About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Multisystem autoimmune disease — relapsing-remitting course affecting skin, joints, kidneys, blood, CNS
- Classic presentation: young woman with malar (butterfly) rash, arthralgia, fatigue, and serositis
- Key antibodies: ANA (>95% sensitive but not specific), anti-dsDNA (specific, correlates with disease activity and nephritis), anti-Smith (most specific)
- Lupus nephritis occurs in ~50% — biopsy-guided classification determines treatment
- All patients: hydroxychloroquine (reduces flares, improves survival). Flares: steroids ± immunosuppressants
Overview
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by loss of immune tolerance and production of autoantibodies against nuclear antigens, causing widespread inflammation and tissue damage. It is the archetypal multisystem connective tissue disease, potentially affecting skin, joints, kidneys (lupus nephritis), serosal surfaces, blood cells, and the nervous system. The disease follows a relapsing-remitting course. Pathology is driven by immune complex deposition and complement activation. SLE is heterogeneous — presentation and severity vary widely between patients.
Epidemiology
SLE affects approximately 1 in 1,000 people in the UK. It is 9 times more common in women (F:M = 9:1), with peak onset in the childbearing years (15–45 years). It is more common and more severe in Black African/Caribbean, South Asian, and East Asian populations compared to White Europeans. Risk factors include female sex, reproductive age, family history, UV light exposure, and drug triggers (drug-induced lupus: hydralazine, isoniazid, minocycline — resolves on stopping drug). Complement deficiencies (C1q, C2, C4) predispose to SLE.
Clinical Features
Symptoms
Fatigue — the most common symptom, often debilitating
Arthralgia and non-erosive arthritis (symmetrical, small joints — similar distribution to RA but non-deforming)
Malar (butterfly) rash: erythematous rash across cheeks and nose, sparing nasolabial folds, photosensitive
Photosensitivity: rash provoked or worsened by UV exposure
Oral ulcers (usually painless)
Hair loss (diffuse, non-scarring alopecia)
Raynaud phenomenon (cold-triggered digital colour changes)
Serositis: pleuritic chest pain (pleuritis) or pericardial chest pain (pericarditis)
Renal involvement: proteinuria, haematuria, oedema, hypertension (lupus nephritis)
Signs
Malar rash: butterfly-shaped erythema across cheeks, sparing nasolabial folds
Discoid lupus: scarring, atrophic plaques (may occur without systemic disease)
Joint swelling (non-erosive, non-deforming — Jaccoud arthropathy is reducible deformity)
Lymphadenopathy, splenomegaly
Hypertension, oedema (nephritic/nephrotic from lupus nephritis)
Pleural or pericardial rub (serositis)
Investigations
First-line
ANA (anti-nuclear antibody)Positive in >95% of SLE — very sensitive but not specific (positive in many other conditions). Negative ANA makes SLE very unlikely
Anti-dsDNA antibodySpecific for SLE (~95% specificity). Titres correlate with disease activity, particularly lupus nephritis
Complement levels (C3, C4)LOW in active SLE (consumed by immune complexes). Rising complement = improving disease
FBCLymphopenia (most common), thrombocytopenia, Coombs-positive haemolytic anaemia, leucopenia
U&Es, urinalysis, urine protein:creatinine ratioScreen for lupus nephritis — proteinuria, haematuria, active sediment, rising creatinine
Second-line
Anti-Smith (anti-Sm)Most SPECIFIC antibody for SLE (~99% specificity) but only ~30% sensitive
Antiphospholipid antibodiesAnti-cardiolipin, lupus anticoagulant, anti-beta-2-glycoprotein I — screen for antiphospholipid syndrome (thrombosis risk, pregnancy morbidity)
ESRUsually raised in active SLE. CRP is typically NORMAL in SLE flares (raised CRP in SLE = think infection or serositis)
Specialist
Renal biopsyMANDATORY if lupus nephritis suspected (proteinuria, active sediment, rising creatinine). ISN/RPS classification (class I-VI) guides treatment
Anti-Ro (SSA) and anti-La (SSB)Associated with neonatal lupus (congenital heart block) and secondary Sjögren syndrome. Check in ALL women of childbearing age with SLE
1
All patients
- Hydroxychloroquine 200–400 mg OD — ALL patients with SLE should be on hydroxychloroquine (reduces flares, damage accrual, thrombosis risk, and improves survival)
- Sun protection: high-factor sunscreen, avoid prolonged UV exposure
- Cardiovascular risk management: SLE is a CV risk factor — lipids, BP, smoking cessation
- Vitamin D supplementation
- Annual eye screening for hydroxychloroquine retinal toxicity (after 5 years or sooner if risk factors)
2
Mild disease (skin, joints, fatigue)
- NSAIDs for joint pain (short courses)
- Low-dose prednisolone (≤7.5 mg/day) for flares — aim to minimise steroid exposure
- Methotrexate or azathioprine as steroid-sparing agents
3
Moderate-severe disease (nephritis, serositis, cytopenias)
- High-dose prednisolone for acute flares (0.5–1 mg/kg) — taper as rapidly as possible
- Lupus nephritis class III/IV: mycophenolate mofetil (first-line induction) or cyclophosphamide, then mycophenolate maintenance
- Class V (membranous): mycophenolate or cyclophosphamide
- Belimumab (anti-BLyS): add-on for active disease despite standard therapy (NICE approved)
- Rituximab: for refractory SLE (off-label but widely used)
- Voclosporin: newer option for lupus nephritis (NICE TA945)
4
Pregnancy in SLE
- Plan pregnancy during disease remission (≥6 months inactive)
- Continue hydroxychloroquine throughout pregnancy (safe and reduces flares)
- Stop teratogenic drugs ≥3 months before conception: methotrexate, mycophenolate, cyclophosphamide
- Switch to azathioprine (pregnancy-safe immunosuppressant)
- Anti-Ro positive: risk of neonatal lupus and congenital heart block — fetal echocardiography monitoring
- Antiphospholipid positive: low-dose aspirin ± LMWH to reduce pregnancy loss
Complications
- Lupus nephritis: Affects ~50% — leading cause of morbidity. Can progress to ESRD. Biopsy-guided treatment
- Antiphospholipid syndrome: ~30% have antiphospholipid antibodies — risk of arterial/venous thrombosis and recurrent miscarriage
- Cardiovascular disease: Accelerated atherosclerosis — SLE is an independent CV risk factor
- Infections: From immunosuppressive therapy and intrinsic immune dysfunction — leading cause of death in early disease
- Avascular necrosis (AVN): Especially femoral head — from steroid use and disease itself
- Neuropsychiatric lupus: Seizures, psychosis, cerebrovascular disease, cognitive dysfunction
UKMLA Exam Tips
- 1Young woman + malar rash + arthralgia + cytopenias + renal disease = SLE
- 2ANA is >95% SENSITIVE (screening test). Anti-dsDNA is SPECIFIC and correlates with nephritis activity. Anti-Sm is MOST SPECIFIC
- 3Low complement (C3/C4) = active disease. Rising complement = improving
- 4ESR raised but CRP NORMAL in SLE flares — raised CRP in SLE = think INFECTION (important discriminator)
- 5Hydroxychloroquine: ALL patients should be on it — improves outcomes, reduces flares, safe in pregnancy
- 6Drug-induced lupus: hydralazine, isoniazid. Features: serositis, arthralgia. Anti-HISTONE antibodies (not anti-dsDNA). Resolves on stopping drug
- 7Anti-Ro positive in pregnancy: risk of congenital heart block in neonate — needs fetal cardiac monitoring
Put your reading into practice
Topic-specific question practice is not linked for this article yet.
Choose UKMLA questions from the existing bank. General exam practice covers your selected topics; it is not filtered to this article. Your usual question-bank access applies.
Choose UKMLA practiceAfter your session, return to this section to revisit the reading and choose your next review.
Verified Sources & References
related resources
Save your place and choose what comes next
Musculoskeletal · Article 9 of 22