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 DL_CO
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; DL_CO = 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

Histology

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 (DL_CO) 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
Infectious pneumonia
Idiopathic pulmonary fibrosis
Pulmonary edemas
Sarcoidosis
Usual interstitial pneumonia
Desquamative interstitial pneumonia
Silicosis
HIV pneumonitis
Drug-induced pneumonitis
Nonspecific interstitial pneumonia

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.

Epidemiology

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

Etiologies

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

Pathophysiology

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

Treatment

Removal from antigen exposure
Corticosteroid therapy if indicated

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use: Initial testing

Test name: Sedimentation Rate, Westergren (ESR)

ARUP #: 0040325

Methodology: Westergren

Use:

Initial testing

Test name: Immunoglobulin E

ARUP #: 0050345

Methodology: Quantitative ImmunoCAP®

Use:

Initial testing

Test name: Hypersensitivity Pneumonitis I

ARUP #: 0055076

Methodology: Qualitative Immunodiffusion

Use:

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

Test name: Hypersensitivity Pneumonitis II

ARUP #: 0055226

Methodology: Qualitative Immunodiffusion

Use:

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

Test name: Hypersensitivity Pneumonitis Extended Panel (Farmer's Lung Panel)

ARUP #: 0050157

Methodology: Qualitative Immunodiffusion/Quantitative ImmunoCAP®

Use:

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

Test name: Lymphocyte Subset Panel 4 - T-Cell Subsets Percents and Ratio, Bronchoalveolar Lavage

ARUP #: 0093420

Methodology: Flow Cytometry

Use: Help determine activity of the disease

Guidelines

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) :839-844.PubMed

General

Tebo, Anne E., PhD. Assistant Medical Director, Immunology at ARUP Laboratories; Assistant Professor of Pathology (Clinical), University of Utah

Comprehensive Review: November 2011
Last Update: November 2011

Allergic Disease

Eosinophilic Diseases

Mold-Associated Infections

Respiratory Viruses

Sarcoidosis

Schistosoma Species