History of Lupus, brief overview

What is the history of Lupus

https://resources.lupus.org/entry/history-of-lupus

The history of lupus can be divided into three periods: classical, neoclassical, and modern. This article concentrates on developments in the present century which have greatly expanded our knowledge about the pathophysiology, clinical-laboratory features, and treatment of this disorder.

Lupus in the classical period (1230-1856)

The history of lupus during the classical period was reviewed by Smith and Cyr in 1988. Of note are the derivation of the term lupus and the clinical descriptions of the cutaneous lesions of lupus vulgaris, lupus profundus, discoid lupus, and the photosensitive nature of the malar or butterfly rash.

The word ‘lupus’ (Latin for ‘wolf’) is attributed to the thirteenth century physician Rogerius who used it to describe erosive facial lesions that were reminiscent of a wolf's bite. Classical descriptions of the various dermatologic features of lupus were made by Thomas Bateman, a student of the British dermatologist Robert William, in the early nineteenth century; Cazenave, a student of the French dermatologist Laurent Biett, in the mid-nineteenth century; and Moriz Kaposi (born Moriz Kohn), student and son-in-law of the Austrian dermatologist Ferdinand von Hebra, in the late nineteenth century.

The lesions now referred to as discoid lupus were described in 1833 by Cazenave under the term “erythema centrifugum,” while the butterfly distribution of the facial rash was noted by von Hebra in 1846. The first published illustrations of lupus erythematosus were included in von Hebra's text, Atlas of Skin Diseases, published in 1856.

1872Systemic lupus identified as distinct from cutaneous lupus.

The Neoclassical era of the history of lupus began in 1872 when Kaposi first described the systemic nature of the disorder: “...experience has shown that lupus erythematosus ... may be attended by altogether more severe pathological changes, and even dangerous constitutional symptoms may be intimately associated with the process in question, and that death may result from conditions which must be considered to arise from the local malady.”

Kaposi proposed that there were two types of lupus erythematosus; the discoid form and a disseminated (systemic) form. Furthermore, he enumerated various signs and symptoms which characterized the systemic form, including: 

subcutaneous nodules

arthritis with synovial hypertrophy of both small and large joints

lymphadenopathy

fever

weight loss

anemia

central nervous system involvement

The existence of a systemic form of lupus was firmly established in 1904 by the work of Osler in Baltimore and Jadassohn in Vienna. Over the next thirty years, pathologic studies documented the existence of nonbacterial verrucous endocarditis (Libman-Sacks disease) and wire-loop lesions in individuals with glomerulonephritis; such observations at the autopsy table led to the construct of collagen disease proposed by Kemperer and colleagues in 1941. This terminology, ‘collagen vascular disease,’ persists in usage more than seventy years after its introduction.

Lupus in the modern era (1948-present)

The sentinel event which heralded the modern era was the discovery of the LE cell by Hargraves and colleagues in 1948. The investigators observed these cells in the bone marrow of individuals with acute disseminated lupus erythematosus and postulated that the cell “...is the result of...phagocytosis of free nuclear material with a resulting round vacuole containing this partially digested and lysed nuclear material...”.

1948The Lupus Erythematosus cell is discovered.

This discovery ushered in the present era of the application of immunology to the study of lupus erythematosus; it also allowed the diagnosis of individuals with much milder forms of the disease. This possibility, coupled with the discovery of cortisone as a treatment, changed the natural history of lupus as it was known prior to that time.

Two other immunologic markers were recognized in the 1950s as being associated with lupus: the biologic false-positive test for syphilis and the immunofluorescent test for antinuclear antibodies. Moore, working in Baltimore, demonstrated that systemic lupus developed in 7 percent of 148 individuals with chronic false-positive tests for syphilis and that a further 30 percent had symptoms consistent with collagen disease. 

Friou applied the technique of indirect immunofluorescence to demonstrate the presence of antinuclear antibodies in the blood of individuals with systemic lupus. Subsequently, there was the recognition of antibodies to deoxyribonucleic acid (DNA) and the description of antibodies to extractable nuclear antigens (nuclear ribonucleoprotein [nRNP], Sm, Ro, La), and anticardiolipin antibodies; these autoantibodies are useful in describing clinical subsets and understanding the etiopathogenesis of lupus.

First animal model developed

Two other major advances in the modern era have been the development of animal models of lupus and the recognition of the role of genetic predisposition to the development of lupus. The first animal model of systemic lupus was the F1 hybrid New Zealand Black/New Zealand White mouse. 

This murine (mouse) model has provided many insights into the immunopathogenesis of autoantibody formation, mechanisms of immunologic tolerance, the development of glomerulonephritis, the role of sex hormones in modulating the course of disease, and evaluation of treatments including recently developed biologic agents such as anti-CD4, among others. 

Other animal models that have been used to study systemic lupus include the BXSB and MRL/lpr mice, and the naturally occurring syndrome of lupus in dogs.   

Genetic component recognized  

The familial occurrence of systemic lupus was first noted by Leonhardt in 1954 and later studies by Arnett and Shulman at Johns Hopkins. Subsequently, familial aggregation of lupus, the concordance of lupus in monozygotic twin pairs, and the association of genetic markers with lupus have been described over the past twenty years. 

1954It is discovered that there is a genetic component to lupus.

Molecular biology techniques have been applied to the study of human lymphocyte antigen (HLA) Class II genes to determine specific amino acid sequences in these cell surface molecules that are involved in antigen presentation to T-helper cells in individuals with lupus. These studies have resulted in the identification of genetic-serologic subsets of systemic lupus that complement the clinico-serologic subsets noted earlier. 

It is hoped by investigators working in this field that these studies will lead to the identification of etiologic factors (e.g., viral antigens/proteins) in lupus.

Over the last decade or so, we have witnessed significant advances in the understanding of the genetic basis of lupus, and of the immunological derangements which lead to the clinical manifestations of the disease. 

Advances have been made in the assessment of the impact of the disease in general, and in minority population groups, in particular and efforts are being made towards defining lupus biomarkers which may help both to predict disease outcome and to guide treatments.

Lupus therapies then and now 

Finally, no discussion of the history of lupus is complete without a review of the development of therapy. Payne, in 1894, first reported the usefulness of quinine in the treatment of lupus. Four years later, the use of salicylates in conjunction with quinine was also noted to be of benefit. 

1950Nobel Prize awarded to scientists who discover the effects of corticosteroids.

Cortisone/corticosteroids were introduced for the treatment of lupus in the middle part of the 20th century by Hench. Presently, corticosteroids are the primary therapy for almost all individuals with lupus.

Antimalarials, used in the past principally for lupus skin and joint involvement, are now recognized to prevent the occurrence of flares, the accumulation of damage, and the occurrence of early mortality. 

Cytotoxic/immunosuppressive drugs are used for glomerulonephritis, systemic vasculitis, and other severe life-threatening manifestations of lupus. Newer biologic agents are now used, either off-label or after approval by regulatory agencies in the U.S., Europe, and other countries. 

Other potential drug products are being investigated as new disease pathways are being discovered.

http://www.lupus.org.uk/what-is-lupus/history-of-lupus

Lupus in the 20th Century
In the 1920s and 30s work began on defining a pathological (disease-oriented) description of Lupus. A major breakthrough came in 1941 when pathologists at the Mount Sinai Hospital in New York City wrote detailed pathological descriptions of lupus. Dr Paul Klemperer and his colleagues coined the term "collagen disease", which led ultimately to our modern classification of lupus as an autoimmune disorder.

In 1946 Dr Malcolm Hargraves, a pathologist from the renowned Mayo clinic published a description of the lupus erythematosus or LE cell. This important development identified the systemic inflammatory part of the disease, and allowed doctors to diagnose the disease faster and with greater reliability.

Dr Philip HenchIn 1949, also at the Mayo Clinic, physician Dr Philip Hench demonstrated that a newly discovered hormone called cortisone that could treat rheumatoid arthritis. Cortisone was used to treat SLE patients and immediately showed a dramatic ability to save lives.

In the 1950s the LE cell was shown to be part of the ANA (antinuclear antibody) reaction. This led directly to the development of a series of tests for antibodies, which allowed   doctors and researchers to identify and define the disease in a more rigorous way. These are the so called 'fluorescent tests', which detect the antibodies that attack the nucleus of cells - the ANA.

Further research on antibodies established that the blood of lupus patients have other antibodies present. Some of these were found to bind to the DNA itself (DNA is the unique strand of proteins that are the 'blueprint' which the body uses to build and maintain itself). This ultimately led to a test for the anti-DNA antibodies themselves, which has proved to be one of the best tests available for diagnosing SLE. The anti-DNA test for SLE is still used widely today. There are now a wide variety of other antibody tests used in clinical practice and these are useful in subsetting  patients in order to give the best advice especially when planning pregnancy.