Drug-Induced Lung Disease Caused by Otsuji-to: Report of Three Cases

Abstract

Otsuji-to is a Kampo medicine used to treat hemorrhoids and constipation. Although rare, cases of drug-induced interstitial lung disease (DIILD) associated with Otsuji-to have been reported. Herein, we present three cases of DIILD caused by Otsuji-to. Bronchoalveolar lavage (BAL) findings were analyzed in two cases. Case 1 included an 88-year-old male presented with fever; onset occurred 91 days after Otsuji-to administration. Chest computed tomography (CT) showed a non-specific interstitial pneumonia (NSIP) pattern. BAL revealed lymphocytes at 27.8%, eosinophils at 8.6%, and a CD4/CD8 ratio of 0.47. The patient was treated with steroids. Case 2 included a 77-year-old male presented with fever; onset occurred at 37 days after Otsuji-to administration. Chest CT showed an NSIP pattern. BAL revealed lymphocytes at 80.4%, eosinophils at 1.8%, and a CD4/CD8 ratio of 0.33. The patient was also treated with steroids. Case 3 included a 77-year-old male presented with fever; onset occurred 34 days after Otsuji-to administration. Chest CT showed a non-cardiogenic pulmonary edema pattern. BAL was not performed and treatment included steroids and tacrolimus. Clinicians should monitor patients for fever for up to 3 months after initiating Otsuji-to administration. In two cases, BAL showed lymphocyte predominance and a low CD4/CD8 ratio, consistent with typical findings in Kampo-related DIILD. Treatment involves discontinuation of the drug and administration of steroids; however, immunosuppressants may be beneficial in refractory cases.