Description

• Systemic lupus erythematosus (SLE) is a multisystem autoimmune inflammatory disease characterized by a chronic relapsing/remitting course; can be mild to severe and may be life-threatening (CNS and renal forms)
• System(s) affected: mucocutaneous; musculoskeletal; renal; nervous; pulmonary; cardiac; hematologic; vascular; gastrointestinal (GI)
• Synonym(s): SLE; lupus

ALERT
Women with SLE have a 7- to 50-fold increased risk of coronary artery disease and may present with atypical/nonspecific symptoms.

Epidemiology

Predominant age: 15 to 45 years

• Per year, 1.6 to 7.6/100,000 and increasing due to better diagnosis
• Most common: African American women (8.1 to 11.4/100,000/year)
• Least common: Caucasian men (0.3 to 0.9/100,000/year)

Prevalence
Occurs in 30 to 50/100,000 and increasing due to increased survival

Etiology and Pathophysiology

• Skin: photosensitivity; scaly erythematous, plaques with follicular plugging, dermal atrophy, and scarring; nonscarring erythematous psoriasiform/annular rash; alopecia; mucosal ulcers
• Musculoskeletal: nonerosive arthritis; ligament and tendon laxity, ulnar deviation, and swan neck deformities; avascular necrosis
• Renal: glomerulonephritis
• Pulmonary: pleuritis, pleural effusion, alveolar hemorrhage, pneumonitis, interstitial fibrosis, pulmonary hypertension, pulmonary embolism (PE)
• Cardiac: nonbacterial verrucous endocarditis, pericarditis, myocarditis, atherosclerosis
• CNS: thrombosis of small intracranial vessels ± perivascular inflammation resulting in micro- or macroinfarcts ± hemorrhage
• Peripheral nervous system: mononeuritis multiplex, peripheral neuropathy
• GI: pancreatitis, peritonitis, colitis
• Hematologic: hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia
• Vascular: vasculitis, thromboembolism
• Most cases are idiopathic with possible environmental factors.
• Drug-induced lupus: hydralazine, D penicillamine, quinidine, procainamide, minocycline, isoniazid, etc.

• Identical twins: 24–58% concordance
• Fraternal twins and siblings: 2–5% concordance
• 8-fold risk if first-degree relative with SLE
• Major histocompatibility complex associations: HLA-DR2, HLA-DR3
• Deficiency of early complement components, especially C1q, C1r/s, C2, and C4
• Immunoglobulin receptor polymorphisms: FCγR2A, FCγR3A, and others
• Polymorphism in genes associated with regulation of programmed cell death, protein tyrosine kinases, and interferon production

Risk Factors

• Race: African Americans, Hispanics, Asians, and Native Americans
• Predominant sex: females > males (10:1)
• Environmental: UV light, infectious agents, stress, diet, drugs, hormones, vitamin D deficiency, and tobacco

Commonly Associated Conditions

• Overlap syndromes: rheumatoid arthritis (RA), Sjögren syndrome, scleroderma
• Antiphospholipid syndrome; coronary artery disease; nephritis; depression