Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey.
BACKGROUND
Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose-effect on AEs.


METHODS
A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception.


RESULTS
Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose-effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported.


CONCLUSIONS
IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.
['Naganuma|Makoto|M|http://orcid.org/0000-0002-4244-3243', 'Sugimoto|Shinya|S|', 'Suzuki|Hideo|H|', 'Matsuno|Yuichi|Y|', 'Araki|Toshimitsu|T|', 'Shimizu|Hirotaka|H|', 'Hayashi|Ryohei|R|', 'Fukuda|Tomohiro|T|', 'Nakamoto|Nobuhiro|N|', 'Iijima|Hideki|H|', 'Nakamura|Shiro|S|', 'Kataoka|Masaharu|M|', 'Tamura|Yuichi|Y|', 'Tatsumi|Koichiro|K|', 'Hibi|Toshifumi|T|', 'Suzuki|Yasuo|Y|', 'Kanai|Takanori|T|', '|||']
D000328:Adult D056486:Chemical and Drug Induced Liver Injury D003093:Colitis, Ulcerative D004305:Dose-Response Relationship, Drug D004365:Drugs, Chinese Herbal D005260:Female D005765:Gastrointestinal Agents D006306:Health Surveys D006801:Humans D006976:Hypertension, Pulmonary D007443:Intussusception D007564:Japan D008297:Male D008875:Middle Aged
Ulcerative colitis Indigo naturalis Pulmonary arterial hypertension Liver dysfunction Intussusception