Summary
Hypersensitivity pneumonitis (HP) is a hypersensitivity reaction caused by inhalation of environmental and/or occupational antigens, manifesting in interstitial lung disease (ILD). Individuals affected by HP are most commonly exposed to animal proteins (especially birds), fungi, bacteria, or inorganic chemicals. HP can be classified as fibrotic or nonfibrotic based on findings on high-resolution CT (HRCT) of the chest. Onset may be acute with constitutional symptoms, flu-like symptoms, and leukocytosis, or more insidious (e.g., cough, dyspnea, fatigue, and weight loss). Diagnosis is based on exposure history and evidence of fibrosis on imaging, lymphocytosis on bronchoalveolar lavage, and histopathology showing poorly formed noncaseating granulomas or mononuclear cell infiltrate. Most acute episodes are self-limited and resolve with antigen avoidance. Patients with persistent symptoms after antigen removal often receive immunosuppressants (e.g., glucocorticoids). Patients with refractory fibrotic HP may ultimately require lung transplantation.
Etiology
- 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
| Overview of antigens and diseases in hypersensitivity pneumonitis | ||
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| Animal proteins |
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| Microorganisms |
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| Chemical substances |
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Smokers are less likely to be symptomatic because they have a decreased immune response to new antigens.
Clinical features
- Acute: typically within 12 hours of exposure to the inciting antigen [4]
- Chronic: after weeks to years of antigen exposure [4]
Patients with chronic HP do not necessarily have a history of acute HP. [7]
A recurrent common cold with an irritating cough and fever may indicate hypersensitivity pneumonitis.
Diagnosis
The diagnosis of HP is based on a history of antigen exposure, typical clinical and radiologic features, and supportive diagnostic studies.
Approach [7][8]
- Perform a thorough occupational and environmental exposure history to identify potential inciting antigens.
- Obtain a high-resolution CT (HRCT) for all patients.
- Consult a multidisciplinary care team to guide additional studies. [7][8]
Clinical improvement after antigen avoidance supports the diagnosis of HP, but lack of improvement should not be used to rule out the diagnosis. [7]
High-resolution CT [7][8]
Findings are used to classify HP as fibrotic or nonfibrotic (i.e., purely inflammatory), which impacts further workup, treatment, and prognosis.
- Obtain an HRCT for all patients. [9]
- Typical findings include:
- Ill-defined centrilobular nodules
- Honeycombing (irreversible fibrotic changes) with or without emphysema
- Thickening of alveolar septa
- Traction bronchiectasis or bronchiolectasis
- Ground-glass opacities with inspiratory mosaic attenuation or three-density pattern [8]
- Upper or midlung predominance and diffuse distribution in the axial plane
Atypical HRCT findings for HP (e.g., usual interstitial pneumonia pattern) may still be compatible with HP. Specialist consultation is recommended for determining the likelihood of HP versus other causes of ILD. [7]
Classification of HP patients into acute, subacute, or chronic HP does not have clear treatment or prognostic implications and is no longer recommended; patients are now classified based on the presence or absence of fibrosis. [7][8]
Additional studies [7][8]
Additional studies should be considered in consultation with a multidisciplinary care team (e.g., pulmonology, radiology, pathology, and occupational medicine). See also “Diagnostics for ILD” for a broader workup.
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Bronchoalveolar lavage (BAL)
- Consider BAL for all patients to further support the diagnosis or exclude differential diagnoses (e.g., infection). [7]
- Supportive findings: Lymphocytosis (e.g., ≥ 20–30%) is highly sensitive for HP. [7][8]
- Serology: The targeted use of antigen-specific IgA and/or IgG antibodies can support the diagnosis. [7]
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Lung biopsy
- Consider if noninvasive testing has yielded inconclusive results. [7][8]
- Supportive findings: noncaseating granulomas with lymphocytes and polynuclear giant cells
- Pulmonary function testing: restrictive pattern; see “PFT findings in obstructive vs. restrictive lung diseases.” [9][10]
Antigen-specific inhalation challenge and specific lymphocyte proliferation testing (i.e., in-vitro assessment of polyclonal T-cell response after antigen exposure) are no longer recommended. [7]
Differential diagnoses
- See “Differential diagnosis of acute cough.”
- See “Differential diagnosis of chronic cough.”
- See “Etiology of interstitial lung disease.”
The differential diagnoses listed here are not exhaustive.
Treatment
Antigen avoidance, supportive management of ILD, and specialist-directed pharmacotherapy are the mainstays of therapy. Consider lung transplantation for patients with fibrotic HP that does not respond to medical therapy.
Pharmacotherapy [4]
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Immunosuppressants
- Glucocorticoid therapy
- Additional agents (e.g., mycophenolate mofetil, azathioprine, rituximab) may also be used in combination with glucocorticoids and/or as glucocorticoid-sparing agents.
- Antifibrotic drugs (e.g., nintedanib, pirfenidone): may decrease disease progression in patients with fibrotic HP. [11][12]
Complications
We list the most important complications. The selection is not exhaustive.