Pathophysiology
Loss of self-tolerance leads to autoantibodies against nuclear antigens. Immune complexes deposit in tissues (glomeruli, skin, joints, serosa), activating complement (low C3/C4) and driving inflammation. Female predominance (9:1), often African/Hispanic descent, HLA-DR2/DR3 associations.
Sources: EULAR 2023 Recommendations for SLE (Ann Rheum Dis 2024;83:15); ACR/EULAR 2019 Classification Criteria for SLE (Ann Rheum Dis 2019;78:1151)
Clinical presentation
Constitutional (fever, fatigue, weight loss). Skin: malar (butterfly) rash sparing nasolabial folds, discoid lesions, photosensitivity, oral/nasal ulcers. Musculoskeletal: non-erosive symmetric polyarthritis, avascular necrosis. Renal: lupus nephritis (classes I-VI on biopsy). Serositis (pleuritis, pericarditis). Haematologic: cytopenias. Neuropsychiatric: seizures, psychosis, stroke. Antiphospholipid syndrome: thrombosis and recurrent miscarriage.
Sources: EULAR 2023 Recommendations for SLE (Ann Rheum Dis 2024;83:15); ACR/EULAR 2019 Classification Criteria for SLE (Ann Rheum Dis 2019;78:1151)
Diagnosis
EULAR/ACR 2019 criteria require ANA positivity ≥1:80 plus weighted clinical and immunologic domains (score ≥10). Highly specific antibodies: anti-dsDNA (nephritis, disease activity) and anti-Sm. Low C3/C4 correlate with active disease. Renal biopsy classifies lupus nephritis and guides therapy.
Sources: EULAR 2023 Recommendations for SLE (Ann Rheum Dis 2024;83:15); ACR/EULAR 2019 Classification Criteria for SLE (Ann Rheum Dis 2019;78:1151)
Management
All patients: hydroxychloroquine (reduces flares, improves survival) plus sun protection. Mild disease: NSAIDs, short prednisolone. Moderate-severe or organ threat: high-dose steroids plus mycophenolate mofetil or cyclophosphamide (proliferative lupus nephritis). Belimumab (anti-BLyS) and anifrolumab (anti-IFN-α receptor) for refractory disease. Rituximab for refractory or cytopenia-predominant disease. Antiphospholipid syndrome: lifelong warfarin (INR 2-3) after thrombosis.
Sources: EULAR 2023 Recommendations for SLE (Ann Rheum Dis 2024;83:15); ACR/EULAR 2019 Classification Criteria for SLE (Ann Rheum Dis 2019;78:1151)
Monitoring & pregnancy
Screen for hypertension, cardiovascular risk, osteoporosis, avascular necrosis, and infection (encapsulated organisms). Regular urinalysis, complement, anti-dsDNA and disease activity index. Pregnancy: plan during remission, continue hydroxychloroquine, add aspirin ± LMWH if antiphospholipid positive; monitor for neonatal lupus (anti-Ro/La associated congenital heart block).
Sources: EULAR 2023 Recommendations for SLE (Ann Rheum Dis 2024;83:15); ACR/EULAR 2019 Classification Criteria for SLE (Ann Rheum Dis 2019;78:1151)
