extrinsic allergic alveolitis
Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis (EAA), represents a group of pulmonary disorders mediated by an inflammatory reaction to inhalation of an allergen that can lead to lung fibrosis.
Its 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.
Most cases of hypersensitivity pneumonitis develop only after many years of continuous or intermittent inhalation of the inciting agent (e.g. ~ 10 years among those with bird fancier’s lung) .
Although the symptomatic disease has been classically divided into acute, subacute, and chronic types, given contradictory definitions, it has been more recently divided in acute/inflammatory type (non-fibrotic hypersensitivity pneumonitis) and chronic/fibrosis type (fibrotic hypersensitivity pneumonitis) .
In the acute hypersensitivity pneumonitis, presentation symptoms may include fevers, rigors, myalgia, coughing, chest tightness, dyspnea, and leukocytosis .
In the chronic hypersensitivity pneumonitis, the disease usually manifests as a gradual onset of exertional dyspnea, fatigue, coughing, sputum production, and weight loss. The clinical examination may demonstrate lung basal crackles and finger clubbing. There is a restriction pattern with decreased diffusing capacity on pulmonary function tests .
The triggering particles are usually in the range of 1-5 micrometers in size .
More than 200 different antigens have been associated with the development of hypersensitivity pneumonitis, including plant products, animal products, aerosolized microorganisms, and organic chemicals.
Depending on the type of precipitant, numerous other more precipitant-specific terms have been used such as:
- bird fancier's lung (also known as pigeon fancier's lung)
- farmer's lung
- cheese workers' lung
- mushroom worker’s lung
- malt worker’s lung
- maple bark disease
- hot tub lung
- organic chemicals such as isocyanates found in paint hardeners
- immunosuppressants used in organ transplantation: e.g. sirolimus/everolimus
- wine maker’s lung
- woodsman’s disease
- thatched roof lung
- tobacco grower’s lung
- potato riddler’s lung
- summer-type pneumonitis
- dry rot lung
- machine operator’s lung
- humidifier lung
- shower curtain disease
- furrier’s lung
- miller’s lung
- saxophone lung
The histopathologic process consists of chronic inflammation of the bronchi and peribronchiolar 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 .
- 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-necrotizing (non-caseating) granulomas: consisting of lymphocytes, plasma cells, and epithelioid histiocytes, with or without giant cells
- individual giant cells in the alveoli or interstitium
Smoking is protective against hypersensitivity pneumonitis, presumably by the inhibitory action of nicotine on macrophage activation and lymphocyte proliferation and function . However, when smokers do develop hypersensitivity pneumonitis, it is more commonly fibrosing disease with a worse prognosis .
According to the time of onset, it may be classically divided into three broad categories :
- acute hypersensitivity pneumonitis
- subacute hypersensitivity pneumonitis
- chronic hypersensitivity pneumonitis
Another more recently proposed system based on pathology is as:
- predominant fibrosis - fibrotic hypersensitivity pneumonitis
- no predominant fibrosis - non-fibrotic hypersensitivity pneumonitis (some may progress to a fibrotic form)
While the exact radiographic pattern depends on subtype (acute/inflammatory, vs chronic/fibrotic), this article will focus on its general features.
In population-based studies, the sensitivity of chest radiography for detection of this disease is relatively low . Many patients may indeed have normal radiographs .
Abnormal plain radiographic findings may be observed in some patients can include
- 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 edema) or, more rarely, as consolidation
- a pattern of fine reticulation may also occur
- zonal distribution is variable from patient to patient and may even 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 peribronchial 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 :
- 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 organizing pneumonia
- numerous round centrilobular nodules: 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
- 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 the differential for a particular radiographic feature: