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xvii
xviii INTRODUCTION
(1802e1877), was the first physician to use the term pathology prior to the 1930s concerned themselves
lupus erythematosus [2, 3]. This new name evolved only with the pathologic changes and not the clinical
over many years. Biett divided Willon’s skin lesions condition of the patients. The atypical bacterial endocar-
called lupus into three categories as it appeared in the ditis of Emmanuel Libman and Benjamin Sacks,
fourth edition of their famous dermatology textbook reported in 1924, were carefully described and were
entitled Abrege Practique Des Maladies de la Peau [2]. There explained some 60 years later as a consequence of phos-
were the first, lupus qui detruit en surface (lupus which pholipid antibodies [8]. Following that description,
destroys on the surface); the second, lupus qui detruit en George Baehr published a series of 23 autopsied cases
profondeur (lupus which destroys at a depth); and third, of the renal wire loop lesions of lupus nephritis and
lupus avec hypertrophic (lupus with hypertrophy). Caze- described the solar sensitivity so well known in this
nave was responsible for producing the fourth edition disease. Knowledge of lupus pathology was evolving
of the Abrege textbook in 1851 and in that edition he in the early twentieth century. In 1936 Freiberg, Gross
identified a fourth category of the skin classification and Wallach autopsied a young woman with lupus
noting atrophy, telangiectasias, fixed erythema, and no skin lesions showing that the disease was not
adherent scaling and follicular plugging. He called this restricted to include skin lesions and not associated or
fourth category lupus erythemateux. In 1846, Ferdinand caused by tuberculosis. Klempner Pollack and
von Hebra (1816e1880), an accomplished Viennese Baehr, in 1941, suggested that collagen was a part of
physician, used “butterfly rash” or “bat wing rash” to the disease because of the many instances of fibrinoid
describe the familiar malar rash of the disease. The necrosis that they found with the disease. Thus evolved
butterfly rash was more accepted and is a term used the name collagen disease which was used for many years
today. In his 1856 book, Von Hebra published the first to describe all of the diseases involving connective
illustrations of the disease in the Atlas of Skin Diseases. tissue.
In 1872, Moretz Kaposi described the visceral forms of Hack and Reinhart were the first to describe the false-
the illness and physicians began to suspect that this positive syphilis test in SLE and, in 1940, Keil similarly
illness was more generalized than the skin and used reported ten cases of SLE with false-positive syphilis
the term acute disseminated in their descriptions [4]. tests. Haserick and Lang wrote about an additional
Kaposi proposed two types of lupus: disseminated and series of cases where the presence of the false-positive
discoid. In his writings, he supposed that the dissemi- serology predated the clinical lupus by up to 8 years.
nated form consisted of subcutaneous nodules, arthritis, In all of these cases, the false-positive syphilis tests prob-
lymphadenopathy, fever, weight loss, anemia, and ably resulted from the presence of antiphospholipid
central nervous system involvement. In 1894, Payne at antibodies, the discovery of which was to take an addi-
Saint Thomas Hospital in London suggested that there tional 30 years. In 1955, Moore studied another
was “a vascular disturbance causing hyperemia” that 148 patients who were positive for syphilis and found
could be influenced by quinine. In 1904, William Osler that some 7% developed lupus over time, whereas 30%
described two women who developed renal failure had symptoms relegated to collagen vascular disease [9].
within ten months of developing facial erythema, which In 1949, Phillip Hench discovered cortisone and the
in retrospect was the facial rash described by Von Hebra future of the connective tissue diseases changed forever
[5]. Osler described a number of other illnesses at the e rheumatoid arthritis (RA) patients and those with
time, among them Henoch Schoenlein purpura and lupus were manageable and “cures” were reported [10].
disseminated gonococcemia which could be confused In 1948, Hargraves, Richmond, and Morton described
with the lesions in the two women with lupus. In the LE cell in the bone marrow of SLE patients [11]. This
Vienna, at the same time, Jadassohn [6] described similar test was later adapted to peripheral blood. This discovery
syndromes in a few patients. Both he and Osler estab- laid the foundation for our confirmation of the disease
lished SLE as a distinct entity by the turn of the century, lupus as an autoimmune disease. These were phagocytes
even though many general practitioners still thought of eating cells coated with autoantibody. Until it was
SLE as a form of skin tuberculosis. described in other illnesses like RA, it was thought to
In 1902, Sequira and Balean of the London Hospital be pathognomonic of lupus. Dubois, in 1953, and Harvey,
published 71 cases of lupus erythematosus: 60 had in 1954 [12], sought to set the record straight by stressing
discoid and 11 had disseminated disease. The new the chronicity of SLE and recognized the diagnostic
description of acroasphyxia (Raynaud phenomenon) importance of the LE test. The presence of this finding
was a common feature. in only 50e70% of lupus patients and the rapid develop-
Typical cases of SLE were reported under a variety of ment of more specific tests of autoimmune disease
names during this period and not until the 1920s and made its use limited. Other serum abnormalities like
1930s were the cases well defined [7]. This was mainly hypergammaglobulinemia detected in newer techniques
because the pathologists who studied morbid anatomic like immunoelectrophoresis suggested that gamma
INTRODUCTION xix
globulins were abundant in the sera of lupus patients and and scientific advances until we find the cause of
these were in reality the antibodies that reacted with this disease.
normal tissues. These were later called autoantibodies.
Robert G. Lahita
George Friou, in 1957 [13], applied the indirect immuno- Newark, NJ 2010
fluorescent test of Coons to the study of these autoanti-
bodies. The fluorescent antinuclear antibody test
(FANA) is positive in some 95e98% of SLE cases. At
about the time of the Friou discovery, Deicher, Holman, References
and Kunkel at Rockefeller University [14], along with [1] C.D. Smith, M. Cyr, The History of Lupus from Hippocrates to
three other groups, described the antibodies to DNA, Osler, in: J.H. Klippel (Ed.), Rheumatic Disease Clinics of North
both double and single stranded. Thus, began one of America, Philadelphia, W.B., Saunders, Inc., 1988, pp. 1e14.
[2] P. Cazenave, H. Schedel, Abrege pratique des maladies de la
the most influential and prolific laboratories for the study
peau, Labe, Paris, 1847.
of lupus in the entire world. In 1956, Eng Tan and Kunkel [3] P.L.A. Cazanave, Lupus erythemateaux (erytheme centrifuge),
described an antibody to a glycoprotein called SM after Annales de Maladies de la peau et de la syphilis 3 (1850) 297e299.
the first initials of one of the many patients followed in [4] M.K. Kaposi, Neue Beitrage zur Keantiss des lupus eryth-
the research clinic [15]. The patient’s name was Smith ematosus, Arch Dermatol Syphilol 4 (1872) 36.
[5] W. Osler, On the visceral manifestations of the erythema group
and she was one of many patients from whom new auto-
of skin diseases, Am J Med Sci 127 (1904) 1.
antibodies were described. Following that autoantibody [6] J. Jadassohn, Lupus erythematodes. in: F. Mracek (Ed). Hanbuch
came the discovery of antibodies to ribonucleoprotein der Hautkrankheiten. Alfred Holder; 1904, pp. 298e404.
and other cellular components which later helped to [7] E.C. Reifenstein, Jr.E.C. Refifenstein, G.H. Reifenstein, Variable
dissect cell function and open the doors to molecular symptom complex of undetermined etiology with fatal
termination, Arch Int Med 63 (1939) 553.
biology.
[8] E. Libmann, B. Sacks, A hitherto undescribed form of valvular
As more and more antibodies were described, clinical and murla endocarditis, Arch Int Med 33 (1924) 701.
conditions like the overlap syndrome of mixed connec- [9] J.E. Moore, W.B. Lutz, The natural history of systemic lupus
tive tissue disease of Gordon Sharp followed. erythematosus: an approach to the study through chronic
Dixon and colleagues [16] assisted with the develop- biological false positive reactions, J Chron Dis 2 (1955) 297.
[10] P.S. Hench, The reversibility of certain rheumatic and non-
ment of many murine strains of the disease driven by
rheumatic conditions by the use of cortisone or of the pituitary
genetics of the mouse strain and sharing many of the adrenocorticotrophic hormone, Ann Int Med 36 (1952) 1.
features of the human disease. In 1954, Leonhardt [11] M.M. Hargraves, H. Richmond, R. Morton, Presentation of two
described the familial nature of lupus, later studied by bone marrow elements: The tart cell and the LE cell, Proc Staff
Schulman and Arnett at Hopkins [17] and subsequently Meet Mayo Clinic 23 (1948) 25.
[12] E.L. Dubois, The effect of the LE cell test on the clinical picture
by Hahn, Harley, and Behrens [18]. Studies provided
of systemic lupus erythematosus, Ann Int Med 38 (1953) 6.
discussions of multiplex families and twins as well as [13] G.J. Friou, Clinical applicatoin of lupus serum nucleoprotein
gender-specific inheritance and the presence of constitu- reaction using fluorescent antibody technique, J Clin Invest 36
tive MHC II and MHC III relationships. All the while, (1957) 390.
our understanding of the cellular components of the [14] H.R. Deicher, H.R. Holman, H.G. Kunkel, The precipitin reac-
tion between DNA and a serum factorin SLE, J Exp Med 109
innate and adaptive immune system as well as the fine
(1959) 97.
nuances of the various antibodies in understanding [15] E.M. Tan, H.G. Kunkel, Characteristics of a soluble nuclear
cell functions led to today’s revolution in our knowledge antigen precipitating with sera from patients with systemic
of this important illness. lupus erythematosus, J Immunol 96 (1966) 464.
Finally, the work of Hughes [19] and others opened [16] A.N. Theofilopoulos, F.J. Dixon, Murine models of systemic
lupus erythematosus, Adv Immunol 37 (1985) 269e390.
the door to our understanding of antiphospholipid anti-
[17] F.C. Arnett, L.E. Shulman, Studies in familial systemic lupus
body syndrome as an important aspect of lupus. The erythematosus, Medicine 55 (1976) 313.
frequency of this syndrome within the disease lupus is [18] J.B. Harley, A.L. Sestak, L.G. Willis, S.M. Fu, J.A. Hansen,
a great curiosity and we have given an entire section M. Reichlin, A model for disease heterogeneity in systemic
to this syndrome within the book. lupus erythematosus: relationship between histocompatibility
antigens, autoantibodies, and lymphopenia or renal disease,
No history of lupus gives credit to the countless
Arthritis Rheum 32 (1989) 826e836.
investigators who have provided data to enhance our [19] E.N. Harris, A.E. Gharavi, G.R.V. Hughes, Antiphospholipid
knowledge of the disease. The history of lupus is not antibodies, in: R. Williams (Ed.), Clinics in Rheumatic Disease,
static and there will be many more years of clinical W.B. Saunders, Philadelphia, 1985, pp. 591e609.