Systemic lupus erythematosus — diagnosis, serology and flare management

Diagnosis: systemic lupus erythematosus (SLE) with likely lupus nephritis and cytopenias. Multisystem autoimmune disease in a young woman: malar/photosensitive rash, oral ulcers, non-erosive polyarthritis, alopecia, fever, cytopenias, hypertension and active urinary sediment.^[3]

Classification logic (ACR/EULAR 2019): ANA at titre ≥1:80 on HEp-2 is the entry criterion; then additive weighted clinical and immunological criteria, classification if score ≥10 with ≥1 clinical criterion. Classification aids standardisation; diagnosis remains clinical.^[1]

Essential investigations:

• Bloods: FBC (cytopenias, haemolysis film/reticulocytes/LDH/haptoglobin/DAT if anaemia), U&E, LFT, ESR (often high) vs CRP (often normal unless serositis/infection), CK if myositis suspected
• Serology:
  • ANA — sensitive screening test (not specific)
  • Anti-dsDNA — more specific; tracks activity, especially renal
  • Anti-Smith — highly specific
  • C3 and C4 — low in active disease/flare (classical pathway consumption)
  • Anti-Ro/La (neonatal lupus, sicca), anti-RNP (MCTD overlap), antiphospholipid antibodies (APS overlap), anti-histone if drug-induced lupus suspected
• Urine: dipstick, microscopy, urine protein:creatinine ratio
• Infection screen before heavy immunosuppression (cultures if febrile)
• Renal ultrasound and plan kidney biopsy if significant proteinuria/haematuria/falling eGFR

Lupus nephritis approach:

• Biopsy classifies ISN/RPS class (I–VI). Class III/IV (proliferative) needs aggressive induction; Class V (membranous) has a different regimen emphasis; Class VI is advanced sclerosis.
• Induction (proliferative): high-dose glucocorticoids plus mycophenolate mofetil or cyclophosphamide, then maintenance (MMF or azathioprine).^[2]
• Adjuncts: hydroxychloroquine, BP control (ACE inhibitor/ARB if proteinuric and not pregnant), statin/bone protection/PCP prophylaxis as indicated, thrombosis assessment if APS antibodies present.

Stepwise systemic management:

1. Foundation for almost all patients: sun protection, smoking cessation, vaccination (avoid live vaccines if heavily immunosuppressed), hydroxychloroquine 200–400 mg/day (max 5 mg/kg actual body weight/day) — reduces flares, thrombosis and damage; annual retinal screening.^[2]
2. Mild mucocutaneous/MSK disease: HCQ ± short low-dose prednisolone ± NSAID (caution renal/APS).
3. Moderate flare: higher steroid + steroid-sparing agent (methotrexate, azathioprine, MMF).
4. Severe organ-threatening disease (nephritis, CNS, severe cytopenias, vasculitis): high-dose steroids ± IV methylprednisolone pulses + MMF/cyclophosphamide; consider belimumab/anifrolumab/voclosporin in specialist pathways; rituximab in refractory disease.
5. Always exclude infection before escalating immunosuppression in a febrile patient.
6. Pregnancy counselling: continue HCQ; avoid MMF, cyclophosphamide, methotrexate, warfarin; low-dose aspirin often indicated; screen anti-Ro (neonatal heart block risk).