Systemic Lupus Erythematosus (SLE) — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease characterised by loss of immune tolerance, production of pathogenic autoantibodies (especially anti-dsDNA and anti-Smith), and immune complex deposition causing inflammation and organ damage. It follows a relapsing-remitting course of flares and remissions and can affect virtually any organ system — most commonly the skin, joints, kidneys, brain, heart, lungs, and blood. SLE affects an estimated 5 million people worldwide, with a 9:1 female predominance and peak onset during the reproductive years (15-45 years). Incidence is highest in Black, Hispanic, and Asian women, who also experience more severe disease. The 10-year survival rate has improved dramatically to over 90% with modern management, but lupus nephritis and cardiovascular complications remain major causes of morbidity and mortality. SLE is classified using the 2019 EULAR/ACR classification criteria based on a weighted scoring system across clinical and immunological domains.

SLE results from a complex interplay of genetic predisposition, hormonal factors, and environmental triggers leading to defective clearance of apoptotic cells and nuclear debris, persistent autoantigen exposure, and breakdown of B and T cell tolerance. Over 100 genetic loci have been associated with SLE risk, including HLA-DR2 and HLA-DR3, complement deficiencies (C1q, C2, C4 — loss of immune complex clearance), IRF5, TREX1, STAT4, and BLK. Oestrogen drives disease activity, explaining the female predominance and flares during pregnancy and with oral contraceptives. Environmental triggers include ultraviolet light (induces apoptosis of skin cells and photosensitive rashes), certain medications (drug-induced lupus: hydralazine, procainamide, isoniazid, minocycline, anti-TNF agents), Epstein-Barr virus (molecular mimicry), cigarette smoking (worsens anti-dsDNA positivity), and silica dust exposure. Black and Hispanic women have significantly higher incidence and more severe renal and haematological manifestations.

SLE presents with diverse, fluctuating symptoms across multiple organ systems. Constitutional features are nearly universal: fatigue (affecting 80-100%), fever, weight loss, and lymphadenopathy during flares. Musculoskeletal: polyarthritis or polyarthralgia in 90% of patients — symmetrical, migratory, and non-erosive (Jaccoud's arthropathy in chronic disease). Cutaneous (70-80%): butterfly (malar) rash — fixed erythema over the cheeks and nose sparing the nasolabial folds — is pathognomonic; discoid lupus — scarring, photosensitive plaques; photosensitivity; oral ulcers; alopecia. Renal (lupus nephritis — 50%): proteinuria, haematuria, hypertension, oedema, and progressive renal impairment — the WHO/ISN classification grades from Class I (minimal mesangial) to Class VI (advanced sclerosis); Class III and IV carry the worst prognosis. Neuropsychiatric SLE (NPSLE — 25-75%): headaches, seizures, psychosis, cognitive dysfunction, stroke (associated with antiphospholipid antibodies — APS). Haematological: leucopenia, lymphopenia, haemolytic anaemia (Coombs-positive), thrombocytopaenia. Serositis: pleuritis (chest pain worsened by deep breathing), pericarditis. Antiphospholipid syndrome (APS) — secondary to SLE in 30%: arterial and venous thrombosis and recurrent pregnancy loss.

Diagnosis requires clinical and immunological assessment. Anti-nuclear antibody (ANA) by immunofluorescence is positive in 95% of SLE patients and serves as a screening test — a negative ANA makes SLE very unlikely. Anti-double-stranded DNA (anti-dsDNA) antibodies are highly specific for SLE (95%) and titres correlate with disease activity, particularly nephritis. Anti-Smith (anti-Sm) antibodies are highly specific (99%) but less sensitive (25-30%). Other autoantibodies: anti-Ro/SSA (photosensitivity, neonatal lupus, congenital heart block), anti-La/SSB, anti-U1-RNP, antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin IgG/IgM, anti-beta-2 glycoprotein I). Complement C3 and C4 are consumed during active disease (low levels indicate active immune complex deposition). Full blood count (cytopenias), urinalysis and urine protein:creatinine ratio, renal function, and CRP/ESR guide activity assessment. Renal biopsy is essential to classify lupus nephritis and guide treatment. SLEDAI-2K score quantifies disease activity across 16 domains.

Hydroxychloroquine (HCQ) 200-400 mg daily is the foundation of SLE treatment for all patients — it reduces flare frequency by 50%, lowers thrombosis risk, improves pregnancy outcomes, and reduces mortality. Annual ophthalmology monitoring for retinal toxicity is required. Corticosteroids (prednisolone) manage acute flares; long-term high doses are minimised due to cumulative toxicity. Immunosuppressants for organ-threatening disease: mycophenolate mofetil (MMF) and cyclophosphamide (Euro-Lupus Protocol: IV 500mg every 2 weeks x6) are standard for class III/IV/V lupus nephritis. Belimumab (anti-BLYS biologic, IV or SC monthly) reduces flare rates and steroid requirements in seropositive SLE and active nephritis. Voclosporin (calcineurin inhibitor) combined with MMF is approved for lupus nephritis, achieving complete renal response in 41% at 52 weeks. Anifrolumab (anti-interferon-1 receptor) for moderate-severe active SLE on background therapy. Aspirin 75-100mg for antiphospholipid antibody positivity; warfarin or DOAC anticoagulation for confirmed APS thrombosis. Strict photoprotection (SPF50+, UV-protective clothing) is essential for all SLE patients. Annual influenza and 5-yearly pneumococcal vaccinations are recommended.

Untreated SLE causes progressive multi-organ damage with potentially fatal consequences. Lupus nephritis — occurring in 50% of patients, usually within the first 5 years — progresses to end-stage renal disease requiring dialysis or transplantation in 10-15% without aggressive immunosuppression; class IV diffuse proliferative lupus nephritis has the worst renal prognosis. Neuropsychiatric lupus (NPSLE) causes seizures, stroke (often from antiphospholipid syndrome-associated thrombosis), psychosis, and cognitive decline. Antiphospholipid syndrome, present in 30% of SLE patients, causes arterial and venous thrombosis including stroke, pulmonary embolism, deep vein thrombosis, and recurrent pregnancy loss — fatal in some cases without anticoagulation. Pericarditis and Libman-Sacks endocarditis (sterile cardiac valvular vegetations) increase risk of systemic emboli. Lupus pneumonitis and pulmonary hypertension cause progressive respiratory failure. Avascular necrosis (osteonecrosis) of the femoral and humeral heads — from vascular occlusion and corticosteroid use — requires hip and shoulder replacement surgery in up to 10-15% of SLE patients. Cytopenias from haemolytic anaemia and thrombocytopenia increase risk of bleeding and infections. Premature cardiovascular disease (myocardial infarction and stroke) is 5-10x more frequent in SLE women aged 35-44 than age-matched controls — the leading long-term cause of death in SLE.

No prevention exists for SLE but flares can be minimised. Consistent hydroxychloroquine use is the single most effective flare-prevention strategy — missed doses are a common flare trigger. Strict sun avoidance and SPF50+ sunscreen application daily reduce photosensitive rashes and UV-triggered flares. Avoid drugs known to cause drug-induced lupus (DIL): procainamide, hydralazine, minocycline, isoniazid, anti-TNF agents. Smoking cessation reduces autoantibody production and cardiovascular risk. Pregnancy in SLE requires pre-conception planning with rheumatology — ideally conceived during >6 months of clinical remission, continuing HCQ throughout pregnancy (reduces neonatal lupus risk), and specialist monitoring for pregnancy complications (pre-eclampsia, lupus nephritis flares, foetal growth restriction). Vaccinations are recommended but live vaccines should be avoided during immunosuppression. Women with SLE have 2-3x higher cardiovascular risk — manage hypertension, hyperlipidaemia, and diabetes aggressively.

Seek emergency care for: sudden severe headache with neck stiffness (lupus meningitis), new seizures, stroke symptoms (face drooping, arm weakness, speech difficulty), sudden chest pain with breathlessness (pericarditis, pleuritis, or pulmonary embolism), or suspected sepsis — immunocompromised patients can deteriorate rapidly. Contact your rheumatologist promptly for: significant increase in joint pains or new rash during a known SLE flare, unexplained fever (distinguish flare from infection — both can look similar), new or worsening swelling of ankles/legs (lupus nephritis), blood in urine, or sudden drop in platelet count causing bruising or nosebleeds. Women of childbearing age should seek preconception rheumatology review before attempting pregnancy. Annual review with your rheumatologist is the minimum monitoring frequency even in remission.