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
    • 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
    • ESR – frequently elevated
    • 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 – presence of interstitial lymphocytic infiltration, noncaseating granulomas and bronchiolitis obliterans confirms acute disease in appropriate clinical setting

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
    • 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 – initially demonstrate hypoxemia only with exercise
  • Invasive testing
    • Indicated when above testing is negative
    • Bronchoalveolar lavage using bronchoscopy
      • Lymphocytosis – usual presentation is ≥30% in nonsmokers and ≥20% in smokers
      • 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

Differential Diagnosis

  • Asthma
  • Bronchiolitis obliterans
  • Chronic obstructive pulmonary disease (COPD)
  • Eosinophilic lung disease
    • Allergic bronchopulmonary aspergillosis
  • Infectious pneumonia
  • Idiopathic pulmonary fibrosis
  • Pulmonary edemas
  • Sarcoidosis
  • Usual interstitial pneumonia
  • Desquamative interstitial pneumonia
  • Silicosis
  • HIV pneumonitis
  • Drug-induced pneumonitis
  • Nonspecific interstitial pneumonia

Clinical Background

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


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


  • More than 200 different antigens have been associated with HP, including the following
    • Thermophilic actinomyces – farmer's lung, bagassosis, humidifier fever
    • Mycobacterium species – hot-tub lung, machine worker’s lung
    • Fungi/mold – maple bark disease, malt-worker's lung, suberosis, sequoiosis, mushroom worker’s lung
    • Animal proteins – pituitary snuff lung, pigeon breeder's disease, bird fancier’s lung, furrier’s lung
    • Chemicals – bathtub finisher's lung


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

Clinical Presentation

  • Acute/subacute – symptoms typically begin 4-8 hours after exposure
    • Chills, fever, influenza-like presentation
    • Dyspnea, cough – more common in subacute presentation
  • Chronic
    • Airway obstruction with increasing cough and dyspnea
    • Weight loss
    • Disease process may be progressive with eventual fibrotic lung disease after insidious onset


  • Removal from antigen exposure
  • Corticosteroid therapy if indicated

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
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential
Initial testing    
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Initial testing

Immunoglobulin E 0050345
Method: Quantitative ImmunoCAP® Fluorescent Enzyme Immunoassay

Initial testing

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