Can Granulomatosis with Polyangiitis (GPA) be confined to the bronchial airways without involving the lung parenchyma?

Can GPA Be Confined to the Bronchial Airways Without Lung Parenchymal Involvement?

Yes, GPA can be confined to the bronchial airways without involving the lung parenchyma, representing a form of localized or limited disease that affects the tracheobronchial tree in isolation.

Airway-Specific GPA Manifestations

GPA commonly involves the airways as part of its respiratory manifestations, and this can occur independently of parenchymal disease:

• Subglottic and endobronchial involvement occurs as a distinct manifestation of GPA, with actively inflamed tissue causing stenosis that requires specific management with immunosuppressive therapy rather than surgical intervention alone 1
• The larynx, trachea, and bronchi can be affected by GPA's characteristic necrotizing granulomatous inflammation and vasculitis, presenting with symptoms such as cough, wheezing, stridor, dyspnea, or hoarseness 2
• Bronchial involvement may manifest as bronchial wall inflammation and stenosis without necessarily extending into the surrounding lung parenchyma 1

Localized vs. Systemic Disease Patterns

The spectrum of GPA includes both localized and systemic forms with varying organ involvement:

• Localized GPA affects approximately 50% of patients with c-ANCA positivity, compared to 90% in systemic forms, and can be confined to specific anatomical sites including the airways 1
• The disease demonstrates heterogeneous severity, ranging from indolent single-site involvement to fulminant multiorgan vasculitis 3
• ENT involvement occurs in 70-100% of cases and may be the first clinical manifestation, but this does not necessarily coincide with lung parenchymal disease 2

Imaging Considerations for Airway-Confined Disease

When GPA is limited to the airways, imaging findings differ from parenchymal involvement:

• Chest CT is more sensitive than conventional radiographs for detecting pulmonary manifestations, but may show airway-specific abnormalities such as bronchial wall thickening or stenosis without parenchymal nodules, infiltrates, or cavitary lesions 4
• Classic parenchymal findings include diffuse infiltration, multiple pulmonary nodules (2-4cm), or large necrotic cavitating masses (≥10cm), which would be absent in purely airway-confined disease 1
• Bronchoscopy may be necessary to visualize inflammation, collapse, and stenosis of the airways directly when imaging is inconclusive 5

Diagnostic Approach for Airway-Limited GPA

• PR3-ANCA testing should be performed, though it is positive in only 50% of localized forms compared to 84-85% of systemic GPA 4, 1
• Biopsy of affected airway tissue is recommended whenever possible to confirm the diagnosis, looking for the characteristic triad of necrotizing vasculitis, granulomatous inflammation, and necrosis 4, 2
• Pulmonary function tests including inspiratory and expiratory flow-volume curves can identify clinically subtle airway involvement even when parenchymal disease is absent 5

Treatment Implications

Airway-confined GPA requires specific therapeutic considerations:

• For patients with actively inflamed subglottic and/or endobronchial tissue with stenosis, immunosuppressive therapy is conditionally recommended over surgical dilation with intralesional glucocorticoid injection alone 1
• The standard approach involves glucocorticoids combined with either rituximab or cyclophosphamide for remission induction, even in localized disease with significant airway involvement 4
• Maintenance therapy with rituximab, azathioprine, or methotrexate should be continued for at least 18-24 months to prevent relapse 4

Clinical Pitfalls

• Do not assume that absence of parenchymal findings on imaging excludes significant GPA; airway involvement can be life-threatening due to stenosis and respiratory compromise 2
• Persistent or chronic cough may be one of the first and most important symptoms signifying respiratory involvement, even without parenchymal disease 5
• The consistency rate between radiological and histological findings in GPA is high (100%), but when lung involvement is suspected, biopsy should still be considered for proper classification 6