Hypersensitivity Pneumonitis - Extrinsic Allergic Alveolitis


Indications for Testing

  • Recurring pneumonias or pneumonitis
  • Interstitial lung disease of unknown cause

Criteria for Diagnosis

  • No validated diagnostic criteria; however, Richerson or recent Schuyler criteria may be used
    • Most apply only to acute cases
    • All rely upon abnormal chest radiograph 
    • Diagnostic criteria
      Schuyler and Cormier

      Combination of four or more major and two minor criteria supports the diagnosis of HP

      Major criteria

      • History of symptoms compatible with HP appearing within hours of exposure to the antigen
      • Confirmation of inciting antigen by history, investigation of environment, serum precipitin test, or BAL antibody
      • X-ray or HRCT of chest showing changes consistent with HP
      • BAL lymphocytosis (usually >40%)
      • Histopathological changes on lung biopsy consistent with HP
      • Positive inhalation provocation test

      Minor criteria

      • Bibasilar rales
      • Decreased DLCO
      • Arterial hypoxemia, either at rest or during exercise
      Richerson et al
      • History, physical findings and pulmonary function tests indicate interstitial lung disease
      • Radiographs consistent with disease
      • Exposure to recognized antigen
      • Antibody to recognized antigen
      HP = hypersensitivity pneumonitis; BAL = bronchoalveolar lavage; HRCT = high-resolution computed tomography; DLCO = diffusion capacity of the lung for carbon monoxide

Laboratory Testing

  • Nonspecific testing
    • CBC – neutrophilic leukocytosis most common abnormality
    • C-reactive protein (CRP)
    • IgE – usually normal
  • Serum precipitating antibodies – testing based on suspected exposure
    • Positive findings are only suggestive and help document patient exposure to antigen
    • Low titers do not exclude disease
    • ELISA more sensitive than immunodiffusion


  • Lung biopsy if clinical uncertainty remains after initial testing and bronchoscopic BAL
    • Multiple biopsies from affected area should be taken
  • Histologic features of clinical subtypes of hypersensitivity pneumonitis (HP)

    Histologic features of clinical subtypes of hypersensitivity pneumonitis

    Acute HP

    Subacute HP

    Chronic HP

    • Peribronchiolar inflammation without fibrosis
    • Neutrophilic interstitial and intra-alveolar inflammation
    • Intra-alveolar fibrin
    • Capillaritis in some reports
    • Chronic peribronchiolar inflammation
    • Peribronchiolar fibrosis and/or metaplasia
    • Poorly formed non necrotizing granulomas
    • Cellular NSIP pattern exclusively in some cases
    • Chronic fibrosis resembling UIP or NSIP or with overlapping features
    • Retained subacute features providing diagnostic clues
      • Chronic peribronchiolar inflammation and fibrosis
      • Poorly formed non necrotizing granulomas or Schaumann bodies

    NSIP – nonspecific interstitial pneumonia; UIP – usual interstitial pneumonia

    Compiled from Grunes, 2013 

Imaging Studies

  • Chest x-ray – acute ground glass appearance suggesting pneumonia; mainly used to rule out other diseases
    • ~20% are normal
  • High-resolution CT (HRCT)
    • More sensitive than chest x-ray; perform at end of expiration
    • Central lobular ground glass attenuation and multiple poorly defined nodular opacities <5 mm in diameter (usually in lower lobes)
    • Absence of honeycombing
    • Upper- and mid-zone predominance
    • Air trapping
    • Normal CT argues against HP

Other Testing

  • Pulmonary function studies
    • Restrictive or mixed obstructive and restrictive patterns with decrease in diffusing capacity of lung for carbon monoxide (DLCO) usually <80%
      • Normal results do not exclude disease
    • No discriminatory power to differentiate HP from other interstitial lung diseases
  • Arterial blood gases – demonstrate hypoxemia only with exercise in acute and subacute disease
  • Invasive testing – bronchoalveolar lavage using bronchoscopy
    • Lymphocytosis – usual presentation is ≥30% in nonsmokers and ≥20% in smokers 
      • CD3+/CD8+/CD56+/CD57+/CD10-
    • CD4+/CD8+ – usually <1 in acute disease but may be >1 in chronic disease
      • May help differentiate HP from sarcoidosis, where ratio is usually >1
    • Eosinophilia common (75%) in advanced disease

Differential Diagnosis

  • Acute presentation
  • Subacute presentation
    • Sarcoidosis
    • Idiopathic pulmonary fibrosis
    • Bronchiolitis obliterans
    • Infectious pneumonia – especially M. tuberculosis
    • Usual interstitial pneumonia
    • Desquamative interstitial pneumonia
    • Nonspecific interstitial pneumonia
    • Drug-induced pneumonitis
  • Chronic presentation
    • Nonspecific interstitial pneumonia
    • Unusual interstitial pneumonia
    • Bronchiolitis obliterans
    • Chronic obstructive pulmonary disease (COPD)
    • Idiopathic pulmonary fibrosis
    • Sarcoidosis
    • Asthma
    • Silicosis
    • Drug-induced pneumonitis

Clinical Background

Hypersensitivity pneumonitis (HP) (also called extrinsic allergic alveolitis) is a hypersensitivity syndrome that causes diffuse interstitial lung disease as a result of inhalation of antigenic organic particles.


  • Incidence – interstitial lung disease, 30/100,000
    • 20% are HP
  • Sex – M>F (minimal)


  • More than 300 different antigens have been associated with HP involving a range of occupations
    • Common provoking antigens


      Type of HP

      Thermophilic actinomyces

      Farmer's lung, bagassosis, humidifier fever, suberosis, potato riddler’s lung, mushroom worker’s lung

      Mycobacterium species

      Hot-tub lung, machine operator’s lung

      Fungi/mold (eg, aspergillus sp, botrytis sp, mucor sp)

      Maple bark stripper’s lung, malt worker's lung, suberosis, sequoiosis, woodworker’s lung, cheese washer’s lung, paprika slicer’s lung, wine maker’s lung, tobacco grower’s lung

      Animal proteins

      Pituitary snuff taker’s lung, pigeon breeder's lung, bird fancier’s disease, furrier’s lung, poultry worker's lung


      Bathtub finisher's lung, coptic lung


  • Type III immune complex disease and type IV cell-mediated immunity
  • Repeated exposure to antigen activates alveolar macrophages that release enzymes and cause inflammation and fibrosis
  • Repeated exposure leads to recrudescence of symptoms

Clinical Presentation

  • Acute – symptoms typically begin 4-8 hours after exposure
    • Influenza-like presentation
    • Usually resolves within 48 hours
  • Subacute
    • Dyspnea, cough, fatigue over weeks to months
  • Chronic
    • Airway obstruction with increasing cough and dyspnea
    • Weight loss
    • Disease process may be progressive with eventual fibrotic lung disease after insidious onset

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Hypersensitivity Pneumonitis I 0055076
Method: Qualitative Immunodiffusion

Detects antibodies to Aspergillus fumigatus 1 & 6, Aureobasidium pullulans, pigeon serum, Micropolyspora faeni and Thermoactinomyces vulgaris

Hypersensitivity Pneumonitis II 0055226
Method: Qualitative Immunodiffusion

Detects antibodies to Aspergillus flavus, Aspergillus fumigatus 2 & 3, Saccharomonospora viridis, Thermoactinomyces candidus and Thermoactinomyces sacchari

Hypersensitivity Pneumonitis Extended Panel (Farmer's Lung Panel) 0050157
Method: Qualitative Immunodiffusion/Quantitative ImmunoCAP® Fluorescent Enzyme Immunoassay

Includes allergen and antibody testing from hypersensitivity pneumonitis I and II tests as well as allergen testing, Phoma betae, food, beef, pork, epidermals & animal proteins and feathers

Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Ratio, Bronchoalveolar Lavage 0093420
Method: Flow Cytometry
Help determine activity of the disease    
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Preferred test to detect inflammatory processes

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Initial testing

Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Test for inflammatory processes

Immunoglobulin E 0050345
Method: Quantitative ImmunoCAP® Fluorescent Enzyme Immunoassay

Initial testing