Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, represents a group of pulmonary disorders mediated by an inflammatory reaction to inhalation of an allergen. These may be organic or inorganic particles (microbes, animal or plant proteins, and certain chemicals) that form haptens by sensitised individuals.
More than 200 different antigens have been associated with the development of HP, including plant products, animal products, aerosolized microorganisms, and organic chemicals. Smoking is protective against HP.
Depending on the type of precipitant, numerous other more precipitant specific terms have been used such as:
- bird fancier's lung: pigeon fancier's lung
- farmer's lung
- cheese worker’s lung
- mushroom worker’s lung
- malt worker’s lung
- maple bark disease
- hot tub lung
- organic chemicals such as isocyanates found in paint hardeners
- from immunosuppressant used in organ transplantation: e.g. sirolimus/everolimus 8
The diagnosis relies on a constellation of findings: exposure to an offending antigen, characteristic signs and symptoms, abnormal chest findings on physical examination, and abnormalities on pulmonary function tests and radiographic evaluation.
The triggering particles are usually in the range of 1-5 micrometres in size 5.
The histopathologic process consists of chronic inflammation of the bronchi and peri-bronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli. Fibrosis and emphysema may develop later on.
Most cases of hypersensitivity pneumonitis, whether acute or insidious, include the following four histologic features in variable amounts and combinations 3.
- cellular bronchiolitis: chronic inflammatory cells lining the small airways, sometimes with resultant epithelial ulceration
- diffuse chronic interstitial inflammatory infiltrates: primarily consisting of lymphocytes and plasma cells but often including eosinophils, neutrophils, and mast cells
- poorly circumscribed interstitial non-necrotising (non-caseating) granulomas: consisting of lymphocytes, plasma cells, and epithelioid histiocytes, with or without giant cells
- individual giant cells in the alveoli or interstitium
According to the time of onset it may be divided into three broad categories 5:
- acute hypersensitivity pneumonitis
- subacute hypersensitivity pneumonitis
- chronic hypersensitivity pneumonitis
Most cases of hypersensitivity pneumonitis develop only after many years of inhaling allergens.
While the exact radiographic pattern depends on subtype, reported general features include:
In population-based studies, the sensitivity of chest radiography for detection of this disease is relatively low 1. Many patients may indeed have normal radiographs 3.
Abnormal plain film findings may be observed in some patients can include 3
- numerous poorly defined small (<5 mm) opacities throughout both lungs, sometimes with sparing of the apices and bases
- airspace disease: usually seen as ground-glass opacities (can be patchy or diffuse, resembling pulmonary oedema) or, more rarely, as consolidation
- a pattern of fine reticulation may also occur
- zonal distribution is variable from patient-to-patient and also may show temporal variation within the same patient
- when fibrosis develops: there may be a reticular pattern and honeycombing, which sometimes are more severe in the upper lobes than in the lower ones
- volume loss may occur: particularly in the upper lungs, and peri-bronchial thickening may be visible
- cardiomegaly may develop as a result of cor pulmonale
Several features on HRCT chest may appear at any stage of the disease and include 3-4:
- homogeneous ground-glass opacity: bilateral and symmetric but sometimes patchy and concentrated in the middle part and base of the lungs or having a bronchovascular distribution
- ground-glass opacity usually represents chronic interstitial inflammation but occasionally may be caused by fine fibrosis or organising pneumonia
- numerous round centrilobular opacities: usually <5 mm in diameter (occasionally these opacities have well-defined borders and soft-tissue attenuation)
- hypoattenuation and hypovascularity of scattered secondary lobules: hypoattenuating regions that persist on expiratory CT scans are indicative of air trapping, which is caused by bronchiolar inflammation and obstruction: this may give a mosaic attenuation pattern 4
- head cheese sign: the combination of patchy ground-glass opacities, normal regions, and air trapping
Other associated features include:
- small volume mediastinal lymphadenopathy (generally 10-20 mm in short-axis diameter)
- occasional pulmonary arterial enlargement
- centrilobular emphysema
- with developing fibrosis, there can be reticulation, mainly in the middle portion of the lungs or fairly evenly throughout the lungs but with relative sparing of the extreme apices and bases
Treatment and prognosis
Removal of the precipitant is often the key to management.
Due to a variable radiographic presentation, it may not be meaningful to give a differential diagnosis for hypersensitivity pneumonitis per se. It is better to refer to differential for particular radiographic feature:
Interstitial lung disease
interstitial lung disease
- drug-induced interstitial lung disease
- hypersensitivity pneumonitis
idiopathic interstitial pneumonia (mnemonic)
- acute interstitial pneumonia (AIP)
- cryptogenic organising pneumonia (COP)
- desquamative interstitial pneumonia (DIP)
- idiopathic nonspecific interstitial pneumonia (NSIP)
- idiopathic pleuroparenchymal fibroelastosis
- lymphoid interstitial pneumonia (LIP)
- respiratory bronchiolitis–associated interstitial lung disease (RB-ILD)
- usual interstitial pneumonia / idiopathic pulmonary fibrosis (UIP/IPF)
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