Elsevier

Autoimmunity Reviews

Volume 11, Issue 8, June 2012, Pages 593-595
Autoimmunity Reviews

Review
Systemic lupus erythematosus one disease or many?

https://doi.org/10.1016/j.autrev.2011.10.020Get rights and content

Abstract

Systemic lupus erythematosus (SLE) characterizes by a variety of clinical manifestations and the presence of a wide profile of autoantibodies. This clinical and serological heterogeneity raised the question: is SLE a single disease with varied phenotypes, or a similar phenotype shared by different diseases with diverse pathogenic mechanisms?

Herein we debate the clinical, genetic, hormonal and serological differences typically observed in SLE on the one hand, and the numerous similarities between subtypes of this disease on the other. Leading to the conclusion that SLE may be considered not as a single disease but rather as a single syndrome, which defines by a set of signs, symptoms, or phenomena that occur together and suggest a particular abnormality. Additionally, the accumulated knowledge on gene expression pathways, autoantibodies clusters, hormonal and environmental factors associated with SLE may allow a better classification of this syndrome and updating of SLE criteria. This may further allow targeted biologics and other therapies as well as “personalized medicine” to begin.

Introduction

Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune diseases. It characterizes by heterogeneity of clinical manifestations, degrees of severity as well as alternating phases of remission and flares [1]. In the course of SLE, patients may present with arthritis, rashes, serositis, various cytopenias, kidney disease, psychiatric, neurological and other manifestations [2]. This multi systemic disease can be predicted by the presence of specific autoantibodies years before it is clinically overt [3], [4]. In addition several autoantibodies and cluster of autoantibodies were noticeably associated not only with the occurrence of the disease but also with its specific manifestations [5].

The great heterogeneity of SLE raised the debate is it a single disease with varied phenotypes, or a similar phenotype shared by a variety of different diseases with diverse pathogenic mechanisms?

One aspect of this debate is the intimate link between SLE and the antiphospholipid syndrome (APS), primarily described by Graham Hughes in a group of patients with SLE [6]. APS is defined by obstetric morbidity and/or recurrent thromboses in the presence of anti-phospholipid (aPL) antibodies [6]. Previously, it was noted that patients may exhibit APS manifestations with no characteristic of SLE, and therefore were classified as primary APS (PAPS) whereas the presence of APS concomitantly with SLE was termed secondary APS (SAPS). For years clinicians and scientist have tried to better discriminate PAPS from SAPS. Unlike SLE, PAPS was primarily not considered to be a systemic disease. However, in the course of time PAPS was found to be associated with damage to various organs and systems and to evolve into SLE in up to 10% of patients [7]. Moreover, the expression lupus-like APS was coined to define APS patients displaying systemic “SLE features” although SLE criteria are not fulfilled [7], [8]. Certain manifestations of SLE such as the presence of anti-nuclear antibodies, complement activation or immune mediated kidney disease was accepted as markers to distinguish this disease from primary APS. In the last decade the presence of anti-nuclear antibodies, hypocomplementemia, non-thrombotic kidney disease and renal failure were all documented in patients diagnosed with PAPS, and the activation of complement was found to be closely related with APS in experimental models [7].

Hence, the concept of SLE–APS spectrum was suggested to support the many similarities between SAPS and PAPS. In the same manner, one may consider SLE itself to be a single heterogeneous disease with a variety of manifestations or a collection of comparable signs and symptoms among patients with apparently different clinical conditions. Thus, herein we shall discuss the clinical and scientific data supporting each of those opposite points of view.

Section snippets

Lupus is a group of diseases because…

Lupus is already accepted as many diseases similar to other autoimmune/rheumatic conditions. Rheumatoid arthritis is split into seropositive and seronegative varieties. Juvenile idiopathic arthritis has multiple types. Why should SLE be any different? In fact, lupus is already accepted as different diseases: SLE, chronic cutaneous lupus, sub-acute cutaneous lupus, drug-induced lupus and neonatal lupus. As our knowledge advances, we should expect the term SLE to be further subdivided.

Genetics

Lupus is one disease with a wide clinical spectrum because…

Systemic lupus erythematosus (SLE) is characterized by a wide range of clinical manifestations and autoantibodies and virtually any manifestation is considered to be possible in patients with SLE [18], [19]. As was once declared in the Greenwald's law of lupus: “anything happening to a patient with SLE which is not immediately otherwise explicable will automatically be blamed on the lupus, regardless of pathophysiologic validity” [20].

As clinicians we all see SLE patients presenting with very

Conclusions

Taking it all together, it seems that the “truth” stays in between these opposite points of view, and SLE is not a single disease but rather a single syndrome. A syndrome is defined by a set of signs, symptoms, phenomena or characteristics that are known to occur together and suggest a particular abnormality. So, that the presence of one or more of those features alerts the physician to the possible presence of the others. Syndromes tend to have a range of possible etiologies or diseases that

Take-home messages

  • SLE is not a single disease but rather a single syndrome characterized by a variety of clinical manifestations and a wide profile of autoantibodies.

  • The newly identified SLE genes map shed some light on the different subtypes of SLE although currently risk alleles explain only between 5 and 15% of the whole genetic contribution to this syndrome.

  • The complex interplay of different environmental, hormonal and genetic factors can determine different clinical expressions of SLE.

  • The accumulated

References (26)

  • Y. Shoenfeld et al.

    Antiphospholipid syndrome and systemic lupus erythematosus: are they separate entities or just clinical presentations on the same scale?

    Curr Opin Rheumatol

    (2009)
  • T. Tarr et al.

    Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus

    Lupus

    (2007)
  • D. Glass et al.

    Inherited deficiency of the second component of complement: rheumatic disease associations

    J Clin Invest

    (1976)
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