A 42-year-old Indian woman with a 6-month history of progressive dyspnea, hemoptysis, and constitutional symptoms presents with a productive cough and fever. Chest X-ray shows bilateral pulmonary infiltrates with cavitation. Serum creatinine is 2.8 mg/dL, and urinalysis reveals hematuria with red blood cell casts. Antineutrophil cytoplasmic antibody (ANCA) testing is positive for cytoplasmic ANCA (c-ANCA) with anti-PR3 antibodies. Chest computed tomography confirms multiple cavitary lung lesions. What is the most likely diagnosis?

Explanation

## Diagnosis: Granulomatosis with Polyangiitis (GPA) ### Clinical Presentation Recognition **Key Point:** The triad of upper respiratory involvement (cavitary lung disease), lower respiratory involvement (hemoptysis, pulmonary infiltrates with cavitation), and glomerulonephritis (hematuria with RBC casts, elevated creatinine) is pathognomonic for GPA (formerly Wegener granulomatosis). ### Differential Diagnosis of ANCA-Associated Vasculitides | Feature | GPA | MPA | EGPA | |---------|-----|-----|------| | **ANCA type** | c-ANCA (anti-PR3) | p-ANCA (anti-MPO) | p-ANCA (anti-MPO) | | **Lung involvement** | Cavitary nodules, infiltrates | Non-cavitary infiltrates | Infiltrates, asthma | | **Upper respiratory tract** | Sinusitis, nasal granulomas | Absent | Absent | | **Glomerulonephritis** | Necrotizing, crescentic | Necrotizing, crescentic | Necrotizing, crescentic | | **Granulomas** | Present (necrotizing) | Absent | Present (non-necrotizing) | | **Eosinophilia** | Absent | Absent | Prominent (>1500/μL) | | **Asthma history** | Absent | Absent | Present (usually precedes vasculitis) | ### Why GPA Is the Correct Diagnosis 1. **c-ANCA with anti-PR3 antibodies:** Highly specific for GPA (>95% specificity) 2. **Cavitary lung lesions:** Characteristic of GPA; MPA typically presents with non-cavitary infiltrates 3. **Upper respiratory involvement:** The clinical context suggests sinus/respiratory tract disease typical of GPA (though not explicitly stated, cavitary lung disease in this context is GPA-specific) 4. **Glomerulonephritis with hematuria and RBC casts:** All three ANCA-associated vasculitides cause necrotizing glomerulonephritis, but the combination with cavitary lung disease and c-ANCA/anti-PR3 is diagnostic for GPA **High-Yield:** c-ANCA/anti-PR3 = GPA; p-ANCA/anti-MPO = MPA or EGPA. The presence of cavitary lung lesions distinguishes GPA from MPA (which causes non-cavitary infiltrates). ### Pathophysiology GPA is a systemic necrotizing vasculitis affecting small and medium vessels. The disease is characterized by: - Necrotizing granulomatous inflammation - Necrotizing vasculitis of small and medium vessels - Necrotizing glomerulonephritis The classic triad involves: 1. **Upper respiratory tract:** Sinusitis, nasal granulomas, epistaxis 2. **Lower respiratory tract:** Pulmonary nodules (often cavitary), hemoptysis 3. **Kidneys:** Rapidly progressive glomerulonephritis (RPGN) **Clinical Pearl:** Cavitary lung lesions in an ANCA-positive patient with glomerulonephritis should immediately raise suspicion for GPA. MPA does not typically cause cavitary disease. ### Management Overview ```mermaid flowchart TD A[Suspected GPA]:::outcome --> B{Organ involvement severity?}:::decision B -->|Severe: lung/kidney involvement| C[Induction: Cyclophosphamide or Rituximab + Corticosteroids]:::action B -->|Localized: upper respiratory only| D[Induction: Corticosteroids + Methotrexate]:::action C --> E[Remission achieved]:::outcome D --> E E --> F[Maintenance: Azathioprine or Rituximab]:::action F --> G[Monitor for relapse and toxicity]:::action ``` [cite:Harrison 21e Ch 319; ACR 2021 Guidelines on ANCA-Associated Vasculitis]