MINOCYCLINE-INDUCED CELL-MEDIATED HYPERSENSITIVITY PNEUMONITIS

Objective: To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Design: Case study. Setting: Intensive care unit of a referral hospital. Patient: A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. Intervention: Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. Measurements: Immunologic analysis of the phenotype and function of alveolar lymphocytes. Results: Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. Conclusion: These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.