A young woman with Raynaud's, rash and rising creatinine
A 32-year-old woman presents with 3 weeks of fatigue, arthralgia and a new facial rash. Over the past week she has developed puffy fingers, Raynaud's phenomenon and progressive breathlessness. She has no prior medical history and takes no regular medication. Examination: temperature 37.8°C, blood pressure 148/92 mmHg, malar erythema sparing the nasolabial folds, sclerodactyly of the fingers, and fine basal crackles on chest auscultation. Laboratory tests: creatinine 168 µmol/L (baseline 70), urinalysis shows 3+ protein and 2+ blood with red cell casts, haemoglobin 92 g/L, platelets 88 × 10⁹/L, ESR 60 mm/h. ANA is positive at 1:1280 with a speckled pattern.
1. What is the likely unifying diagnosis and which specific autoantibodies and investigations would you request?
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The combination of malar rash, arthralgia, Raynaud's, puffy fingers, proteinuria with red cell casts, rising creatinine, cytopenias and a high-titre speckled ANA points to a systemic autoimmune rheumatic disease with renal involvement - most likely systemic lupus erythematosus with lupus nephritis, or an overlap syndrome / mixed connective tissue disease (MCTD) given the puffy fingers and Raynaud's.
Autoantibodies to request:
- Anti-dsDNA - specific for SLE and correlates with nephritis activity.
- Anti-Sm - highly specific for SLE.
- Anti-U1-RNP - high titres suggest MCTD/overlap.
- Anti-Ro/La, anti-histone, anti-C1q - additional information.
- Complement C3 and C4 - low levels support active immune-complex disease.
- ANCA - to exclude a small-vessel vasculitis if the picture is atypical.
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) - important for thrombotic risk and pregnancy.
- Anti-topoisomerase I (Scl-70) and anti-centromere - to assess for scleroderma spectrum disease, given the sclerodactyly.
Other investigations:
- Urine protein:creatinine ratio or 24-hour protein, and renal biopsy - essential to classify nephritis (ISN/RPS class) and guide treatment.
- Full blood count, blood film (to exclude microangiopathic haemolysis), LDH, haptoglobin, direct Coombs.
- Chest radiograph and high-resolution CT plus pulmonary function tests with DLCO for interstitial lung disease or pulmonary hypertension.
- Echocardiogram, blood pressure monitoring, and infection screen (hepatitis B/C, HIV, TB) before immunosuppression.
2. Outline the immediate management priorities, including treatment of the renal disease and the precautions before starting immunosuppression.
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Immediate priorities:
- Assess severity - blood pressure control (target <130/80), fluid balance, and monitoring for pulmonary oedema or rapidly progressive glomerulonephritis. Admit for observation if creatinine is rising quickly.
- Renal biopsy before or very soon after starting treatment to classify lupus nephritis and exclude thrombotic microangiopathy.
- Induction immunosuppression for active lupus nephritis: high-dose glucocorticoids (intravenous methylprednisolone pulses followed by oral prednisolone) plus mycophenolate mofetil or low-dose intravenous cyclophosphamide; add hydroxychloroquine unless contraindicated (retinal screening).
- Renal protection: ACE inhibitor or ARB for proteinuria once creatinine is stable, and blood pressure control.
- Consider plasma exchange or rituximab if there is a thrombotic microangiopathy or refractory disease.
Precautions before immunosuppression:
- Screen for hepatitis B and C, HIV, and latent TB (IGRA and chest radiograph); treat latent TB before or alongside.
- Update vaccinations where possible (avoid live vaccines on immunosuppression); advise on infection risk.
- Pregnancy test and contraception counselling - mycophenolate and cyclophosphamide are teratogenic; cyclophosphamide can cause infertility, so discuss ovarian protection.
- Baseline blood count, liver function, glucose and bone protection (calcium/vitamin D, consider bisphosphonate with prolonged steroids).
- Monitor for cytopenias, infection, and disease activity with complement, dsDNA and urine protein regularly.
Long-term: maintenance with mycophenolate or azathioprine, hydroxychloroquine, cardiovascular risk reduction, and pregnancy planning in remission.