title: Japanese herbal medicine-induced pneumonitis: A review of 73 patients.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Enomoto
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujisawa
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan. Electronic address: suda@hama-med.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016516:CD4-CD8 Ratio; D002648:Child; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000737:chemistry; D005260:Female; D006801:Humans; D008218:Lymphocytosis; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D013902:Radiography, Thoracic; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D004365:Drugs, Chinese Herbal; C098310:bofu-tsusho-san; C080903:sairei-to; C461320:shosaiko-to
keywords: Drug-induced abnormalities; Herbal medicine; Interstitial lung diseases; Kampo; Pneumonitis