- 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:
- Fever, chills, diaphoresis, myalgias, nausea; cough and dyspnea common but not necessary.
- Occurs 2–9 hours after exposure
- Lasts hours to days
- More severe respiratory symptoms (cough, dyspnea, cyanosis)
- Develops over days to weeks
- 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]
- 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]
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]:
- 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)
- 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)
- Isocyanates (paints, plastics)
- Anhydrides (plastics)
- 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
- Inspiratory crackles
- Progressive hypoxia
- Weight loss
- Diffuse rales
- 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
Usually start with CXR; may progress to CT based on findings
- 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
- 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.
- Diffuse inflammation, as noted in acute form
- Noncaseating granulomas, constrictive bronchiolitis
- Develop fibrosis as disease progresses (may resemble usual interstitial pneumonitis)
- Acute infectious pneumonia
- Influenza (or other viral pneumonia)
- Pneumocystis jirovecii pneumonia
- Chronic bronchitis
- Chronic obstructive pulmonary disease
- Collagen vascular disease
- Idiopathic pulmonary fibrosis
- Fungal infections
- Pneumocystis jirovecii pneumonia
- 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:
- Salt and water retention
- 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.
- 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.
- 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.
Supportive management as needed to maintain oxygenation and ventilation.
- Unstable ventilation
- Oxygen requirement
- Mental status changes
- Need for invasive evaluation (lung biopsy)
Activity as tolerated based on severity
- 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
- 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.
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)
- 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.