What is the recommended treatment approach for hypersensitivity pneumonitis?

Treatment of Hypersensitivity Pneumonitis

The cornerstone of HP treatment is complete and immediate antigen avoidance, which must be achieved within days if the source cannot be remediated, followed by phenotype-specific pharmacotherapy: corticosteroids for nonfibrotic disease with severe symptoms and immunosuppression for fibrotic disease. 1

Step 1: Immediate Antigen Identification and Complete Avoidance

This is the single most critical intervention that directly impacts mortality and disease progression—pharmacotherapy without antigen removal is futile. 1, 2

• Conduct a thorough exposure history focusing on occupational exposures (farmers, bird breeders, industrial workers), household sources (birds, molds, hot tubs, humidifiers), and recreational activities to establish temporal relationship between exposures and symptom onset 1, 3
• Remove the patient from the suspected environment within days if the antigen source cannot be remediated 1
• Involve occupational medicine specialists and environmental hygienists when the exposure source remains unclear despite thorough history 1
• Consider a 2-week hospital antigen avoidance test if the antigen remains unidentified 2

Critical caveat: Up to 60% of HP cases have unidentified antigens despite extensive evaluation, which is independently associated with shortened survival (HR 2.08; 95% CI 1.02-4.24) 1, 2. Do not delay treatment while searching for the antigen—proceed with phenotype-based therapy while continuing exposure investigation 2.

Step 2: Classify Disease Phenotype (Determines Treatment Strategy)

Categorize HP as either nonfibrotic or fibrotic based on high-resolution CT and/or lung biopsy—this classification fundamentally determines treatment approach and prognosis. 1, 3

Nonfibrotic HP characteristics:

• Purely inflammatory without radiological/histopathological evidence of fibrosis 3, 1
• Favorable prognosis with possibility of complete recovery after antigen avoidance 1, 3
• Clinical improvement typically occurs within 2 weeks to 3.4 months after antigen cessation 1

Fibrotic HP characteristics:

• Radiological and/or histopathological evidence of fibrosis (including UIP pattern, NSIP pattern, organizing pneumonia, airway-centric fibrosis) 2
• Reduced survival, particularly with UIP-like pattern 3
• May progress even with complete exposure avoidance 4

Step 3: Pharmacologic Treatment Algorithm

For Nonfibrotic HP:

Antigen avoidance alone is sufficient for mild disease. 1

For severe symptoms or respiratory failure: 1

• Initiate prednisone 1-2 mg/kg/day (typically 40-60 mg daily) 1
• Taper over 4-8 weeks based on clinical response 1
• Evidence: Prednisone 40 mg daily for 8 weeks showed lung function improvement at 1 month (P = 0.03) and reversed lung function decline from -0.35% monthly to +0.84% monthly (P < 0.01) 1

Expected outcomes with complete antigen avoidance: 1, 5

• Patients who avoid antigens for at least 2 years show significant improvement in all lung function parameters (P < 0.01) 1
• Complete antigen avoidance (CAA) in nonfibrotic HP results in no recurrence or development of fibrosis 5
• Incomplete antigen avoidance (IAA) leads to recurrence and/or fibrosis development in 54.5% of patients 5

For Fibrotic HP:

Immunosuppression is the primary pharmacologic treatment—unlike IPF where it is harmful. 2, 1

First-line therapy: 1, 2

• Initiate prednisone 0.5-1 mg/kg/day (typically 40-60 mg daily) 1, 2
• Taper over 3-6 months based on clinical response 1, 2
• Higher doses may be needed for longer periods, though response is often limited 1

For severe disease: 2

• High-dose intravenous methylprednisolone 2-4 mg/kg/day 2
• Monitor closely for fluid retention and electrolyte disturbances 2

Steroid-sparing agents for prolonged therapy: 1

• Mycophenolate mofetil 500-1000 mg/m² body surface area 1
• Azathioprine (alternative option) 1
• Evidence: Mycophenolate mofetil has shown benefit in altering the slope of FVC decline and improving DLCO even when FVC improvement is limited 1

Antifibrotic therapy: 4

• Reserve for progressive fibrotic disease despite immunosuppression and antigen avoidance 2, 4
• Do not use as first-line—fibrotic HP requires antigen remediation and immunosuppression first 2

Step 4: Monitoring and Follow-up

Serial assessments are essential to detect progression and guide therapy adjustments: 1, 2

• Pulmonary function tests (FVC, DLCO) every 3-6 months 1, 2
• High-resolution CT at 6-12 months to assess radiographic response 1, 2
• Clinical effect of corticosteroid treatment should be expected within 3 days to weeks 6

Critical Pitfalls to Avoid

Do not initiate immunosuppression without ensuring complete antigen avoidance first—the benefit of antigen avoidance greatly exceeds the potential harm of immunosuppressive treatment with continued exposure 2

Do not treat fibrotic HP like IPF—the NSIP pattern in fibrotic HP responds to immunosuppression (unlike IPF where it causes harm), and antigen remediation remains paramount 2

Do not assume fibrotic HP is irreversible—even in fibrotic disease, antigen avoidance can stabilize or improve lung function (mean FVC improvement 0.28% monthly vs. 0.28% decline without avoidance) 2

Do not delay antigen identification efforts—though up to 60% of cases have unidentified antigens, this is associated with worse outcomes (HR 1.76-2.08) 2, 1

Do not use long-term corticosteroids without documented objective improvement in clinical signs, pulmonary function, or radiographic abnormalities 7

Prognostic Factors

Poor prognosis indicators in fibrotic HP: 3, 5

• UIP-like pattern on imaging 3
• BAL lymphocytosis <30% (or <50% in some studies) 5
• Honeycombing on HRCT 5
• Cigarette smoking 3
• Lower baseline VC 3
• Persistent exposure or unidentified antigen 3, 1
• All-cause 5-year mortality rate in fibrotic HP: 47.8% 5