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 recognition and prompt immunosuppression are critical to prevent irreversible organ damage. If GPA is suspected, urgently request c-ANCA (PR3). Without treatment, GPA can destroy kidneys within weeks.

ℹ️ Overview

• 🧑‍⚕️ First described by Dr. Friedrich Wegener in 1936 (now renamed GPA due to historical associations).
• 📛 Granulomatosis with Polyangiitis (GPA) is a systemic necrotizing vasculitis affecting ENT, lungs, and kidneys.
• ⏱️ Untreated mortality: ~90% within 2 years.

🧬 Pathophysiology

• 🌡️ Autoimmune, small-to-medium vessel vasculitis, likely triggered by environmental antigens.
• 🦠 Staphylococcus aureus carriage increases relapse risk; eradication reduces recurrence.
• 🩺 Renal involvement: 40% at presentation, up to 90% over disease course.
• 🪢 Granulomatous inflammation → necrosis of affected tissues (ENT, lungs, kidneys).

📊 Epidemiology

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

🧱 Granuloma Formation

🩺 Clinical Features

• 🛏️ Constitutional: fever, night sweats, malaise, fatigue.
• 👃 ENT: chronic sinusitis, epistaxis, otitis media, nasal septal perforation, saddle nose deformity.
• 🫁 Lungs: cough, haemoptysis, pulmonary haemorrhage (↑DLCO), nodules ± cavitation.
• 🧽 Kidneys: hypertension, haematuria, pauci-immune necrotizing glomerulonephritis.
• 👁️ Ocular: uveitis, scleritis, proptosis.

🔬 Investigations

• 🩸 FBC: anaemia, leukocytosis.
• 🧪 U&E: rising creatinine/urea; renal impairment.
• 🔥 ESR/CRP: elevated.
• 🧪 Complement: sometimes low.
• 🫁 CXR: nodules, infiltrates, cavitations, pulmonary haemorrhage.
• 🧫 Urinalysis: proteinuria, haematuria, dysmorphic RBCs, RBC casts.
• 🖥️ HRCT chest: alveolar haemorrhage, nodules, airway stenosis.
• 🔑 ANCA serology: c-ANCA (PR3) positive 80–90% (correlates with activity), p-ANCA (MPO) positive 10–20%.
• 🔍 Biopsy (ENT/lung/kidney): necrotizing granulomatous vasculitis.
• 🫁 BAL: blood in alveoli for pulmonary haemorrhage.
• 💨 DLCO: increased in alveolar haemorrhage due to Hb CO-binding.

🖼️ Imaging

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

💊 Management

• ⚠️ Untreated mortality ~90% at 2 years; early treatment dramatically improves survival.
• Induction therapy: • Severe/organ-threatening: high-dose corticosteroids + cyclophosphamide (CYC) or rituximab (RTX). • Non-severe: methotrexate (MTX) or RTX ± steroids.
• Maintenance therapy: azathioprine, MTX, or RTX (especially PR3+ high-risk relapsers). • RTX infusions can extend up to 42 months for high relapse risk.
• Adjunctive therapy: • Co-trimoxazole prophylaxis (for Pneumocystis and reduces Staph. nasal colonisation). • Long-term mupirocin nasal therapy. • Plasma exchange (PLEX) if severe renal disease (Cr >500 μmol/L) or pulmonary haemorrhage.

Case – Granulomatosis with Polyangiitis (GPA)

42M with chronic sinusitis, epistaxis, conductive hearing loss, pleuritic chest pain, blood-streaked sputum, fatigue, and ankle oedema. Exam: saddle nose, crackles; BP 158/92. Labs: normocytic anaemia, rising creatinine, RBC casts; CXR: multiple cavitating nodules. Serology: strongly positive c-ANCA (PR3). Nasal/renal biopsy: necrotising granulomatous vasculitis. Management: IV methylprednisolone → high-dose oral taper + rituximab (or cyclophosphamide), PPI, bone protection, PJP prophylaxis. Consider plasmapheresis if severe pulmonary haemorrhage or dialysis-dependent RPGN. Maintenance with rituximab/azathioprine; multidisciplinary follow-up (ENT, respiratory, nephrology). Monitor for relapse and treatment toxicity. Differentials: microscopic polyangiitis, EGPA, infection (TB/fungal), malignancy.

📚 References

• Radiologic-Pathologic Correlation of GPA (RSNA)
• NICE Guideline: Vasculitis (ANCA-associated)