A 42-year-old woman presents with a 3-month history of chronic sinusitis, epistaxis, saddle-nose deformity, hoarseness, and progressive dyspnea on exertion with audible stridor. Laboratory investigations reveal hematuria and c-ANCA positivity with anti-PR3 antibodies. Chest X-ray shows a cavitary lung lesion. Spirometry reveals a fixed upper airway obstruction pattern with flattening of both inspiratory and expiratory limbs of the flow-volume loop (marked as **C** in the diagram), and CT neck confirms circumferential subglottic narrowing. What is the most likely diagnosis?
A. Polyarteritis nodosa with upper airway vasculitis
B. Microscopic polyangiitis with secondary laryngeal involvement
C. Granulomatosis with Polyangiitis (GPA/Wegener granulomatosis)
D. Eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss)
Explanation
Why Granulomatosis with Polyangiitis (GPA/Wegener granulomatosis) is right
The clinical presentation is pathognomonic for GPA: the classic triad of upper airway disease (chronic sinusitis, epistaxis, saddle-nose deformity, and subglottic stenosis), lower airway involvement (cavitary lung lesion), and renal disease (hematuria). The spirometric pattern marked C — fixed upper airway obstruction with flattening of both inspiratory and expiratory limbs of the flow-volume loop — is the hallmark of subglottic stenosis, which occurs in approximately 16% of GPA patients. The rigid, scarred subglottic ring cannot vary with respiratory phase, producing the characteristic "box-like" flow-volume loop. The c-ANCA/anti-PR3 serology is positive in 80–90% of generalized GPA and is the classic serologic marker. GPA is an ANCA-associated small-vessel vasculitis with necrotizing granulomatous inflammation. (Chapel Hill Consensus Conference 2012; Harrison's 21e Vasculitis)
Why each distractor is wrong
Microscopic polyangiitis with secondary laryngeal involvement: Microscopic polyangiitis is a pauci-immune crescentic glomerulonephritis without granulomatous inflammation. It does not produce the characteristic upper airway manifestations (saddle-nose deformity, subglottic stenosis) or cavitary lung lesions that define GPA. Subglottic stenosis is a hallmark of GPA, not MPA.
Polyarteritis nodosa with upper airway vasculitis: PAN is a medium-vessel vasculitis that spares the lungs and glomeruli; it does not cause pulmonary cavitary lesions, glomerulonephritis, or the necrotizing granulomatous inflammation seen here. PAN is ANCA-negative.
Eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss): EGPA is characterized by asthma, eosinophilia, and pulmonary infiltrates, but does not typically present with the classic upper airway triad (sinusitis, saddle-nose, subglottic stenosis) or cavitary lung lesions. EGPA is usually p-ANCA/MPO-positive, not c-ANCA/PR3-positive.
