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]

SAQ 2 — A 72-year-old woman with new headache and jaw claudication (10 marks, 20 minutes)

Question

A 72-year-old woman presents with a two-week history of new-onset right-sided temporal headache, fatigue, and pain in the jaw on chewing that resolves after a few minutes of rest. She has had polymyalgia rheumatica for six months, treated with prednisolone 10 mg daily. Her ESR is 92 mm/hour and CRP is 68 mg/L. Describe the diagnosis, the immediate management, the investigation strategy, and the steroid-sparing approach. [1]

Model answer

Diagnosis (2 marks) [1]

This is giant cell arteritis (GCA, temporal arteritis) with visual symptoms not yet present but imminent. The combination of new temporal headache, jaw claudication (the most specific symptom), elevated inflammatory markers, age over 50, and pre-existing polymyalgia rheumatica makes the diagnosis highly likely. Jaw claudication reflects external carotid artery branch involvement and is a strong predictor of GCA. [1]

Immediate management (3 marks) [1]

Start high-dose glucocorticoids immediately — do NOT wait for biopsy or imaging. The dose is prednisolone 40 to 60 mg daily (not less than 40 mg per EULAR guidance) for GCA without visual symptoms. The response is typically dramatic within 24 to 72 hours. [1]

If there were any visual symptoms (amaurosis fugax, diplopia, visual loss), the dose would be intravenous methylprednisolone 500 mg to 1 g daily for 3 days before transitioning to oral prednisolone, with same-day ophthalmology referral. Anterior ischaemic optic neuropathy causes irreversible blindness within hours — prevention through immediate steroids is the only effective strategy [2].

Investigation strategy (3 marks) [1]

• Temporal artery biopsy within 2 weeks of starting steroids — the finding is granulomatous inflammation with multinucleated giant cells and internal elastic lamina disruption. A negative biopsy does NOT exclude GCA because of skip lesions (sensitivity about 77 per cent for unilateral biopsy).
• Temporal artery ultrasound showing the halo sign (hypoechogenic wall thickening) is an accepted diagnostic alternative.
• Large-vessel imaging (CT angiography, MR angiography or FDG-PET) to detect extracranial large-vessel involvement in up to a third of patients. [1]

Steroid-sparing approach (2 marks) [1]

Tocilizumab (an IL-6 receptor blocker) is the evidence-based steroid-sparing agent for relapsing or refractory GCA. The GiACTA trial showed that subcutaneous tocilizumab 162 mg weekly (with a 26-week steroid taper) achieved sustained glucocorticoid-free remission in 56 per cent at 52 weeks versus 14 per cent with steroid taper alone [2]. Use it for relapsing disease, high steroid requirements, or difficulty tapering. The standard taper for steroids is to maintain the starting dose for 2 to 4 weeks, then taper by 10 per cent every 2 weeks, aiming for 10 to 15 mg by 3 months, then slower — most patients need 1 to 2 years of treatment.

Bone protection (calcium, vitamin D, bisphosphonate), gastric protection, and pneumocystis prophylaxis (co-trimoxazole) are essential during prolonged high-dose steroids. Aspirin is no longer routinely recommended unless indicated for another reason. [1]