Systemic Lupus Erythematosus - SLE

Systemic Lupus Erythematosus - SLE

 

Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoantibodies and immune complexes damage organs.

Epidemiology

  • Incidence – 1/2000
  • Age – peak onset teens to 40 year olds
  • Gender – F>M
  • Ethnicity – Blacks:Caucasians; 3:1

Risk Factors

  • Genetics
    • Maybe associated with the deletion of the long arm of chromosome 1
  • Sunlight
  • Drugs
  • Epstein-Barr virus
  • Occupational exposures
    • Silica
    • Pesticides
    • Mercury

Pathophysiology

  • Apoptosis (programmed cell death appears to play a role in development of autoantibodies)
  • B-cells are overactive
  • T-cell regulation is disrupted

Clinical Presentation

  • Dermatologic – malar or discoid rash
  • Musculoskeletal – arthritis, myositis, myalgias
  • Serositis – pleuritis, pericarditis
  • Renal – nephritis
  • Neurologic – seizures, psychosis
  • Hematologic – hemolytic anemia, leukopenia, thrombocytopenia, anti-phospholipid syndrome
  • Vascular – vasculitis, transient ischemic attack
  • Ocular – Sicca syndrome

Diagnosis

  • Laboratory testing
    • Antibodies to native DNA found in most patients with SLE
    • While anti-nuclear antibody (ANA) test is useful as initial screen for SLE, follow-up of ANA-positive samples are necessary to identify antibodies to nuclear antigens such as:
      • DNA
        • Double stranded DNA (dsDNA) antibodies (1:10 or greater) are found in 50-60% of SLE
        • High antibody titers to native dsDNA are specific for SLE
      • Histones
      • Saline-extractable nuclear antigens
        • Smith (Sm) antibodies are highly specific for SLE, but occur in only 30-35% of cases
        • Patients with only antibodies to Sm have high incidence of renal and central nervous system (CNS) involvement
        • Sm antibodies also predict disease relapse in 50% of patients
    • Ribonucleic protein (RNP) antibodies in SLE are associated with a relatively benign disease course and lower incidence of renal disease
    • Nephritis in patients with RNP antibodies is usually associated with antibodies against antigens other than RNP, most notably DNA
    • SSA and SSB antibodies occur in some patients with clinical features of SLE, including prominent cutaneous features, but who fail to demonstrate a positive ANA

 

Distribution of Antibodies in Connective Tissue Disease Types
  Systemic Lupus Erythematosus (SLE) Sjögren Syndrome Mixed Connective Tissue Disease (MCTD) Progressive Systemic Sclerosis (PSS) Scleroderma
dsDNA abs 50-60% 20-30% 20-25% <5%  
Histone abs Idiopathic 18-53%
Drug-induced 80-95%		   <20% <20% <20%
RNP 20-30%   95-100% 15-25% 5-10%
Scl-70       25% 20-60%
SSA ANA positive patients
30-40%		 70-75%   5-10%  
SSB 15-25% 50-60%   5-10%  
Jo-1 abs Found in polymyositis, dermatomyositis, myositis associated with rheumatic disease

Differential Diagnosis

  • Other connective tissue disease
  • Fibromyalgia
  • Vasculitides

Treatment

  • Immunosuppressives have been the mainstay of therapy
  • Newer biologics hold promise

See Also