Granulomatosis with polyangiitis (GPA, formerly Wegener) is one of those “you either recognize it instantly or you miss a lot of points” diagnoses—because it’s not just a lung disease. It’s a small-vessel necrotizing vasculitis that loves to hit the upper airway + lungs + kidneys, and Step questions often hide it inside a pulmonary presentation.
The Draw-it-out Method (30 seconds, blank paper)
Draw a face + lungs + a kidney. Then add three signature lesions:
-
Nose/sinuses: draw a cracked bridge of the nose
→ “Saddle-nose” from destructive sinus/nasal inflammation -
Lungs: draw a few round “cannonball-ish” circles, some with a hollow center
→ “Nodules that can cavitate” + hemoptysis -
Kidney: draw a glomerulus with “leaking” lines
→ “RPGN” (rapidly progressive glomerulonephritis) with hematuria
Now label a big arrow pointing to all three: c‑ANCA (PR3).
The visual mnemonic (what you should see on your sketch)
“ENT + Cavitating lung nodules + Kidney bleed = GPA (c‑ANCA/PR3)”
One-liner (the USMLE-style diagnosis sentence)
GPA is a c‑ANCA (PR3)-associated necrotizing granulomatous small-vessel vasculitis causing chronic sinusitis/otitis ± saddle nose, cavitating lung nodules/hemoptysis, and rapidly progressive GN.
Why it shows up under “Pulmonary / Interstitial” (test logic)
Even though GPA is a systemic vasculitis, it often presents as pulmonary disease:
- Hemoptysis + anemia (diffuse alveolar hemorrhage can occur)
- Cough, dyspnea
- Imaging with nodules (often bilateral) that may cavitate
- Can mimic infection, malignancy, TB—until you connect the ENT + renal clues
Quick pattern recognition: If the stem says chronic sinusitis + hemoptysis + hematuria → stop and think GPA.
High-yield triad (commit this)
| Site | Classic clue | What it means |
|---|---|---|
| Upper airway | Chronic sinusitis, otitis media, epistaxis, saddle-nose deformity | Necrotizing granulomatous inflammation |
| Lungs | Cavitating nodules, hemoptysis, pleuritic chest pain | Granulomas + capillaritis (may cause alveolar hemorrhage) |
| Kidneys | Hematuria, RBC casts, rising creatinine | RPGN (crescentic GN), typically pauci-immune |
Labs/path that Step loves
Antibodies
- c‑ANCA (PR3-ANCA): strongly associated with GPA
- Remember: c = cytoplasmic, PR3 = proteinase-3
Biopsy buzzwords
- Necrotizing granulomatous inflammation
- Necrotizing vasculitis of small to medium vessels
- Kidney: pauci-immune crescentic GN (little/no immune complex deposition on immunofluorescence)
Imaging: what to expect (and what not to overthink)
CXR/CT commonly shows:
- Multiple pulmonary nodules, often bilateral
- Cavitation (a big clue)
- Sometimes patchy opacities if hemorrhage is present
Don’t confuse:
- Sarcoidosis → bilateral hilar adenopathy, noncaseating granulomas (not cavitating nodules + GN)
- TB → cavitation plus infectious risk factors; doesn’t usually give pauci-immune RPGN
- Septic emboli → cavitary nodules, but look for endocarditis/IVDU and bacteremia story
How they’ll try to trick you (classic stem “tells”)
Look for two-organ confirmation:
- ENT symptoms plus pulmonary findings
- Pulmonary findings plus renal findings
- ENT plus renal findings (even if lungs are subtle)
And don’t miss these high-yield extras:
- Otitis media / conductive hearing issues can be part of GPA
- Nasal ulcers / chronic epistaxis
- Hematuria with RBC casts = glomerular bleeding (think nephritic)
Treatment: what you should answer on exams
Depends on severity, but the classic Step framing is:
- Induction (organ-threatening disease):
High-dose glucocorticoids + cyclophosphamide or rituximab - Maintenance (after control):
often azathioprine, methotrexate, or rituximab (protocol-dependent)
If they mention diffuse alveolar hemorrhage or severe RPGN, think: this is emergent and needs aggressive induction therapy.
Micro–mega takeaway (what to recall under time pressure)
Draw face + lungs + kidney. Label c‑ANCA (PR3).
If the question gives you sinusitis + cavitating lung nodules/hemoptysis + hematuria/RPGN, you’re looking at GPA until proven otherwise.