AKT · Musculoskeletal/Connective tissue disease

Systemic lupus erythematosus

Multisystem autoimmune disease with autoantibodies + immune-complex deposition

Overview

A multisystem autoimmune disease, predominantly in women of reproductive age (and more common/severe in those of African/Asian ancestry), characterised by autoantibodies, immune-complex deposition and a relapsing-remitting course. ANA is the sensitive screen; anti-dsDNA and anti-Smith are specific. It is a great mimic — joints, skin, kidneys, blood, serosa, CNS — and lupus nephritis drives prognosis.

Recognise

Constitutional (fatigue, fever, weight loss); photosensitive malar (butterfly) rash, discoid lesions, oral ulcers, alopecia, Raynaud's
Non-erosive arthritis, serositis (pleuritis/pericarditis), nephritis, cytopenias, neuropsychiatric features
Antiphospholipid syndrome association (thrombosis, recurrent miscarriage); flares track disease activity

Red flags

Lupus nephritis (proteinuria/active sediment/rising creatinine) → renal biopsy + immunosuppression — determines prognosis
Neuropsychiatric lupus, severe cytopenias, or catastrophic antiphospholipid syndrome → emergency

Differentials & how to tell them apart

Rheumatoid arthritiserosive symmetrical arthritis, anti-CCP; SLE arthritis is non-erosive

Drug-induced lupusanti-histone antibodies, culprit drug (hydralazine, procainamide, isoniazid); resolves on stopping

Mixed connective tissue disease / other CTDanti-U1-RNP; overlapping features

Infection / vasculitisraised CRP, different serology

Malar (butterfly) rash of systemic lupus erythematosus
CNX OpenStax / CC BY 4.0 — Wikimedia Commons

Investigations

ANA (sensitive screen — if negative SLE is unlikely); anti-dsDNA and anti-Smith (specific); complement C3/C4 (low in active disease); FBC (cytopenias), urinalysis + urine PCR (nephritis), renal function; antiphospholipid antibodies; ESR raised with normal CRP (CRP rise suggests infection/serositis).

Management

Hydroxychloroquine backbone + sun protection; immunosuppression for organ disease

1Confirm with ANA then specific antibodies (anti-dsDNA/Smith) and assess organ involvement (urinalysis, renal function, FBC, complement). Start hydroxychloroquine for almost all patients, with sun protection, plus corticosteroids for flares.Gate: Lupus nephritis (proteinuria/active sediment) → renal biopsy and immunosuppression (mycophenolate/cyclophosphamide) — renal involvement determines prognosis and must not be missed.
2Organ-threatening or refractory disease → immunosuppressants (azathioprine/mycophenolate) or biologics (rituximab/belimumab); manage cardiovascular risk and antiphospholipid syndrome.

Hydroxychloroquine (+ sun protection) — backbone for almost all patients — reduces flares; baseline + annual retinopathy screening

Corticosteroids for flares — lowest effective dose; topical for skin

Immunosuppressants (azathioprine, mycophenolate, methotrexate); cyclophosphamide/rituximab/belimumab for severe disease — steroid-sparing; mycophenolate/cyclophosphamide for lupus nephritis

Manage CV risk and antiphospholipid syndrome — anticoagulation if thrombotic APS

Key points

Young woman + photosensitive malar rash + non-erosive arthritis + cytopenias + ANA-positive (anti-dsDNA/Smith specific, low complement in flares) = SLE → hydroxychloroquine backbone. ALWAYS check urine for lupus nephritis (prognosis). ESR up, CRP normal (CRP rise → think infection).

Monitor & prognosis

Anti-dsDNA/complement for activity, urinalysis for nephritis, hydroxychloroquine retinal screening, CV risk.

Relapsing-remitting; prognosis driven by renal and neuropsychiatric involvement; much improved with modern therapy.

Source: NICE CKS; BSR lupus guideline