Hypersensitivity pneumonitis

Hypersensitivity pneumonitis (or extrinsic allergic alveolitis) is a hypersensitivity reaction following exposure to environmental allergens. It is associated with inflammatory interstitial lung disease. Occupational groups affected by hypersensitivity pneumonitis are most commonly exposed to birds, hay, or certain reactive chemical species. Hypersensitivity pneumonitis can be classified into acute, subacute, or chronic forms depending on the frequency, length, and intensity of exposure, severity of symptoms, and duration of subsequent illness. The acute form is characterized by fever, flu-like symptoms, and leukocytosis. The subacute form is characterized by the insidious onset of productive cough, dyspnea, and fatigue over weeks to months. Chronic hypersensitivity pneumonitis is characterized by long-term progressive dyspnea, weight loss, cough, and fatigue. Diagnosis is usually based on occupational history and evidence of fibrosis on imaging, bronchoalveolar lavage with lymphocytosis, positive inhalation challenge testing, or histopathology showing poorly formed noncaseating granulomas or mononuclear cell infiltrate. The preferred treatment for the acute form includes allergen avoidance (e.g., change of occupation) and administration of glucocorticoids for symptomatic relief. The prognosis for the acute form is good. Once severe damage to lung structures has occurred, however, few treatment options remain. Chronic hypersensitivity pneumonitis may lead to pulmonary fibrosis, which may ultimately require transplantation.

• Combined type III hypersensitivity reaction and type IV hypersensitivity reaction with genetic predisposition
• Inhalation of organic particles (< 5 microns), primarily through occupational exposure (notifiable occupational disease) ^[1]
• Farmers are frequently affected

Smokers are less likely to be symptomatic because they have a decreased immune response to new antigens.

• Acute (commencing 4–8 hours after exposure) ^[2]
  • Flu-like symptoms: fever, chills, malaise, cough, headache
  • Dyspnea without wheezing
  • Chest tightness ^[4]
  • Diffuse fine crackles upon auscultation
  • Symptoms subside after 12 hours to several days (in the absence of additional exposure)
• Subacute (weeks to months after continuous exposure)
  • Insidious onset of fatigue
  • Possible progression to persistent productive cough and dyspnea
  • May begin noticing weight loss
• Chronic (months after continuous exposure)
  • Insidious onset of fatigue, productive cough, progressive dyspnea, cyanosis
  • Bilateral rales
  • Weight loss

A recurrent common cold with an irritating cough and fever may indicate hypersensitivity pneumonitis.

Primarily a clinical diagnosis based on history of exposure and typical clinical presentation, which is supported by the presence of any one of the following:

• Positive serology: IgG, IgA, and/or IgM antibodies
• Chest x-ray or CT
  • Acute: Patchy reticulonodular or diffuse infiltrates may be found in the mid to upper zone.
  • Chronic
    • Ground-glass attenuation with honeycombing (irreversible fibrotic changes) with or without emphysema
    • Traction bronchiectasis
    • Thickening of alveolar septa
• Pulmonary function test: restrictive pattern
• Bronchoalveolar lavage (BAL): lymphocytic predominance
• Inhalation challenge
  • Procedure: inhalation of known antigens to observe symptoms within 8–12 hours after exposure in a controlled setting
  • Not routinely done
• Lung biopsy: histopathological confirmation

In hypersensitivity pneumonitis, IgG antibodies are found during an allergic reaction.

• Noncaseating granulomas with lymphocytes and polynuclear giant cells ^[2]

• See “Differential diagnosis of acute cough.”
• See “Differential diagnosis of chronic cough.”

The differential diagnoses listed here are not exhaustive.

• Antigen avoidance
• Glucocorticoid therapy
• Antifibrotic drugs (e.g., nintedanib, pirfenidone) ^[5][6]
• Last resort: lung transplant for persistent cases that are not responsive to medical therapy

• Respiratory failure
• Pulmonary heart disease ^[2]

We list the most important complications. The selection is not exhaustive.

• Favorable in the acute stage, but the disease recurs and worsens upon re-exposure
• Worsens with severity of fibrosis