What is the treatment approach for an adult patient with hypersensitivity pneumonitis, possibly due to occupational exposure, and pre-existing gastrointestinal symptoms?

Treatment of Hypersensitivity Pneumonitis

Complete and immediate antigen avoidance is the single most critical intervention that directly impacts mortality and disease progression, and must be implemented before any pharmacologic therapy. 1, 2

Immediate Priority: Antigen Identification and Removal

• Conduct a thorough exposure history focusing on occupational exposures (metalworking fluids, polyurethane, contaminated humidifiers), household sources (birds, indoor molds, hot tubs), and recreational activities, establishing temporal relationship between exposures and symptom onset 3, 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) 3, 1, 2
• Consider involving occupational medicine specialists and environmental hygienists when the exposure source remains unclear despite thorough history 1
• Recognize that up to 60% of HP cases have unidentified antigens despite extensive evaluation, but this is independently associated with shortened survival 3, 2

Disease Classification: Critical for Treatment Decisions

Categorize as either nonfibrotic (purely inflammatory) or fibrotic HP based on high-resolution CT and/or lung biopsy, as this fundamentally determines treatment approach and prognosis 3, 1

Nonfibrotic HP:

• Favorable prognosis with possibility of complete recovery after antigen avoidance 3
• 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:

• Reduced survival, particularly with UIP-like pattern on imaging 3
• Often shows no improvement regardless of intervention, though antigen avoidance can stabilize disease 1, 2
• Clinical improvement with antigen avoidance decreases mortality (HR 0.18; 95% CI 0.04-0.77) even in established fibrosis 1

Pharmacologic Treatment Algorithm

For Nonfibrotic HP with Severe Symptoms or Respiratory Failure:

• Prednisone 1-2 mg/kg/day (typically 40-60 mg daily) tapered over 4-8 weeks 1, 4, 5
• 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 1

For Fibrotic HP:

• Initiate prednisone 0.5-1 mg/kg/day tapered over 3-6 months based on clinical response 2
• Higher doses may be needed for longer periods, though response is often limited 1, 4
• Consider immunosuppressive agents (mycophenolate mofetil 500-1000 mg/m² body surface area or azathioprine) as steroid-sparing agents for patients requiring prolonged therapy 1, 4
• Mycophenolate mofetil has shown benefit in altering the slope of FVC decline and improving DLCO even when FVC improvement is limited 1

Special Considerations for Occupational Exposure

• For metalworking fluid exposure: Complete avoidance of metalworking fluid exposure is essential 1
• For hot tub-related HP: Complete avoidance of indoor hot tub use is mandatory 1
• Workplace inspection may help identify the antigen source in occupational cases 1

Addressing Pre-existing Gastrointestinal Symptoms

• Mycophenolate mofetil's most common adverse effects are GI disturbances (along with lymphopenia, anemia, thrombocytopenia, and increased infection risk), but it is relatively less toxic compared to other immunosuppressive agents 1
• Prednisone should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, as steroids may increase perforation risk 5
• Signs of peritoneal irritation following GI perforation may be minimal or absent in patients receiving corticosteroids 5

Monitoring and Follow-up

• Serial pulmonary function tests (FVC, DLCO) every 3-6 months to detect progression 2
• High-resolution CT at 6-12 months to assess radiographic response 2
• Patients who avoid antigens for at least 2 years show significant improvement in all lung function parameters (P < 0.01) in nonfibrotic HP, while continued exposure results in no improvement 1

Critical Pitfalls to Avoid

• Never initiate or escalate immunosuppression without ensuring complete antigen avoidance first—continued exposure negates treatment benefits and increases mortality 1, 2, 4
• Do not assume lack of improvement rules out HP, as fibrotic HP commonly fails to improve with any intervention 1, 2, 4
• Do not treat fibrotic HP like idiopathic pulmonary fibrosis—fibrotic HP with NSIP pattern responds to immunosuppression (unlike IPF where it causes harm), and antigen remediation remains paramount 2
• Do not delay antigen identification efforts despite difficulty, as unidentified exposure is associated with worse outcomes 2
• Do not overlook the need for steroid-sparing agents in patients requiring prolonged corticosteroid therapy 1, 4