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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Three conditions: GPA (Wegener — cANCA/PR3), MPA (pANCA/MPO), EGPA (Churg-Strauss — eosinophilia + asthma)
- GPA classic triad: upper airway disease (epistaxis, nasal crusting, saddle nose) + lower airway (haemoptysis, nodules) + glomerulonephritis
- Rapidly progressive glomerulonephritis (RPGN) is the most serious manifestation — can cause ESRD within weeks
- Treatment: induction with cyclophosphamide or rituximab + high-dose steroids. Maintenance with azathioprine or rituximab
- ANCA testing: cANCA/anti-PR3 = GPA. pANCA/anti-MPO = MPA. Request BOTH immunofluorescence and ELISA
Overview
ANCA-associated vasculitides (AAV) are a group of systemic small-vessel vasculitides characterised by necrotising inflammation of small blood vessels and the presence of ANCA (anti-neutrophil cytoplasmic antibodies). The three conditions are: granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) — upper and lower respiratory tract granulomatous inflammation + necrotising glomerulonephritis; microscopic polyangiitis (MPA) — pauci-immune necrotising glomerulonephritis + pulmonary capillaritis without granulomata; and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) — asthma + eosinophilia + granulomatous vasculitis. All can cause life-threatening organ damage and require urgent immunosuppression.
Epidemiology
AAV has a combined UK incidence of approximately 10–20 per million per year. GPA and MPA are approximately equal in incidence and are more common than EGPA. Peak onset is 55–70 years. Male:female ratio is approximately equal for GPA and MPA. EGPA is associated with pre-existing asthma. Overall, AAV is rare but carries significant morbidity and mortality if untreated.
Clinical Features
Symptoms
Constitutional: fatigue, weight loss, fever, myalgia, arthralgia (common to all AAV)
GPA — upper airway: recurrent epistaxis, nasal crusting, sinusitis, nasal septal perforation (saddle nose deformity)
GPA — lower airway: cough, haemoptysis, pulmonary nodules or cavitating lesions on CXR
Renal (GPA and MPA): haematuria, proteinuria, rapidly rising creatinine (RPGN) — can progress to ESRD within weeks
MPA: predominantly renal and pulmonary (pulmonary-renal syndrome with pulmonary haemorrhage)
EGPA: late-onset asthma, allergic rhinitis, peripheral neuropathy (mononeuritis multiplex), eosinophilia, cardiac involvement
Skin: purpura, ulcers, nodules (small vessel vasculitis)
Eyes: episcleritis, scleritis, orbital granuloma (GPA)
Signs
Nasal crusting, septal perforation, saddle nose (GPA)
Haematuria on urinalysis (active nephritis)
Pulmonary crackles or haemoptysis (pulmonary haemorrhage or infiltrates)
Peripheral neuropathy: foot drop, wrist drop (mononeuritis multiplex — especially EGPA)
Purpuric rash (palpable purpura — small vessel vasculitis)
Red eye: scleritis (painful, deep red) or episcleritis
Investigations
First-line
ANCA testingImmunofluorescence: cANCA (cytoplasmic staining) or pANCA (perinuclear). ELISA: anti-PR3 (GPA) or anti-MPO (MPA/EGPA). cANCA/PR3 = GPA (~90%). pANCA/MPO = MPA (~70%) and EGPA (~40%)
Renal function and urinalysisU&Es (rising creatinine = RPGN), urinalysis (haematuria, proteinuria, red cell casts = active nephritis). Urine protein:creatinine ratio
Inflammatory markersCRP and ESR raised. FBC: eosinophilia in EGPA (often >10%); normocytic anaemia, thrombocytosis
Second-line
CXRGPA: pulmonary nodules (may cavitate), infiltrates. MPA: diffuse alveolar haemorrhage. EGPA: transient pulmonary infiltrates
CT chestBetter characterisation of pulmonary nodules, cavities, and ground-glass change (haemorrhage)
Renal biopsyIf renal involvement — pauci-immune necrotising crescentic glomerulonephritis (few immune deposits on immunofluorescence — distinguishes from immune complex GN)
Specialist
Tissue biopsy (nasal, renal, skin, nerve)Histological confirmation: GPA shows necrotising granulomatous inflammation. MPA shows necrotising vasculitis without granulomata. EGPA shows eosinophilic granulomatous inflammation
1
Remission induction (severe/organ-threatening)
- Cyclophosphamide (IV pulsed or oral) + high-dose prednisolone (1 mg/kg, max 60 mg, taper over months)
- OR rituximab (375 mg/m² weekly × 4 or 1 g × 2) + prednisolone — equally effective and preferred if relapsing disease, young patient, or concern about fertility
- Plasma exchange: consider if severe RPGN (creatinine >500 µmol/L) or pulmonary haemorrhage (evidence from PEXIVAS trial — modest benefit)
- IV methylprednisolone 500 mg–1 g for 3 days if severe presentation
2
Maintenance therapy
- Azathioprine (first-line maintenance) OR rituximab (superior for relapse prevention)
- Mycophenolate: alternative if azathioprine not tolerated
- Continue maintenance for at least 2–5 years (longer if PR3-positive — higher relapse risk)
- Taper prednisolone to lowest effective dose — aim to stop or reduce to ≤5 mg/day
3
Supportive
- Bone protection: bisphosphonate, calcium, vitamin D
- Pneumocystis prophylaxis: co-trimoxazole 480 mg OD during cyclophosphamide induction
- Monitor renal function, FBC, inflammatory markers regularly
- Vaccination: influenza, pneumococcal, COVID-19 — ideally before starting immunosuppression
Complications
- End-stage renal disease: From RPGN — requires dialysis. May need renal transplant
- Pulmonary haemorrhage: Life-threatening — massive haemoptysis and respiratory failure
- Saddle nose deformity: From nasal cartilage destruction in GPA
- Subglottic stenosis: GPA — causes stridor and requires surgical intervention
- Relapse: PR3/cANCA positive disease has higher relapse rate than MPO/pANCA
- Treatment toxicity: Cyclophosphamide — haemorrhagic cystitis, bladder cancer, infertility, myelosuppression. Rituximab — hypogammaglobulinaemia, infection risk
UKMLA Exam Tips
- 1cANCA/PR3 = GPA (Wegener). pANCA/MPO = MPA. Remember: C for Cytoplasmic, P for Perinuclear
- 2GPA triad: upper airway (sinusitis, saddle nose) + lungs (nodules, haemoptysis) + kidneys (RPGN)
- 3Pulmonary-renal syndrome (haemoptysis + rapidly rising creatinine): think MPA or GPA
- 4EGPA: asthma + eosinophilia + vasculitis (mononeuritis multiplex, cardiac involvement)
- 5Pauci-immune crescentic GN on renal biopsy = ANCA vasculitis (few/no immune deposits)
- 6Induction: cyclophosphamide or rituximab. Maintenance: azathioprine or rituximab
- 7Co-trimoxazole prophylaxis during cyclophosphamide — prevents Pneumocystis pneumonia
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