Definition
• Bilateral inflammatory interstitial lung disease caused by inhaled organic antigens or chemicals with poorly formed nonnecrotizing granulomas and upper lobe predominance
Pathogenesis
• Immune-mediated reaction (hypersensitivity) to repeated inhalations of airborne environmental antigens; usually type III and IV hypersensitivity reactions
Clinical Features
Epidemiology
• More than 300 organic antigens have been reported; farming, birds, and water contamination (typically in basements, leading to molds) account for about 75% of cases
• Prototype HSPs includes “farmer’s lung,” which is caused by thermophilic actinomyces in hay, and “bird fancier’s lung” caused by avian antigens
Presentation
• Main respiratory symptoms are dyspnea and coughing; however, the clinical course is variable
• Acute HSP: acute onset within 4 to 8 hours of antigen exposure (usually heavy) with resolution within 24 to 48 hours; fever, chills, and chest tightness in addition to dyspnea and coughing
• Subacute HSP: slowly progressive respiratory symptoms developing over months’ or years’ continuous exposure to low levels of antigen, with episodes of discrete attacks caused by intermittent heavy antigen exposure
• Chronic HSP: similar to subacute form without discrete attacks; patients present with increasing shortness of breath and chronic coughing; some patients present with extensive end-stage fibrotic disease without ever having been given a diagnosis of HSP
Prognosis and treatment
• Treatment:
• Antigen avoidance is most effective
• Corticosteroids are used to control the symptoms but do not improve overall long-term outcome
• Prognosis:
• Acute and subacute HSP: disease is reversible if antigen exposure can be identified and eliminated
• Chronic HSP: fibrosis is irreversible but may not progress if antigen exposure can be avoided
Pathology
Histology
• Acute HSP: tissues are rarely sampled, and little is known
• Subacute HSP: interstitial pneumonitis characterized by
• Interstitial lymphoplasmacytic infiltrates
• Cellular bronchiolitis
• Interstitial and/or intraalveolar poorly formed nonnecrotizing granulomas comprised of clusters of epithelioid histiocytes with multinucleated giant cells together with lymphocytes and plasma cells; the granulomas are usually small and ill-defined; giant cells may contain occasional cholesterol clefts or asteroid bodies
• A triad of the aforementioned three features are present in more than 80% of cases
• In some cases obliterative bronchiolitis may also be present
• Organizing pneumonia can also be present, and in some cases, it may be the most prominent feature
• Chronic HSP:
• Fibrosis develops in addition to subacute HSP; it may present in three distinct histological patterns:
– Usual interstitial pneumonia (UIP)-like pattern: subpleural, patchy, paucicellular fibrosis with fibroblastic foci and microscopic honeycombing; features to distinguish from UIP:
Upper lobe predominance
Giant cells and poorly formed granulomas
– Nonspecific interstitial pneumonia (NSIP)-like pattern: interstitial fibrosis with preservation of alveolar architecture
Usually there are giant cells and poorly formed granulomas
Sometimes NSIP may be the only histological finding; careful correlation with antigen exposure history is very important
– Irregular peribronchiolar pattern: peribronchiolar fibrosis
Immunopathology/special stains
• GMS and AFB stains are negative
Main differential diagnoses
• Microaspiration pneumonitis:
• Usually with lower lobe predominance
• Poorly formed nonnecrotizing granulomas; giant cells may have large vacuoles (exogenous lipoid pneumonia); foreign body material (e.g., vegetable) only rarely seen
• Sarcoidosis:
• Granulomas are well formed, tightly packed, and sharply delineated
• Characteristic distribution is along bronchovascular bundles and pleura
• UIP:
• Lower lobes are more severely involved
• Giant cells and granulomas are not features of UIP
• NSIP:
• Giant cells and granulomas are not features of NSIP
• It is important to rule out any antigen exposure history
• Chronic eosinophilic pneumonia: inconspicuous granulomas, if present
• Lymphocytic interstitial pneumonia: much more florid lymphocytic infiltrate; without granulomas
Fig 1 Hypersensitivity pneumonitis. Subacute HSP with (A) interstitial lymphoplasmacytic inflammation and (B) cellular bronchiolitis.
Fig 2 Hypersensitivity pneumonitis. The interstitial lymphoplasmacytic infiltrates may be exuberant and associated with eosinophils: low (A), medium (B), and high (C) powers; note multinucleated giant cells within alveolar space in A and B.
Fig 3 Hypersensitivity pneumonitis. Subacute HSP with interstitial and intraalveolar nonnecrotizing granulomas: A and B, Granulomas are poorly formed and are composed of small clusters of epithelioid histiocytes with multinucleated giant cells surrounded by lymphocytes and plasma cells. C-D, Granulomas can be subtle and blend with background inflammation and may contain cholesterol clefts (E) or asteroid bodies (F).
Fig 4 Hypersensitivity pneumonitis. Chronic HSP mimics UIP with interstitial fibrosis with honeycombing (A and B) and fibroblastic foci (C). D and E, The presence of poorly formed granulomas helps to distinguish chronic HSP from UIP.