Systemic Lupus Erythematosus (SLE)

Epidemiology
  • SLE is has a fairly high prevalence of roughly 4 per 1000 individuals and occurs most commonly in women with diagnosis typically occurring in the second or third decades of life. There is a slight preponderance in African Americans.
Etiology
  • Overview
    • The etiology of SLE is clearly complex and multifactorial with both genetic and environmental factors contributing. Ultimately, disease likely manifests following an environmental trigger in a genetically susceptible individual.
  • Genetic Factors
    • A family history of SLE is a risk factor for the disease; however, large studies performed to identify genetic susceptibility loci have been disappointing, revealing a large number of chromosomal loci which increase risk only mildly. While the female preponderance of the disease is largely attributed to the presence of estrogen, several important susceptibility loci have been identified on the X Chromosome.
  • Environmental Factors
    • A SLE-like syndrome can be triggered by administration of drugs, especially procainamide and hydralazine. As mentioned above, the presence of estrogens are thought to be a major risk factor. Finally, as described further below, exposure to ultraviolet light can significantly tigger flares of clinical symptoms.
Pathogenesis
  • SLE is ultimately thought to be an autoimmune disease resulting from defects in mechanisms of immune tolerance yielding excess activation of both humoral and cellular arms of the immune response. In recent years an increasing appreciation has focused on derangements of the innate immunity as an additional pathogenic contributor. Our understanding of the pathogenesis of SLE is rapidly evolving and is far beyond the scope of this resource. However, suffice it to say that multiple derangements in immunity likely contribute to SLE pathogenesis.
Laboratory Features
  • Overview
    • Whatever the defects that lead to the immune derangements of SLE, a prominent feature of the disease is the presence of large numbers of auto-antibodies. These auto-antibodies are not only useful for diagnosis but are thought to contribute to pathology, especially by generating immune complexes that can deposit in multiple organs and trigger inflammation, essentially amounting to a Type III Hypersensitivity reaction.
  • Anti-Nuclear Antibodies (ANAs)
    • ANAs refer to antibodies that cross-react with nuclear components including DNA, histones, ribonucleoproteins, and nucleolar antigens. ANAs are the prototypical auto-antibody of SLE and are observed in nearly all patients. However, because they are also present in a number of other autoimmune conditions, their presence is seen as a highly sensitive but non-specific test.
  • Anti-dsDNA Antibodies
    • In contrast to ANAs, Anti-double stranded DNA (Anti-dsDNA) Antibodies are highly specific to SLE; however, they are only found in a proportion of SLE patients and thus have incomplete sensitivity.
  • Anti-phospholipid Antibodies
    • Antibodies to blood phosopholipids are present in some patients and frequently interfere with coagulation, specifically lengthening the PT. As a consequence, these have been historically termed "Lupus Anticoagulant". However, this term can be confusing as the presence of these antibodies renders patients hypercoagulable.
  • Anti-cardiolipin Antibodies
    • Antibodies to cardiolipin are frequently encountered in patients with SLE and may render a false positive RPR tests for syphilis
  • Complement
    • In acute flares of disease, serum levels of complement may be reduced, likely a result of increased consumption as a result of diffuse immune complex deposition
Pathology and Clinical Consequences
  • Overview
    • SLE is a clinical diagnosis and now requires the presence of a certain number of clinical criteria. We highlight these and other prominent features below along with relevant histomorphological correlations. SLE can affect nearly every organ of the body and the pathology appears to largely result from the deposition of immune complexes. Immune complexes typically cause a necrotizing vasculitis in small arteries and arterioles associated with leukocytic infiltrates and luminal narrowing.
    • SLE typically charts a relapsing-remitting course with acute flares that require immunosuppressants to control interspersed between periods of relative quiescence. Flares can often be precipitated by viral infections or exposure to ultraviolet light.
  • Joints
    • [Polyarthritis is a common feature of SLE and typically presents with tenderness and swelling of the distal joints, including those of the hands, wrists, and knees. Importantly, the arthritis of SLE is not erosive and does not cause joint deformity, an important point of contrast from Rheumatoid Arthritis
  • Skin and Mucous Membranes
    • An erythematous, slightly raised, scaling rash on the malar prominences in a "butterfly" pattern, characteristically sparing the nasiolabial folds, is highly suggestive of SLE, especially when it is exacerbated by sunlight. Immunofluorescence will show deposition of immunoglobulins and complement at the dermoepidermal junction along with a lymphocytic infiltrate surrounding cutaneous vasculature.
    • Small, painful oral ulcers are also a common feature of SLE and makeup one of the diagnostic criteria.
  • Renal
    • Lupus Nephritis is perhaps the leading initial cause of mortality in patients with SLE can progress fairly rapidly to chronic renal failure and ultimately uremia if left untreated. The pathogenesis is due to immune complex deposition within the glomeruli capillaries, yielding a glomerulonephritis of varying severity. The pathogenesis, pathology, and clinical consequences are discussed in more detail on the lupus nephritis page.
  • Neurological
    • Both the central and peripheral nervous system can be affected by SLE. These can manifest as focal neurological impairments, severe headaches, cognitive impairments, as well as psychosis. The precise mechanisms underlying neurological dysfunction in SLE is unclear and may be due to micro-infarcts secondary to small vessel occlusions or direct antibody binding to neuronal membranes.
  • Cardiopulmonary
    • Serositis is a common feature of SLE and can affect the pleura or the pericardium, resulting in either pleuritis or pericarditis
    • Patients with SLE can also develop a sterile endocarditis termed "Libman-Sacks Endocarditis" which manifests as verrucous growths characteristically on both sides of the heart valve leaflets.
  • Blood
  • Constitutional Symptoms
    • Fatigue is a nearly constant feature of SLE and can worsen with flares. Other constitutional symptoms such as night sweats and fevers an also occur.