A 28-year-old woman presents with one week of fever and chills, 10 lb weight loss, several years of chronic sinusitis with obstruction, and chest imaging showing multiple pulmonary nodules. Antibodies against proteinase 3 are positive. Which diagnosis best explains these findings?

• A. Wegener's granulomatosis
• B. Churg-Strauss syndrome
• C. Microscopic polyangiitis
• D. Systemic lupus erythematosus

Answer: (A)

This presentation is best explained by granulomatosis with polyangiitis, a necrotizing granulomatous vasculitis of small- to medium-sized vessels that classically involves the upper airways, lungs, and kidneys. The combination of chronic sinusitis with obstruction and multiple pulmonary nodules (which can cavitate) fits the pattern of upper and lower airway disease with lung nodules. The positive proteinase 3–ANCA (c-ANCA) is highly characteristic for this condition and strongly supports the diagnosis.

Churg-Strauss would typically feature asthma and eosinophilia with granulomatous inflammation but not this sinus-dominant presentation. Microscopic polyangiitis involves small-vessel vasculitis with necrosis but usually lacks granulomatous inflammation and is more often associated with MPO-ANCA (p-ANCA). Systemic lupus erythematosus presents with a different constellation of symptoms and autoantibodies (like ANA, anti-dsDNA) rather than the upper-airway granulomatous disease seen here.