refers the reader to the network of voluntary health organizations for additional information about lupus. A large print version of this booklet is also available. ·
Kidney Disease and Lupus Source: Rockville, MD: Lupus Foundation of America. 1999. 6 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Price: Available as part of a package of 21 different lupus related brochures for $3.95 plus shipping and handling. Summary: This pamphlet provides people who have systemic lupus erythematosus (SLE) with information on the kidney disease that accompanies it. This type of kidney disease, which is known as lupus nephritis or lupus glomerulonephritis, may affect about one third of those who have SLE. Symptoms that indicate the possibility of lupus nephritis include foamy, frothy urine; nocturnal urination; and fluid retention with weight gain and swelling. The clinical path of lupus nephritis is highly variable, with some people experiencing mild abnormalities and others experiencing more persistent, severe ones. Studies that can be performed to test for lupus nephritis are urinalysis, blood studies, 24 hour urine collection, imaging, and kidney biopsy. Corticosteroids and cytotoxic or immunosuppressive drugs are the major forms of drug therapy used to treat lupus nephritis. Despite treatment, some people may experience progressive loss of kidney function. These people will need hemodialysis or peritoneal dialysis and eventually kidney transplantation. The pamphlet also provides information on the Lupus Foundation of America. 1 table.
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The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “lupus” or synonyms. Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·
Handout on Health: Systemic Lupus Erythematosus (SLE) Summary: This consumer health education booklet describes this disease and its symptoms and contains information about diagnosis and treatment as well as current research efforts supported by the National Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2929
·
Lupus Nephritis Summary: Brief overview of the symptoms, diagnosis, and treatment of lupus nephritis. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6519
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·
Lupus: A Patient Guide for Nurses and Other Health Professionals Summary: Lupus: A Patient Care Guide for Nurses and Other Health Professionals Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6763
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Lupus: Causes, Symptoms, Testing, Treatment Summary: Provides a general overview of lupus, including the definition, types, causes, symptoms, diagnosis, triggers, treatment, and prognosis. Source: Lupus Foundation of America http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6439
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The Many Shades of Lupus: Information for Multicultural Communities Summary: This consumer health education booklet describes this disease and its symptoms as it relates to multicultural communities. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2930
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The Neurological Sequelae Of Lupus Summary: A general overview of neurological sequelae of lupus that includes a description of the disorder, treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=3798
40 Lupus
·
What is Lupus? Summary: A general overview of lupus, a disease that affects the immune system. Source: Lupus Foundation of Greater Washington http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6053
The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to lupus. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing, for a nominal fee, short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is www.rarediseases.org. To see if a recent fact sheet has been published on lupus, simply go to the following hyperlink: http://www.rarediseases.org/cgi-bin/nord/alphalist. A complete guide on lupus can be purchased from NORD for a nominal fee.
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Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
·
drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html
·
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
·
Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
·
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
·
WebMDÒHealth: http://my.webmd.com/health_topics
Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins,
42 Lupus
etc. [EU] Anticoagulants: Agents that prevent blood clotting. Naturally occurring agents in the blood are included only when they are used as drugs. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized Tlymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Chronic: Persisting over a long period of time. [EU] Contraception: The prevention of conception or impregnation. [EU] Contraceptive: conception. [EU]
An agent that diminishes the likelihood of or prevents
Cutaneous: Pertaining to the skin; dermal; dermic. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH]
Guidelines 43
Diflunisal: A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of aspirin. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Etodolac: A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and in the alleviation of postoperative pain. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Glomerulonephritis: A variety of nephritis characterized by inflammation of the capillary loops in the glomeruli of the kidney. It occurs in acute, subacute, and chronic forms and may be secondary to haemolytic streptococcal infection. Evidence also supports possible immune or autoimmune mechanisms. [EU] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of
44 Lupus
allografts. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU] Intravenous: Within a vein or veins. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Ketoprofen:
An
ibuprofen-type
anti-inflammatory
analgesic
and
Guidelines 45
antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Menopause: Cessation of menstruation in the human female, occurring usually around the age of 50. [EU] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU] Morale: The prevailing temper or spirit of an individual or group in relation to the tasks or functions which are expected. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myositis: Inflammation of a voluntary muscle. [EU] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Ointments: Semisolid preparations used topically for protective emollient
46 Lupus
effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280-400 mm. There are two main types : photoallergy and photoxicity. [EU] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3carboxamide 1,1-dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pneumonia: Inflammation of the lungs with consolidation. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]
Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU]
Guidelines 47
Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]
Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic
48 Lupus
phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Syphilis: A contagious venereal disease caused by the spirochete treponema pallidum. [NIH] Systemic: Pertaining to or affecting the body as a whole. [EU] Tendinitis: Inflammation of tendons and of tendon-muscle attachments. [EU] Thrombocytopenia: Decrease in the number of blood platelets. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU]
Vaccination: The introduction of vaccine into the body for the purpose of inducing immunity. Coined originally to apply to the injection of smallpox vaccine, the term has come to mean any immunizing procedure in which vaccine is injected. [EU]
Guidelines 49
Vasculitis: Inflammation of a vessel, angiitis. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH] Withdrawal: 1. a pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) a substancespecific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]
Seeking Guidance 51
CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with lupus. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with lupus. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Lupus As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9
52 Lupus
influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·
American Juvenile Arthritis Organization Address: American Juvenile Arthritis Organization 1330 West Peachtree Street, Atlanta, GA 30309 Telephone: (404) 872-7100 Toll-free: (800) 283-7800 Fax: (404) 872-0457 Email:
[email protected] Web Site: http://www.arthritis.org Background: The American Juvenile Arthritis Organization (AJAO), a not-for-profit organization, is a Council of the Arthritis Foundation devoted to serving the needs of children, teens, and young adults with childhood rheumatic diseases and their families. These diseases include Juvenile Rheumatoid Arthritis, Lupus (Systemic Lupus Erythematosis), and Ankylosing Spondylitis. Juvenile Arthritis is medically different from the adult form of arthritis and may be far more severe in some cases. The American Juvenile Arthritis Organization was founded in 1981 to help serve the special needs of affected individuals and families, friends, and health care professionals. The Organization enables members to exchange ideas and support and serves as a clearinghouse of information for the public on topics from medications to educational rights to social services. It sponsors an annual conference; monitors and promotes legislation that benefits individuals with Juvenile Arthritis; provides appropriate referrals; and sponsors research concerning potential causes, improved treatments, preventive measures, and possible cures. The American Juvenile Arthritis Organization provides a variety of educational materials including a quarterly newsletter, pamphlets, fact sheets, selfhelp manuals, and a video lending library. Relevant area(s) of interest: Lupus
Seeking Guidance 53
·
European Lupus Erythematosus Federation Address: European Lupus Erythematosus Federation 1 Eastern Road, Romford, Essex, RM1 3NH, United Kingdom Telephone: 44- 1708-73 12 51 Toll-free: (800) 558-0121 Fax: 44-1708-73 12 52 Email:
[email protected] Web Site: http://www.elef.rheumanet.org/ Background: The European Lupus Erythematosus Federation (ELEF) is an international voluntary federation that consists of national lupus groups throughout Europe. Systemic lupus erythematosus (SLE), also known as lupus, is an autoimmune disorder characterized by chronic inflammation affecting connective tissues of the body. Different tissues and organs may be affected, and the range and severity of associated symptoms and findings may vary from case to case. In some affected individuals, symptoms may include extreme fatigue; muscle pain; joint swelling, stiffness, and pain; skin rashes; hair loss; and other abnormalities. Established in 1989, the European Lupus Erythematosus Federation currently represents 15 countries, 16 lupus organizations, and approximately 16,500 affected individuals and family members. The ELEF is committed to collecting information on all medical and psychosocial aspects of lupus; promoting awareness of the disease among individuals with lupus, the general public, and members of the health, welfare, and medical professions; and encouraging and conducting surveys and research projects related to the disease and publishing the results of such research. The Federation is also dedicated to promoting awareness of lupus support groups that are available for affected individuals and family members in each member country; sponsoring or promoting European symposia on all aspects of lupus; gaining representation on any European or international body whose interests will be of benefit to members of the Federation; and assisting with the establishment of support groups in other European countries where none currently exists. The Federation also conducts international surveys on lupus, publishes a biannual newsletter entitled 'Caring and Sharing,' and has a web site on the Internet. Relevant area(s) of interest: Disseminated Lupus Erythematosus, Lupus, Systemic Lupus Erythematosus
·
Lupus Canada Address: Lupus Canada P.O. Box 64034, 5512 - 4 Street N.W., Calgary, Alberta, T2K 6J1, Canada
54 Lupus
Telephone: (403) 274-5599 Toll-free: (800) 661-1468 Fax: (403) 274-5599 Email:
[email protected] Web Site: http://www.lupuscanada.org Background: Lupus Canada is a national association of regional lupus support groups and their various branches. These groups of volunteers are dedicated to providing support and information to people who have lupus, their families, and friends. Lupus is a chronic autoimmune disorder that can affect any organ of the body. In lupus, the body's immune system that defends against invading or 'foreign' organisms (e.g., viruses, bacteria, germs) begins to malfunction and fails to distinguish between the body's own tissues and these foreign invaders. As a result, the body's natural defenses (antibodies) begin to attack the body's own tissue. Established in 1987, Lupus Canada produces educational materials including a pamphlet entitled 'Lupus: An Introduction,' and a booklet entitled 'Lupus: The Disease With 1000 Faces.' Interested individuals can contact Lupus Canada at its e-mail address lupuscanatcadvision.com or on the world wide web at http://www.lupuscanada.org. Relevant area(s) of interest: Disseminated Lupus Erythematosus, Lupus, Systemic Lupus Erythematosus ·
Lupus Foundation of America (LFA) Address: us Foundation of America (LFA). 4 Research Place, Suite 180, Rockville, MD 20850-3226. (301) 670- 9292 or (800) 558-0121; FAX (301) 670-9486. Telephone: (518) 851-2612 Toll-free: (800) 558-0121 Background: This catalog lists and briefly describes resources available from the Lupus Foundation of America (LFA). These resources include brochures, fact sheets, books, booklets, materials for low literacy populations, and videotapes for individuals with lupus and the health professionals who care for them. Some of the items are not available through LFA but have been approved by the Patient Education Committee. Price and ordering information is included, and items available in Spanish are noted. Relevant area(s) of interest: Systemic Lupus Erythematosus
Seeking Guidance 55
·
Lupus Foundation of America, Inc Address: Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850 Telephone: (301) 670-9292 Toll-free: (800) 558-0121 Fax: (301) 670-9486 Web Site: http://www.lupus.org/lupus Background: The Lupus Foundation of America is a national not-forprofit organization that was established in 1977. The primary purposes of the Foundation are the eradication of Lupus through research, the early detection of undiagnosed cases through awareness promotion, and the alleviation of suffering through patient support programs. The Lupus Foundation has more than 90 local chapters serving hundreds of thousands of people throughout the United States and 73 International Associated Groups in 37 countries worldwide. The Services provided by the Foundation and its chapters include informational materials, referrals, patient educational meetings and seminars, support groups, hospital visits, grants, and bequests. The Foundation functions as an advocate for people with Lupus and seeks to raise awareness and understanding of the disorder among elected and appointed government officials. To this end, the Foundation participates in coalitions with other health agencies to make its mission known to decision and policy makers. A wide variety of educational materials are produced by the organization including brochures, pamphlets, and a newsletter entitled 'Lupus News.' Some materials are available in Spanish. Relevant area(s) of interest: Lupus, Systemic Lupus Erythematosus
·
Lupus UK Address: Lupus UK 1 Eastern Road, Romford, Essex, RM1 3NH, United Kingdom Telephone: 01708 731251 Toll-free: (800) 661-1468 Fax: 01708 731252 Email:
[email protected] Web Site: http://www.geocities.com/HotSprings/2911/ Background: Lupus UK is a voluntary organization in the United Kingdom dedicated to providing information and support to individuals affected by systemic lupus erythematosus (SLE), an autoimmune disorder that is characterized by chronic inflammation affecting the skin, joints, or other connective tissues of the body. Different tissues and organs may be involved, and the range and severity of associated
56 Lupus
symptoms and findings may vary greatly from case to case. In some individuals with the disorder, symptoms may include weakness and fatigue; persistent flu- like symptoms; joint inflammation, swelling, stiffness, and pain; skin rashes, such as the appearance of a rash across the bridge of the nose and the cheeks ('butterfly' rash); abnormal sensitivity of the skin to light; hair loss; and other abnormalities. Lupus UK was established in 1978 and currently consists of 27 regional groups throughout Great Britain and Northern Ireland. The organization, which is a self-help group run by volunteers, is committed to providing support and assistance to all affected individuals; promoting communication between members and the medical professionals involved in their care; and offering practical assistance. Lupus UK is also dedicated to promoting professional and public awareness of lupus by gathering and publishing information on all aspects of the disease; raising funds to assist affected individuals and to finance research projects; and working with other organizations to promote the aims of Lupus UK. Affected individuals and family members who join the organization are automatically enrolled in a Lupus UK regional support group; have the opportunity to participate in educational and social meetings; and receive a local newsletter as well as a national newsletter entitled 'News and Views.' Lupus UK also offers a factsheet series and several books on the disorder and has a web site on the Internet. Relevant area(s) of interest: Disseminated Lupus Erythematosus, Lupus, Systemic Lupus Erythematosus ·
Toxic Discovery Network, Inc Address: Toxic Discovery Network, Inc. 1906 Grant Lane, Columbia, MO 65203 Telephone: (573) 445-0861 Toll-free: (800) 558-0121 Fax: (573) 445-8539 EBackground: The Toxic Discovery Network, Inc. (TDN) is a voluntary not-for- profit organization dedicated to disseminating information and providing support concerning silicone related issues. TDN's primary goals are to be a source of support for people seeking help with silicone related issues; to be a centralized information center for silicone issues; to aid in the identification of symptoms related to silicone illness; to develop a professional networking team of doctors, lawyers, and other medical professionals who will see and treat people with silicone disease; to explore current and future silicone issues; to educate the nation about the danger of silicone related problems; to network with the National Breast Implant Task Force, Inc.; and to raise funds for silicone research and
Seeking Guidance 57
possible cure. Established in 1994 and consisting of 1,500 members, TDN produces educational materials including a newsletter, brochures, and a registry. The organization coordinates support groups, supports advocacy efforts, encourages networking, supports research, promotes education, and provides appropriate referrals. Relevant area(s) of interest: Lupus, Scleroderma
Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.
The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about lupus. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “lupus” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.
The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “lupus”. Type the following hyperlink into your Web browser:
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http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “lupus” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with lupus. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “lupus” (or a synonym) in the search box.
Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·
Lupus Foundation of America http://www.lupus.org/support/groups.html
·
Lupus Foundation of Pennsylvania http://www.lupuspa.org/newfiles/support.html
Seeking Guidance 59
Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with lupus must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:11 ·
If you are in a managed care plan, check the plan's list of doctors first.
·
Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.
·
Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.
·
Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.
Additional steps you can take to locate doctors include the following: ·
Check with the associations listed earlier in this chapter.
·
Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.
·
The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at http://www.abms.org/newsearch.asp.12 You can also contact the ABMS by phone at 1-866-ASK-ABMS.
·
You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found
This section has been adapted from the AHRQ: http://www.ahrq.gov/consumer/qntascii/qntdr.htm. 12 While board certification is a good measure of a doctor's knowledge, it is possible to receive quality care from doctors who are not board certified. 11
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in “Physician Select” at the AMA's Web site: http://www.amaassn.org/aps/amahg.htm. If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.
Finding a Rheumatologist The American College of Rheumatology (ACR) maintains a geographic directory of member physicians called “Find a Rheumatologist.” To access this database, log on to http://www.rheumatology.org/directory/geo.asp. You will be given the option to search for a rheumatologist by name, by U.S. State, or by country. To contact the ACR, you can use the following information: American College of Rheumatology 1800 Century Place, Suite 250 Atlanta, GA 30345 Phone: (404) 633-3777 Fax: (404) 633-1870 E-mail:
[email protected] Selecting Your Doctor13 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·
Give me a chance to ask questions about lupus?
·
Really listen to my questions?
13 This
section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
Seeking Guidance 61
·
Answer in terms I understood?
·
Show respect for me?
·
Ask me questions?
·
Make me feel comfortable?
·
Address the health problem(s) I came with?
·
Ask me my preferences about different kinds of treatments for lupus?
·
Spend enough time with me?
Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.
Working with Your Doctor14 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·
You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.
·
It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.
·
Bring a “health history” list with you (and keep it up to date).
·
Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.
·
Tell your doctor about any natural or alternative medicines you are taking.
·
Bring other medical information, such as x-ray films, test results, and medical records.
·
Ask questions. If you don't, your doctor will assume that you understood everything that was said.
This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
14
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·
Write down your questions before your visit. List the most important ones first to make sure that they are addressed.
·
Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.
·
Ask your doctor to draw pictures if you think that this would help you understand.
·
Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.
·
Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.
·
Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.
·
After leaving the doctor's office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.
By following these steps, you will enhance the relationship you will have with your physician.
Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:15 ·
Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html
·
Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
15
Seeking Guidance 63
·
Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html
Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Keratoconjunctivitis: Inflammation of the cornea and conjunctiva. [EU] Lacrimal: Pertaining to the tears. [EU] Mucus: The free slime of the mucous membranes, composed of secretion of the glands, along with various inorganic salts, desquamated cells, and leucocytes. [EU] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Urinary: Pertaining to the urine; containing or secreting urine. [EU] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Xerostomia: Dryness of the mouth from salivary gland dysfunction, as in Sjögren's syndrome. [EU]
Clinical Trials 65
CHAPTER 3. CLINICAL TRIALS AND LUPUS Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning lupus.
What Is a Clinical Trial?16 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for lupus is to try it on patients in a clinical trial.
The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.
16
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What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·
Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.
·
Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on lupus.
·
Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for lupus compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment.
How Is a Clinical Trial Conducted? Various organizations support clinical trials at medical centers, hospitals, universities, and doctors' offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on lupus carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on lupus. In other clinical trials, where a new surgery or device (not a medicine) is being tested,
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patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on lupus and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how lupus develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for lupus. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial's investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo
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surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.
Recent Trials on Lupus The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to lupus.17 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·
Anti-CD20 in Systemic Lupus Erythematosus Condition(s): Lupus Erythematosus, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to determine the safety and effectiveness of rituximab (anti-CD20) in treating systemic lupus erythematosus (SLE). White blood cells in the body called B cells give off substances that are active in promoting SLE disease. Researchers have found that anti-CD20 can block production of these substances in another disease. This study explores whether anti-CD20 will also be safe in people with SLE and whether it may be effective in treating SLE. Phase(s): Phase I Study Type: Interventional
17
These are listed at www.ClinicalTrials.gov.
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Contact(s): Jan Stansberry, RN, MSN 215-662-4658
[email protected]; Pennsylvania; Jan Stansberry, RN, MSN, Philadelphia, Pennsylvania, 19104, United States; Recruiting Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00036491;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases Condition(s): Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis Study Status: This study is currently recruiting patients. Sponsor(s): Fairview University Medical Center Purpose - Excerpt: Objectives: I. Determine whether there is prompt engraftment after autologous peripheral blood stem cell transplantation using filgrastim (G-CSF) mobilization in patients with life threatening autoimmune diseases. II. Determine the kinetics of T- and B-cell immune reconstitution after a combination of timed plasmapheresis, high dose cyclophosphamide and total lymphoid irradiation, and posttransplant immunosuppression with cyclosporine in these patients. III. Determine whether this treatment regimen beneficially influences the clinical course of these patients. Study Type: Interventional Contact(s): Minnesota; Fairview University Medical Center, Minneapolis, Minnesota, 55455, United States; Recruiting; Arne Slungaard 612-2732800. Study chairs or principal investigators: Arne Slungaard, Study Chair; Fairview University Medical Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006055;jsessionid=C86124 E234F08730F120E192C53539F4
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Dexamethasone in Lupus Congenital Heart Block of Newborns Condition(s): Congenital heart block; Neonatal lupus; Atrioventricular nodal dysfunction; Myocardial injury Study Status: This study is currently recruiting patients.
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Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study has two parts. The goal of the first part is to find out the usefulness of giving medications known as fluorinated steroids to pregnant women whose unborn children have a heart condition called congenital heart block (CHB). CHB occurs in some babies with neonatal lupus, a form of lupus that affects newborns but usually disappears by the time the infant is 3-6 months old. We will look at whether giving the steroid drug dexamethasone to pregnant women every day by mouth improves the heart function and general health of newborns who have autoantibody-associated CHB. This form of CHB is linked to the presence of certain blood proteins (antibodies) in the mother. Participants in this study will be pregnant women requiring less than 10 milligrams (mg) of prednisone per day, whose doctors identify them before 30 weeks of pregnancy to be carrying a fetus with CHB. Study participants will take either 4 mg per day of dexamethasone or a placebo (inactive drug) for at least 6 weeks. We will assign each woman at random to receive either dexamethasone or placebo. The second part of the study will examine pregnant women who are at high risk for having babies with CHB to identify the earliest signs of heart problems in the unborn child that can be detected using ultrasound testing. We will follow 100 mothers considered at high risk for having a child with CHB by doing weekly echocardiograms (a noninvasive method that uses ultrasound to produce images of the heart) of the fetus from the 16th week of pregnancy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00007358;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Genetic Analysis of Immune Disorders Condition(s): Healthy; Immunologic Deficiency Syndrome; Severe Combined Immunodeficiency
Syndrome;
Job's
Study Status: This study is currently recruiting patients. Sponsor(s): National Human Genome Research Institute (NHGRI) Purpose - Excerpt: The purposes of this study are to 1) identify the genes responsible for certain immune disorders, 2) learn about the medical problems they cause, and 3) learn how to predict who is likely to develop
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these disorders and what the risk is of passing them on to children. The immune system is the body's defense system. Some immune deficiencies impair a person's ability to fight infections; others render a person susceptible to allergies, or to autoimmune diseases such as lupus or arthritis, in which the immune cells (white blood cells) attack and destroy the body's own tissues. Patients with immune disorders known or suspected to have a genetic basis and their family members may enroll in this study. Eligibility will be determined by a review of the patient's medical records and family medical history. Participants will provide a small blood sample for genetic (DNA) and white blood cell analysis. Gene samples (but not white blood cells) may also be obtained by mouth brushing or skin biopsy. For the mouth brushing, a small brush is rubbed against the inside of the cheeks for 1 minute to wipe off some cells. For the skin biopsy, a small circle of skin (about 1/8 inch) is removed under local anesthetic. Pregnant women may be asked to provide a fetal sample (amniotic fluid cells or chorionic villus sample). All samples will be used for immune or genetic studies of the family's immune disorder. If test results show a specific genetic variation responsible for the family's immune disorder, a report will be sent to the patient's doctor or genetic counselor, who will discuss the implications for the family. NIH researchers and genetic counselors will also be available to explain results and answer questions. Information will not be available in the case of disorders that cannot yet be linked to a specific genetic abnormality. Information from this study will increase knowledge about the immune system and what causes immune deficiencies. Participants may also learn the underlying cause of an immune disorder that affects them or someone in their family-information may be useful in guiding treatment and in making decisions regarding family planning. Study Type: Observational Contact(s): Maryland; National Human Genome Research Institute (NHGRI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001467;jsessionid=C86124 E234F08730F120E192C53539F4 ·
High-Dose Intravenous (IV) Cyclophosphamide Versus Monthly IV Cyclophosphamide Condition(s): Lupus Erythematosus, Systemic Study Status: This study is currently recruiting patients.
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Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study compares the effectiveness of high-dose cyclophosphamide treatment with the "gold standard" treatment, monthly intravenous (IV) cyclophosphamide, in people with moderate to severe lupus that does not respond to high-dose corticosteroid therapy. We will give patients either IV cyclophosphamide (750 milligrams per square meter of body surface area) monthly for 6 months, followed by quarterly maintenance therapy, or high-dose IV cyclophosphamide (50 milligrams per kilogram body weight per day) for the first four days of the study. Patients will be followed for 24 months after therapy. Phase(s): Phase II Study Type: Interventional Contact(s): Michelle Petri, M.D., M.P.H. 410-614-1573
[email protected]; Maryland; Johns Hopkins University Division of Rheumatology, Baltimore, Maryland, 21205, United States; Recruiting; Philip Seaman 410-614-1573
[email protected]. Study chairs or principal investigators: Michelle Petri, M.D., M.P.H., Principal Investigator; Johns Hopkins University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005778;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Humanized LL2IGG to Treat Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will examine the safety of a new genetically engineered antibody called hLL2 (epratuzumab) in patients with systemic lupus erythematosus (SLE). It will also evaluate whether hLL2 can lessen overall disease activity in SLE or kidney damage in patients with lupus nephritis. Patients 18 years of age and older with mild to moderately active SLE may be eligible for this study. Candidates will be screened with blood and urine tests, a chest X-ray, electrocardiogram (EKG), tuberculin skin test, and screening tests for certain cancers. All participants will receive weekly infusions of hLL2 for 4 weeks. The drug is given through a catheter (small plastic tube) placed through a needle in an arm vein. Each infusion takes about 2 hours, after which the patient is observed in the clinic for 1 to 2 hours before being discharged from the
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clinic. The first 3 patients in the study will receive the lowest of three different doses used in the study. If this dose is well tolerated, the next 5 patients will receive a higher dose. If the second dose is tolerated, the last 5 patients will be given the highest dose. If any serious problems are encountered at a dose, patients in the next group will receive either the same or lower dose before being advanced to the next level. Patients in the first group will continue taking prednisone at their regular dose. All other patients will have their prednisone tapered gradually, if their condition permits. Patients who have a disease flare may have their prednisone increased for up to 2 weeks, followed by a gradual taper. If the flare is severe or does not respond to the increased prednisone, the patient will be taken off the study and treated to control the disease. Patients will be evaluated at various intervals for up to 8 weeks after the last dose. Several of the screening tests will be repeated throughout the study. No more than 500 ml of blood-the equivalent of a single blood donation-will be collected during a 2-month period. Participants may also be asked to undergo the following optional procedures before starting treatment, 1 week after the last dose and 8 weeks after the last treatment dose: - Bone marrow aspiration - to collect cells from the bone marrow. The hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone. - Tonsil biopsy - The area to be biopsied is numbed with a local anesthetic and small pieces of tissue will be removed with a special type of forceps. (The procedure may be done under general anesthetic.) - Magnetic resonance imaging (MRI) of the abdomen - The patient lies on a table within a metal cylinder (the MRI scanner) for about 30 to 40 minutes while images are obtained with the use of a strong magnetic field and radio waves. Phase(s): Phase I Study Type: Interventional Contact(s): Maryland; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00011908;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Immune System Related Kidney Disease Condition(s): Glomerulonephritis; Lupus Nephritis; Glomerulonephritis; Nephritis; Nephrotic Syndrome Study Status: This study is currently recruiting patients.
Membranous
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Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Kidney diseases related to the immune system include, nephrotic syndrome, glomerulonephritis, membranous nephropathy, lupus nephritis, and nephritis associated with connective tissue disorders. This study will allow researchers to admit and follow patients suffering from autoimmune diseases of the kidney. It will attempt to provide information about the causes and specific abnormalities associated with autoimmune kidney disease. Patients with kidney disease as a result of their immune system, and patients with diseases of the immune system who may later develop kidney disease, will be potential subjects for this study. Patients will undergo a history and physical examination, and standard laboratory test to more closely understand the causes, signs, symptoms, and responses to medication of these diseases. Based on these evaluations the patients may qualify as candidates for other experimental studies. At any time these patients may be asked to submit blood or urine samples for further research. Study Type: Observational Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001979;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Phase I Study of Immune Ablation and CD34+ Peripheral Blood Stem Cell Support in Patients With Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): Northwestern Memorial Hospital Purpose - Excerpt: Objectives: I. Determine the safety of immune ablation with high-dose cyclophosphamide and anti-thymocyte globulin followed by peripheral blood stem cell support in patients with systemic lupus erythematosus. Phase(s): Phase I Study Type: Interventional Contact(s): Illinois; Northwestern Memorial Hospital, Chicago, Illinois, 60611, United States; Recruiting; Ann Traynor 312-908-5284; Wisconsin; University of Wisconsin Hospital and Clinics, Madison, Wisconsin,
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53792-0001, United States; Recruiting; Frank Graziano 608-263-6186. Study chairs or principal investigators: Ann Traynor, Study Chair; Northwestern Memorial Hospital Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00017641;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Phase II Study of Ultraviolet A-1 Light Therapy for Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Louisiana State University Purpose - Excerpt: Objectives: I. Evaluate the mechanisms of ultraviolet A-1 light therapy in patients with systemic lupus erythematosus and normal controls. Phase(s): Phase II Study Type: Interventional Contact(s): Louisiana; Alton Ochsner Medical Foundation Hospital, New Orleans, Louisiana, 70121, United States; Recruiting; Jawed Alam 504842-3314; Louisiana State University School of Medicine, New Orleans, Louisiana, 70112-2822, United States; Recruiting; Hugh McGrath, Jr. 504568-4939. Study chairs or principal investigators: Hugh McGrath, Jr., Study Chair; Louisiana State University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004375;jsessionid=C86124 E234F08730F120E192C53539F4
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Pilot Study of Cyclophosphamide in Patients With Life-Threatening Systemic Lupus Erythematosus or Antiphospholipid Antibody Syndrome Condition(s): Systemic Antibody Syndrome
Lupus
Erythematosus;
Antiphospholipid
Study Status: This study is currently recruiting patients. Sponsor(s): Johns Hopkins Oncology Center Purpose - Excerpt: Objectives: I. Determine the induction of durable remission in patients with life-threatening systemic lupus erythematosus or antiphospholipid antibody syndrome treated with cyclophosphamide. II. Determine the toxicity of this drug in these patients.
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Study Type: Interventional Contact(s): Maryland; Johns Hopkins Oncology Center, Baltimore, Maryland, 21231, United States; Recruiting; Robert A. Brodsky 410-9552813; Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States; Recruiting; Michelle Petri 410-955-3823. Study chairs or principal investigators: Robert A. Brodsky, Study Chair; Johns Hopkins Oncology Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00010400;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Pilot Study of Total Body Irradiation in Combination With Cyclophosphamide, Anti-thymocyte Globulin, and Autologous CD34Selected Peripheral Blood Stem Cell Transplantation in Children With Refractory Autoimmune Disorders Condition(s): Systemic Sclerosis; Systemic Lupus Erythematosus; Dermatomyositis; Juvenile Rheumatoid Arthritis; Autoimmune Diseases Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center Purpose - Excerpt: Objectives: I. Determine the safety and long term complications of total body irradiation in combination with cyclophosphamide, anti-thymocyte globulin, and autologous CD34selected peripheral blood stem cell (PBSC) transplantation in children with refractory autoimmune disorders. II. Determine the efficacy of this treatment regimen in these patients. III. Determine the reconstitution of immunity after autologous CD34-selected PBSC transplantation in these patients. IV. Determine engraftment of autologous CD34-selected PBSC in these patients. Study Type: Interventional Contact(s): Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States; Recruiting; Ann Woolfrey 206667-4453. Study chairs or principal investigators: Ann Woolfrey, Study Chair; Fred Hutchinson Cancer Research Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00010335;jsessionid=C86124 E234F08730F120E192C53539F4
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Positron Emission Tomography (PET) to Locate Areas of White Blood Cell Activity Condition(s): Lupus Erythematosus; Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will examine whether PET imaging can reveal what is happening in lymph nodes of patients with systemic lupus erythematosus, or lupus, during periods of active disease. Patients may have periods of active disease when they may feel sick with fever, fatigue, and aching or swollen joints. Their blood tests are abnormal and their kidney, lungs or heart may be affected. At other times, the disease is inactive, and patients feel well, their blood is normal, and there is no evidence of organ disease. In lupus, like other autoimmune diseases, the body's immune system attacks it own healthy tissues. Activated lymphocytes (a type of immune cell) lead to the production of antibodies and chemical signals that contribute to the disease process. In animals with lupus, these cells are activated in the lymphoid organs, such as the lymph nodes or spleen. It is not known exactly where these cells are activated in humans. Because some lymph nodes are located deep inside the chest and abdomen; surgery is currently the only way to examining them. PET imaging may provide an alternative, non-invasive, means of obtaining information on lymph node activity in humans. This test uses a radioactive sugar molecule called F18-FDG to find areas of increased cellular activity in the body. (Cells use sugar for fuel, so active cells, such as active lymphocytes, uses more FDG than other body tissues.) This study will determine whether PET can detect these areas of increased activity in lupus during active disease. Patients with active or inactive lupus may be eligible for this study. Candidates are screened with a history, physical examination, and routine blood and urine tests. Women who are pregnant or breastfeeding may not participate. Participants will undergo PET scanning. On the day of the scan they have a brief medical history and physical examination and a blood sample is drawn to check blood count and look for markers of lymphocyte activation. Then, a small plastic tube (catheter) is placed into a vein in the patient's arm, the FDG is injected through the catheter, and the patient rests for an hour. For the scan, the patient lies flat in a cradle that is moved into the central hole of the doughnut-shaped PET camera, and pictures are taken over the next 2 hours, with the patient lies quietly, without moving the head or arms. After the scan is finished, the patient empties the bladder approximately every hour for 6 hours to excrete the radioactive sugar. Study Type: Observational
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Contact(s): Maryland; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00029926;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Randomized Study of Oral Contraceptives or Hormone Replacement Therapy in Women With Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Determine the effect of oral contraceptives containing low-dose synthetic estrogens and progestins on disease activity in premenopausal women with inactive, stable, or moderate systemic lupus erythematosus (SLE). II. Determine the effect of hormone replacement therapy with conjugated estrogens and progestins on disease activity in postmenopausal women with inactive, stable, or moderate SLE. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006133;jsessionid=C86124 E234F08730F120E192C53539F4
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Role of altered CD40-Ligand gene transcription in systemic lupus erythematosus Condition(s): Lupus Erythematosus, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Arthritis Foundation Purpose - Excerpt: Systemic lupus erythematosus is an often devastating autoimmune disease which affects 1 in 2,000 women in the United States. Recently, several research laboratories have reported that a protein, named CD40-ligand (CD154), is overpressed by a subset of white blood cells, called lymphocytes, in patients with lupus. Expression of CD154 appears critical to the generation of antibodies that cause disease in
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lupus. Blocking CD154 interactions in the immune system has been shown to decrease disease activity in animal models of lupus. We propose to study the regulation of CD154 in patients with lupus in hopes of inhibiting its abnormal and deleterious expression. Study Type: Observational Contact(s): Randy Q Cron, MD, Ph.D. 215-590-1844; Pennsylvania; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 191044318, United States; Recruiting; Randy Q Cron, M.D., Ph.D. 215-590-1844 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00008749;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Role of the Antibody Against NR2 Glutamate Receptor in Cognitive Dysfunction in Patients with Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Cognitive dysfunction is common in patients with systemic lupus erythematosus (SLE), observed in as many as two-thirds of patients. Cognitive dysfunction of long duration or with deterioration can have a significant impact on occupational functioning of SLE patients and also compromise compliance to treatment. The pathogenesis of cognitive dysfunction in SLE patients is likely multifactorial, including vascular origin, direct neuronal damage due to autoantibodies or cytokines, metabolic effects, or effects of certain medications. More than one half of SLE patients have anti-DNA antibodies, and it was recently demonstrated that a subset of anti-DNA antibodies cross-reacts with a pentapeptide consensus sequence (residues 283-287) of the human Nmethyl-D-aspartate (NMDA) receptor NR2a and NR2b subunits and can cause excitotoxic death of neurons. NMDA receptors are important in memory function and learning, and thus such antibodies may mediate cognitive dysfunction in SLE. In this cross-sectional study, up to 60 patients with SLE may be enrolled. Participants will undergo neuropsychological testing, neuroimaging studies, and blood tests for antibody with the reactivity to the pentapeptide consensus sequence of the human NMDA receptor NR2a and NR2b subunits (anti-pentapeptide Ab). The primary objective of this study is to evaluate the association between cognitive dysfunction and serum anti-pentapeptide Ab. Magnetic resonance imaging (MRI) will be performed for evaluation of potentially confounding central nervous system (CNS) disease such as cerebral infarction, and of blood brain barrier breakdown by employing
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gadolinium enhancement. Furthermore, in participants who agree, a lumbar puncture will be performed and cerebrospinal fluid will be obtained for preliminary evaluation of the intrathecal levels of the antipentapeptide Ab associated with cognitive dysfunction. If the antipentapeptide Ab is associated with cognitive dysfunction, therapeutic interventions via NR2 receptor blockade or the blockade of the antipentapeptide Ab may be considered in a future study. Study Type: Observational Contact(s): Maryland; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00042523;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Safety and Efficacy Study of LJP 394 (abetimus sodium) to treat lupus kidney disease Condition(s): Immunologic Diseases; Autoimmune Diseases; Systemic Lupus Erythematosus; Lupus Nephritis; Lupus Glomerulonephritis Study Status: This study is currently recruiting patients. Sponsor(s): La Jolla Pharmaceutical Company Purpose - Excerpt: The purpose of this study is to determine whether LJP 394 (abetimus sodium) is safe and effective in delaying and reducing renal flares in patients with lupus nephritis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00035308;jsessionid=C86124 E234F08730F120E192C53539F4
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Safety of Estrogens in Lupus: Birth Control Pills Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Research on Women's Health (ORWH)
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Purpose - Excerpt: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test whether women with systemic lupus erythematosus (SLE or lupus) can safely use estrogen. We will determine this by looking at the effects of oral contraceptives (birth control pills, also known as "the pill") on disease activity and severity in women with SLE. The results of the study will show whether it is safe for women with SLE to use the pill. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000420;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Six month clinical research study for patients with moderate or severe dry eye syndrome Condition(s): Keratoconjunctivitis Sicca; Sjogren's Syndrome; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Scleroderma, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): Allergan Purpose - Excerpt: A six-month clinical research trial to evaluate the effectiveness of an investigational medication for the treatment of dry eye syndrome in patients that have been diagnosed with moderate to severe dry eye syndrome, an autoimmune disorder AND/OR females 65 years of age or older. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025818;jsessionid=C86124 E234F08730F120E192C53539F4
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Study of GL701 in Men with Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): Genelabs Technologies Purpose - Excerpt: Lupus flares and other symptoms associated with systemic lupus erythematosus (SLE) may be caused by a deficiency of
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dehydroepiandrosterone (DHEA). GL701 is an investigational new drug meant to enhance DHEA levels. This study is designed to evaluate both the safety and efficacy of GL701 in male lupus patients. Phase(s): Phase III Study Type: Interventional Contact(s): Betty Quarles (650) 562-1425
[email protected]; California; Genelabs Technologies, Inc., Redwood City, California, 94063, United States; Recruiting Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00037128;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Study of Systemic Lupus Erythematosus Condition(s): Lupus Nephritis; Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This protocol will evaluate patients with systemic lupus erythematosus (SLE) and their relatives to learn more about how the disease develops and changes over time. It will also study genetic factors that make a person susceptible to SLE. Patients 10 years of age and older with known or suspected SLE and their relatives may be eligible for this study. Patients will be evaluated with a medical history and physical examination, blood and urine tests. Other procedures may include: 1. Electrocardiogram 2. 24-hour urine collection 3. Imaging studies, such as chest and joint X-rays, magnetic resonance imaging (MRI) scans, bone scans, and bone densitometry. 4. Questionnaire about the degree of disease activity, and survey of risk factors for disease complications. 5. Apheresis-Collection of plasma (fluid portion of blood) or blood cells for analysis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The required component (plasma or cells) is removed and the rest of the blood is returned to the body through the same needle or through a second needle in the other arm. 6. Skin biopsy-Removal of a small skin sample for microscopic analysis. An area of skin is numbed with an anesthetic and a small circular portion (about 1/4 inch in diameter) is removed, using a sharp cookie cutter-type instrument. 7. Kidney, bone marrow or other organ biopsy-Removal of a small sample of organ tissue. These biopsies are done only if they can provide information useful in better understanding the disease or making
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treatment decisions. 8. Genetic studies-Collection of a blood sample for gene testing. Patients will be followed at least once a year with a brief history and physical examination and routine blood and urine tests. Some patients may be seen more often. Treatment recommendations will be offered to patients' physicians, and patients who are eligible for other research treatment studies will be invited to enroll. Participating relatives of patients will fill out a brief medical history questionnaire and provide a DNA sample (either a blood sample or tissue swab from the inside of the cheek) for genetic testing. Study Type: Observational Contact(s): Maryland; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001372;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Study of the Predictors of the Course and Early Outcome of Patients With Systemic Lupus Erythematosus: Nature Versus Nurture Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Continue yearly ascertainment visits of all patients of the established Lupus in Minority Populations: Nature vs Nurture (LUMINA) study cohort. II. Recruit into the LUMINA cohort newly diagnosed patients with systemic lupus erythematosus (SLE). III. Determine the impact of additional major histocompatibility complex (MHC) and non-MHC genetic factors not previously examined, specifically tumor necrosis factor, mannose binding protein, interleukin-1 receptor antagonist, and bcl-2, on the course and outcome of SLE. IV. Refine the assessment of those clinical and behavioral-cultural factors found to be important predictors of disease activity, damage, and functioning, thus far in these patients. V. Determine the relationships among disease activity, disease damage, and physical and mental functioning in these patients as the SLE progresses and the factors that predict them. Study Type: Observational Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006134;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Cyclophosphamide and Fludarabine to Treat Lupus Nephritis Condition(s): Glomerulonephritis; Lupus Nephritis; Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will test the safety and effectiveness of combination therapy with cyclophosphamide (Cytoxan) and fludarabine in treating lupus nephritis (kidney inflammation). This condition, common in patients with systemic lupus erythematosus, is caused by abnormal action of immune cells called lymphocytes against the kidneys. Left untreated, severe cases can result in loss of kidney function. The current treatment of choice-intermittent high doses (pulses) of cyclophosphamide-does not work in all patients and causes infertility in many women. The rate of infertility in men is not known. This study will examine whether fludarabine can safely be given with significantly lower doses of cyclophosphamide, and if this combination controls kidney inflammation. Patients 18 years of age and older with severe lupus nephritis (called proliferative lupus nephritis) may be eligible for this study. Candidates will have a history and physical examination; blood and urine tests; chest X-ray; electrocardiogram; cancer screening that may include a Pap smear, mammogram, rectal examination, PSA testing, and sigmoidoscopy. Participants will be divided into one of the following treatment groups: Group 1-Patients undergo three treatment cycles of cyclophosphamide, taken by mouth, and fludarabine, injected subcutaneously (under the skin). Patients receive both drugs on day 1 of the cycle, and fludarabine alone on days 2 and 3. This regimen is repeated once every 5 weeks for three cycles. Group 2-Same as for Group 1, except fludarabine injections are given intravenously (through a vein) for the second treatment cycle. Patients in this group have frequent blood sampling during the first and second treatment cycles to monitor blood levels of the drug. Samples are collected before the first injection is given and at 0.5, 1, 1.5, 2, 4, 8, 24 and 48 hours after the third injection. A total 12 tablespoons of blood is drawn over a 2-month period. All patients will have blood drawn once or twice a week during the first two cycles and then less frequently to monitor blood counts. Some patients will have the following additional procedures to test the effects of treatment on
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lymphocytes: 1. Blood sample collection 2. Bone marrow aspiration-The skin over the hip bone is cleaned and a local anesthetic is injected into the outer covering of the bone. Bone marrow is suctioned through the needle into an attached syringe. The procedure is done before treatment begins, at the end of treatment, and 6 months after treatment. 3. Tonsillar biopsyThe tonsils are numbed with a local anesthetic and 1 to 4 pieces of tissue are removed using special forceps. The procedure is done before treatment begins, at the end of treatment, and 6 months after treatment. 4. Magnetic resonance imaging (MRI) of the abdomen-The patients lies on a table in a narrow cylinder (the MRI scanner) containing a strong magnetic field, which is used to create images of parts of the body in small section views. Patients will be followed for at least 24 months to monitor late side effects and the response to treatment. Phase(s): Phase I Study Type: Interventional Contact(s): Maryland; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001676;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Drug Therapy in Lupus Nephropathy Condition(s): Nephrotic Syndrome; Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Studies have shown that up to 26% of patients with systemic lupus erythematoses nephritis may suffer from membranous lupus nephropathy. The disease is characterized by high levels of protein in the urine and may eventually lead to kidney failure. This study will evaluate the effectiveness and toxic effects of immunosuppressive drug therapy in patients with membranous lupus nephropathy over a 12 month period. The major goal of this therapy is to decrease protein losses and ultimately prevent kidney failure. Patients enrolled in the study will undergo a routine history and physical examination. In addition, several diagnostic tests will be conducted including; chest x-ray ECG, blood and urine laboratory tests. Patients will be divided and grouped according to the severity of their disease as shown by kidney function. Each group will
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then randomly be subcategorized by different treatment plans. Each treatment plan will made up of immunosuppressive medications including prednisone, cyclophosphamide, cyclosporin A, and combinations of these drugs. Patients will receive the medications as directed by the study. The study will last 12 months and require patients to be admitted for two to five days before the study begins and once the study is completed. Patients will be followed as outpatients throughout the 12 month study. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001212;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Psychoeducational Approach to Improve Health in Lupus Condition(s): Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: We will study the relationships among patient/partner communication, social support, and self-efficacy (a person's belief in the ability to manage his or her disease) as they affect the health of people with systemic lupus erythematosus (SLE, or lupus) over time. We are assigning 150 people with lupus and their partners to either (1) receive counseling to improve self-efficacy, partner support, and patient/partner problem solving or (2) see an informational film about lupus. We will follow study participants for 12 months to find out about their physical and mental health, disease activity, beliefs that they can take steps that help them feel better, coping, social support, and couples communication. Phase(s): Phase II Study Type: Interventional Contact(s): Massachusetts; Brigham & Women's Hospital, Boston, Massachusetts, 02115, United States. Study chairs or principal investigators: Lawren H. Daltroy, Dr.P.H., Principal Investigator; Brigham & Women's Hospital
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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000417;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Safety of Estrogens in Lupus: Hormone Replacement Therapy Condition(s): Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Research on Women's Health (ORWH) Purpose - Excerpt: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test whether postmenopausal women with systemic lupus erythematosus (SLE, or lupus) can safely use the hormone estrogen. In this part of the study, we will look at the effects of estrogen replacement therapy on the activity and severity of disease in women with SLE. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000419;jsessionid=C86124 E234F08730F120E192C53539F4
·
Serologically Active, Clinically Stable Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The first part of this study will use the database of a large, ongoing NIH-sponsored lupus study, Safety of Estrogen in Lupus Erythematosus National Assessment. We will examine the levels of a blood protein known as C3a in a series of patient blood samples to see if C3a levels predict lupus flares or are better than other blood tests, and therefore should be used more widely in managing lupus. In the second part of the study we will add or increase prednisone treatment on the basis of abnormalities in blood tests for C3a and dsDNA antibodies. Early treatment based on increases in C3a and dsDNA antibodies, before the patient develops physical signs of disease, may reduce lupus flares and, ultimately, the patient's total steroid exposure. We will follow study participants for 1 year on a monthly basis and do full physical
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examinations and laboratory evaluations. If C3a and dsDNA antibody levels are increased significantly above baseline levels while a patient is clinically stable, we will give the patient either prednisone or an inactive pill (placebo) for 1 month. We will follow these patients monthly to compare how often lupus flares occur in the two groups. This approach could provide a novel method of preventing lupus flares, using C3a as a sensitive predictor of flare. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000421;jsessionid=C86124 E234F08730F120E192C53539F4 ·
DHEA Treatment for Sjogren's Syndrome Condition(s): Lacrimal Apparatus Disease; Salivary Gland Disease; Sjogren's Syndrome; Xerostomia Study Status: This study is completed. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate the effectiveness of the male hormone dehydroepiandrosterone (DHEA) in treating Sjogren's syndrome. This autoimmune disorder, in which the immune system attacks the salivary glands and tear glands, affects primarily women. Patients' eyes and mouth become drier over time, and can lead to problems such as serious tooth decay and eye irritations. Sex hormones seem to influence the immune response and may help decrease disease severity. DHEA has benefited some patients with two other autoimmune diseases, rheumatoid arthritis and systemic lupus erythematosus. Women 18 to 75 years of age with Sjogren's syndrome may be eligible for this 7-month study. At the initial visit, candidates will have a physical examination, routine blood and urine tests and eye and dental examinations, including a test to measure saliva production for screening purposes and to establish baseline values for participants. Those enrolled in the study will be randomly assigned to take either DHEA or placebo (look-alike tablet with no active ingredient) once a day for 6 months and will be monitored with follow-up visits at months 1, 3, 6 and 7. Physical examination, blood tests and urinalysis will be repeated at months 1, 3, 6 and 7; saliva will be collected at months 3, 6 and 7; and eyes will be examined at 3 and 6 months. Because hormone changes may have both
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physical and emotional effects, patients will be asked questions about their mood, symptoms and side effects of treatment. It is not known if Sjogren's syndrome is associated with osteoporosis (bone thinning), but since this condition occurs in other autoimmune disorders, patient's bone density will be measured at the first visit, and blood drawn at 3 and 6 months will be tested for various substances associated with changes in bone density. A 24-hour urine collection at the first visit and later urine tests will also be tested for substances associated with bone thinning. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Dental And Craniofacial Research (NIDCR), 9000 Rockville Pike Bethesda, Maryland, 20892, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001598;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Epidemiologic Study of Reproductive Outcome in Women with Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Northwestern University Purpose - Excerpt: Objectives: I. Evaluate whether pregnancy is an independent risk factor that affects disease activity in women with systemic lupus erythematosus. II. Evaluate whether maternal disease activity is a risk factor for adverse pregnancy outcome. Study Type: Observational Contact(s):. Study chairs or principal investigators: Rosalind RamseyGoldman, Study Chair; Northwestern University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004663;jsessionid=C86124 E234F08730F120E192C53539F4
·
Lupus Cohort--Thrombotic Events and Coronary Artery Disease Condition(s): Cardiovascular Diseases; Coronary Disease; Thrombosis; Heart Diseases; Lupus erythematosus, systemic Study Status: This study is completed.
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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To study longitudinally the incidence, pathogenesis, and risk factors for thrombotic events and coronary artery disease in a cohort of patients with systemic lupus erythematosus (SLE). Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005436;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Phase II Pilot Study of Cytarabine for Refractory Systemic Lupus Erythematosus Condition(s): Lupus Erythematosus, Systemic Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Michigan Purpose - Excerpt: Objectives: I. Evaluate the toxicity of cytarabine in patients with refractory systemic lupus erythematosus. II. Evaluate objective disease parameters, including serum complement levels, antiDNA antibody titers, sedimentation rate, and the systemic lupus activity measure in these patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004643;jsessionid=C86124 E234F08730F120E192C53539F4
·
Phase II Study of Long-Term Dehydroepiandrosterone for Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center Northwestern University
for
Research
Resources
(NCRR);
Purpose - Excerpt: Objectives: I. Evaluate the long-term safety and tolerance of a synthetic formulation of dehydroepiandrosterone, GL701, in patients with systemic lupus erythematosus who have completed a prior GL701 protocol.
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Phase(s): Phase II Study Type: Interventional Contact(s):. Study chairs or principal investigators: Rosalind RamseyGoldman, Study Chair; Northwestern University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004665;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Phase II/III Randomized, Double-Blind, Placebo-Controlled Study of Dehydroepiandrosterone in Women with Mild to Moderate Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center Northwestern University
for
Research
Resources
(NCRR);
Purpose - Excerpt: Objectives: I. Evaluate the safety and efficacy of synthetic dehydroepiandrosterone (GL701) in women with prednisonedependent systemic lupus erythematosus. II. Describe the pharmacokinetics of GL701. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s):. Study chairs or principal investigators: Rosalind RamseyGoldman, Study Chair; Northwestern University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004795;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dehydroepiandrosterone in Women with Active Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center Northwestern University
for
Research
Resources
(NCRR);
Purpose - Excerpt: Objectives: I. Evaluate the safety and efficacy of synthetic dehydroepiandrosterone, GL701, in women with active systemic lupus erythematosus. Phase(s): Phase III
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Study Type: Interventional Contact(s):. Study chairs or principal investigators: Rosalind RamseyGoldman, Study Chair; Northwestern University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004662;jsessionid=C86124 E234F08730F120E192C53539F4 ·
Study of Individualized Instruction versus Pamphlet in Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Virginia Commonwealth University Purpose - Excerpt: Objectives: I. Evaluate an educational program that has been pretested for cultural appropriateness and literacy requirements in patients with systemic lupus erythematosus (SLE). II. Assess the impact of this educational program on patients with SLE, with an emphasis on recognizing cardinal symptoms, coping with fatigue, regulating medications, and communicating with the physician. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004756;jsessionid=C86124 E234F08730F120E192C53539F4
Benefits and Risks18 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·
A new treatment could be more effective than the current treatment for lupus. Although only half of the participants in a clinical trial receive the
This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f2 91. 18
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experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over. ·
If the treatment is effective, then it may improve health or prevent diseases or disorders.
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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.
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People who take part in trials contribute to scientific discoveries that may help other people with lupus. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent
Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial's risks and benefits, the researcher’s expectations of you, and your rights as a patient.
What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention. How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital's Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully
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monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient's Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·
Information on all known risks and benefits of the treatments in the study.
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Know how the researchers plan to carry out the study, for how long, and where.
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Know what is expected of you.
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Know any costs involved for you or your insurance provider.
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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.
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Talk openly with doctors and ask any questions.
After you join a clinical trial, you have the right to: ·
Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.
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Receive any new information about the new treatment.
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Continue to ask questions and get answers.
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Maintain your privacy. Your name will not appear in any reports based on the study.
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Know whether you participated in the treatment group or the control group (once the study has been completed). What about Costs?
In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should
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find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don't have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·
What is the purpose of the clinical trial?
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What are the standard treatments for lupus? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?
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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?
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How long will the treatment last? How often will I have to come back for follow-up exams?
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What are the treatment's possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?
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Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?
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How will my health be monitored?
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Where will I need to go for the clinical trial? How will I get there?
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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?
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Will I be able to see my own doctor? Who will be in charge of my care?
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Will taking part in the study affect my daily life? Do I have time to participate?
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How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?
Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has
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developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “lupus” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
A Guide to Patient Recruitment : Today's Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001),
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CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna ·
A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna
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The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna
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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna
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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna
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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna
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Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna
Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aspiration: The act of inhaling. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Catheter: A tubular, flexible, surgical instrument for withdrawing fluids from (or introducing fluids into) a cavity of the body, especially one for introduction into the bladder through the urethra for the withdraw of urine.
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[EU]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Gadolinium: Gadolinium. An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Hepatitis: Inflammation of the liver. [EU] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of
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a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Osteoarthritis: Noninflammatory degenerative joint disease occurring chiefly in older persons, characterized by degeneration of the articular cartilage, hypertrophy of bone at the margins, and changes in the synovial membrane. It is accompanied by pain and stiffness, particularly after prolonged activity. [EU] Outpatients: Persons who receive ambulatory care at an outpatient department or clinic without room and board being provided. [NIH] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Pulmonary: Pertaining to the lungs. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Reconstitution: 1. a type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. the restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: Pertaining to the rectum (= distal portion of the large intestine). [EU] Refractory: Not readily yielding to treatment. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a nonbarbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays
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immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH]
Thrombosis: The formation, development, or presence of a thrombus. [EU] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]
Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]
Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU]
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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL
ABOUT PART II In Part II, we introduce you to additional resources and advanced research on lupus. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on lupus. In Part II, as in Part I, our objective is not to interpret the latest advances on lupus or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with lupus is suggested.
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CHAPTER 4. STUDIES ON LUPUS Overview Every year, academic studies are published on lupus or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on lupus. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on lupus and teach you how to keep current on new studies as they are published or undertaken by the scientific community.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and lupus, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the
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format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “lupus” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·
Research Advances in Systemic Lupus Erythematosus Source: Journal of the American Medical Association. JAMA. 285(5): 650651. February 7, 2001. Summary: This journal article provides health professionals with information on research advances in systemic lupus erythematosus (SLE). This multisystem autoimmune disease with a significant genetic component to susceptibility involves both humoral and cellular aspects of the innate and acquired immune system. Deficiencies of complement and other opsonins, genetic variants of immunoglobulin G and C reactive protein receptors, and inflammatory cytokine promoter variants have been implicated as components of genetic susceptibility. SLE occurs worldwide and affects women more than men and African Americans and Hispanics more than other ethnic groups. The disease is characterized by autoantibodies with a spectrum of specificities that participate in disease pathogenesis. Some environmental risk factors are known, and identification of specific genetic factors promises to define new molecular targets for therapy. Broad, nonspecific immunosuppression will be replaced by early, selective, and individualized intervention. Assessment of individual genetic portfolios with gene array technology, combined with advances in knowledge about exogenous stimuli, will facilitate prevention of SLE. Mortality rates will decline, and insights into therapy may apply to other autoimmune conditions. 6 references.
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Systemic Lupus Erythematosus: Guidelines for Control Source: Consultant. 40(2): 332-334. February 2000. Summary: This journal article provides health professionals with highlights from guidelines for the referral and management of systemic lupus erythematous (SLE) recently published by the American College of Rheumatology. The guidelines focus on the epidemiology, diagnosis, and treatment of SLE. They also include criteria for specialist referral and collaboration with a specialist in long term care. Most cases of SLE involve women of child bearing age. Symptoms can involve almost any
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area of the body, and SLE should be suspected in any patient who has disease manifestations that affect two or more organ systems. Serologic tests are frequently used to help confirm the diagnosis, including tests for antinuclear antibodies, antibodies to double stranded DNA, and antibodies to the Smith antigen. Treatment for mild SLE involves pharmacologic therapy with agents such as topical sunscreens, topical and oral corticosteroids, nonsteroidal antiinflammatory drugs, and antimalarial drugs. Therapeutic options for serious SLE include high dose corticosteroids and immunosuppressive or cytotoxic agents. All patients who have SLE require lifelong monitoring, and those who have moderate or severe disease need a specialist's supervision. The frequency of the evaluations depends on the severity of the patient's condition. Patients may obtain information and support from various organizations. 2 tables and 7 references. ·
Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): i-xi,199-413. May 2000. Summary: This journal provides health professionals with information on new advances in the pathogenesis of systemic lupus erythematosus (SLE), risk factors for and management of complications of SLE, and approaches to treating SLE. The journal begins with a review of the Hopkins Lupus Cohort, a decade long prospective study. This is followed by an article that provides an apoptosis centered hypothesis for the initiation and propagation of SLE. The focus of the next article is on genetics, including the goals of genetic analysis of SLE, the strategies to define genetic susceptibility factors in SLE, and current understanding of the genetics of SLE. The next article summarizes evidence on the clinical and subclinical spectra of premature atherosclerosis in SLE. This is followed by an article that provides information on the epidemiology, diagnosis, and management of patients with SLE and osteonecrosis. The sixth article discusses the mechanisms of glucocorticoid induced osteoporosis in SLE and outlines prevention and treatment strategies. The focus of the next article is on the clinical features, diagnosis, and management of antiphospholipid syndrome in SLE. This is followed by an article that reviews the physiology of dehydroepiandrosterone (DHEA), the rationale for its use as a pharmacologic agent in SLE, the clinical results obtained with DHEA in patients with SLE, and expected and future developments regarding DHEA. The next article reviews the most recent studies on the use of cyclophosphamide in various manifestations of SLE and addresses issues related to dose regimens and clinically relevant toxicities. The focus of the subsequent article is on the
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use of hematopoietic stem cell transplantation to treat SLE. The final article summarizes various therapies under study to treat. 21 figures, 6 tables, and numerous references. ·
Apoptosis in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 215-227. May 2000. Summary: This journal article provides health professionals with information on an apoptosis centered hypothesis for the initiation and propagation of systemic lupus erythematosus (SLE), a heterogeneous and complex group of disorders of uncertain cause. Recent studies have suggested that abnormalities in the apoptotic cell death process may have a role in the initiation and propagation of this disease spectrum by altering the generation and cleavage of antigens and through abnormalities in immunoregulation. The article reviews studies on the clustering and concentration of autoantigens in and on the surface blebs of apoptotic cells, modifications of antigen structure during certain forms of apoptotic death, and abnormalities in apoptotic cell clearance in humans with SLE and in certain animal models. In addition, the article presents a comprehensive model of systemic autoimmunity. In this model, autoantigens are clustered and concentrated in the surface blebs of apoptic cells where they are modified by apoptosis specific proteolysis and phosphorylation. When this event occurs in a genetically susceptible individual, involves a microenvironment containing high concentrations of the targeted antigens, is proimmune in nature, and allows suprathreshold concentrations of antigen with nontolerized structure to enter the major histocompatibility complex class II processing pathway, a primary immune response directed against the nontolerized structure is initiated. Once the primary immune response to apoptotic antigens is initiated, other apoptotic events may stimulate the secondary immune response with less stringency, resulting in flares. 3 figures and 66 references. (AA-M).
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Genetics of Systemic Lupus Erythematosus: Clinical Implications Source: Rheumatic Disease Clinics of North America. 26(2): 229-256. May 2000. Summary: This journal article provides health professionals with information on the genetics of systemic lupus erythematosus (SLE), focusing on the goals of genetic analysis of SLE, the strategies to define the genetic susceptibility factors in SLE, and current understanding of the genetics of SLE. The traditional goal of genetic analysis is to identify the single gene implicated in the disease. SLE is generally a polygenic
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disorder with contributions from multiple genes. Recent estimates have indicated that over 100 genes may be implicated in the SLE disease process. In polygenic disorders, genetics are likely to provide information on etiopathogenesis. The main methods of identifying genetic susceptibility factors in polygenic disorders are association studies and linkage analysis. Association studies examine the frequency of mutation or polymorphism in the affected population and compare the frequency to that seen in a matched control population. The basis of linkage analysis is the exploitation of highly polymorphic minisatellites scattered throughout the genome. The genetic factors identified in SLE to date include genes known to affect immune complex clearance, genes implicated in tolerance, major histocompatibility complex genes, and genes regulating inflammation. The article reviews research on these factors and highlights the development of new biologic strategies through human and murine studies. 3 tables and 190 references. (AA-M). ·
Premature Atherosclerosis in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 257-278. May 2000. Summary: This journal article provides health professionals with information on current evidence concerning the clinical and subclinical spectra of premature atherosclerosis in systemic lupus erythematosus (SLE). Topics include the clinical problems of premature atherosclerosis, studies on the prevalence of subclinical atherosclerotic disease, studies on factors associated with the development of coronary artery disease (CAD) in SLE, and the screening and prevention of CAD in patients with SLE. SLE is associated with at least a fivefold increased risk of CAD and it appears to eliminate a woman's premenopausal protection against CAD. Subclinical disease can be identified in up to 40 percent of patients. The pathogenesis of atherosclerosis in this context appears to be a complex interaction of factors associated with the disease, its therapy, and traditional risk factors. Hypercholesterolemia is predictive of future CAD events. In addition, SLE appears to be a strong risk factor for CAD over and above the effect of known, traditional CAD risk factors. An aggressive approach to management of traditional CAD risk factors in patients with SLE is likely to have a major impact on morbidity and mortality in this population. Therefore, patients must be educated about this issue. Clinicians who care for patients with SLE also need to assume a primary role in screening and coordinating the management of CAD risk factors in these high risk patients. 1 figure, 1 table, and 75 references. (AA-M).
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Management of Osteonecrosis in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 279-309. May 2000. Summary: This journal article provides health professionals with information on the epidemiology, diagnosis, and management of patients with systemic lupus erythematosus (SLE) and osteonecrosis (ON). ON of the femoral head is common in patients who have SLE. The effects are magnified because these patients commonly have multiple other joints involved in addition to the hip. Risk factors for ON in patients who have SLE include prednisolone therapy with doses greater than 20 milligrams a day, evidence of end organ effect of corticosteroid use, certain pathophysiologic variables, and altered coagulability. The primary observation in the ON diagnosis is a deep pain that is localized to the bone. Radiographic evaluation should begin with standard radiographs of all symptomatic joints. Osteonecrotic lesions can be divided radiographically into precollapse and postcollapse. Magnetic resonance imaging has been found to be 99 percent sensitive and specific for ON. In patients with suspected multiple joint involvement, bone scanning has been suggested as a screening method. Early diagnosis is important for medical and surgical management to try to avoid total joint replacements in this young patient population. Various nonoperative and operative treatments are available for managing ON. The conservative approach can be divided into modification of activity with restricted weight bearing, stimulation of repair with ultrasound or electric signals, and pharmaceutical treatment. Surgical methods of treating femoral heads with precollapse disease include core decompression, osteotomy, nonvascularized bone grafting, and vascularized bone grafting. Postcollapse disease may be treated with limited femoral resurfacing or total hip arthroplasty. In the future, pharmacologic agents and growth and differentiation factors may be effective in the early treatment of this disease and may lead to more successful outcomes with surgical options. 13 figures and 135 references. (AA-M).
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Steroid-Induced Osteoporosis in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 311-329. May 2000. Summary: This journal article provides health professionals with information on the mechanisms of glucocorticoid induced osteoporosis in systemic lupus erythematosus (SLE) and outlines strategies for prevention and treatment. The patient with SLE is at considerable risk of osteoporosis because of the inflammatory disease itself, its consequences,
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and its treatments. Risk factors and mechanisms for osteoporosis in SLE include environmental factors, hormonal factors, the effects of inflammation, renal disease, and medications used to treat SLE. Because of their extensive use, glucocorticoids are thought to be the most frequent cause of drug induced osteoporosis and may be responsible for much of the bone loss in SLE. Glucocorticoids predominantly affect trabecular bone and the cortical rim of the vertebral body, but over time, the cortex of long bones also becomes susceptible to the demineralizing effects of these drugs. Mechanisms of steroid induced osteoporosis include abnormalities of gonadal function, mineral metabolism, and bone cell function, and steroid effects on local skeletal growth factors and on muscles. Assessment of the patient with SLE may involve determining bone mineral density and measuring baseline serum levels of vitamin D1 and osteocalcin, as well as urinary calcium excretion and pyridinoline cross links. Calcium, vitamin D, and a weightbearing program are suitable first line measures. Thiazides are useful for the glucocorticoid treated patient with hypercalciuria. Unless otherwise contraindicated, hormone replacement therapy should be used in patients who are deficient in sex hormones. If bone loss continues despite these therapies, antiresorptive therapies are recommended. Therapies under investigation include parathyroid hormone, ipriflavone, growth hormone, and insulin like growth factor. 120 references. (AA-M). ·
Antiphospholipid (Hughes) Syndrome in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 331-348. May 2000. Summary: This journal article uses a question and answer format to provide health professionals with information on the clinical features, diagnosis, and management of antiphospholipid syndrome (APS) in systemic lupus erythematosus (SLE). APS occurs in approximately 30 percent of patients who have SLE. Clinical features and antiphospholipid antibody (aPL) specificities are similar between the primary and secondary forms of APS. Major features of APS include thrombosis, cytopenias, recurrent pregnancy loss, and cardiac valve lesions. The clinical course of the secondary syndrome is independent of the activity and severity of lupus, but the presence of APS worsens the prognosis. Lupus anticoagulant and anticardiolipin antibody tests confirm APS. Preliminary classification criteria consider that APS is present when one or more clinical and one or more laboratory criteria occur in the same patient. The differential diagnosis of APS includes autoimmune diseases, malignancies, drug induced disease, infectious diseases, and vasculitis.
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Treatment for APS remains empirical and directed at coagulation and immune mechanisms because of the limited amount of controlled prospective data. There is strong evidence that patients with aPL associated thrombosis are subject to recurrences and require prophylactic therapy. The treatment of choice for recurrent fetal loss is anticoagulation with heparin. 85 references. (AA-M). ·
Dehydroepiandrosterone in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 349-362. May 2000. Summary: This journal article provides health professionals with information on the use of the adrenal androgen dehydroepiandrosterone (DHEA) in the treatment of systemic lupus erythematosus (SLE). DHEA has hormonal and immunomodulatory properties that suggest possible benefits for patients with SLE. The article reviews the physiology of DHEA and presents the rationale for its use as a pharmacologic agent in SLE. The main reasons for considering this agent include the following: Androgens might favorably affect the clinical expression of SLE, DHEA levels are low among patients with SLE, DHEA has immunomodulatory effects, and DHEA is beneficial in the NZB/NZW mouse model of SLE. In addition, the article summarizes the clinical results obtained with DHEA in patients with SLE. A small controlled trial has suggested overall clinical benefits. A large multicenter trial has pointed to a steroid sparing effect for DHEA. Other clinical studies have suggested possible benefits for bone metabolism and cognitive function. Side effects include acne and a lowering of high density lipoprotein cholesterol. The article concludes with a discussion of expected and future developments regarding DHEA. 3 figures and 39 references. (AA-M).
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Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 377-387. May 2000. Summary: This journal article provides health professionals with information on the use of hematopoietic stem cell transplantation (HSCT) to treat systemic lupus erythematosus (SLE). Most allogenic HSCTs are from a human leukocyte antigen matched sibling donor. Bone marrow from the donor is infused into the patient following completion of a myeloablative preparative regimen. Autologous HSCT involves removal, cryopreservation, and reinfusion of hematopoietic stem cells following myeloablative therapy. The source of autologous stem cells can be either the bone marrow or peripheral blood progenitors. Many institutions
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throughout the world are conducting clinical studies using immunoablative therapy followed by HSCT for the treatment of SLE. Interpretation of these studies will be complicated by the differences in patient selection, conditioning regimens, and methods of stem cell collection. A major concern with this approach is that autoreactive effector cells will be reinfused with the autologous graft. The recent demonstration that immunoablative therapy can be safely delivered without the need for stem cell rescue offers a possible way to circumvent this problem. Early results using immunoablative therapy, with or without stem cell rescue, are encouraging; however, longer followup and additional patients are needed to validate this approach. 51 references. (AA-M). ·
New Therapies for Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 389-406. May 2000. Summary: This journal article provides health professionals with information on various new therapies under study for the treatment of SLE. New therapies have gained increased attention, as demonstrated by a growing number of new modalities being studied. This increase is partly the result of the efforts of various groups to establish standard measurable end points for disease response and provide guidance in the design of clinical studies. The article describes various new modalities, including novel biologic agents that target specific immunologic responses and more traditional pharmaceutical agents. Biologic agents have been designed to interfere with T cell activation, T cell to B cell collaboration, anti-dsDNA antibody production, anti-dsDNA Ab complex deposition, complement activation and deposition, and cytokine activation and modulation. Pharmaceutical interventions include immunomodulators such as thalidomide, AS101, 2cholordeoxyadenosine, mycophenolate mofetil, bindarit, and methimazole, and sex hormones such as dehydroepiandrosterone, selective estrogen receptor modulators, and bromocriptine. The article explains the mechanism of action of these new therapies and highlights the most recent research performed to characterize their safety and efficacy. 1 table and 105 references. (AA-M).
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Update on Cyclophosphamide for Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 363-375. May 2000. Summary: This journal article provides health professionals with information on the most recent studies on the use of cyclophosphamide
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in various manifestations of systemic lupus erythematosus (SLE) and addresses issues related to dose regimens and clinically relevant toxicities. Over the past decade, cyclophosphamide has assumed an increasingly prominent role in the management of severe, life threatening manifestations of SLE. Intermittent, intravenous pulse cyclophosphamide has become the standard of treatment for diffuse proliferative lupus nephritis, and there is now substantial clinical literature to suggest an indication for most other forms of serious lupus affecting major organ systems, in particular lupus vasculitis and acute central nervous system manifestations. Cyclophosphamide is typically given with corticosteroids either orally or intravenously. Although there is no clear evidence that oral and intravenous regimens differ in clinical efficacy, oral cyclophosphamide has been largely replaced by intermittent intravenous bolus therapy in clinical practice. The most commonly used intravenous regimen consists of monthly infusions for 6 months followed by infusions every several months. The most common side effects of cyclophosphamide treatment are nausea and vomiting. The most common potentially serious toxicities of cyclophosphamide include infection, gonadal failure, bladder complications, and malignancy. Recent clinical investigations of cyclophosphamide in SLE have focused on drug combinations, relapses after treatment, combined apheresis cyclophosphamide therapy, and higher dose immunoablative strategies. 1 table and 78 references. (AA-M).
Federally-Funded Research on Lupus The U.S. Government supports a variety of research studies relating to lupus and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to lupus and related conditions.
19 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore lupus and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for lupus: ·
Project Title: ACE Inhibitors Autoantibody Production
in
Lupus
Nephritis--Tgfb
and
Principal Investigator & Institution: Singh, Ram R.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 5-MAR-2001; Project End 8-FEB2006 Summary: Angiotensin-converting enzyme inhibitors (ACEIs), such as captopril, are widely used to control hypertension in patients who have chronic renal disease. ACEIs improve renal function in patients with chronic renal disease, however, than would be expected from their suppression of hypertension. ACEI-induced improvement in renal function is associated with decreased renal TGF-beta expression and matrix deposition. We anticipate that ACEIs may have a similar effect on TGF-beta production, renal fibrosis and end stage renal disease in patients with lupus. However, because TGF-beta can inhibit T and B cell activation and auto-antibody productions, an ACEI-induced decrease in TGF-beta may exacerbate auto-antibody-mediated disease in lupus by enhancing auto-antibody production. Consequently, this proposal will explore potential therapeutic and damaging effects of ACEIs in SLE, inflammatory component of lupus nephritis, its continued presence enhances renal matrix deposition and fibrosis. To test this hypothesis we will: 1) evaluate autoantibody responses and renal disease in lupus-prone mice treated with ACEIs; and 2) generate and characterize mice that have kidney-specific deletion of the Tgfb1 gene. These mice will be used in future to determine the effect of TGF-beta deletion on lupus nephritis. Lupus-prone and control mice will be treated with captopril or a control anti-hypertensive agent; the effect on blood pressure, renal functions, renal histology, renal immune and collagen deposition will be determined. These changes will be correlated with TGF-beta expression in kidneys and spleens, and serum auto-antibodies. We will then generate mice that have renal-specific Tgfb1 gene deletion, and characterize their phenotype, specifically for any inflammatory changes in kidneys and other organs. The broad objectives of this proposal are to
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understand the role of TGF- beta in the pathogenesis of lupus nephritis, to explore how manipulation of in vivo TGF-beta can influence lupus, and to elucidate the mechanism and clinical utility of ACEIs in lupus. Delineation of pathways that cause matrix deposition in kidneys, but do not affect T and B cell activation, may lead to treatment strategies that improve end stage renal disease in SLE. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Delineation of Genetic Pathways to Lupus Pathogenesis Principal Investigator & Institution: Liu, Kui; Microbiology; University of Texas Sw Med Ctr/Dallas Southwestern Medical Ctr/Dallas Dallas, Tx 75390 Timing: Fiscal Year 2001; Project Start 1-SEP-2001 Summary: (provided by the applicant): Systemic lupus erythematosus (SLE) is characterized by the presence of anti-nuclear antibodies (ANA) directed against naked DNA and entire nucleosomes. Development of congenic mouse models carrying lupus susceptibility gene intervals has provided powerful tools for studying the mechanism of lupus pathogenesis. Sle1 mediates the loss of tolerance to nuclear antigens and the initiation of autoimmunity. Our recent study demonstrated that Sle1 mediates the abnormal expression of several genes, including the c-myc protooncogene, that control B-cell activation and proliferation. We hypothesize that autoreactive B-cells are generated from B-cell populations that have aberrant c-myc expression. We propose to identify the mechanisms leading to the aberrant c-myc expression and to characterize the B-cell populations that have aberrant c-myc expression in B6.Sle1 mice. We also propose to use powerful, microarray-based approaches to identify the molecular mechanisms by which Sle1 and S1e3 interact to cause lupus. Furthermore, we propose to identify lupus susceptibility gene(s) in the S1e3 interval using fine mapping in combination with functional genomics. By identifying the lupus susceptibility genes and the molecules involved in the pathogenesis, we can select candidate therapeutic targets for curing lupus. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Epidemiology of Osteoporosis in Women with Lupus MAMDC Project Principal Investigator & Institution: Ramsey-Goldman, Rosalind; Professor; Northwestern University 303 E Chicago Ave Chicago, Il 60611 Timing: Fiscal Year 2000
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Summary: The specific aims to be addressed in this study are: 1) To estimate the differences in bone mineral density (BMD) at the hip and lumbar spine between 128 Caucasian and 128 African-American women with lupus and a comparable control group matched by age, race, and menopause status; 2) To determine the association of lupus risk factors with low BMD in women with lupus, after controlling for traditional risk factors for low BMD; 3) To follow the subjects entered in the crosssectional study over a two year period in order to estimate the difference in the rate of bone loss at the hip and lumbar spine between women with lupus and a comparable control group matched by age, race, and menopause status; and 4) To determine the association of lupus risk factors with increased rates of bone loss in women with lupus, after controlling for traditional risk factors for low BMD. The hypotheses to be examined in this study are: 1a) Women with lupus have lower BMD at the hip and spine than matched controls; 1b) the negative effect of lupus on bone mineral density at the hip and spine is greater in Caucasian than in African-American women; 2a) Traditional risk factors for low BMD (nulliparty and menopause status, irregular menstrual cycles or premature menopause, avoidance of oral contraceptives and/or hormone replacement therapy, lower physical activity level, and decreased vitamin D levels) are associated with lower BMD at the hip or lumbar spine in women with lupus; 2b) lupus risk factors (greater disease activity, greater disease severity, higher corticosteroid burden, use of anticonvulsant drugs, and the presence of renal disease) are associated with lower BMD at the hip or lumbar spine in women with lupus, after controlling for traditional risk factors forlow BMD; 3a) Women with lupus have accelerated bone loss at the hip and spine during two additional years of lupus disease compared with matched controls followed for two years; 3b) the effect of lupus on the rate of bone loss at the hip and spine is greater in Caucasian than in African-American women; 4a) Traditional osteoporosis risk factors (mentioned in 2a above) are associated with accelerated bone loss in women with lupus; and 4b) lupus risk factors (mentioned in 2b above) are associated with accelerated bone loss at the hip or lumbar spine in women with lupus, after controlling for traditional risk factors for low BMD. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Genetic Analysis of Lupus Autoimmunity Principal Investigator & Institution: James, Judith A.; Associate Professor; Oklahoma Medical Research Foundation 825 Ne 13Th St, Ms 31 Oklahoma City, Ok 73104
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Timing: Fiscal Year 2000; Project Start 0-SEP-1996; Project End 1-AUG2001 Summary: Description The applicant, and her mentor, John Harley, M.D., Ph.D., have recently demonstrated that normal rabbits immunized with specific short peptides derived from the Sm autoantigen develop high levels of both anti-Sm and anti-nRNP antibodies; the peptides used as immunogens were selected since they are also bound by human lupus autoantibodies. The peptide-immunized rabbits, in addition to anti-Sm and anti-nRNP antibodies, also develop positive ANA, antibodies to DNA, and clinical features reminiscent of human lupus including proteinuria, red cell casts, renal insufficiency, hypoalbuminemia, thrombocytopenia, alopecia, and seizures. The antibodies that develop to Sm and nRNP are apparently of high titer in that they precipitate in double immunodiffusion assays and bind RNP antigens in solution phase and by immunoblots. In essence, by immunizing rabbits with peptides, Dr. James and Dr. Harley have induced a syndrome in rabbits that resembles human lupus. In more recent, preliminary studies that form the foundation of the present proposal, Dr. James has shown that certain strains of inbred mice also respond to Sm peptide immunization with epitope spreading and genesis of autoantibodies to other parts of the Sm and nRNP autoantigens, as well as positive ANA and antibodies to DNA. In comparison, certain other strains respond to peptide immunization with antibodies against the immunogenetic peptide, but do not develop epitope spreading and other humoral features of lupus. Dr. James now proposes in the current project to identify the genes involved in this peptide-induced lupus model, using the technique of recombinant inbred (RI) mice strains. Human homologies to murine genes will then be sought. Five specific aims are proposed. First, progenitor strains of recombinant inbred mice which do and do not develop peptide induced autoimmunity will be ascertained. The essence of this aim is to carefully identify strains of mice which do and do not develop lupus autoimmunity after immunization, with lupus autoimmunity being defined as spreading of the humoral immune response beyond the peptide of immunization to other regions of the Sm and nRNP autoantigens, as well as the development of positive ANA and anti-DNA antibodies as determined by Crithidiae immunofluorescence. These experiments are already underway with eleven different RI progenitor strains. Preliminary results from these studies suggest that both responder and non-responder strains have been identified. Second, recombinant inbred substrains, produced from a cross between a progenitor responder and non-responder, will be analyzed for evidence of peptide-induced lupus. In these experiments, the RI set derived from the progenitor strains selected in Aim 1 will be immunized with an Sm
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(spliceosomal) peptide and analyzed along with control mice. Animals will be assessed for development of lupus autoimmunity as defined in Aim 1. In the third specific aim, the murine locus (or loci) associated with peptide-induced lupus will be defined. In these experiments, RI sets will be analyzed for linkage of known markers of the affected progenitor strain that has evidence of peptide-induced lupus autoimmunity and/or clinical symptoms. These analyses will be accomplished using a computer program, MapManager V.2.5. Linkage will be determined by Chi square analysis using confidence intervals of p
