ReviewSystemic lupus erythematosus one disease or many?
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)
Lessons from the “Euro-Phospholipid” project
Autoimmun Rev
(2008)- et al.
Development of quality indicators to evaluate the monitoring of SLE patients in routine clinical practice
Autoimmun Rev
(2011) - et al.
Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients
Semin Arthritis Rheum
(2004) Clinical and genetic features of vascular Ehlers–Danlos syndrome
Ann Vasc Surg
(2002)Systemic lupus erythematosus Europe at the change of the millennium: lessons from the “Euro-Lupus Project”
Autoimmun Rev
(2006)- et al.
Clusters of clinical and immunologic features in systemic lupus erythematosus: analysis of 600 patients from a single center
Semin Arthritis Rheum
(2004) - et al.
Infections and autoimmunity — friends or foes?
Trends Immunol
(2009) - et al.
Development of autoantibodies before the clinical onset of systemic lupus erythematosus
N Engl J Med
(Oct 16 2003) - et al.
The mosaic of autoimmunity: genetic factors involved in autoimmune diseases — 2008
Isr Med Assoc J
(Jan 2008) The anticardiolipin syndrome
Clin Exp Rheumatol
(1985)