Granulomatosis with Polyangiitis GPA (Wegeners)

Related Subjects: Granulomatosis with Polyangiitis (GPA, formerly Wegener's) | Goodpasture's Syndrome (Anti-GBM Disease) | Respiratory Failure | Acute Kidney Injury

Early diagnosis and immunosuppression are key to reducing damage. If suspicious, get an urgent cANCA (proteinase 3). Without intervention, GPA can destroy kidneys within weeks.

ℹ️ About

• 🧑‍⚕️ First described by Dr. Friedrich Wegener in 1936 (renamed GPA due to his Nazi association).
• 📛 Now called Granulomatosis with Polyangiitis (GPA).
• 🩸 Systemic necrotizing vasculitis affecting ENT, lungs, kidneys.
• ⏱️ Untreated → 90% mortality within 2 years.

🧬 Aetiology & Pathophysiology

• 🌡️ Medium-sized vessel vasculitis, likely autoimmune/hypersensitivity to environmental antigen.
• 🦠 Staphylococcus aureus carriage linked to recurrence; eradication reduces relapse risk.
• 🩺 Renal involvement in 40% at presentation, up to 90% during disease course.
• 🪢 Granulomatous inflammation → necrosis of affected tissues.

📊 Epidemiology

• 👥 Incidence: ~3/100,000 (USA).
• ⏱️ Mean onset age ~50 yrs.
• ⚖️ M:F ratio = 1:1.
• 🌍 90% in Caucasian populations.

🧱 Granuloma Formation

🩺 Clinical Presentation

• 🛏️ Constitutional: Fever, night sweats, malaise, lethargy.
• 👃 ENT: Rhinorrhoea, epistaxis, sinusitis, otitis media, nasal septal perforation, saddle nose deformity.
• 🫁 Lungs: Cough, haemoptysis, pulmonary haemorrhage (↑DLCO), nodules ± cavitation.
• 🧽 Kidneys: Hypertension, haematuria, pauci-immune necrotizing glomerulonephritis (hallmark lesion).
• 👁️ Ocular: Uveitis, scleritis, proptosis.

🔬 Investigations

• 🩸 FBC: Anaemia, leukocytosis.
• 🧪 U&E: Raised urea/creatinine → renal impairment.
• 🔥 Inflammatory markers: ↑ ESR/CRP.
• 🧪 Complement: Often low.
• 🫁 CXR: Nodules, infiltrates, cavitations, haemorrhage.
• 🧫 Urinalysis: Proteinuria, haematuria, dysmorphic RBCs, RBC casts.
• 🖥️ HRCT: Alveolar haemorrhage, nodules, airway stenosis.
• 🔑 ANCA: • cANCA (PR3) → positive in 80–90% (correlates with activity). • pANCA (MPO) → positive in 10–20%.
• 🔍 Biopsy: ENT/lung/renal tissue → necrotizing granulomatous inflammation.
• 🫁 BAL: Helpful in alveolar haemorrhage (blood in alveoli).
• 💨 DLCO: Raised in alveolar haemorrhage (Hb binding CO).

🖼️ CT Findings

📸 CT shows multiple cavitary (arrows) and non-cavitary (arrowheads) pulmonary nodules typical of GPA.

💊 Management

• ⚠️ Untreated mortality: 90% in 2 years. Treatment dramatically improves survival.
• Induction: • Severe disease → high-dose corticosteroids + Cyclophosphamide (CYC) or Rituximab (RTX). • Non-severe → Methotrexate (MTX) or Rituximab ± steroids.
• Maintenance: • Azathioprine, Methotrexate, or Rituximab (esp. PR3+ relapsers). • Rituximab infusions can be extended up to 42 months in high-risk relapse cases.
• Adjuncts: • Co-trimoxazole prophylaxis (for Pneumocystis jirovecii + reduces Staph. nasal colonisation). • Long-term mupirocin cream for Staph. carriage. • Plasma exchange (PLEX) for severe renal disease (Cr >500 μmol/L) or pulmonary haemorrhage.

📚 References

• Radiologic-Pathologic Correlation of GPA (RSNA)

Case – Granulomatosis with Polyangiitis (GPA, Wegener’s)

A 42-year-old with months of chronic sinusitis, epistaxis, and conductive hearing loss presents with pleuritic chest pain, cough with blood-streaked sputum, fatigue, and new ankle oedema. Exam: saddle-nose deformity, crackles; BP 158/92. Labs: normocytic anaemia, creatinine rising, active urine sediment with RBC casts; CXR shows multiple cavitating nodules. Serology: c-ANCA (PR3) strongly positive. Urgent renal tract ultrasound is normal; CT chest confirms nodules; nasal/renal biopsy shows necrotising granulomatous vasculitis. Treat as organ-threatening AAV: IV methylprednisolone (then high-dose oral taper) plus rituximab (or cyclophosphamide) with PPI, bone protection, and PJP prophylaxis. Add plasmapheresis only if severe pulmonary haemorrhage or dialysis-dependent RPGN per local policy. Once in remission, maintain with rituximab/azathioprine; involve ENT, respiratory, nephrology; vaccinate and monitor for relapse and treatment toxicity. Differentials: microscopic polyangiitis, EGPA, TB/fungal infection, malignancy.