Systemic Lupus Erythematosus, Fourth Edition (SYSTEMIC LUPUS ERYTHEMATOSUS)

1316 Pages·2004·38.67 MB·English

by  Robert G. Lahita

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LIST OF CONTRIBUTORS
Numbers in parentheses indicate the chapter numbers of the authors’ contribution.
GYÖRGY ÁBEL (6), Clinical Immunology Laboratory, DIMITRI BOUMPAS (30),National Institutes of Health,
Lahey Clinic Medical Center,Burlington,Massachu- Bethesda,Maryland 20892-1818.
setts 01805-0001.
ROBINL.BREY(26),Department of Medicine,Division
VINCENT AGNELLO (6), Department of Immunology of Neurology, University of Texas Health Science
Research,Lahey Clinic Medical Center,Edith Norse Center,San Antonio,Texas 78229.
Rogers Memorial Veterans Affairs Hospital,Burling-
JILL BUYON (17),Department of Rheumatology,Hos-
ton,Massachusetts 01805-0001.
pital for Joint Diseases,New York,New York 10003
DONATO ALARCÓN-SEGOVIA (3), National Auto-
EDWARDK.L.CHAN(13),Department of Oral Biology,
nomous University of Mexico, Department of
University of Florida College of Dentistry,
Immunology and Rheumatology, Instituto Nacional
Gainesville,Florida 32610–0424.
de Ciencias Médicas y Nutrición Salvador Zubirán,
14000 Mexico,D.F. RICARD CERVERA (41), Department of Autoimmune
Diseases,Hospital Clinic,08036 Barcelona,Catalonia,
MARTA E. ALARCÓN-RIQUELME (3), Department of
Spain.
Genetics and Pathology, Rudbeck Laboratories,
Uppsala University,Uppsala,Sweden. WENDY S.COHEN (27),School of Medicine,New York
University,New York,New York 10016.
HOWARD AMITAL (1), Center for Autoimmune Dis-
eases and Department of Medicine “B,” Affliated JOHN C. DAVIS (47), Clinical Trials Center, Lupus
with Sackler Faculty of Medicine, Sheba Medical Clinic,San Francisco,California 94143.
Center, Tel-Aviv University, Tel-Hashomer 52621,
Israel. CRAIG J. DELLA VALLE (37), Department of
Orthopaedic Surgery,Rush-Presbyterian-St.Lu8ke’s
RONALD A. ASHERSON (41), Rheumatic Diseases Medical Center,Chicago,Illinois 60612.
Unit, Department of Medicine, University of Cape
town School of Medicine, Cape Town 8001, South PAUL J.DEMARCO (18),Department of Psychological
and Brain Sciences, University of Louisville,
Africa.
Lousville,Kentucky 40292.
JOHNP.ATKINSON(5),School of Medicine,Washington
JUDAH A. DENBURG (28), Department of Psychiatry
University,St.Louis,Missouri 63110.
and Behavioural neurosciences, McMaster Univer-
TATSUYA ATSUMI (39), Department of Medicine II, sity,Hamilton,Ontario L8N 3Z5,Canada.
School of Medicine, Hokkaido University, Sapporo
SUSAN D. DENBURG (28), Department of Psychiatry
060-8638,Japan.
and Behavioural neurosciences, McMaster Univer-
HOWARDA.AUSTIN(30),National Institutes of Health, sity,Hamilton,Ontario L8N 3Z5,Canada.
Bethesda,Maryland 20892-1818.
BETTY DIAMOND (10), Albert Einstein College of
ROBERTO BACCALA (8), Centre Hospitalier Universi- Medicine,Bronx,New York 10461.
taire Vaudois,Lausanne,Switzerland.
PAUL E. DICESARE (37), Department of Orthopaedic
JAMES E. BALOW (30), National Institutes of Health, Surgery,Hospital for Joint Diseases,New York Uni-
Bethesda,Maryland 20892-1818. versity,New York,New York 10003.
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List of Contributors xxiii
IRIS DOTAN (34), Division of Clinical Immunology, LYNNELAROCQUE(28),department of Psychiatry and
Mount Sinai Medical Center, New York, New York Behavioural Neurosciences, McMaster University,
10029-6574. Hamilton,Ontario L8N 3Z5,Canada.
BARRI FESSLER (32),Division of Clinical Immunology JAMES L. LEVENSON (27),Liaison Psychiatry,Medical
and Rheumatology,University of Alabama,Birming- College of Virginia,Virginia Commonwealth Univer-
ham,Alabama 35294. sity,Richmond,Virginia 23298.
MARTIN J. FRITZLER (13), University of Calgary, JEFFREY LAURENCE (36), Weill Medical College,
Calgary ALB T2N 4N1,Canada. Cornell University,New York,New York 10021.
DAFNA D. GLADMAN (23), Centre for Prognosis E. CLINTON LAWRENCE (33), McKelvey Lung
Studies in the Rheumatic Diseases,Toronto Western Transplantation Center, School of Medicine, Emory
Hospital,Toronto,Ontario M5T 2S8,Canada. University,Atlanta,Georgia 30322.
OSCAR S. GLUCK (38), Department of Medicine, MATTHEW LIANG (20), Department of Medicine/
College of Medicine and Arizona Rheumatology Rheumatology/Immunology/PBB-B2, Brigham and
Center,Phoenix,Arizona. Women’s Hospital,Boston,Massachusetts 02115.
RICHARD E. W. HALLIWELL (9), Veterinary Field MICHAEL D. LOCKSHIN (22), Barbara Volker Center,
Station, University of Edinburgh, Easter Bush, Hospital for Special Surgery, Weill-Cornell Medical
Rosling,Midlothian EH25 9RG,Scotland. College,New York,New York 10021.
EVELYN V. HESS (45), Division of Immunology, Uni- LISA A. MANDL (20), Department of Medicine,
versity of Cincinnati Medical Center, Cincinnati, Weill Cornell Medical College, Hospital for Special
Ohio 45221. Surgery,New York,New York 10021.
GARYS.HOFFMAN(32),Department of Rheumatic and MART MANNIK (14), Department of Medicine, Uni-
Immunologic Diseases,Cleveland Clinic Foundation, versity of Washington, Seattle, Washington
Cleveland,Ohio 44195. 98195.
ROBERTW.HOFFMAN(24),Division of Rheumatology MICHAEL J. MARICIC (38), University of Arizona,
and Immunology, University of Miami, Miami, Southern V.A.Health Care System,Tucson,Arizona
Florida 33101. 85723.
GRAHAM R. V. HUGHES (40), Lupus Research Unit, EIJI MATSUURA (39), Department of Cell Chemistry,
Department of Rheumatology, Rayne Institute, St. Graduate School of Medicine and Dentistry,
Thomas Hospital,London SE1 7EH,England. Okayama University,Okayama,Japan.
MUNTHER A. KHAMASHTA (40), Lupus Research LLOYD MAYER (34),Division of Clinical Immunology,
Unit, Department of Rheumatology, Rayne Mount Sinai Medical Center, New York, New York
Institute, St. Thomas Hospital, London SE1 7EH, 10029-6574.
England.
IANR.MACKAY(35),Department of Biochemistry and
JOHN KLIPPEL (47), NIAMS, Arthritis Foundation, Molecular Biology,Monash University,Clayton 3800,
Atlanta,Georgia 30309. Victoria,Australia.
ROBERT P. KIMBERLY (46), Division of Clinical JOAN T. MERRILL (43), Clinical Pharmacology
Immunology and Rheumatology, University of Research Program, Oklahoma Medical Research
Alabama,Birmingham,Alabama 35294. Foundation,Oklahoma City,Oklahoma 73104.
TAKAOKOIKE(39),Department of Medicine II,School DANIELMIMOUNI(29),Division of Dermatoimmunol-
of Medicine,Hokkaido University,Sapporo 060-8638, ogy, Johns Hopkins Hospital, Baltimore, Maryland
Japan. 21205.
DWIGHT H. KONO (8), Department of Immunology, ANNE-BARBARA MONGEY (45),Division of Immunol-
Scripps Research Institute,La Jolla,California 92037. ogy,University of Cincinnati Medical Center,Cincin-
nati,Ohio 45267.
ROBERT G. LAHITA (7, 16), Department of Medicine
and Rheumatology, LibertyHealth, Jersey City, New CARLOS H. NOUSARI (29), Department of Dermatol-
Jersey 07304. ogy,Cleveland Clinic Florida,Weston,Florida 33326.
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xxiv List of Contributors
ELENA PEEVA (10),Albert Einstein College of Medi- JOSEPH C. SHANAHAN (46), Division of Clinical
cine,Bronx,New York 10461. Immunology and Rheumatology, University of
Alabama,Birmingham,Alabama 35294-0007.
MICHELLE PETRI (31), School of Medicine, Johns
Hopkins University,Baltimore,Maryland 21205. LORRAINE G.SHAPEERO (19),Department of Muscu-
loskeletal Radiology,Bone and Soft Tissue Program,
WESLEY H. REEVES (15), Division of Rheumatology U.S. Military Cancer Institute, Uniformed Services
and Clinical Immunology, University of Florida,
University,Bethesda,Maryland 20814.
Gainesville,Florida 32610.
SANDOR S. SHAPIRO (42), Cardeza Foundation for
MORRIS REICHLIN (11), Arthritis/Immunology Hematologic Research, Jefferson Medical College,
Program, Oklahoma Medical Research Foundation,
Thomas Jefferson University, Philadelphia, Pennsyl-
Department of Medicine, Oklahoma University
vania 19107.
Health Sciences Center, Oklahma City, Oklahoma
73104. YEHUDA SHOENFELD (1), Department of Medicine,
Concepts of Autoimmunity, Sheba Medical Center,
KARENE.RENDT(32),Department of Rheumatic and Tel-Aviv University,Tel-Hashomer 52621,Israel.
Immunologic Diseases,Cleveland Clinic Foundation,
Cleveland,Ohio 44195. RONIT SIMANTOV (36),Weill Medical College,Cornell
University,New York,New York 10021.
JOHND.REVEILLE(4),Department of Rheumatology,
University of Texas at Houston, Health Science STEPHENE.F.SPURGEON(42),Cardeza Foundation for
Hematologic Research, Jefferson Medical College,
Center,Houston,Texas 77225.
Thomas Jefferson University, Philadelphia, Pennsyl-
HANNO B.RICHARDS (15),Division of Rheumatology vania 19107.
and Clinical Immunology, University of Florida,
ILONASZER(18),Division of Rheumatology,Children’s
Gainesville,Florida 32610.
Hospital of San Diego,San Diego,California 92123.
W. NEAL ROBERTS (27), School of Medicine, Medical
ARGYRIOS N. THEOFILOPOULOS (8), Department of
College of Virginia,Virginia Commonwealth Univer-
Immunology, Scripps Research Institute, La Jolla,
sity,Richmond,Virginia 23298.
California 92037.
GARCIA-CAVAZOS ROGELIO (26), Department of
GEORGEC.TSOKOS(2),Department of Medicine Uni-
Medicine,University of Texas Health Science Center,
formed Services, University of the Health Sciences,
San Antonio,Texas 78229.
Bethesda,Maryland 20814.
ROBERT L. RUBIN (12), Department of Molecular MURRAY UROWITZ (Foreword), Department of
Genetics and Microbiology,School of Medicine,Uni-
Medicine, University of Toronto Hospital, Toronto,
versity of New Mexico, Albuquerque, New Mexico
Ontario M5T2S8,Canada.
87131.
RONALD F. VAN VOLLENHOVEN (48), Rheumatology
LISA R. SAMMARITANO (22), Barbara Volker Center, Unit, Karolinska Hospital and Institute, Stockholm,
Hospital for Special Surgery, Weill-Cornell Medical
Sweden.
College,New York,New York 10021.
MARK H. WENER (14), Department of Laboratory
MINORU SATOH (15), Division of Rheumatology Medicine, Division of Rheumatology, University of
and Clincal Immunolgoy, University of Florida, Washington,Seattle,Washington 98195.
Gainesville,Florida 32610.
JOHN B. WINFIELD (25), Department of Medicine,
PETERM.SCHNEIDER(5),Institute of Legal Medicine, University of North Carolina, Chapel Hill, North
University of Mainz,Mainz,Germany D55131. Carolina 27599.
PETER H. SCHUR (21), Harvard Medical School, RAYMOND L. YUNG (44), Department of Medicine,
Department of Rheumatology, Brigham and University of Michigan, Ann Arbor, Michigan
Women’s Hospital,Boston,Massachusetts 02115. 48109.
SERGIO SCHWARTZMAN (22), Barbara Volker Center, JOSEPHD.ZUCKERMAN(37),Department of Orthope-
Hospital for Special Surgery, Weill-Cornell Medical dic Surgery, Hospital for Joint Disease, New York,
College,New York,New York 10021. New York 10003.
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FOREWORD
“One small step for man...” Neal Armstrong’s tive dysfunction, osteoporosis/osteonecrosis, and
intended first utterance when he stepped onto the antiphospholipid antibody syndrome. The inten-
surface of the moon on July 20, 1969 can indeed sive investigations of these new features in lupus
be the motto of every researcher and clinician will give insights into their underlying mechanisms
involved in the investigation of systemic lupus in people in the general population with athero-
erythematosus, which also blossomed in the late sclerosis, dementia, osteoporosis, and clotting dis-
1960s.Each can point to their contribution as one orders.However,the etiology section of the puzzle
small piece of the puzzle in the understanding of still continues to elude us.Although investigations
the etiology, pathogenesis, clinical presentation in many laboratories and clinics around the world
and treatment of lupus. In the last three decades continue to probe the genome, no clear under-
the puzzle has indeed begun to take shape! standing of susceptibility genes or disease expres-
The immune system abnormalities and their sion genes has yet emerged.Similarly,the putative
pathogeneic consequences have been extensively viral or hormonal etiologic factors remain elusive.
elaborated and are now serving as guides for the Systemic Lupus Erythematosus, Fourth Edition,
development of new therapies. Prognosis has brings together the many pieces of the lupus puzzle
improved dramatically from less than 50% at 5 to allow the researcher, clinician, teacher, and
years in the 1950s to 70% at 20 years today. student to begin to see the puzzle coming together.
Quality of life has also improved as we learn to Researchers,physicians,and patients look forward
modulate our therapies more appropriately.At the to the day when the puzzle will come together as
same time,new clinical presentations have come to a clear picture...“one giant leap for mankind.”
the forefront, either as unrecognized features of
the disease itself or as a consequence of our ther- Murray Urowitz,MD
apies,including accelerated atherosclerosis,cogni- University of Toronto
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PREFACE
A book about the disease systemic lupus ery- who take the findings at the patient’s bedside and
thematosus (SLE) has to be remarkable. As we bring it to the laboratory in order to understand.
have heard many times, patients who acquire this Wherever possible, I have taken the progeny of
illness are young,in the prime of life,surprised,and the many investigators who passed through the
often diagnosed on average of five years after their Kunkel laboratory and included their work
first symptoms.Moreover,this is a deadly disease, between these covers. Dr. Kunkel wrote the first
even though patients look well. More and more Foreword for this book and encouraged me to
people develop related autoimmune diseases like include as much science as possible in the first
lupus,and the disease shares many clinical charac- edition. The inclusion of science continues. Eng
teristics with these other maladies. In fact, I will Tan, Graham Hughes, and now Murray Urowitz
reiterate the notion held by some that SLE is more followed Dr. Kunkel’s tradition and wrote fore-
than one illness.This notion is likely based on the words for the next three editions. Dr. Urowitz,
varied presentation, organ selectivity, and waxing author of the current Foreword, is the director of
severity even after therapy is complete. Under- the successful Toronto Center for Lupus Research
standing this complexity, this book is designed to and is a guiding force in the current thinking of the
explore both the clinical and basic aspects of science of SLE.
immunology as it applies to lupus. The book is Many authors from the last edition have revised
divided into sections, which deal with the basic their chapters, and much new material has been
immunology, the overall clinical presentations, added.By necessity,overlap has occurred in some
system analysis, and then treatment options. of the chapters. Purposefully, Some material is
However, it is not that easy, since conditions like presented in different ways in different chapters.
fibromyalgia and the antiphospholipid syndrome Some newer additions to the book include George
have to be included.I have attempted to make the Tsokos, who covers the molecular aspects of
division of sections and the grouping of chapters cellular immunology as it applies to lupus in great
logical and easy to follow. detail. James Levenson and colleagues chapter on
It is a book directed to both the student of the psychiatry of SLE,which places some perspec-
immunology and the experienced clinician. In tive on the variant forms of behavior that can occur
addition, it is a book that includes work by some either because of the effects lupus has on a patient
of the most experienced clinicians and researchers due to the severity of the illness or the actual
among us.Each chapter is a compelling treatment production of psychosis by the effects of the
of a specific area in exhaustive detail, and the immune dysfunction on the brain.Robin Brey and
authors of these detailed chapters have taken colleagues present the latest information on all
great time to write for this book.For them we are aspects of the nervous system and lupus,a particu-
grateful. larly challenging area. Carlos H. Nousari, De-
This fourth edition of Systemic Lupus Erythe- partment of Dermatology, Cleveland Clinic
matosus, a book born at the Rockefeller Univer- Florida,details the dermatologic aspects of lupus,a
sity in the laboratory of the late Professor Henry system that was studied at Johns Hopkins by
G.Kunkel,serves as a testimony to his dedication William Osler more than 100 years ago. John
and work in immunology.It is an inspiration for all Winfield, in a new chapter, carefully dissects
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xxviii Preface
fibromyalgia in association with SLE.Finally,Oscar of an eventual cure.I salute the patients and their
Gluck presents osteoporosis and lupus in a chapter families for their efforts on behalf of our knowl-
that covers both the steroid-treated patient and the edge. I hope that the accuracy of the information
effects of natural loss of bone in a patient with a given here in this book will educate and inform
chronic disease. until the fifth edition comes forward. It is always
Lupus is a complex illness that often requires a the hope of this editor that subsequent editions
physician’s considerable time and effort. It is not might include both the cause and cure of this dev-
an easy disease to diagnose or manage.This book astating illness.
is written as an aid to help the physician under- Finally, I thank my publisher Elsevier for its
stand the subtle nuances of this enigma and use patience and high standards of excellence and ded-
knowledge herein to manage the patient. It is ication to helping the sick. I specifically note my
written with the idea that new knowledge is developmental editors Tari Paschall and Judy
urgently needed to diagnose and treat those Meyer for sticking with the project and enduring
patients for whom this illness is nothing short of a my many letters, telephone calls, and emails
major catastrophe—a life emergency that deserves regarding the authors and their materials included
all our efforts and attention. in the book.
Numerous worldwide groups of patients dedi-
cate their time and effort to social programs and Robert G.Lahita
funding of basic and clinical research,in the hope Jersey City,N.J.,2003
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INTRODUCTION
OVERVIEW because the immune system seems to become
more complex by the year. In this fourth edition,
As I have noted in previous editions of this the issues remain the same for clinicians and inves-
work,systemic lupus erythematosus (SLE),known tigators.Reading the chapters in this book will not
to the public as lupus, is not a rare disease, but it solve the mystery, but it will give you the impres-
is not common either. It is a chronic disease of sion that we are closer to understanding the illness.
unknown etiology that is very difficult to diagnose, Most importantly,you will understand the disease
not easy to treat, and yet sometimes over diag- better. The newer association of fibromyalgia
nosed. Since the last edition of this book, major and phospholipid antibody with this illness and
advances have been noted in the treatment of ill- the presence of cognitive disability apart from any
nesses like rheumatoid arthritis using biological gross neurological findings would seem to indicate
therapy but still nothing that is able to completely the lupus is also evolving as time goes on. The
reverse the ravages of a autoimmune diseases like limited numbers of drugs available to treat lupus
lupus. This absence of therapeutic agents is the despite years of research speak for the difficulty
subject of discussion by a host of groups estab- the scientific community has with understanding
lished to look at criteria for diagnosis,biomarkers the biology of lupus.
of severity,and instruments of clinical activity.The In this fourth edition, we have revised every
establishment of clear indices that would allow chapter. It includes new chapters on fibromyalgia
regulatory agencies to see some consistency of and certain aspects of treatment. New authors
response is lacking because lupus is a disease that write older topics like the dermatology of lupus.
often does not respond to either therapy or con- Older chapters such as the imaging of lupus are
ventional wisdom. considerably enhanced with a thorough discussion
I am unsure that lupus is really only one illness, of the current and future roles of the different
and that may be one of the difficulties.I am more modalities for imaging each organ system of
convinced that lupus is a series of illnesses that has, patients with SLE.The section on the overview of
as its basis, an autoimmune response that devas- the cellular and molecular aspects of lupus is prob-
tates the whole body or destroys a single organ.Its ably the most comprehensive treatment of this
classification and drugs for treatment might be area in print.The central nervous system and psy-
better designed if it were a simple organ-specific chiatric aspects of lupus are written by new authors
entity that had consistency of presentation. and are new and exciting. Apart from books
This protean illness presents in a variety of ways. dealing solely with the antiphospholipid syndrome,
It really depends on the organ chosen by the there is no better discussion of this topic and all of
immune system for attack.The diagnostic difficulty the aspects of the syndrome from clinical presen-
revolves around the standard issues surrounding tation to theories about pathogenesis.All in all,the
all illnesses,namely,the factors associated with the book is enhanced in all areas to provide the reader
disease.This disease favors women, has a genetic with the latest information about SLE,its science,
association, and has an elusive trigger. Although presentation,and treatment.
we get closer to a cause by looking at many dif- We have also produced a CD-ROM of the illus-
ferent possibilities,the problem is not easily solved trations in this book in hopes that you might use it
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xxx Introduction
to teach students and young physicians who may was not until the 1920s and 30s that the disease was
delight in a new frontier in medicine.Lupus gives well defined.The disease,at that time,was carefully
us a handle on molecular biology, insight into described by pathologists who studied the morbid
common ailments like atherosclerosis,and a better anatomic changes that so characterized someone
understanding of the way the brain works. I have with lupus. The atypical bacterial endocarditis of
said before that it is a disease of the twenty- Emmanuel Libman and Benjamin Sacks,described
first century, and this book is testimony to that in 1924, was a classic example of the pathology
statement. found in some patients with SLE and were likely
lesions associated with antiphospholipid antibody
(7). Following that description, George Baehr,
HISTORY OF LUPUS published a series of 23 autopsied cases of the renal
wire loop lesions of lupus nephritis and described
The history of the disease SLE is colorful.The the solar sensitivity we know so well.Thus,pathol-
term lupus is attributed to the thirteenth century ogists further elucidated the disease known as
physician Rogerius, who described the facial lupus.In 1936 Frieberg,Gross and Wallach autop-
lesions that were reminiscent of a “wolf’s bite”(1). sied a young woman with lupus and no skin lesions,
In 1851, Cazenave applied the term lupus erythe- indicating that the disease was not primarily a skin
matosusfor the first time to a disease described by condition and was even less associated with tuber-
his teacher Laurent Biett (2).In 1845,von Hebra, culosis. Klempner, Pollack, and Baehr in 1941
a Viennese physician, used butterfly rash to suggested that collagen was a part of the disease
describe the familiar malar rash of the disease.For because of the many instances of fibrinoid necro-
most of the nineteenth century,lupus was thought sis that they found with the disease.This gave rise
to be a dermatologic disease. Von Hebra, in his to the name collagen disease as a grouping for all
1856 book, published the first illustrations of the of the diseases that affected connective tissue, a
disease in the Atlas of Skin Diseases. However, term that is not used widely today.
when Moretz Kaposi described the visceral forms Hack and Reinhart were the first to describe the
of the disease in 1872,physicians began to suspect false-positive syphilis test in SLE,and in 1940 Keil
that this disease was a more generalized form of similarly reported ten cases of SLE with false-pos-
the illness and the term acute disseminated was itive syphilis tests.Haserick and Lang wrote about
included in the description (3). Kaposi proposed an additional series of cases where the presence of
two types of lupus:disseminated and discoid.In his the false-positive syphilis serology predated the
early writings, he supposed that the disseminated clinical lupus by up to eight years. In all of these
form consisted of (1) subcutaneous nodules, (2) cases, the false-positive syphilis tests probably
arthritis, (3) lymphadenopathy, (4) fever, (5) resulted from the presence of antiphospholipid
weight loss, (6) anemia, and (7) central nervous antibodies, the discovery of which was to take an
system involvement. In 1904, William Osler additional 30 years. In 1955, Moore (8) studied
described two women who developed renal failure another 148 patients who were positive for syphilis
within 10 months of the appearance of a facial ery- and found that some 7% developed lupus with
thema, which in retrospect was the facial rash of time,whereas 30% had symptoms relegated to col-
von Hebra (4).Osler described a number of other lagen vascular disease. In 1949, Phillip Hench (9)
illnesses at the time,among them,Henoch Schoen- discovered cortisone, and the future of the con-
lein purpura and disseminated gonococcemia, nective tissue diseases changed. Rheumatoid
which could be confused with the lesions on the arthritis patients and those with lupus erythe-
two women. In Vienna at this time, Jedasson matosus (LE) were manageable,and “cures”were
described similar syndromes in a few patients.Both reported.
he and Osler therefore established SLE as a dis- In 1948 Hargraves, Richmond, and Morton
tinct entity by the turn of the century,even though described the LE cell in the bone marrow of SLE
many practitioners still thought of SLE as a form patients (10).The test was later adapted to periph-
of skin tuberculosis (5).Very typical cases of SLE eral blood.This discovery laid the foundation for
were reported under a variety of names (6),and it our confirmation of the disease lupus as an autoim-
SLEPR 2/11/04 8:24 PM Page xxxi
Introduction xxxi
mune disease.These were phagocytes eating cells nature of lupus, something studied later by
coated with autoantibody.Until it was described in Shulman and Arnett at Hopkins (17) and more
other illnesses like rheumatoid arthritis (RA), it deeply by Hahn, Harley, and others in recent
was thought to be pathognomonic of lupus.Dubois years (18).Such studies allowed for the description
in 1953 and Harvey in 1954 (11, 12) sought to set of large multiplex families, identical twins, and
the record straight by stressing the chronicity of again the application of these studies to molecular
SLE and stressed the diagnostic importance of the biology. From this came our knowledge of the
LE test.However,its presence in only 50% to 70% role of the MHC class II and III in lupus and
of lupus cases made it a useful adjunct to the diag- other related illnesses, work which goes forward
nosis of SLE,but the discovery later of more sen- today.
sitive and more specific tests made its use limited. Finally, the work of Hughes, Harris, Gharavi,
Meanwhile, other serum abnormalities such as Asherson, and Alarcón-Segovia (19) to name a
hypergammaglobulinemia, detected in newly dis- few opened the door to our understanding of
covered techniques like immunoelectrophoresis, the antiphospholipid antibody as an important
suggested that gamma globulins were present in aspect of lupus.The frequency of this unusual syn-
great numbers that behaved like antibodies that drome, which can be secondary to SLE, is one
reacted with normal tissues.These were later called of great curiosity and the subject of intensive
autoantibodies. George Friou in 1957 (13) applied research much as the early studies of autoantibody
the indirect immunofluorescent test of Coons to were. The role of these antibodies in lipid
the study of these autoantibodies.The fluorescent metabolism and biological processes such as ath-
antinuclear antibody test (FANA) is positive in erosclerosis again places lupus in the knowledge
some 95% to 98% of SLE cases. At about the “revolution”and makes this global scourge known
time of the Friou discovery, Deicher, Holman, as SLE relevant to the most common causes of
and Kunkel (14), along with three other groups, morbidity and mortality, something that the early
described antibodies to DNA. In 1956, Eng Tan researchers found implicit in the urgency of their
and Henry Kunkel described an antibody to a gly- work.
coprotein called SM after the first two initials of This brief history of lupus does not give justice
the patient’s name,Smith (15).This was a practice to the countless investigators who make history
that would follow over many years after for several every day with small steps. In this book, you will
new antibodies.Although present in only 30% of find that many of the historical discoveries that
patients with lupus, this antibody would be one provided data and added terms to our immuno-
of the few that is found with relative specificity logical lexicon are discussed within the cover of
to SLE. this book in great detail. Moreover, the academic
Many more antibodies were described after the progeny of those who I mention previously are
findings of the antiDNA and the antiSM.Among those who write about lupus and this disease as
these were the discovery of Gordon Sharp of an it applies to modern medicine. I am among those
overlap syndrome characterized by high titers of progeny. We write with humility and eloquence,
anti ribonucleoprotein antibody, a syndrome that since our knowledge of lupus and all of medical
we now call mixed connective tissue disease science is very young and evolving for the good of
(MCTD). Moreover the discovery of countless all humanity.
autoantibodies to cellular components such as the
signal proteins of the nucleus, high molecular Robert G.Lahita
group proteins, and others have in large part Jersey City,N.J.,2003
helped the foment revolution in molecular biology
by providing reagents with which to study cell
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