What are the pulmonary manifestations of granulomatosis with polyangiitis (GPA)?

Pulmonary Manifestations of Granulomatosis with Polyangiitis (GPA)

The lungs are involved in the majority of GPA patients, with pulmonary nodules and masses being the most characteristic findings, often accompanied by cavitation, ground-glass opacities, and consolidation; diffuse alveolar hemorrhage represents the most life-threatening pulmonary complication. 1, 2, 3

Primary Pulmonary Findings

Nodules and Masses

• Pulmonary nodules and masses are the most common thoracic manifestation, occurring in approximately 50% of patients with GPA 1, 3
• These lesions are typically multiple, bilateral, and range from small nodules to large masses 2, 3
• Cavitation occurs frequently, present in approximately 30-50% of nodular lesions, which is a highly characteristic feature distinguishing GPA from other conditions 2, 3
• Nodules may demonstrate spiculated margins and can invade the pulmonary fissure, pleura, or diaphragm, mimicking malignancy 2

Parenchymal Infiltrates

• Ground-glass opacities and patches of consolidation are frequently observed on chest imaging 3
• Bilateral pulmonary infiltrates occur in the majority of cases 1
• These infiltrates may be migratory and typically respond to immunosuppressive therapy 3

Life-Threatening Complications

• Diffuse alveolar hemorrhage represents the most severe pulmonary manifestation, occurring in a subset of patients and requiring urgent intervention 1, 3
• This complication manifests as diffuse alveolar infiltrates on imaging and can present with hemoptysis, though hemoptysis may be absent in some cases 1
• Alveolar hemorrhage is an indication for consideration of plasma exchange in addition to standard immunosuppression 1

Airway Involvement

Tracheobronchial Disease

• Subglottic stenosis develops in 5-23% of treated patients, presenting insidiously with persistent cough, wheezing, and dyspnea that is frequently misdiagnosed as asthma 1
• Tracheobronchial stenosis occurs in approximately 15% of patients 1
• Bronchial wall thickening is observed in a subset of patients 3

Clinical Pitfall

• Abnormal inspiratory and expiratory flow-volume loops should prompt investigation for subglottic stenosis rather than assuming asthma as the diagnosis 1

Respiratory Symptoms

Common Presentations

• Cough and hemoptysis occur in more than 95% of patients with lower respiratory tract disease 1
• Clinical presentation ranges from subacute nonspecific respiratory illness to rapidly progressive respiratory insufficiency 1
• Non-specific systemic symptoms including fever, malaise, and weight loss frequently accompany pulmonary manifestations 1

Pleural and Diaphragmatic Involvement

• Pulmonary lesions may invade the pleura or diaphragm, creating spiculated appearances that mimic malignancy 2
• While pleural involvement can occur, it is not among the most typical features of GPA 2

Diagnostic Approach for Pulmonary GPA

Essential Imaging

• High-resolution chest CT is mandatory for all suspected GPA cases to characterize pulmonary involvement 1
• Chest imaging findings include nodules, infiltrates, cavitation, masses, and consolidation 1, 3

Pulmonary Function Assessment

• Pulmonary function testing should be performed to detect restrictive or obstructive ventilatory patterns and assess for subglottic stenosis 1
• Serial monitoring of lung function is recommended during follow-up 1

Tissue Confirmation

• Open lung biopsy or bronchoscopic biopsy may be necessary when diagnosis is uncertain 3
• Histologic features include necrotizing vasculitis of small vessels, extensive geographic necrosis, and granulomatous inflammation 4
• Bronchoalveolar lavage should be performed to exclude infectious etiologies (bacterial, mycobacterial, fungal) that can mimic GPA 3

Differential Diagnosis Considerations

Key Distinctions

• GPA must be differentiated from tuberculosis, as both can present with cavitary lung lesions and granulomatous inflammation 5
• Lung malignancy should be excluded, particularly when spiculated masses invading the pleura are present 1, 2
• Other granulomatous conditions including sarcoidosis and fungal infections require exclusion 3

Diagnostic Confirmation

• PR3-ANCA (c-ANCA) is positive in 80-90% of generalized GPA cases, providing strong supportive evidence when combined with characteristic clinical and radiologic findings 1
• In limited disease confined to the respiratory tract, ANCA may be negative in up to 50% of cases, making tissue diagnosis more critical 1

Treatment Response and Monitoring

• Clinical and radiological improvement typically occurs within 6-12 months of initiating immunosuppressive therapy 3
• Disease recurrence is common, occurring in approximately 54% of patients, necessitating long-term monitoring 3
• Routine monitoring of lung function is recommended to detect early relapse or treatment-related complications 1