Hypersensitivity pneumonitis (ORPHA:31740)
A rare, immunologically mediated, interstitial lung disease characterized by respiratory symptoms (cough, dyspnea) due to sensitization and subsequent hypersensitivity to environmental antigens. The disorder may be accompanied by systemic manifestations (weight loss, fatigue).
Epidemiology
The estimated worldwide incidence of hypersensitivity pneumonitis (HP) is in the 1/125,000-143,000 range and is highly dependent on climatic, geographical, occupational and industrial factors. It has a higher incidence rate among pigeon breeders and farmers. The prevalence is 1/33,000-100,000 in the general population. A large number of acute cases and chronic cases related to mold probably go undiagnosed.
Clinical description
HP covers a very wide spectrum of clinical presentations with acute, subacute, and chronic forms. The disease can develop in any age group and the main clinical signs in all forms are cough, dyspnea, and fatigue. The manifestations overlap with a large number of other pulmonary disorders. HP is distinguished between fibrotic (always chronic) and non-fibrotic forms (mostly with acute or subacute manifestations). Acute manifestations, occurring a few hours after intense exposure (4-16 hours), may involve fever, headache, cough, dyspnea and myalgia. Chronic disease develops due to low level continual exposure over months to years manifesting with severe dyspnea, cough, clubbing, weight loss and hypoxemia, which may worsen gradually in patients with progressive pulmonary fibrosis. Acute and subacute disease can progress to a chronic presentation in the absence of appropriate treatment. The most common long-term complication in chronic disease is pulmonary fibrosis that may be accompanied by emphysema, which may lead to respiratory failure or cor pulmonale.
Etiology
An extremely broad range of antigens, generally smaller than 5 µ in size, may trigger HP. The most common sources of these antigens (thermophilic actinomycetes) include farming activities (moldy hay), feces/urine of wild and domestic birds and animals (e.g pigeons and most birds), sources of humidity and exposure to mold, air conditioners, and a long list of rare (often occupational) causes. The disease is caused by a type III or IV hypersensitivity reaction following repeated exposure, possibly in genetically susceptible individuals. This causes diffuse inflammation of the lung parenchyma and airways. Mutations in telomerase-related genes, and polymorphism of the MUC5B gene, have been linked with increased risk of fibrotic HP.
Diagnostic methods
The diagnosis is based on the combination of features, including clinical manifestations, which are determined by performing a physical examination, imaging (HRCT showing diffuse nodules or ground glass opacities in non-fibrotic HP; mosaicism and air trapping in addition to fibrotic features in fibrotic HP), bronchoalveolar lavage (showing an increased level of lymphocytes), positive serology testing (IgG: precipitins), and rarely, lung biopsy. HP may be difficult to diagnose due to non-specific clinical signs. It may be suspected in individuals with manifestations suggestive of HP who have occupational, recreational, or domestic exposure to specific antigens.
Differential diagnosis
Non-fibrotic HP may be confused with allergic asthma, chronic obstructive pulmonary disease, bacterial pneumonia, and recurrent infections. Fibrotic HP may be confused with : idiopathic pulmonary fibrosis, sarcoidosis, and other forms of pulmonary fibrosis.
Management and treatment
Acute forms generally resolve spontaneously on removal of the causative antigen. Short-term treatment of non-fibrotic cases is based on oral corticosteroids. The recommended treatment is prednisone, which may be initiated at 0.5 mg/kg/day and tapered over 2 to 8 weeks. Inhaled corticosteroids and bronchodilators, may also be beneficial. Fibrotic HP may be treated with low-dose prednisone, immunosuppressive therapy especially mycophenolate, and in case of progressive pulmonary fibrosis, antifibrotics. Longer term treatment relies on avoidance of the offending allergen. In occupational settings, risk avoidance may be difficult but can include preventive measures and personal protection equipment.
Prognosis
If the offending antigen is removed, the prognosis of non-fibrotic HP is very good. When detected and treated early, the disease is self-limiting with antigen avoidance. Fibrotic HP is more complicated possibly leading to permanent damage and disability.

                            Last update: 
                            January 2023


                            - Expert reviewer(s): 
                            Pr Vincent COTTIN