What are the current treatment guidelines for hypersensitivity pneumonitis in adults, including antigen avoidance, corticosteroid dosing, and second‑line immunosuppressive options?

Treatment Guidelines for Hypersensitivity Pneumonitis

Complete and immediate antigen avoidance is the single most critical intervention that must be implemented before any pharmacologic therapy, as this directly impacts mortality and disease progression even in established fibrotic disease. 1

Antigen Identification and Removal: The Foundation of Treatment

Conduct a comprehensive exposure history focusing on three key domains: occupational exposures (farming, bird breeding, industrial work), household sources (birds, molds, hot tubs, humidifiers), and recreational activities to establish a temporal relationship between exposures and symptom onset. 1

• Remove the patient from the suspected environment within days if the antigen source cannot be remediated, as patients with unidentified antigens have significantly worse survival (HR 2.08; 95% CI 1.02-4.24). 1, 2
• Involve occupational medicine specialists and environmental hygienists when the exposure source remains unclear despite thorough history. 1
• Up to 60% of HP cases have unidentified antigens despite extensive evaluation, which is independently associated with shortened survival. 1, 2

Disease Classification: Critical Decision Point

Categorize HP as either nonfibrotic or fibrotic based on high-resolution CT and/or lung biopsy, as this fundamentally determines treatment approach and prognosis. 1, 2

Nonfibrotic HP Characteristics:

• Purely inflammatory disease lacking radiologic or histopathologic evidence of fibrosis. 1
• Favorable prognosis with possibility of complete recovery after antigen avoidance. 3, 1
• Clinical improvement typically occurs within 2 weeks to 3.4 months after antigen cessation. 1
• Lung function improvement averages 3.4 ± 2.4 months after exposure elimination. 1

Fibrotic HP Characteristics:

• Exhibits radiologic or histopathologic fibrosis (including UIP-like pattern, NSIP pattern, organizing pneumonia, or airway-centric fibrosis). 1, 2
• Associated with reduced survival, particularly with UIP-like pattern. 3, 1
• All-cause 5-year mortality rate approximately 48%. 1

Pharmacologic Treatment Algorithm

For Nonfibrotic HP:

Initiate corticosteroids only for severe symptoms or respiratory failure: prednisone 1-2 mg/kg/day (typically 40-60 mg daily) tapered over 4-8 weeks. 1

• Prednisone at 40 mg daily for 8 weeks showed lung function improvement at 1 month (P = 0.03) in acute nonfibrotic HP. 1
• Corticosteroid treatment reversed lung function decline from -0.35% monthly to +0.84% monthly (P < 0.01) in nonfibrotic HP. 3, 1
• Patients who avoid antigens for at least 2 years show significant improvement in all lung function parameters (P < 0.01), while continued exposure results in no improvement. 3, 1

For Fibrotic HP:

Initiate prednisone 0.5-1 mg/kg/day (typically 40-60 mg daily) tapered over 3-6 months based on clinical response. 1, 2

• Higher doses may be needed for longer periods in fibrotic HP, though response is often limited. 1
• In fibrotic HP, corticosteroid treatment showed no significant changes in lung function (FVC%, P = .96; DLCO%, P = .59). 3

Add steroid-sparing immunosuppressive agents for patients requiring prolonged therapy: mycophenolate mofetil 500-1000 mg/m² body surface area or azathioprine. 1, 2

• Mycophenolate mofetil or azathioprine significantly altered the slope of monthly FVC decline (0.7% vs 0.2%; P = 0.001). 3
• Mycophenolate mofetil increased DLCO% after 1 year of treatment (mean increase 4.2%; 95% CI, 2.6-5.9; P < 0.01). 3
• Consider antifibrotic medications as second-line therapy for progressive fibrotic HP despite immunosuppression. 4

Monitoring Protocol

Serial pulmonary function tests (FVC, DLCO) every 3-6 months are required to detect progression. 1, 2

• High-resolution CT at 6-12 months to assess radiographic response. 1, 2
• Monitor for treatment response: improvement in nonfibrotic HP is much more common than in fibrotic HP. 3

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 delay antigen identification efforts, as unidentified antigen exposure is independently associated with shortened survival (HR 1.76-2.08). 2
• Do not assume fibrotic HP is irreversible, as even in fibrotic disease, antigen avoidance can stabilize or improve lung function. 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 rely solely on lack of clinical improvement with antigen avoidance to rule out HP, as measurable improvement may not occur if the remediated antigen is not causative, if there are multiple exposures, if complete avoidance cannot be achieved, or in subjects with severe or progressive pulmonary fibrosis. 3

Prognostic Factors Associated with Poor Outcomes

Features linked to worse prognosis in fibrotic HP include: 1

• UIP-like pattern on imaging
• Bronchoalveolar lavage lymphocytosis < 30%
• Honeycombing on HRCT
• Cigarette smoking
• Lower baseline vital capacity
• Persistent exposure or unidentified antigen