Hypersensitivity Pneumonitis - Extrinsic Allergic Alveolitis

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

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 

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

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

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


  • 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
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.

Hypersensitivity Pneumonitis I 0055076
Method: Qualitative Immunodiffusion

Hypersensitivity Pneumonitis II 0055226
Method: Qualitative Immunodiffusion

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

Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Ratio, Bronchoalveolar Lavage 0093420
Method: Flow Cytometry

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry


Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Sep 2017]

Richerson HB, Bernstein IL, Fink JN, Hunninghake GW, Novey HS, Reed CE, Salvaggio JE, Schuyler MR, Schwartz HJ, Stechschulte DJ. Guidelines for the clinical evaluation of hypersensitivity pneumonitis. Report of the Subcommittee on Hypersensitivity Pneumonitis. J Allergy Clin Immunol. 1989; 84(5 Pt 2): 839-44. PubMed

General References

Cordeiro CR, Jones JC, Alfaro T, Ferreira AJ. Bronchoalveolar lavage in occupational lung diseases. Semin Respir Crit Care Med. 2007; 28(5): 504-13. PubMed

Grunes D, Beasley MB. Hypersensitivity pneumonitis: a review and update of histologic findings. J Clin Pathol. 2013; 66(10): 888-95. PubMed

Madison M. Hypersensitivity pneumonitis: clinical perspectives. Arch Pathol Lab Med. 2008; 132(2): 195-8. PubMed

Myers JL. Hypersensitivity pneumonia: the role of lung Mod Pathol. 2012; 25 Suppl 1: S58-67. PubMed

Ohshimo S, Bonella F, Guzman J, Costabel U. Hypersensitivity pneumonitis. Immunol Allergy Clin North Am. 2012; 32(4): 537-56. PubMed

Schuyler M, Cormier Y. The diagnosis of hypersensitivity pneumonitis. Chest. 1997; 111(3): 534-6. PubMed

Selman M, Pardo A, King TE. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med. 2012; 186(4): 314-24. PubMed

Woda BA. Hypersensitivity pneumonitis: an immunopathology review. Arch Pathol Lab Med. 2008; 132(2): 204-5. PubMed

Medical Reviewers

Last Update: July 2017