How should hypersensitivity pneumonitis be treated?

Treatment of Hypersensitivity Pneumonitis

Complete and immediate antigen avoidance is the single most critical intervention that alters disease trajectory and mortality in hypersensitivity pneumonitis, and must be implemented before or alongside any pharmacologic therapy. 1

Step 1: Immediate Antigen Identification and Removal

• Conduct a thorough exposure history focusing on occupational settings (farming, bird breeding, industrial work with isocyanates or metalworking fluids), household sources (pet birds, indoor molds, hot tubs, humidifiers), and recreational activities to establish a temporal relationship between exposures and symptom onset 1, 2

• Remove the patient from the suspected environment within days if the antigen source cannot be remediated—this is non-negotiable 1

• For hot tub-related HP, move indoor hot tubs outdoors or remove them completely 2, 3

• Involve occupational medicine specialists and environmental hygienists when the exposure source remains unclear despite thorough history 1, 2

• Critical caveat: Up to 60% of HP cases have unidentified antigens despite extensive evaluation, which independently worsens survival (HR 2.08; 95% CI 1.02-4.24) 1, 3

Step 2: Classify Disease Phenotype

This classification fundamentally determines your treatment approach and prognosis. 1

Nonfibrotic HP

• Purely inflammatory disease without radiologic or histopathologic fibrosis on high-resolution CT and/or lung biopsy 1
• Favorable prognosis with possibility of complete recovery after antigen avoidance 1
• Clinical improvement typically occurs within 2 weeks to 3.4 months after antigen cessation 1, 3
• Lung function improvement averages 3.4 ± 2.4 months after exposure elimination 1

Fibrotic HP

• Exhibits radiologic or histopathologic fibrosis (including UIP, NSIP, organizing pneumonia, or airway-centric fibrosis) 1
• All-cause 5-year mortality rate is 48% 1
• UIP-like pattern, BAL lymphocytosis <30%, honeycombing, smoking, and lower baseline vital capacity predict worse outcomes 1, 4

Step 3: Pharmacologic Treatment Algorithm

For Nonfibrotic HP

Mild disease with antigen avoidance:

• Antigen avoidance alone may be sufficient 1
• Monitor with serial PFTs every 3-6 months 1

Severe symptoms or respiratory failure:

• Initiate prednisone 1-2 mg/kg/day (typically 40-60 mg daily) 1, 2
• Taper over 4-8 weeks 1
• Prednisone reverses lung function decline from -0.35% monthly to +0.84% monthly (P < 0.01) 1
• Improvement typically seen at 1 month (P = 0.03) 1

For Fibrotic HP

Initial therapy:

• Start prednisone 0.5-1 mg/kg/day (or 1-2 mg/kg/day for severe disease/respiratory failure) 1, 2
• Taper over 3-6 months based on clinical response 1
• Important limitation: Corticosteroids alone do NOT produce significant changes in FVC (P = 0.96) or DLCO (P = 0.59) in fibrotic disease 1

Add steroid-sparing immunosuppression early:

• Initiate mycophenolate mofetil 500-1000 mg/m² body surface area (typically 2-3 g/day) or azathioprine 1, 2
• Adding immunosuppressants markedly slows monthly FVC decline from 0.7% to 0.2% (P = 0.001) 1
• Mycophenolate improves DLCO by an average of 4.2% after one year (95% CI 2.6-5.9; P < 0.01) 1
• Do not use mycophenolate as monotherapy—it must be combined with corticosteroids 2

Progressive disease despite immunosuppression:

• Consider adding nintedanib (antifibrotic therapy) for progressive fibrotic HP 2, 5, 6

Step 4: Monitoring and Expected Response

• Perform serial pulmonary function tests (FVC, DLCO) every 3-6 months to detect progression 1, 3
• Obtain high-resolution CT at 6-12 months to assess radiographic response 1
• Patients who avoid antigens for at least 2 years show significant improvement in all lung function parameters (P < 0.01) in nonfibrotic HP 1
• In nonfibrotic HP with complete antigen avoidance, zero recurrence or fibrosis development occurs 4
• With incomplete antigen avoidance, 54.5% experience recurrence and/or fibrosis development 4

Critical Pitfalls to Avoid

• Never escalate immunosuppression without ensuring complete antigen avoidance first—continued exposure negates treatment benefits and increases mortality 1, 2

• Do not assume lack of improvement rules out HP, especially in fibrotic disease where improvement may be absent due to advanced fibrosis, incomplete avoidance, or unidentified antigen 1, 3

• Do not rely solely on clinical improvement to confirm diagnosis—fibrotic HP commonly fails to improve with any intervention 2, 3

• In fibrotic HP, clinical improvement with antigen avoidance is associated with 82% reduction in mortality (HR 0.18; 95% CI 0.04-0.77) 1, 3

• Recognize that continued exposure in nonfibrotic HP results in no improvement in lung function parameters 1