Synopsis
Recognise granulomatosis with polyangiitis across ENT, lung, kidney, eye and nerve systems, confirm vasculitis with targeted serology and tissue, and deliver severity-matched induction, maintenance and infection prevention without waiting for irreversible organ loss.
- Think GPA when chronic destructive sinus or ear disease, epistaxis, nasal crust, hearing loss, pulmonary nodules or haemorrhage, glomerular urine, scleritis or mononeuritis occur together.
- Obtain FBC, CRP or ESR, creatinine, electrolytes, urinalysis, microscopy and quantitative protein immediately; a small creatinine rise can represent substantial loss from a low baseline.
- Request PR3-ANCA and MPO-ANCA by antigen-specific immunoassay, but do not diagnose from ANCA alone or exclude tissue-proven disease after a negative result.
- CT sinuses and HRCT chest define destructive, nodular, cavitating and haemorrhagic disease and identify the safest biopsy site.
- Biopsy the kidney, lung, skin, nasal or orbital tissue that gives the highest diagnostic yield at acceptable risk; renal biopsy rapidly confirms pauci-immune crescentic injury and chronicity.
- For organ- or life-threatening disease use rituximab or cyclophosphamide plus a reduced-dose glucocorticoid regimen; begin urgent treatment when delay is dangerous while obtaining tissue and cultures.
- Rituximab is preferred for relapsing PR3 disease and when fertility or cumulative cyclophosphamide toxicity matters; cyclophosphamide remains an effective alternative for severe new disease.
- Avacopan 30 mg twice daily can replace much oral glucocorticoid in eligible severe active GPA or MPA under NICE criteria, but it does not replace rituximab or cyclophosphamide.
- Plasma exchange is not routine for all severe AAV; consider it selectively for very severe renal failure or hypoxaemic alveolar haemorrhage after specialist benefit-risk assessment.
- Maintenance usually uses rituximab or azathioprine for at least 24–48 months, longer in high-relapse PR3 disease, with vaccination, Pneumocystis prevention and infection monitoring.
Key red flags
Haemoptysis may be absent in diffuse alveolar haemorrhage; falling haemoglobin, hypoxia and diffuse opacities with active urine is an emergency.
Rising creatinine, oliguria, glomerular haematuria, casts, hyperkalaemia or pulmonary oedema requires urgent renal biopsy and kidney-support planning.
Painful red eye, reduced vision, proptosis, diplopia or severe orbital pain requires same-day ophthalmology and imaging.
Stridor, voice change or increasing work of breathing may indicate subglottic stenosis and requires early expert airway assessment.
Fever and opacity during immunosuppression may be infection rather than relapse; investigate both before reflex escalation.
Multiple nodules, cavities or diffuse opacities with falling haemoglobin and hypoxia suggest granulomatous lung disease or alveolar haemorrhage.
Dysmorphic haematuria, casts, proteinuria, pressure rise and creatinine progression indicates pauci-immune renal capillary injury.
Investigation priorities
Detect glomerulonephritis early and quantify renal trajectory and complications.
Management branches
ENT, lung, kidney, eye or nerve findings form a credible GPA pattern.
- Assess physiology and threatened organs, obtain blood, urine, PR3 or MPO assays, cultures and CT chest or affected anatomy.
- Choose the highest-yield safe biopsy, commonly kidney with active sediment, and send necrotic respiratory tissue for microbiology.
- Begin emergency induction before final histology when pulmonary haemorrhage, rapidly progressive renal or sight-threatening disease makes delay unsafe.