What is the diagnostic approach for hypersensitivity pneumonitis?

Diagnostic Approach for Hypersensitivity Pneumonitis

Diagnose hypersensitivity pneumonitis using a systematic approach that begins with classifying the disease as nonfibrotic versus fibrotic on high-resolution CT, followed by detailed exposure history, bronchoalveolar lavage with lymphocyte analysis, and multidisciplinary discussion before considering lung biopsy. 1

Initial Classification and Imaging

First, obtain high-resolution CT (HRCT) of the chest to classify the disease phenotype as either nonfibrotic or fibrotic HP, as this fundamentally changes your diagnostic pathway. 1

Nonfibrotic HP Features on HRCT:

• Ground-glass opacities 2
• Mosaic attenuation pattern with air trapping 3
• Centrilobular nodules 2
• Absence of reticular abnormalities or traction bronchiectasis 1

Fibrotic HP Features on HRCT:

• Reticular abnormalities 1
• Traction bronchiectasis 2
• Architectural distortion 3
• Honeycombing in advanced cases 1

Exposure History Assessment

Conduct an exhaustive environmental and occupational exposure history using a comprehensive questionnaire tailored to your geographic region, focusing on the type, extent, and temporal relationship of exposures to symptoms. 1

Critical Exposures to Identify:

• Bird exposure (feather pillows, pet birds, outdoor exposure) 1
• Mold exposure (water damage, humidifiers, hot tubs) 1
• Occupational antigens (farming, metalworking fluids, wood dust) 1
• Home environment (down comforters, carpeting, ventilation systems) 1

Important caveat: An unrevealing exposure history does NOT exclude HP—up to 60% of patients have no identifiable antigen despite thorough investigation. 1, 3

If occupational exposure is suspected, include an occupational medicine specialist and environmental hygienist in the workup, especially when the source is obscure. 1

Serum Testing

Obtain serum IgG testing against potential antigens associated with HP to help identify exposures, but interpret results cautiously as they have variable sensitivity (25-96%) and specificity (60-100%). 1, 3

• Positive serum precipitins support exposure but do not confirm disease 3
• Negative serum testing does not exclude HP 3

Bronchoalveolar Lavage (BAL)

For Nonfibrotic HP:

Perform BAL with lymphocyte cellular analysis—this is a formal recommendation, not just a suggestion. 1

For Fibrotic HP:

Obtain BAL for lymphocyte cellular analysis before considering more invasive procedures. 1, 3

BAL lymphocytosis (typically >20-30% lymphocytes with CD4/CD8 ratio <1) strongly supports HP diagnosis but is not pathognomonic. 3

Biopsy Considerations

For Nonfibrotic HP:

• Consider transbronchial forceps lung biopsy if diagnosis remains uncertain after HRCT, exposure history, and BAL. 1
• Reserve surgical lung biopsy only when all other diagnostic testing has failed to yield a diagnosis. 1
• No recommendation can be made for or against transbronchial cryobiopsy in nonfibrotic HP 1

For Fibrotic HP:

• Consider transbronchial lung cryobiopsy when diagnosis is uncertain after initial workup. 1
• Surgical lung biopsy remains an option when less invasive testing is inconclusive. 1, 3

Histopathologic Features Supporting HP:

• Cellular interstitial pneumonia 4
• Cellular bronchiolitis 4
• Poorly formed non-necrotizing granulomas 4, 5
• Organizing pneumonia pattern 4
• Fibrosis (in fibrotic phenotype) 4

Multidisciplinary Discussion

Integrate all findings through multidisciplinary discussion involving pulmonologists, radiologists, and pathologists to establish diagnostic confidence before finalizing the diagnosis. 1, 4

The diagnosis should synthesize:

• Compatible HRCT pattern 3
• Exposure history (when identifiable) 3
• BAL lymphocytosis 3
• Histopathology (when obtained) 3

Critical Diagnostic Pitfalls

Do not rely solely on clinical improvement with corticosteroids to confirm diagnosis—HP and other interstitial lung diseases may improve with steroids, creating diagnostic confusion. 2

Do not exclude HP based on lack of improvement with antigen avoidance—disease may progress despite apparent remediation, suggesting other contributing factors or unidentified exposures. 1, 2

Recognize that fibrotic HP can be misdiagnosed as idiopathic pulmonary fibrosis, which has critical therapeutic and prognostic implications. 1

Consider dual pathology, particularly coexisting infection and HP in immunosuppressed patients. 2

Diagnostic Algorithm Summary

1. Obtain HRCT to classify as nonfibrotic vs. fibrotic 1
2. Conduct comprehensive exposure assessment 1
3. Perform serum IgG testing 1, 3
4. Obtain BAL with lymphocyte analysis 1, 3
5. Consider biopsy only if diagnosis remains uncertain 1, 3
6. Integrate findings through multidisciplinary discussion 1, 4

The presence of fibrosis on HRCT or histopathology has significant prognostic implications and should guide both diagnostic intensity and therapeutic approach. 1, 4