Japanese herbal medicine-induced pneumonitis: A review of 73 patients

Abstract

Background: The number of reports concerning Japanese herbal medicine (JHM)-induced pneumonitis has increased. However, comprehensive data are lacking in this regard, and the clinical characteristics of the disease remain unclear.

Methods: A literature review was performed using PubMed and Ichushi-Web-the database of the Japan Medical Abstracts Society-to identify articles published between 1996 and 2015 describing patients with JHM-induced pneumonitis. The final cohort included 73 patients in 59 articles (7 in English; 52 in Japanese).

Results: Among the various JHMs reported, sho-saiko-to was the most frequently used drug (26%), followed by sairei-to (16%), seishin-renshi-in (8%), and bofu-tsusyo-san (8%). These drugs commonly contain ougon (skullcap) and kanzo (liquorice). The mean age at pneumonitis diagnosis was 63.2 ± 15.5 years (range: 7-89 years). The male/female ratio was 44/29. Sixty-five patients (89%) developed pneumonitis within 3 months of beginning JHM treatment. Bilateral ground-glass attenuations on chest computed tomography, as well as lymphocytosis with a low CD4/CD8 T-cell ratio in bronchoalveolar lavage fluid, were common findings. Twenty-six patients (36%) recovered from the pneumonitis after simply discontinuing the causative JHM. However, the remainder required immunosuppressive therapy, and 13 patients (18%) received mechanical ventilation. Importantly, three patients (4%) did not survive, with two showing pathological diffuse alveolar damage upon autopsy.

Conclusions: Clinicians should be cautious regarding JHM-induced pneumonitis, particularly when using drugs/ingredients known to cause this complication, and during the early treatment period. Although most events are non-severe, critical cases should be recognized.

Keywords: Drug-induced abnormalities; Herbal medicine; Interstitial lung diseases; Kampo; Pneumonitis.