A 50-year-old man has had a chronic cough for the past 18 months. Physical examination shows nasopharyngeal ulcers, and the lungs have diffuse crackles bilaterally on auscultation. Laboratory studies include a serum urea nitrogen level of 75 mg/dL and a creatinine concentration of 6.7 mg/dL. Urinalysis shows 50 RBCs per high-power field and RBC casts. His serologic titer for C-ANCA (proteinase 3) is elevated. A chest radiograph shows multiple, small, bilateral pulmonary nodules. A transbronchial lung biopsy specimen shows a necrotizing inflammatory process involving the small peripheral pulmonary arteries and arterioles. Which of the following is the most likely diagnosis?
A 50-year-old man has had a chronic cough for the past 18 months. Physical examination shows nasopharyngeal ulcers, and the lungs have diffuse crackles bilaterally on auscultation. Laboratory studies include a serum urea nitrogen level of 75 mg/dL and a creatinine concentration of 6.7 mg/dL. Urinalysis shows 50 RBCs per high-power field and RBC casts. His serologic titer for C-ANCA (proteinase 3) is elevated. A chest radiograph shows multiple, small, bilateral pulmonary nodules. A transbronchial lung biopsy specimen shows a necrotizing inflammatory process involving the small peripheral pulmonary arteries and arterioles. Which of the following is the most likely diagnosis?
💡 Explanation
Okay, let's tackle this question. The patient has a chronic cough, nasopharyngeal ulcers, diffuse pulmonary crackles, renal failure with elevated BUN and creatinine, hematuria with RBC casts, elevated c-ANCA, and bilateral pulmonary nodules with necrotizing vasculitis in the small arteries.
First, I need to recall the key features of vasculitis. C-ANCA is typically associated with Wegener's granulomatosis, now called Granulomatosis with Polyangiitis (GPA). GPA affects the upper and lower respiratory tracts and kidneys. The presence of nasal ulcers, pulmonary nodules, and renal involvement fits. The vasculitis in small vessels (arterioles) is a hallmark. The RBC casts in urine indicate glomerulonephritis, which is common in GPA.
The other options might be other vasculitides like Churg-Strauss or Microscopic Polyangiitis. But Churg-Strauss has eosinophilia and asthma, which aren't mentioned here. Microscopic Polyangiitis also has pauci-immune GN but doesn't have the granulomas that GPA does. The transbronchial biopsy showing necrotizing inflammation in small vessels supports GPA. The c-ANCA (PR3) is specific for GPA. The renal failure and hematuria fit with RPGN, which is seen in GPA. So the most likely diagnosis is Granulomatosis with Polyangiitis.
**Core Concept**
This question tests recognition of Granulomatosis with Polyangiitis (GPA), a small-vessel vasculitis associated with c-ANCA (proteinase 3) targeting the upper/lower respiratory tract and kidneys. Key features include granulomatous inflammation, necrotizing vasculitis, and pauci-immune glomerulonephritis.
**Why the Correct Answer is Right**
The patient’s clinical triad of upper airway ulcers (nasopharyngeal), pulmonary nodules, and glomerulonephritis (RBC casts, elevated creatinine) aligns with GPA. The transbronchial biopsy showing necrotizing vasculitis in small pulmonary arteries confirms vasculitis. c-ANCA positivity (PR3) is diagnostic for GPA, distinguishing it from other vasculitides like Microscopic Polyangiitis (MPO-associated p-ANCA).
**Why Each Wrong Option is Incorrect**
**Option A:** Wegener’s granulomatosis is an outdated name for GPA, so this is the correct answer.
**Option B:** Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) presents with asthma, eosinophilia, and peripheral neuropathy—not renal failure or c-ANCA positivity.
**Option C:** Behçet’s disease features oral/genital ulcers, uveitis, and thrombophlebitis but lacks vasculitis or c-ANCA.
**Option D:** Systemic lupus erythematosus (SLE) can cause glomerulonephritis and pulmonary nodules but is ANCA-negative and associated with antinuclear antibodies (ANA), not c-ANCA.