Pathogenesis

The cause is unknown. It is thought to be multifactorial involving genetic and environmental elements with female sex strongly influencing pathogenesis (1,2).

Recognised genetic and epidemiological predisposing factors include:

• hereditary:
  • the concordance for identical twins is 30% compared to 5% for other sibs
• complement deficiencies:
  • the strongest disease susceptibility genes are those associated with homozygous complement deficiencies (C1q, C1r, C1s, C2 and C4)
• female sex
  • female hormones are thought to play an important role although the mechanism is unclear (3)
• associated with HLA-DR2, HLA-DR3 and C4A null complement alleles
• a particular MHC haplotype that is commonly found in caucasian patients with SLE is (HLA-A1, HLA-B8, HLA-DR3, C4AQ*O); this is often a marker of a subset of the disease that is associated with anti-Ro antibodies
• drugs e.g. hydralazine, procainamide or griseofulvin
• environmental influences
  • Epstein–Barr virus (EBV) infection
  • ultraviolet light (associated with the presence of the anti-Ro antibody) (4)

Note:

• lupus flares can be caused by different precipitants at different time in the same patient (1).

Reference:

• (1) Manson JJ, Rahman A. Systemic lupus erythematosus. Orphanet J Rare Dis. 2006 Mar;1:6.
• (2) EULAR Textbook on Rheumatic Diseases. Chapter 20. Systemic Lupus Erythematosu: Pathogenesis and clinical features
• (3) Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-39.
• (4) Tsokos GC.Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110-21.