Key Facts

Pulmonary vasculitis refers to inflammation affecting the pulmonary vasculature, ranging from capillaritis causing diffuse alveolar haemorrhage to granulomatous inflammation with cavitating lung nodules. The ANCA-associated vasculitides (AAV) are the most important causes.

Epidemiology

AAV combined incidence is approximately 20 per million per year in the UK. GPA is the commonest (8-10 per million), followed by MPA (5-8 per million) and EGPA (1-3 per million). Peak incidence is 65-74 years for GPA and MPA. Large-vessel vasculitides (Takayasu, giant cell arteritis) can also involve the pulmonary arteries but are much less common.

Aetiology

• ANCA-associated: GPA, MPA, EGPA — autoimmune; ANCA target neutrophil antigens (PR3, MPO)
• Immune complex: anti-GBM disease, SLE, IgA vasculitis (Henoch-Schönlein), cryoglobulinaemic vasculitis
• Large vessel: Takayasu arteritis (pulmonary artery stenosis), Behçet disease (pulmonary artery aneurysms)
• Drug-induced: hydralazine, propylthiouracil, minocycline (drug-induced ANCA vasculitis)

Pathophysiology

In AAV, ANCA (anti-PR3 or anti-MPO) activate primed neutrophils, causing adhesion to endothelium, degranulation, and vessel wall damage. In GPA, granulomatous inflammation causes tissue destruction (e.g. nasal cartilage, lung parenchyma). In MPA, non-granulomatous necrotising vasculitis predominantly affects capillaries and venules. Pulmonary capillaritis in any AAV leads to disruption of the alveolar-capillary membrane and diffuse alveolar haemorrhage.

GPA (Granulomatosis with Polyangiitis)

• Upper respiratory: bloody nasal discharge, crusting, saddle nose deformity, subglottic stenosis, otitis media, sinusitis
• Lower respiratory: cough, haemoptysis, dyspnoea; cavitating pulmonary nodules on CT
• Renal: rapidly progressive glomerulonephritis (haematuria, proteinuria, rising creatinine)
• Other: scleritis/episcleritis, skin vasculitis, peripheral neuropathy

MPA (Microscopic Polyangiitis)

• Renal-predominant: RPGN is the presenting feature in most
• Pulmonary capillaritis with DAH (15-30%)
• Constitutional symptoms: fever, weight loss, myalgia
• Less upper respiratory tract involvement than GPA

Red Flags

• Haemoptysis with rising creatinine (pulmonary-renal syndrome) — treat as emergency
• Massive haemoptysis (DAH)
• Rapidly progressive renal failure (creatinine doubling in days)
• Saddle nose deformity / subglottic stenosis (GPA)
• Stridor (subglottic stenosis — may need emergency intervention)

Bedside

• Urinalysis: haematuria, proteinuria, red cell casts
• SpO₂: may be reduced (DAH)
• ENT examination: nasal crusting, septal perforation (GPA)

Bloods

• ANCA: cANCA/anti-PR3 (GPA ~90%), pANCA/anti-MPO (MPA ~70%, EGPA ~40%)
• Anti-GBM: to exclude concurrent anti-GBM disease
• FBC: anaemia (haemorrhage/chronic disease), eosinophilia (EGPA)
• U&Es: creatinine, eGFR (renal involvement)
• CRP/ESR: active vasculitis
• Complement (C3/C4): normal in AAV (low in SLE, cryoglobulinaemia)
• Immunoglobulins, cryoglobulins: if immune complex vasculitis suspected

Imaging

• CXR: bilateral infiltrates (DAH), nodules ± cavitation (GPA)
• HRCT: cavitating nodules (GPA), ground-glass (DAH), consolidation
• CT sinuses: mucosal thickening, bony erosion (GPA)
• Renal ultrasound: normal-sized kidneys in acute disease

Special Tests

• Renal biopsy: pauci-immune crescentic glomerulonephritis (AAV); gold standard
• BAL: haemosiderin-laden macrophages, progressively bloody aliquots (DAH)
• Lung biopsy: granulomatous vasculitis (GPA), capillaritis (MPA)
• DLCO: paradoxically raised in acute DAH
• NCS/EMG: if peripheral neuropathy suspected

Non-pharmacological

• MDT approach: rheumatology, respiratory, nephrology, ENT
• Infection screening before immunosuppression: Hep B/C, HIV, TB (IGRA), varicella immunity
• Pneumocystis prophylaxis: co-trimoxazole 480 mg OD during induction
• Bone protection: calcium/vitamin D, consider bisphosphonate if prolonged steroids

Pharmacological

• Induction (severe/organ-threatening):
  • Rituximab 375 mg/m² weekly × 4 OR 1 g × 2 (day 0 and 14) — RAVE trial, RITUXVAS trial
  • OR cyclophosphamide IV 15 mg/kg (max 1.2 g) every 2 weeks × 3 then every 3 weeks × 3 (CYCLOPS protocol)
  • PLUS methylprednisolone 500 mg-1 g IV × 3 days, then prednisolone 1 mg/kg (max 60 mg) tapering rapidly (PEXIVAS trial supports reduced steroid regimen)
• Plasma exchange: for DAH or severe renal disease (creatinine >500 μmol/L) — PEXIVAS trial did not show clear benefit on renal survival but may benefit DAH
• Maintenance: rituximab 500 mg every 6 months for ≥2 years (MAINRITSAN trial); OR azathioprine 2 mg/kg/day (check TPMT)
• Relapse: re-induce with rituximab (preferred if previously on cyclophosphamide)

Surgical/Interventional

• Subglottic dilatation: for subglottic stenosis in GPA
• Renal transplantation: if ESRD, once disease quiescent for ≥12 months

Referral Criteria

• Urgent rheumatology/vasculitis centre referral
• Nephrology for renal involvement
• ENT for upper respiratory tract GPA
• Respiratory for DAH management

With modern immunosuppressive therapy, 5-year survival for GPA and MPA is 75-85%. Relapse occurs in 30-50% within 5 years (more common in GPA than MPA, and in PR3-ANCA compared to MPO-ANCA). Renal prognosis depends on creatinine at presentation and percentage of crescents on biopsy. Up to 25% of AAV patients require renal replacement therapy. EGPA has >80% 5-year survival. Long-term morbidity includes chronic kidney disease, treatment-related infections, and cardiovascular disease.

ANCA-Associated Vasculitis Comparison

Key Trials in AAV