Management of severe or refractory ulcerative colitis in children and adolescents
- Athos Bousvaros, MD
Athos Bousvaros, MD
- Associate Professor of Pediatrics
- Harvard Medical School
- Mala Setty, MD
Mala Setty, MD
- Assistant Professor, UCSF Department of Pediatrics;
- Associate Gastroenterologist, UCSF Benioff Children's Hospital Oakland
- Jess L Kaplan, MD
Jess L Kaplan, MD
- Instructor of Pediatrics
- Harvard Medical School
Inflammatory bowel disease (IBD) is comprised of two major disorders, ulcerative colitis (UC) and Crohn disease (CD). These disorders have distinct pathologic and clinical characteristics (table 1), but their pathogenesis remains poorly understood. (See "Definition, epidemiology, and risk factors in inflammatory bowel disease".)
UC disease activity varies substantially among patients and over time. Among healthcare encounters for children with active UC, approximately 5 percent have acute severe colitis . Some of these cases will be the initial manifestation of UC, while others represent exacerbations or "flares" of the chronic disease. The management of these patients is reviewed here. Other aspects of the diagnosis and management of children with UC are discussed in separate topic reviews:
- Dotson JL, Crandall WV, Zhang P, et al. Feasibility and validity of the pediatric ulcerative colitis activity index in routine clinical practice. J Pediatr Gastroenterol Nutr 2015; 60:200.
- Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007; 133:423.
- Turner D, Travis SP, Griffiths AM, et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol 2011; 106:574.
- Pascarella F, Martinelli M, Miele E, et al. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr 2009; 154:854.
- Martinelli M, Strisciuglio C, Veres G, et al. Clostridium difficile and pediatric inflammatory bowel disease: a prospective, comparative, multicenter, ESPGHAN study. Inflamm Bowel Dis 2014; 20:2219.
- Sandberg KC, Davis MM, Gebremariam A, Adler J. Disproportionate rise in Clostridium difficile-associated hospitalizations among US youth with inflammatory bowel disease, 1997-2011. J Pediatr Gastroenterol Nutr 2015; 60:486.
- Ayre K, Warren BF, Jeffery K, Travis SP. The role of CMV in steroid-resistant ulcerative colitis: A systematic review. J Crohns Colitis 2009; 3:141.
- Kambham N, Vij R, Cartwright CA, Longacre T. Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol 2004; 28:365.
- Jones A, McCurdy JD, Loftus EV Jr, et al. Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for cytomegalovirus. Clin Gastroenterol Hepatol 2015; 13:949.
- Turner D, Mack D, Leleiko N, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 2010; 138:2282.
- Choshen S, Finnamore H, Auth MK, et al. Corticosteroid Dosing in Pediatric Acute Severe Ulcerative Colitis: A Propensity Score Analysis. J Pediatr Gastroenterol Nutr 2016; 63:58.
- Turner D, Levine A, Kolho KL, et al. Combination of oral antibiotics may be effective in severe pediatric ulcerative colitis: a preliminary report. J Crohns Colitis 2014; 8:1464.
- McIntyre PB, Powell-Tuck J, Wood SR, et al. Controlled trial of bowel rest in the treatment of severe acute colitis. Gut 1986; 27:481.
- Turner D, Griffiths AM. Acute severe ulcerative colitis in children: a systematic review. Inflamm Bowel Dis 2011; 17:440.
- Hyams JS, Lerer T, Griffiths A, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol 2010; 105:1430.
- Watson S, Pensabene L, Mitchell P, Bousvaros A. Outcomes and adverse events in children and young adults undergoing tacrolimus therapy for steroid-refractory colitis. Inflamm Bowel Dis 2011; 17:22.
- Hyams JS, Markowitz J, Wyllie R. Use of infliximab in the treatment of Crohn's disease in children and adolescents. J Pediatr 2000; 137:192.
- Hyams J, Damaraju L, Blank M, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol 2012; 10:391.
- Dan-Nielsen S, Wewer V, Paerregaard A, et al. Does infliximab prevent colectomy in acute and chronic active ulcerative colitis? J Pediatr Gastroenterol Nutr 2014; 58:768.
- Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014; 146:392.
- Navazo L, Salata H, Morales S, et al. Oral microemulsion cyclosporine in the treatment of steroid-refractory attacks of ulcerative and indeterminate colitis. Scand J Gastroenterol 2001; 36:610.
- Laharie D, Bourreille A, Branche J, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet 2012; 380:1909.
- Laharie D, Bourreille A, Branche J, et al. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab. Gut 2017.
- Bousvaros A, Kirschner BS, Werlin SL, et al. Oral tacrolimus treatment of severe colitis in children. J Pediatr 2000; 137:794.
- Ziring DA, Wu SS, Mow WS, et al. Oral tacrolimus for steroid-dependent and steroid-resistant ulcerative colitis in children. J Pediatr Gastroenterol Nutr 2007; 45:306.
- Okafor PN, Nunes DP, Farraye FA. Pneumocystis jiroveci pneumonia in inflammatory bowel disease: when should prophylaxis be considered? Inflamm Bowel Dis 2013; 19:1764.
- Maser EA, Deconda D, Lichtiger S, et al. Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis. Clin Gastroenterol Hepatol 2008; 6:1112.
- Herrlinger KR, Barthel DN, Schmidt KJ, et al. Infliximab as rescue medication for patients with severe ulcerative/indeterminate colitis refractory to tacrolimus. Aliment Pharmacol Ther 2010; 31:1036.
- Narula N, Fine M, Colombel JF, et al. Systematic Review: Sequential Rescue Therapy in Severe Ulcerative Colitis: Do the Benefits Outweigh the Risks? Inflamm Bowel Dis 2015; 21:1683.
- Colombel JF, Sandborn WJ, Ghosh S, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 3. Am J Gastroenterol 2014; 109:1771.
- Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013; 369:699.
- Singh N, Rabizadeh S, Jossen J, et al. Multi-Center Experience of Vedolizumab Effectiveness in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:2121.
- Conrad MA, Stein RE, Maxwell EC, et al. Vedolizumab Therapy in Severe Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:2425.
- Mutalib M, Borrelli O, Blackstock S, et al. The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children. J Crohns Colitis 2014; 8:1730.
- Srinath A, Young E, Szigethy E. Pain management in patients with inflammatory bowel disease: translational approaches from bench to bedside. Inflamm Bowel Dis 2014; 20:2433.
- Poonai N, Paskar D, Konrad SL, et al. Opioid analgesia for acute abdominal pain in children: A systematic review and meta-analysis. Acad Emerg Med 2014; 21:1183.
- Felder JB, Korelitz BI, Rajapakse R, et al. Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a case-control study. Am J Gastroenterol 2000; 95:1949.
- Nylund CM, Goudie A, Garza JM, et al. Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2013; 56:485.
- Turner D, Levine A, Escher JC, et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr 2012; 55:340.
- Melmed GY, Fleshner PR, Bardakcioglu O, et al. Family history and serology predict Crohn's disease after ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum 2008; 51:100.
- Schaufler C, Lerer T, Campbell B, et al. Preoperative immunosuppression is not associated with increased postoperative complications following colectomy in children with colitis. J Pediatr Gastroenterol Nutr 2012; 55:421.
- Yang Z, Wu Q, Wang F, et al. Meta-analysis: effect of preoperative infliximab use on early postoperative complications in patients with ulcerative colitis undergoing abdominal surgery. Aliment Pharmacol Ther 2012; 36:922.
- Gray FL, Turner CG, Zurakowski D, et al. Predictive value of the Pediatric Ulcerative Colitis Activity Index in the surgical management of ulcerative colitis. J Pediatr Surg 2013; 48:1540.
- Weiss EG, Wexner SD. Surgical therapy for ulcerative colitis. Gastroenterol Clin North Am 1995; 24:559.
- Pakarinen MP, Natunen J, Ashorn M, et al. Long-term outcomes of restorative proctocolectomy in children with ulcerative colitis. Pediatrics 2009; 123:1377.
- Koivusalo A, Pakarinen MP, Rintala RJ. Surgical complications in relation to functional outcomes after ileoanal anastomosis in pediatric patients with ulcerative colitis. J Pediatr Surg 2007; 42:290.
- Dalal DH, Patton D, Wojcicki JM, et al. Quality of life in patients postcolectomy for pediatric-onset ulcerative colitis. J Pediatr Gastroenterol Nutr 2012; 55:425.
- Ozdemir Y, Kiran RP, Erem HH, et al. Functional outcomes and complications after restorative proctocolectomy and ileal pouch anal anastomosis in the pediatric population. J Am Coll Surg 2014; 218:328.
- Polites SF, Potter DD, Moir CR, et al. Long-term outcomes of ileal pouch-anal anastomosis for pediatric chronic ulcerative colitis. J Pediatr Surg 2015; 50:1625.
- Oresland T. Review article: colon-saving medical therapy vs. colectomy in ulcerative colitis - the case for colectomy. Aliment Pharmacol Ther 2006; 24 Suppl 3:74.
- Keighley MR. Review article: the management of pouchitis. Aliment Pharmacol Ther 1996; 10:449.
- Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119:305.
- CLINICAL ASSESSMENT
- Disease severity
- Evaluation for infectious colitis
- Evaluation for toxic megacolon
- Other evaluation
- MEDICAL TREATMENT
- Severe disease
- Refractory disease
- - Induction therapy ("rescue")
- Anti-TNF antibodies
- Sequential medical therapy
- - Maintenance phase
- Pain management
- Venous thromboembolism
- Immunosuppressive therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS