Hypersensitivity Pneumonitis

Differential Diagnosis

In all cases, infectious organisms, especially fungi and mycobacteria must be ruled out

Usual Interstitial Pneumonia	Hypersensitivity Pneumonitis
Lacks granulomas and giant cells	Granulomas and giant cells generally present but may be infrequent in late stage
Random distribution	Usually has some component of bronchiolocentric distribution even in late stage

Areas of chronic hypersensitivity pneumonitis may be identical to UIP
Identification of any of these features should prompt efforts to identify an allergen
Multiple biopsy specimens may be required

Hypersensitivity Pneumonitis	Nonspecific Interstitial Pneumonia
Usually has some component of bronchiolocentric distribution even in late stage	Diffuse interstitial inflammation
Granulomas and giant cells generally present but may be infrequent in late stage	No granulomas or giant cells
Some cases progress to honeycomb change, others may have fibrosis indistinguishable from NSIP	Fibrosis usually diffuse and preserves architecture

These may at times be indistinguishable

Lymphocytic Interstitial Pneumonitis	Hypersensitivity Pneumonitis
Diffuse involvement of alveolar septa	Predominantly peribronochiolar
Marked infiltrate	Patchy, less dense infiltrate
No BOOP-like foci	BOOP-like foci common

Both may have loose granulomas and develop honeycomb change

Respiratory Bronchiolitis Associated Interstitial Lung Disease	Hypersensitivity Pneumonitis
Lacks granulomas and giant cells	Granulomas and giant cells generally present but may be infrequent in late stage
Smoking history only	Possible exposure history
May develop mild-moderate peri-bronchiolar fibrosis but architecture is preserved	May develop significant fibrosis with honeycomb change

Follicular Bronchiolitis	Hypersensitivity Pneumonitis
Fibroplasia is not typically seen	Interstitial fibroblastic foci and intra-airway BOOP-like plugs usually present
No granulomas or giant cells	Granulomas and giant cells generally present but may be infrequent in late stage
No fibrosis	May develop peri-bronchiolar fibrosis with honeycomb change in later stage

Langerhans Cell Histiocytosis	Hypersensitivity Pneumonitis
Lacks granulomas and giant cells	Granulomas and giant cells generally present but may be infrequent in late stage
Smoking history only	Possible exposure history
CD1a and langerin positive Langerhans cells present	No Langerhans cells

Late fibrotic stage may be impossible to separate if active foci cannot be found

Sarcoidosis	Hypersensitivity Pneumonitis
Tight, well formed granulomas	Loose, poorly formed granulomas
Usually mild, at most moderate inflammation	Prominent inflammation
No history of allergen exposure	May have history of allergen exposure