Hypersensitivity Pneumonitis - Extrinsic Allergic Alveolitis

Diagnosis

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

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
  • 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.

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

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