Intest Res.  2019 Jan;17(1):144-148. 10.5217/ir.2018.00104.

Acute pancreatitis associated with indigo naturalis in pediatric severe Crohn’s disease

• Kim HA
• Suh HR
• Kang B
• Choe BH
• on behalf of Crohn's and Colitis Association in DaeguGyeongbuk (CCAiD)

• KMID: 2438453
• DOI: http://doi.org/10.5217/ir.2018.00104

Abstract

The incidence of inflammatory bowel disease (IBD) is rapidly increasing worldwide. Indigo naturalis is known to have an antiinflammatory effect. Indigo naturalis has been traditionally used in the treatment of IBD in China and Japan. Currently, it is used as a primary or adjunctive drug in patients with ulcerative colitis. There are some reports of the effects of indigo naturalis when used in patients with ulcerative colitis. However, its usage has been associated with adverse events, including liver dysfunction, headache, gastrointestinal disturbance, and pulmonary hypertension. Pancreatitis as an adverse event during treatment using indigo naturalis has not yet been reported. We report a case of recurrent events of pancreatitis that occurred briefly after starting medication with indigo naturalis in a child with severe Crohn's disease. The pancreatitis improved after indigo naturalis was discontinued in 2 events. This is the first case to report the association between pancreatitis and indigo naturalis in the English literature.

Keyword

Crohn disease; Inflammatory bowel disease; Pancreatitis; Child; Kampo

MeSH Terms

Child
China
Colitis, Ulcerative
Crohn Disease
Headache
Humans
Hypertension, Pulmonary
Incidence
Indigo Carmine*
Inflammatory Bowel Diseases
Japan
Liver Diseases
Medicine, Kampo
Pancreatitis*
Indigo Carmine

Figure

• 

  Fig. 1. Initial gross examination. Anal fistula opening site at the 11 o’clock position without discharge.

• 

  Fig. 2. Initial colonoscopic images. (A) Mucosal erythema with low vascularity is noted in the descending colon and (B) multiple ulcers are noted in the entire colon.

• 

  Fig. 3. Initial magnetic resonance enterography images. Wall thickening is observed in the entire colon, especially the descending colon and transverse colon. (A, C) Mild wall thickening of descending colon; (B) mild wall thickening of descending colon and pericolic fat infiltration.

• 

  Fig. 4. Initial abdominal ultrasonography images. Suspected mild swelling is observed in the pancreas with peripancreatic fat infiltration (arrow in A and B).

Reference

1. Hong SJ, Cho SM, Choe BH, et al. Characteristics and incidence trends for pediatric inflammatory bowel disease in Daegu-Kyungpook Province in Korea: a multi-center study. J Korean Med Sci. 2018; 33:e132.

2. Lee YA, Chun P, Hwang EH, Mun SW, Lee YJ, Park JH. Clinical features and extraintestinal manifestations of Crohn disease in children. Pediatr Gastroenterol Hepatol Nutr. 2016; 19:236–242.

3. Choi J, Kang B, Kim MJ, Sohn I, Lee HJ, Choe YH. Early infliximab yields superior long-term effects on linear growth in pediatric Crohn’s disease patients. Gut Liver. 2018; 12:255–262.

4. Ruemmele FM, Veres G, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014; 8:1179–1207.

5. Kang B, Choe YH. Early biologic treatment in pediatric Crohn’s disease: catching the therapeutic window of opportunity in early disease by treat-to-target. Pediatr Gastroenterol Hepatol Nutr. 2018; 21:1–11.

6. Kang B, Choi SY, Kim HS, Kim K, Lee YM, Choe YH. Mucosal healing in paediatric patients with moderate-to-severe luminal Crohn’s disease under combined immunosuppression: escalation versus early treatment. J Crohns Colitis. 2016; 10:1279–1286.

7. Naganuma M, Sugimoto S, Mitsuyama K, et al. Efficacy of indigo naturalis in a multicenter randomized controlled trial of patients with ulcerative colitis. Gastroenterology. 2018; 154:935–947.

8. Ye BD. Introducing traditional herbal medicine into conventional health care in treating ulcerative colitis: primum non nocere. Gastroenterology. 2018; 154:792–795.

9. Chang HN, Pang JH, Yang SH, et al. Inhibitory effect of indigo naturalis on tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells. Molecules. 2010; 15:6423–6435.

10. Fukunaga K, Hida N, Ohnishi K, et al. A suppository Chinese medicine (xilei-san) for refractory ulcerative proctitis: a pilot clinical trial. Digestion. 2007; 75:146–147.

11. Stasiak N, Kukuła-Koch W, Głowniak K. Modern industrial and pharmacological applications of indigo dye and its derivatives: a review. Acta Pol Pharm. 2014; 71:215–221.

12. Sugimoto S, Naganuma M, Kanai T. Indole compounds may be promising medicines for ulcerative colitis. J Gastroenterol. 2016; 51:853–861.

13. Suzuki H, Kaneko T, Mizokami Y, et al. Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis. World J Gastroenterol. 2013; 19:2718–2722.

14. Zhang F, Li Y, Xu F, Chu Y, Zhao W. Comparison of Xilei-san, a Chinese herbal medicine, and dexamethasone in mild/moderate ulcerative proctitis: a double-blind randomized clinical trial. J Altern Complement Med. 2013; 19:838–842.

15. Ng SC, Lam YT, Tsoi KK, Chan FK, Sung JJ, Wu JC. Systematic review: the efficacy of herbal therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2013; 38:854–863.

16. Yuan G, Ke Q, Su X, Yang J, Xu X. Qing Dai, a traditional Chinese medicine for the treatment of chronic hemorrhagic radiation proctitis. Chin Ger J Clin Oncol. 2009; 8:114.

17. Sugimoto S, Naganuma M, Kiyohara H, et al. Clinical efficacy and safety of oral Qing-Dai in patients with ulcerative colitis: a single-center open-label prospective study. Digestion. 2016; 93:193–201.

18. Nishio M, Hirooka K, Doi Y. Chinese herbal drug natural indigo may cause pulmonary artery hypertension. Eur Heart J. 2016; 37:1992.

19. Moolsintong P, Loftus EV Jr, Chari ST, Egan LJ, Tremaine WJ, Sandborn WJ. Acute pancreatitis in patients with Crohn’s disease: clinical features and outcomes. Inflamm Bowel Dis. 2005; 11:1080–1084.

20. Gallego-Gutiérrez S, Navas-López VM, Kolorz M, et al. Successful mercaptopurine usage despite azathioprine-induced pancreatitis in paediatric Crohn’s disease. J Crohns Colitis. 2015; 9:676–679.