Systemic Lupus Erythematosus (SLE) ✅

Related Subjects: | Systemic Lupus Erythematosus (SLE) | Drug-Induced Lupus Erythematosus | Discoid Lupus Erythematosus (DLE) | Neonatal Lupus Erythematosus | Rheumatology Autoantibodies

🌸 Systemic Lupus Erythematosus (SLE) is a chronic autoimmune connective tissue disorder, mainly affecting young women. ⚠️ Lupus nephritis is the most serious complication; early recognition and aggressive management prevent CKD and ESRD.

📖 About

• 🌐 Chronic multisystem autoimmune disease.
• 🧬 Autoantibodies target nuclear and intracellular antigens, forming immune complexes.
• 👩 Female predominance 9:1 (age 20–40).
• 🌍 Higher prevalence in Afro-Caribbean and Asian populations.
• 💊 Drug-induced lupus possible: hydralazine, isoniazid, procainamide, penicillamine.

🧬 Aetiology & Risk Factors

• Genetic: HLA-B8, DR2/DR3, complement deficiencies (C1q, C2, C4).
• Monozygotic twin concordance ~25%.
• Hormonal: oestrogen-driven; also seen in Klinefelter’s males.
• Environmental triggers: UV light, drugs, viral infections.
• Immune dysregulation → defective apoptosis and impaired clearance of nuclear antigens.

🔬 Pathophysiology

• Immune complex deposition → complement activation → tissue inflammation/damage.
• Fibrinoid necrosis in vessels, haematoxylin bodies, LE cells.
• ↑ Interferon-α and IL-10 → sustain autoimmunity.
• Multisystem involvement: skin, joints, kidneys, CNS, cardiovascular, pulmonary.

📋 Classification Criteria (ACR/EULAR 2019)

• 🌸 Malar rash
• 🔴 Discoid rash
• ☀️ Photosensitivity
• 👄 Oral/nasal ulcers
• 🦴 Non-erosive arthritis
• 🫁 Serositis (pleuritis/pericarditis)
• 🩺 Renal involvement – proteinuria >0.5 g/24h or active urinary sediment
• 🧠 CNS involvement – seizures, psychosis
• 🩸 Haematology – cytopenias, haemolytic anaemia
• 🧪 Immunology – anti-dsDNA, anti-Sm, anti-Ro/La, antiphospholipid antibodies
• 🧫 ANA positive (sensitive, >95%)

🩺 Clinical Features

• Systemic: Fatigue, fever, malaise, weight loss.
• Dermatology: 🌸 Butterfly rash, discoid lesions, photosensitivity, alopecia, livedo reticularis.
• Neuro: Seizures, psychosis, cranial neuropathies, strokes (APS).
• Renal: Lupus nephritis (proteinuria, haematuria, CKD risk).
• Haematology: Anaemia, leucopenia, thrombocytopenia.
• Cardiac/Vascular: Pericarditis, Libman-Sacks endocarditis, Raynaud’s, premature atherosclerosis.
• Pulmonary: Pleurisy, pulmonary hypertension, shrinking lung syndrome.
• MSK: Arthritis, Jaccoud’s arthropathy.
• Pregnancy: 👶 Neonatal lupus, congenital heart block (SSA/SSB positive).

🔎 Investigations – NICE Compliant

• 🩸 FBC, U&E, LFTs, urinalysis (protein, casts).
• 🧪 Autoantibodies: ANA, anti-dsDNA, anti-Sm, anti-Ro/La, antiphospholipid antibodies.
• 🧬 Complement: C3/C4 low in active disease.
• 📈 ESR ↑, CRP usually normal (unless infection).
• 🩺 Renal biopsy for lupus nephritis classification (I–VI) when indicated by proteinuria or active urine sediment.
• 🫀 Echocardiography for Libman-Sacks endocarditis if cardiac features present.
• 🩻 Imaging guided by organ involvement: MRI for CNS lupus, CXR/CT for pulmonary involvement.

🧾 Lupus Nephritis Classification

• I – Minimal mesangial
• II – Mesangial proliferative
• III – Focal proliferative
• IV – Diffuse proliferative (highest risk)
• V – Membranous
• VI – Advanced sclerosing

💊 Management – NICE Principles

• 🟢 Mild (skin/joints): Hydroxychloroquine ± NSAIDs, sun protection, topical steroids.
• 🟡 Moderate: Oral glucocorticoids, steroid-sparing DMARDs (azathioprine, mycophenolate).
• 🔴 Severe (renal/CNS): High-dose steroids ± cyclophosphamide or mycophenolate; rituximab if refractory.
• 💉 APS: Lifelong anticoagulation (warfarin) per NICE guidance.
• 🤰 Pregnancy: HCQ safe; avoid MMF, cyclophosphamide, methotrexate; LMWH + aspirin if APS; fetal echo if anti-Ro/La positive.
• 🧾 Supportive: ACEi/ARB for proteinuria, BP control, osteoporosis prophylaxis, infection prevention (PJP prophylaxis if high-dose immunosuppression).
• 🩺 Regular monitoring: renal function, urinalysis, blood counts, complement, anti-dsDNA titres.
• 🎯 Patient education: sun protection, contraception, infection risk, vaccination (non-live), adherence to therapy, prompt reporting of flares.

📚 References

• NICE Guideline: Systemic Lupus Erythematosus (NG197)
• ACR 2023 SLE Guideline
• SLE and Pregnancy – PubMed

Cases – NICE Compliant Management

Case 1 – Lupus nephritis: 26F, fatigue, malar rash, oral ulcers, oedema, ↑BP. Urine: proteinuria uPCR 450 mg/mmol, RBC casts. Labs: ANA+, anti-dsDNA high, low C3/C4. Start prednisolone + mycophenolate (cyclophosphamide if severe), ACEi/ARB, PJP prophylaxis; arrange renal biopsy, monitor BP, renal function, and disease activity per NICE.

Case 2 – Neuropsychiatric SLE: 32F, arthralgia, malar rash, new generalized seizures, cognitive slowing. MRI: WM lesions. Labs: anti-dsDNA↑, C3/C4↓. Exclude infection/drugs. Treat NPSLE with IV methylpred → oral taper ± cyclophosphamide/rituximab; neurology input, VTE risk assessment.

Case 3 – Serositis flare: 28F, pleuritic chest pain, dyspnoea. Exam: pericardial rub; echo: small effusion. NSAID + colchicine if mild; add glucocorticoids if inadequate; optimize hydroxychloroquine; consider steroid-sparing therapy if recurrent.

Case 4 – Pregnancy with aPL: 30F, 10 wks gestation, anti-Ro/La + triple-positive antiphospholipid antibodies; prior miscarriage. Continue HCQ, start LMWH + low-dose aspirin, serial fetal echocardiography, tight BP control, avoid teratogens, coordinate rheumatology–obstetrics care.