Overview
Definition
A chronic, relapsing, complex autoimmune disease characterized by the production of autoantibodies leading to widespread immune complex deposition and tissue damage.
Epidemiology
Highly disproportionate impact on women of childbearing age (9:1 female-to-male ratio). More common and severe in African American and Hispanic populations.
Etiology & Risk Factors
- Multifactorial: Genetic predisposition, environmental triggers (UV light/sun exposure), and hormonal factors (estrogen).
- Defective clearance of apoptotic cells leads to the production of anti-nuclear antibodies.
Clinical Symptoms
- Constitutional: Fatigue, fever, weight loss
- Dermatologic: Malar 'butterfly' rash (spares nasolabial folds), Discoid rash, Photosensitivity, Oral/Nasal ulcers
- Musculoskeletal: Non-erosive polyarthritis (migratory, symmetrical)
- Renal: Lupus Nephritis (causes hypertension, edema, hematuria, proteinuria)
- Hematologic: Anemia, leukopenia, thrombocytopenia
Clinical Approach
Diagnosis
- Screening: Anti-Nuclear Antibody (ANA) - Highly sensitive, almost 100% positive in SLE. If negative, SLE is extremely unlikely.
- Confirmation: Anti-dsDNA (highly specific, correlates with disease activity/lupus nephritis) and Anti-Smith (highly specific, does not correlate with activity)
- Complement Levels: Decreased C3 and C4 during active flares (due to consumption by immune complexes)
Management
- Hydroxychloroquine: The cornerstone of therapy. Recommended for ALL patients to reduce flares and mortality (Requires annual eye exams for retinal toxicity)
- Mild flares (joint/skin): NSAIDs and low-dose Corticosteroids
- Severe organ-threatening disease (Lupus Nephritis, CNS lupus): High-dose Corticosteroids, Cyclophosphamide, or Mycophenolate Mofetil
Complications
- Lupus Nephritis (a leading cause of morbidity and mortality)
- Accelerated atherosclerosis and premature cardiovascular disease
- Libman-Sacks Endocarditis (non-bacterial verrucous vegetations on heart valves)
- Increased risk of infection (due to disease and immunosuppressants)