What is the diagnosis and treatment for an adult with hypersensitivity pneumonitis due to occupational or environmental exposure to specific antigens?

Diagnosis and Treatment of Hypersensitivity Pneumonitis

For adults with suspected hypersensitivity pneumonitis, diagnosis requires integrating three key domains—exposure history, high-resolution CT patterns, and either BAL lymphocytosis ≥30% or compatible histopathology—through multidisciplinary discussion, with treatment centered on complete antigen avoidance and corticosteroids reserved for severe acute presentations or progressive fibrotic disease. 1, 2

Diagnostic Approach

Step 1: Comprehensive Exposure Assessment

Obtain a detailed environmental and occupational exposure history using a structured, regionally-tailored questionnaire covering household, occupational, and recreational exposures. 1

Key exposures to identify include: 1

• Bird exposure (pet birds, feather bedding, outdoor bird contact)
• Mold exposure (water damage, humidifiers, hot tubs, indoor dampness)
• Farming exposures (hay, grain dust, silage)
• Occupational antigens (metalworking fluids, isocyanates, specific industrial processes)

Critical pitfall: Up to 60% of HP cases have no identifiable antigen despite thorough investigation—absence of identified exposure does NOT exclude HP. 2

When occupational exposure is suspected, include an occupational medicine specialist and environmental hygienist in the evaluation, particularly for obscure or unverified sources. 1

Step 2: Classify Disease as Fibrotic vs. Nonfibrotic

Perform high-resolution CT of the chest to determine presence or absence of fibrosis, as this fundamentally alters prognosis and management. 1

Nonfibrotic HP patterns on HRCT: 2

• Profuse centrilobular ground-glass nodules
• Inspiratory mosaic attenuation with expiratory air-trapping
• Ground-glass opacities

Fibrotic HP patterns on HRCT: 2

• Coarse reticulation with minimal honeycombing
• Architectural distortion with fibrotic changes
• Evidence of small airway disease with air-trapping

Major diagnostic pitfall: Fibrotic HP is frequently misdiagnosed as idiopathic pulmonary fibrosis due to overlapping features and occasional UIP-like patterns on histopathology. 2 The presence of air-trapping, centrilobular nodules, and mosaic attenuation favor HP over IPF.

Step 3: Obtain Bronchoalveolar Lavage

Perform BAL to assess for lymphocytosis ≥30%, which strongly supports HP diagnosis. 2

BAL findings in HP: 3

• Increased total cell count with lymphocyte predominance >50%
• Increased neutrophils >3%
• Increased mast cells >1%

Step 4: Consider Serum Antigen-Specific IgG Testing

Order serum precipitins or antigen-specific IgG panels when exposure history is unclear, but interpret cautiously. 2

Important limitation: Positive serum IgG indicates exposure only, NOT disease (sensitivity 25-96%, specificity 60-100%). Negative testing does not exclude HP. 2 Serum precipitins have high false-positive and false-negative rates. 2

Step 5: Lung Biopsy (When Necessary)

Reserve transbronchial or surgical lung biopsy for cases where clinical, radiologic, and BAL findings remain indeterminate after multidisciplinary discussion. 1, 2

Histopathologic criteria for nonfibrotic HP: 1, 2

• Cellular interstitial pneumonia with bronchiolocentric distribution
• Cellular bronchiolitis with lymphocytic infiltration
• Poorly formed non-necrotizing granulomas and/or multinucleated giant cells
• Small foci of organizing pneumonia

Histopathologic criteria for fibrotic HP: 1, 2

• Airway-centered fibrosis with peribronchiolar metaplasia
• Chronic fibrosing interstitial pneumonia (may show NSIP or UIP-like patterns)
• Poorly formed granulomas with fibrotic bronchiolocentric accentuation

Critical caveat: Isolated histopathologic findings (e.g., granulomas alone) are insufficient for HP diagnosis and can occur in other interstitial lung diseases. All biopsy findings require multidisciplinary reconciliation with clinical and radiologic data. 1, 2

Step 6: Establish Diagnostic Confidence Level

High-confidence HP diagnosis requires: 2

• Identified or highly suspected antigen exposure
• Typical HRCT pattern for HP
• BAL lymphocytosis ≥30% OR compatible histopathology

Provisional HP diagnosis is appropriate when some but not all criteria are met, and these patients should be referred to an interstitial lung disease center. 1

Treatment Strategy

Primary Treatment: Antigen Avoidance

Complete and permanent avoidance of the identified or suspected inciting antigen is the cornerstone of HP management and the only intervention proven to alter disease progression. 1, 4

Implement antigen avoidance strategies: 1

• Remove bird exposure sources (rehome pets, replace feather bedding)
• Remediate water damage and mold contamination
• Modify occupational exposures (engineering controls, respiratory protection, job reassignment)
• Conduct workplace environmental assessment when indicated

Monitor for ongoing exposure at every clinical visit, as disease may progress despite apparent remediation, suggesting unidentified additional exposures. 1

Pharmacologic Treatment

For acute HP with severe symptoms: 5, 4

• Short course of prednisone 0.5-1 mg/kg/day for 2-3 weeks
• Acute HP typically responds to antigen removal alone; corticosteroids provide symptomatic relief

For subacute or chronic progressive fibrotic HP: 4

• Higher-dose corticosteroids (prednisone 0.5-1 mg/kg/day) for longer duration (months)
• Taper based on clinical response

Critical limitation: Long-term efficacy of corticosteroids in chronic HP is not well-defined, and measurable improvement with antigen avoidance occurs primarily in nonfibrotic HP. 2, 5

For progressive fibrotic HP despite antigen avoidance: 4

• Consider antifibrotic therapy (nintedanib or pirfenidone) for patients with progressive phenotype
• This represents emerging evidence for fibrotic HP similar to IPF management

Genetic Risk Factors Affecting Prognosis

The MUC5B promoter variant (rs35705950) increases risk of fibrotic progression and is associated with shortened survival in HP. 6 While not routinely tested, awareness of genetic susceptibility helps explain why some patients progress despite complete antigen avoidance.

Prognosis and Follow-up

Nonfibrotic HP: Generally favorable prognosis with complete antigen avoidance, though some patients develop progressive fibrosis. 5, 7

Fibrotic HP: Poorer prognosis, particularly when antigen remains unidentified or avoidance is incomplete. Some patients progress to severe respiratory insufficiency despite all interventions. 3, 4

Surveillance strategy: Serial pulmonary function testing and HRCT imaging to detect progression, with continued exposure assessment at each visit. 1