Hypersensitivity Pneumonitis - Extrinsic Allergic Alveolitis

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. Nonspecific laboratory testing includes CBC, C-reactive protein (CRP), and IgE. Serum precipitating antibody testing is selected based on suspected exposure.


Indications for Testing

  • Recurring pneumonias or pneumonitis in patient with pertinent exposure
    • Cough, wheezing, shortness of breath
  • Interstitial lung disease of unknown cause

Criteria for Diagnosis

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

      Combination of ≥4 major and ≥2 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
      • History, physical findings, and pulmonary function tests indicate interstitial lung disease
      • Radiographs consistent with disease
      • Exposure to recognized antigen
      • Antibody to recognized antigen

      BAL, bronchoalveolar lavage; DLCO, diffusion capacity of the lung for carbon monoxide; HP, hypersensitivity pneumonitis; HRCT, high-resolution computed tomography

      Source: Compiled from Richerson, 1989; Schuyler and Cormier, 1997

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
    • Enzyme-linked immunosorbent assay (ELISA) more sensitive than immunodiffusion


  • Lung biopsy if clinical uncertainty remains after initial testing and bronchoscopic bronchoalveolar lavage (BAL)
    • Multiple biopsies from affected area should be taken
    • 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 nonnecrotizing 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 nonnecrotizing granulomas or Schaumann bodies

      HP, hypersensitivity pneumonia; NSIP, nonspecific interstitial pneumonia; UIP, usual interstitial pneumonia

      Source: 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 computed tomography (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 – BAL 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



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


  • More than 300 different antigens have been associated with HP involving a range of occupations
  • Common Provoking Antigens
    Antigen Type of Hypersensitivity Pneumonitis

    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
    • In progressive disease – eventual fibrotic lung disease after insidious onset

ARUP Laboratory Tests

Evaluate patients suspected of having hypersensitivity pneumonitis induced by exposure to Aspergillus fumigatus, Thermoactinomyces vulgaris, Aureobasidium pullulans, or Micropolyspora faeni

Evaluate patients suspected of having hypersensitivity pneumonitis induced by exposure to Aspergillus fumigatus, Thermoactinomyces vulgaris, Aureobasidium pullulans, or Micropolyspora faeni

Evaluate patients suspected of having hypersensitivity pneumonitis induced by exposure to Aspergillus fumigatus, Thermoactinomyces vulgaris, Aurebasidium pullulans, Micropolyspora faeni, Aspergillus flavus, Saccharomonospora viridis, or Thermoactinomyces candidus

Support the diagnosis of sarcoidosis

Panel includes allergen and antibody testing from hypersensitivity pneumonitis panels as well as allergen testing, Phoma betae, food, beef, pork, epidermals, and animal proteins and feathers

Preferred initial panel for the evaluation of lung inflammation or injury in various types of ILD

A negative result does not rule out ILD

May aid in the evaluation of lung inflammation or injury in various types of ILD

A negative result does not rule out ILD

Related Tests

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Medical Experts



Patricia R. Slev, PhD
Associate Professor of Clinical Pathology, University of Utah
Section Chief, Immunology; Medical Director, Immunology Core Laboratory, ARUP Laboratories
Medical Director, Serologic Hepatitis and Retrovirus and Immunology Core Laboratory
Co-Medical Director, Microbial Immunology, at ARUP Laboratories


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