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Hypersensitivity Pneumonitis

Definition

  • Pulmonary disease secondary to inhaled allergens

Alternate/Historical Names

  • Extrinsic allergic alveolitis (equvalent term)
  • Many allergen specific names, a few of which are:
    • Bird fancier's lung
    • Farmer's lung
    • Hot tub lung
    • Humidifier lung

Diagnostic Criteria

Clinical

  • May present as acute, subacute or chronic disease
    • Acute
      • Usually follows 2-9 hours after a heavy exposure
        • Patient must be presensitized (frequently unknowingly)
      • Flu-like symptoms
        • Fever, chills, malaise, nausea
        • Cough may progress to respiratory insufficiency
      • If purely acute, usually resolves in 1-2 days with supportive treatment
      • Subacute and chronic patients may present with acute exacerbation
    • Subacute
      • Gradual onset of dyspnea, cough over days or weeks
      • Follows continued intermittent exposure
      • Good response to steroids and avoidance/removal of antigen
    • Chronic
      • Chronic dyspnea, fatigue, weight loss
      • Usually continued low level antigen exposure
        • Antigen may not be identifiable
      • Generally due to irreversible fibrosis
    • Most identified allergens are exogenous fungi (molds) and mycobacteria (hot tubs)
      • Allergic bronchopulmonary aspergillosis may be an allergen source
      • A few examples of molecular antigens have been identified (isocyanates, zinc)

High Resolution Computed Tomography

  • Centrilobular nodularity and ground glass opacities
  • Chronic disease shows reticular fibrosis
    • May progress to honeycomb change
      • Usually central, but may be peripheral
    • Emphysema and cysts may be seen

Pathology

  • Diagnosis can frequently be made based on history, physical findings, radiology and serologic reaction to suspected allergen, without biopsy
  • Bronchoalveolar lavage shows lymphocytosis, frequently >50%
    • Mast cells >1% are very suggestive
  • Role of the biopsy is to suggest the diagnosis when it was not suspected clinically, to rule out iinfection or to evaluate cases with atypical presentation
    • Most cases are not biopsied
    • Even if the biopsy suggests hypersensitivity pneumonitis, the final diagnosis must be made clinically
  • Acute phase is rarely biopsied
    • Neutrophils fill alveoli and respiratory bronchioles
    • Frequent loose, non-caseating granulomas
    • Diffuse alveolar damage pattern with hyaline membranes may be present
  • Subacute and chronic phases show a spectrum of changes
    • Bronchiolocentric cellular interstitial infiltrate
      • Occasional lymphoid follicles may be seen
    • Poorly formed non-caseating granulomas
      • May be associated with multinucleated giant cells
        • Frequently contain cholesterol clefts, Schaumann bodies, asteroid bodies
      • Usually infrequent in chronic disease
    • BOOP-like plugs of intralumenal organizing granulation tissue and interstitial fibroblastic foci
      • Both are decreased in chronic phase but frequently present focally
    • Fibrosis is present in chronic phase
      • May be NSIP-like with homogeneous linear pattern
      • May be UIP-like with subpleural patchy pattern leading to honeycomb change
      • Centrilobular accentuation of peribronchiolar fibrosis is very suggestive of hypersensitivity pneumonitis
        • Surrounds and may occlude bronchiole
        • Fibrosis may bridge from centrilobular to peripheral zones
      • Fibrosis is generally not reversible and imparts a poor prognosis
    • Heavy re-exposure to antigen may lead to a superimposed acute reaction

Gerald J Berry MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 11/20/10

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

Classification / Lists

Idiopathic Interstitial Lung Diseases

Other Diffuse Parenchymal Lung Diseases

 

Bibliography

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