The Systemic Vasculitides — Written Clinical Reasoning

SAQ 1 — Pulmonary-renal syndrome from granulomatosis with polyangiitis (20 marks, 30 minutes)

Model answer

Problem identification and diagnosis (4 marks) ^[1]

This patient has a pulmonary-renal syndrome — the combination of haemoptysis (alveolar haemorrhage) and rapidly progressive glomerulonephritis. The ENT prodrome (nasal crusting, epistaxis, conductive hearing loss from Eustachian tube involvement), the c-ANCA with anti-PR3 specificity, and the pauci-immune crescentic glomerulonephritis on renal biopsy together establish the diagnosis of granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) with organ- and life-threatening disease ^[1][3].

GPA is an ANCA-associated small-vessel vasculitis characterised by the classic triad of ENT, pulmonary and renal involvement. The pauci-immune pattern (minimal immunoglobulin deposition on immunofluorescence) distinguishes it from immune-complex vasculitides (cryoglobulinaemia, IgA vasculitis, lupus). The c-ANCA/PR3 pattern is positive in 75 to 90 per cent of GPA cases and carries a higher relapse risk than p-ANCA/MPO disease. ^[1]

Immediate management (6 marks) ^[1]

This is a medical emergency requiring admission and same-day initiation of treatment: ^[1]

1. Glucocorticoid induction — intravenous methylprednisolone 500 mg to 1 g daily for 3 days, followed by oral prednisolone 1 mg/kg daily (max 60 to 80 mg), with a planned taper to 5 mg daily by 4 to 5 months ^[7].
2. Rituximab — 375 mg per square metre weekly for 4 weeks (RAVE regimen) or 1 g on days 1 and 15 (RITUXVAS regimen). Rituximab is now the preferred induction agent for organ-threatening AAV based on the RAVE trial (non-inferior to cyclophosphamide, superior in relapsing disease) and the RITUXVAS trial (non-inferior in renal AAV) ^[3][4].
3. Exclude mimics before or concurrently with immunosuppression — blood cultures, echocardiogram (endocarditis, myxoma), anti-GBM antibody (overlap syndrome), ANA and anti-dsDNA (lupus), hepatitis B and C serology.
4. Consider plasma exchange — for anti-GBM overlap, for dialysis-dependent renal disease, or for severe diffuse alveolar haemorrhage with hypoxaemia. The MEPEX trial showed short-term renal recovery benefit with plasma exchange in severe renal vasculitis, though the larger PEXIVAS trial did not show benefit on the composite of death or end-stage kidney disease, so plasma exchange is now used more selectively in expert hands ^[5][6][7].
5. Supportive care — oxygen, renal support (nephrology input, dialysis if needed), co-trimoxazole for pneumocystis prophylaxis, bone protection (calcium, vitamin D, bisphosphonate), gastric protection.

Key differential diagnoses to exclude (5 marks) ^[1]

Maintenance strategy (3 marks) ^[1]

After 3 to 6 months of successful induction: ^[1]

• Switch to rituximab maintenance — 1 g every 4 months or 500 mg every 6 months for at least 24 to 36 months. Rituximab is preferred for maintenance, particularly in PR3-ANCA disease which has the highest relapse risk ^[7].
• Alternative maintenance agents — azathioprine 2 mg/kg daily (check TPMT first), mycophenolate mofetil 2 g daily, or methotrexate 20 to 25 mg weekly.
• Continue low-dose prednisolone (5 mg daily or less) for the first 4 to 6 months, then taper if possible.
• Monitoring — ANCA titre, inflammatory markers, renal function, urinalysis every 3 months; full blood count and immunoglobulins (for rituximab-related hypogammaglobulinaemia); bone density and cardiovascular risk assessment.

Communication and follow-up (2 marks) ^[1]

• Discuss the diagnosis as a serious but treatable chronic relapsing disease — sustained remission is achievable with modern therapy.
• Address the treatment burden — immunosuppression, infection risk, bone health, fertility (if relevant), psychosocial impact.
• Set up a relapse-monitoring contract and clear follow-up plan with rheumatology, nephrology and respiratory input. ^[1]