Hypersensitivity pneumonitis: insights in diagnosis and pathobiology

Abstract

Hypersensitivity pneumonitis (HP) is a complex syndrome resulting from repeated exposure to a variety of organic particles. HP may present as acute, subacute, or chronic clinical forms but with frequent overlap of these various forms. An intriguing question is why only few of the exposed individuals develop the disease. According to a two-hit model, antigen exposure associated with genetic or environmental promoting factors provokes an immunopathological response. This response is mediated by immune complexes in the acute form and by Th1 and likely Th17 T cells in subacute/chronic cases. Pathologically, HP is characterized by a bronchiolocentric granulomatous lymphocytic alveolitis, which evolves to fibrosis in chronic advanced cases. On high-resolution computed tomography scan, ground-glass and poorly defined nodules, with patchy areas of air trapping, are seen in acute/subacute cases, whereas reticular opacities, volume loss, and traction bronchiectasis superimposed on subacute changes are observed in chronic cases. Importantly, subacute and chronic HP may mimic several interstitial lung diseases, including nonspecific interstitial pneumonia and usual interstitial pneumonia, making diagnosis extremely difficult. Thus, the diagnosis of HP requires a high index of suspicion and should be considered in any patient presenting with clinical evidence of interstitial lung disease. The definitive diagnosis requires exposure to known antigen, and the assemblage of clinical, radiologic, laboratory, and pathologic findings. Early diagnosis and avoidance of further exposure are keys in management of the disease. Corticosteroids are generally used, although their long-term efficacy has not been proved in prospective clinical trials. Lung transplantation should be recommended in cases of progressive end-stage illness.