Hypersensitivity Pneumonitis– Causes, Symptoms, Diagnosis, Treatment and Ongoing care



  • A diffuse inflammatory disease of the lung caused by an exaggerated immune response to repeated inhalation of airborne environmental antigens.
  • A wide variety of antigens can cause disease.
  • Spectrum of symptoms with controversial classification, but typically divided into:
    • Acute:
      • Fever, chills, diaphoresis, myalgias, nausea; cough and dyspnea common but not necessary.
      • Occurs 2–9 hours after exposure
      • Lasts hours to days
    • Subacute:
      • More severe respiratory symptoms (cough, dyspnea, cyanosis)
      • Develops over days to weeks
    • Chronic:
      • Progressively worsening cough and exertional dyspnea. Also present with fatigue and weight loss.
      • Occurs over several months, can lead to respiratory failure
  • System(s) affected: Pulmonary
  • Synonym(s): Extrinsic allergic alveolitis; Farmer’s lung


  • Predominant age: Tends to occur in adults as a result of occupation-related exposure
  • Male = Female


  • Incidence difficult to classify due to inconsistent definition of disease
  • Makes up ∼2% of all interstitial lung diseases according to 1 study in New Mexico


0.5–3% prevalence among farmers with exposure (for farmer’s lung specifically) (1)[B]

Risk Factors

  • Exposure to known offending antigen
  • Viral infection at time of exposure could increase risk
  • Nonsmokers have increased incidence compared to smokers (nicotine could have protective effect) (1)[B].


  • Not related to atopic predisposition
  • Possible genetic predisposition involving TNF-α and MHC class II genes (1)[B]

General Prevention

Avoidance of offending antigen is the mainstay of prevention and treatment.


Hypersensitivity reaction involving:

  • Immune complex-mediated reaction: Inhaled antigens bind to IgG, triggering complement cascade.
  • Cellular-mediated reaction: Cell infiltration (predominantly lymphocytic, but also involving neutrophils and macrophages) with formation of granulomas (1)[B]


Multiple syndromes with different causative antigens (all have similar presentations) (2)[B]:

  • Microbes:
    • Farmer’s lung (Thermophilic actinomycetes, Sacharopolyspora rectivirgula)
    • Bagassosis (T. sacchari)
    • Humidifier lung (Micropolyspora faeni)
    • Suberosis (Penicillium frequentans)
    • Malt-worker’s lung (Aspergillus clavatus)
    • Woodworker’s lung (Penicillium chrysogenum)
    • Cheese-washer’s lung (Penicillium casei)
    • Maple-bark stripper’s lung (Cryptostroma corticale)
    • Paprika slicer’s lung (Mucor stolanifer)
    • Hot-tub lung (Mycobacterium avium intracellulare)
    • Summer-type hypersensitivity pneumonitis (Trichosporon cutaneum)
    • Sax lung (Candida albicans)
  • Animals:
    • Bird fancier’s disease (avian proteins)
    • Rat handler lung (rat serum proteins)
    • Fish meal worker’s lung (fish meal extract)
    • Animal handler’s lung (lab animals)
  • Chemicals:
    • Isocyanates (paints, plastics)
    • Anhydrides (plastics)

Dyspnea, interstitial lung diseases, fever chills, respiratory failure, cyanosis, antigens, viral infection, genetic predisposition,



  • Acute form: Develops 2–9 hours following exposure
    • Cough, dyspnea, fever, chills, diaphoresis, headache, nausea
    • Symptoms last hours to days
  • Subacute form: Develops after several days to weeks:
    • Marked by worsening respiratory symptoms
  • Chronic form: Develops after several months of exposure:
    • Progressively worsening cough and dyspnea
    • Also develop fatigue, weight loss, anorexia
  • Other important points in history include:
    • History of pulmonary disease or recurrent infections
    • Recent change in work or home
    • Known exposure to pets, hot tubs, areas with water damage
    • Symptomatic improvement when away from work or home

Physical Exam

  • Acute:
    • Fever
    • Tachypnea
    • Inspiratory crackles
  • Chronic:
    • Progressive hypoxia
    • Weight loss
    • Diffuse rales
    • Clubbing
    • Could possibly show signs of right heart failure if advanced

Diagnostic Tests & Interpretation


  • May have increased inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) (2)[B]
  • Leukocytosis and increased gammaglobulins typically seen
  • Specific IgG antibody to offending agent can be detected and checked serially to detect response to treatment (1)[B]:
    • Not always present (likely because many unknown antigens)
    • Low specificity (10% of people exposed to farmer’s lung antigen develop antibodies; only 0.3% show symptoms)
  • Rheumatoid factor often positive (unknown cause)
  • Negative blood, sputum, throat cultures
  • Bronchoalveolar lavage (BAL) (1)[B]:
    • Acute form with neutrophils and CD4 T lymphocytes
    • Chronic form with high number of CD8 T lymphocytes
    • BAL may help to differentiate chronic hypersensitivity pneumonitis from sarcoid, which has high CD4 T lymphocytes
  • Other tests:
    • Inhalation challenge to suspected environments lack standardization and can cause serious reactions (not recommended) (1)[B].


  • Chest x-ray (CXR): Objective not to rule in disease, but to rule out other etiologies
    • Acute: Diffuse ground-glass infiltrates, nodular or striated patchy opacities. Up to 20% have normal CXR.
    • Subacute: Same as acute, may have sparing of lung bases
    • Chronic: Upper lobe fibrosis, reticular opacities, volume loss, honeycombing
  • CT scan of chest:
    • Acute: Presence of centrilobular micronodules (<5 mm) found in mid and lower zones, mosaic perfusion, air trapping, ground-glass opacities.
    • Subacute: Similar to acute, with generalized increase in lung attenuation and reticulonodular pattern, emphysematous changes.
    • Chronic: Fibrosis, irregular opacities, bronchiectasis, loss of lung volume, honeycombing, emphysematous changes

Initial approach

Usually start with CXR; may progress to CT based on findings

Diagnostic Procedures/Surgery

  • Pulmonary function tests (PFTs) (1)[B]:
    • Acute: Restrictive pattern, low diffusing capacity of the lung for carbon monoxide
    • Chronic: Restrictive pattern, may develop obstructive pattern due to emphysematous changes
  • Lung biopsy (1)[B]:
    • Transbronchial: Limited usefulness
    • Open lung biopsy: Usually reserved when difficulty in diagnosis or atypical response to therapy

Pathological Findings

  • Acute:
    • Alveolar lymphocytosis is a major characteristic.
    • Diffuse interstitial inflammation with macrophages, neutrophils, and plasma cells is also found.
    • Eosinophils are rare.
    • Alveolar space contains proteinaceous exudate and edema.
  • Chronic:
    • Diffuse inflammation, as noted in acute form
    • Noncaseating granulomas, constrictive bronchiolitis
    • Develop fibrosis as disease progresses (may resemble usual interstitial pneumonitis)

Differential Diagnosis

  • Acute:
    • Acute infectious pneumonia
    • Influenza (or other viral pneumonia)
    • Mycoplasma
    • Pneumocystis jirovecii pneumonia
    • Asthma
  • Chronic:
    • Sarcoidosis
    • Chronic bronchitis
    • Chronic obstructive pulmonary disease
    • Tuberculosis
    • Collagen vascular disease
    • Idiopathic pulmonary fibrosis
    • Lymphoma
    • Fungal infections
    • Pneumocystis jirovecii pneumonia



First Line

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  • Avoidance of offending antigen is primary therapy.
  • Corticosteroids (1)[B]:
    • Prednisone: 1–2 mg/kg/d, to max of 50–60 mg PO daily
    • Initial course of 1–2 weeks with progressive taper
    • Low-dose therapy (20 mg PO daily) may be as effective as avoidance.
  • Contraindications: Refer to the manufacturer’s literature.
  • Precautions: Observation for side effects:
    • Immunosuppression
    • Salt and water retention
    • Osteoporosis
    • Acne
    • Hirsutism
    • Behavioral changes
    • Weight gain/appetite increase
  • Significant possible interactions: In patients with renal or cardiovascular disease, a corticosteroid with minimal sodium retention should be chosen.

Second Line

  • Bronchodilators and inhaled corticosteroids may symptomatically improve patients with wheeze and chest tightness (1)[B].
  • Oxygen may be needed in advanced cases.
  • Lung transplantation may be last resort in severe cases unresponsive to therapy.

Additional Treatment

General Measures

  • Appropriate health care: Outpatient except for acute pneumonitis cases and admission for workup (BAL, lung biopsy)
  • Avoidance of offending antigen

Issues for Referral

Referral to pulmonologist indicated for further evaluation and management of chronic disease.

In-Patient Considerations

Initial Stabilization

Supportive management as needed to maintain oxygenation and ventilation.

Admission Criteria

  • Unstable ventilation
  • Oxygen requirement
  • Mental status changes
  • Need for invasive evaluation (lung biopsy)

Ongoing Care

Follow-Up Recommendations

Activity as tolerated based on severity

Patient Monitoring

  • Initial follow-up should be weekly–monthly, depending on severity and course.
  • Follow efficacy of treatments with serial CXR, PFTs, circulating antibody levels (2).


No dietary restrictions

Patient Education

  • Stress pathogenesis and critical importance of allergen avoidance.
  • Stress risk of irreversible lung damage with continued exposure.
  • Note that chronic exposure may lead to a loss of acute symptoms with exposure (i.e., patient may lose awareness of exposure–symptom relationship).


  • Acute: Good prognosis with reversal of pathologic findings if elimination of offending antigen in early disease.
  • Chronic: Corticosteroids have been found to improve lung function acutely, but offer no significant difference in long-term outcome (1)[B].


  • Progressive interstitial fibrosis with eventual respiratory failure
  • Cor pulmonale and right-heart failure


1. Girard M, Lacasse Y, Cormier Y. Hypersensitivity pneumonitis. Allergy. 2009.

2. Ismail T, McSharry C, Boyd G. Extrinsic allergic alveolitis. Respirology. 2006;11:262–8.

Additional Reading

Madison JM. Hypersensitivity Pneumonitis: Clinical Perspectives. Arch Pathol Lab Med. 2008;132:195–8.



495.9 Unspecified allergic alveolitis and pneumonitis


37471005 Extrinsic allergic alveolitis (disorder)

Clinical Pearls

  • Hypersensitivity pneumonitis is a poorly defined interstitial lung disease with different levels of severity.
  • Avoidance of offending antigen is primary treatment.
  • Corticosteroids may help acute presentations but do not affect long-term outcome of chronic disease.

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