Etiology
Hypersensitivity pneumonitis develops as a hyperergic reaction to the inhalation of specific antigens. Frequently, the precise antigen remains unidentified, but known triggers are divided into three main groups: thermophilic actinomycetes, molds, and animal-derived antigens.
Depending on the exposure setting, occupational and domestic forms of the disease are distinguished.
Occupational triggers:
- Farmer's lung — caused by spores of moldy hay (Micropolyspora faeni).
- Bagassosis — a reaction to moldy sugar cane (Thermoactinomyces sacchari).
- Sequoiosis — pathology associated with inhaling wood dust mold.
- Suberosis — cork worker's lung.
- Mushroom worker's lung and pituitary snuff-taker's lung.
Domestic triggers are associated with antigens accumulating in the everyday environment:
- Bird fancier's lung (pigeon breeder's disease) — reaction to avian droppings and serum proteins.
- Humidifier lung — resulting from the inhalation of molds from air conditioners, humidifiers, indoor pools, and central heating systems.
- Tobacco worker's lung.
Pathogenesis
The exact pathomechanism of hypersensitivity alveolitis is not fully understood, but its link to immune hypersensitivity reactions has been proven. Tissue injury is driven by two main types of immune reactions against inhaled antigens:
- Immune complex-mediated (Type III) — accompanied by the formation of circulating immune complexes.
- T-cell mediated / Cytotoxic (Type IV) — a cell-mediated response.
An important diagnostic marker is the presence of precipitating IgG class antibodies against the specific antigen in the patient's serum. However, the presence of antibodies alone does not guarantee disease onset — genetic predisposition is required for clinical manifestation.
Clinical Presentation and Management
Clinical manifestations directly depend on the pattern of the disease course, which is determined by the dose and duration of antigen exposure.
- Acute hypersensitivity pneumonitis occurs upon exposure to high concentrations of the antigen. Symptoms (severe dyspnea, cough, chills, and fever) develop rapidly within 4–6 hours post-exposure. With appropriate management, recovery occurs within a few days, but re-exposure risks recurrence.
- Chronic hypersensitivity pneumonitis develops with prolonged inhalation of low concentrations of the antigen. It has an insidious onset, manifesting gradually with progressive dyspnea, cough, and general fatigue.
Diagnosis is complex and requires a multidisciplinary approach: clinical evaluation, imaging, and laboratory tests. Skin testing and identifying specific serum antibodies are mandatory. In diagnostically challenging cases, a lung biopsy is performed.
Initial treatment includes two main steps: complete avoidance of the offending antigen and administration of corticosteroid therapy (particularly effective in the acute phase).
Pathology and Morphology
The morphological pattern of hypersensitivity pneumonitis is stereotypical. It clearly reflects the aerogenic route of antigen entry and the immune-mediated nature of the inflammation. The lesions are predominantly distributed as disseminated foci around respiratory bronchioles, representing a combination of bronchiolitis and interstitial pneumonia.
Microscopic features:
- Formation of non-caseating granulomas in the interstitium (as a consequence of immune hypersensitivity). Unlike tuberculosis, foci of caseous necrosis are absent.
- Development of lymphocytic alveolitis — prominent lymphohistiocytic infiltration mixed with plasma cells. Eosinophils may also be present in the infiltrate.
- In the acute phase, neutrophils are found within the inflammatory infiltrates.
- Involvment of the small airways is invariably present.
In chronic cases, interstitial fibrosis progresses steadily. This leads to areas of carnification and ultimately to the development of 'honeycomb lung'. At this late stage, the histological picture can be exceedingly difficult to distinguish from usual interstitial pneumonia (UIP).