Bit · Rheum/Immuno
GPA vs Goodpasture vs EGPA
Three diseases that all attack the lungs and kidneys. The pivot is the antibody.
Mechanism
All three give pulmonary-renal syndromes (alveolar hemorrhage + glomerulonephritis), but the autoantibody and the rest of the clinical picture differ:
- Granulomatosis with polyangiitis (GPA, formerly Wegener) — c-ANCA / PR3-ANCA positive. Necrotizing granulomatous vasculitis of small/medium vessels. Classic triad: upper airway (sinusitis, saddle-nose deformity, otitis), lower airway (cavitating lung nodules), and kidney (pauci-immune crescentic GN).
- Goodpasture syndrome — antibody against the α3 chain of type IV collagen in basement membranes (anti-GBM antibody). The same antigen is in pulmonary alveolar and glomerular basement membranes → simultaneous alveolar hemorrhage and rapidly progressive GN. Biopsy: linear IgG deposition along GBM on immunofluorescence (Type II hypersensitivity). Often follows a respiratory infection; young men.
- Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss) — p-ANCA / MPO-ANCA positive in ~40%. Distinctive triad: asthma (often new or worsening in adulthood), peripheral eosinophilia, and eosinophilic vasculitis with granulomas. Skin involvement (purpura, nodules), peripheral neuropathy (mononeuritis multiplex), and cardiac involvement are common.
Differentiator Table
| GPA (Wegener) | Goodpasture | EGPA (Churg-Strauss) | |
| Antibody | c-ANCA / PR3-ANCA | Anti-GBM (α3 of type IV collagen) | p-ANCA / MPO-ANCA (~40%) |
| Vessels | Small to medium, granulomatous | Capillaries (lung, kidney) | Small to medium, granulomatous, eosinophilic |
| Upper airway | PROMINENT — sinusitis, saddle-nose, otitis, septal perforation | Absent | Allergic rhinitis, nasal polyps |
| Lung | Cavitating nodules; pulmonary hemorrhage | Diffuse alveolar hemorrhage | Asthma, transient infiltrates, hemorrhage |
| Kidney | Pauci-immune crescentic GN | Linear IgG on IF (anti-GBM) | Pauci-immune crescentic GN (when present) |
| Asthma | No | No | YES (often years before vasculitis) |
| Eosinophilia | No | No | YES (often striking) |
| Renal IF pattern | Pauci-immune (negative or scant immune deposits) | LINEAR (smooth, ribbon-like) | Pauci-immune |
| Treatment | Steroids + cyclophosphamide or rituximab | Plasmapheresis + steroids + cyclophosphamide | Steroids; mepolizumab; cyclophosphamide for severe |
The Pivot
Three questions decide it:
- Is there asthma + eosinophilia? → EGPA.
- Is there upper-airway disease (sinusitis, saddle nose) with cavitating lung nodules? → GPA.
- Pure lung-plus-kidney with linear IF on biopsy? → Goodpasture.
Antibody confirms: c-ANCA → GPA. Anti-GBM → Goodpasture. p-ANCA + eosinophilia → EGPA.
NBME-Style Stem
A 28-year-old man presents with hemoptysis, dyspnea, and cola-coloured urine over 5 days. He had a flu-like illness 2 weeks ago. Creatinine is 4.2 mg/dL. Renal biopsy shows crescentic glomerulonephritis with linear deposition of IgG along the glomerular basement membrane. Which of the following antibodies is most likely responsible?
Concept Anchor
Three pulmonary-renal syndromes, three antibodies: c-ANCA in GPA (with upper-airway granulomas), anti-GBM in Goodpasture (linear IF, no asthma), p-ANCA in EGPA (asthma + eosinophilia announce it). The antibody is always the pivot.