Natural History of Ulcerative Colitis in Children



Defining the natural history of a chronic disease is made difficult by the continuously changing landscape of available therapies, earlier recognition of disease by more sensitive diagnostic techniques, and changes in intrinsic biological behavior. The natural history of ulcerative colitis following therapy with aminosalicylates and corticosteroids as were used in the 1960s and 1970s would be expected to differ from that following the current widespread use of immunomodulators and biological therapy. The data presented in this chapter reflect what we know of natural history now, and will likely be different than what we might describe in 10 years. Discussion of drugs will mostly focus mainly on maintenance of remission. Lastly, possible methodology to predict response to therapy and alter natural history will be addressed.


Ulcerative Colitis Calcineurin Inhibitor Rescue Therapy Mucosal Healing Inactive Disease 
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  1. 1.
    Goel KM, Shanks RA. Long-term prognosis of children with ulcerative colitis. Arch Dis Child. 1973;48(5):337–42.PubMedCrossRefGoogle Scholar
  2. 2.
    Michener WM, Farmer RG, Mortimer EA. Long-term prognosis of ulcerative colitis with onset in childhood or adolescence. J Clin Gastroenterol. 1979;1(4):301–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Hyams JS, Davis P, Grancher K, Lerer T, Justinich CJ, Markowitz J. Clinical outcome of ulcerative colitis in children. J Pediatr. 1996;129(1):81–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Langholz E, Munkholm P, Krasilnikoff PA, Binder V. Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort. Scand J Gastroenterol. 1997;32(2):139–47.PubMedCrossRefGoogle Scholar
  5. 5.
    Gower-Rousseau C, Dauchet L, Vernier-Massouille G, Tilloy E, Brazier F, Merle V, et al. The natural history of pediatric ulcerative colitis: a population-based cohort study. Am J Gastroenterol. 2009;104(8):2080–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Sutherland L, Macdonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2006;(2):CD000543.Google Scholar
  7. 7.
    Sutherland L, Macdonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2006;(2):CD000544.Google Scholar
  8. 8.
    Ford AC, Kane SV, Khan KJ, Achkar JP, Talley NJ, Marshall JK, et al. Efficacy of 5-aminosalicylates in Crohn’s disease: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(4):617–29.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanauer SB, Sandborn WJ, Kornbluth A, Katz S, Safdi M, Woogen S, et al. Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial. Am J Gastroenterol. 2005;100(11):2478–85.PubMedCrossRefGoogle Scholar
  10. 10.
    Ferry GD, Kirschner BS, Grand RJ, Issenman RM, Griffiths AM, Vanderhoof JA, et al. Olsalazine versus sulfasalazine in mild to moderate childhood ulcerative colitis: results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial. J Pediatr Gastroenterol Nutr. 1993;17(1):32–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Zeisler B, Lerer T, Markowitz J, Mack D, Griffiths A, Bousvaros A, et al. Outcome following aminosalicylate therapy in children newly diagnosed with ulcerative colitis: a prospective multicenter registry experience. J Pediatr Gastroenterol Nutr 2012 (epub).PubMedCrossRefGoogle Scholar
  12. 12.
    Hommel KA, Mackner LM, Denson LA, Crandall WV. Treatment regimen adherence in pediatric gastroenterology. J Pediatr Gastroenterol Nutr. 2008;47(5):526–43.PubMedCrossRefGoogle Scholar
  13. 13.
    Faubion Jr WA, Loftus Jr EV, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121(2):255–60.PubMedCrossRefGoogle Scholar
  14. 14.
    Hyams J, Markowitz J, Lerer T, Griffiths A, Mack D, Bousvaros A, et al. The natural history of corticosteroid therapy for ulcerative colitis in children. Clin Gastroenterol Hepatol. 2006;4(9):1118–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Turner D, Travis SP, Griffiths AM, Ruemmele FM, Levine A, Benchimol EI, 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(4):574–88.PubMedCrossRefGoogle Scholar
  16. 16.
    De Iudicibus S, Franca R, Martelossi S, Ventura A, Decorti G. Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease. World J Gastroenterol. 2011;17(9):1095–108.PubMedCrossRefGoogle Scholar
  17. 17.
    Kabakchiev B, Turner D, Hyams J, Mack D, Leleiko N, Crandall W, et al. Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis. PLoS One. 2010;5(9):e13085.PubMedCrossRefGoogle Scholar
  18. 18.
    Sands BE. Immunosuppressive drugs in ulcerative colitis: twisting facts to suit theories? Gut. 2006;55(4):437–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut. 2002;50(4):485–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Khan KJ, Dubinsky MC, Ford AC, Ullman TA, Talley NJ, Moayyedi P. Efficacy of immunosuppressive therapy for inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol. 2011;106(4):630–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Kader HA, Mascarenhas MR, Piccoli DA, Stouffer NO, Baldassano RN. Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis. J Pediatr Gastroenterol Nutr. 1999;28(1):54–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Verhave M, Winter HS, Grand RJ. Azathioprine in the treatment of children with inflammatory bowel disease. J Pediatr. 1990;117(5):809–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Hyams JS, Lerer T, Mack D, Bousvaros A, Griffiths A, Rosh J, et al. Outcome following thiopurine use in children with ulcerative colitis: a prospective multicenter registry study. Am J Gastroenterol. 2011;106(5):981–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Burger DC, Travis S. Colon salvage therapy for acute severe colitis: cyclosporine or infliximab? Curr Opin Gastroenterol. 2011;27(4):358–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Hart AL, Ng SC. Review article: the optimal medical management of acute severe ulcerative colitis. Aliment Pharmacol Ther. 2010;32(5):615–27.PubMedGoogle Scholar
  26. 26.
    Turner D, Griffiths AM. Acute severe ulcerative colitis in children: a systematic review. Inflamm Bowel Dis. 2011;17(1):440–9.PubMedCrossRefGoogle Scholar
  27. 27.
    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(1):22–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Chey WY. Infliximab for patients with refractory ulcerative colitis. Inflamm Bowel Dis. 2001;7 Suppl 1:S30–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Probert CS, Hearing SD, Schreiber S, Kuhbacher T, Ghosh S, Arnott ID, et al. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Gut. 2003;52(7):998–1002.PubMedCrossRefGoogle Scholar
  30. 30.
    Su C, Salzberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, et al. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol. 2002;97(10):2577–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–76.PubMedCrossRefGoogle Scholar
  32. 32.
    Turner D, Mack D, Leleiko N, Walters TD, Uusoue K, Leach ST, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology. 2010;138(7):2282–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Russell GH, Katz AJ. Infliximab is effective in acute but not chronic childhood ulcerative colitis. J Pediatr Gastroenterol Nutr. 2004;39(2):166–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Mamula P, Markowitz JE, Cohen LJ, von Allmen D, Baldassano RN. Infliximab in pediatric ulcerative colitis: two-year follow-up. J Pediatr Gastroenterol Nutr. 2004;38(3):298–301.PubMedCrossRefGoogle Scholar
  35. 35.
    Serrano MS, Schmidt-Sommerfeld E, Kilbaugh TJ, Brown RF, Udall Jr JN, Mannick EE. Use of infliximab in pediatric patients with inflammatory bowel disease. Ann Pharmacother. 2001;35(7–8):823–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Hyams JS, Lerer T, Griffiths A, Pfefferkorn M, Stephens M, Evans J, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol. 2010;105(6):1430–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Hyams J, Damaraju L, Blank M, Johanns J, Guzzo C, Winter HS, et al. Induction and maintenance therapy with infliximab for children with moderate-to-severe ulcerative colitis. Clin Gastroenterol Hepatol. 2012;10(4):391–9.e1.PubMedCrossRefGoogle Scholar
  38. 38.
    Sandborn WJ, Van Assche G, Reinisch W, Colombel JF, D’Haens G, Wolf DC, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257–65.e1–3.Google Scholar
  39. 39.
    Werlin SL, Grand RJ. Severe colitis in children and adolescents: diagnosis. Course, and treatment. Gastroenterology. 1977;73(4 Pt 1):828–32.PubMedGoogle Scholar
  40. 40.
    Carbonnel F, Lavergne A, Lemann M, Bitoun A, Valleur P, Hautefeuille P, et al. Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity. Dig Dis Sci. 1994;39(7):1550–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Kumar S, Ghoshal UC, Aggarwal R, Saraswat VA, Choudhuri G. Severe ulcerative colitis: prospective study of parameters determining outcome. J Gastroenterol Hepatol. 2004;19(11):1247–52.PubMedCrossRefGoogle Scholar
  42. 42.
    Bouma G, Crusius JB, Garcia-Gonzalez MA, Meijer BU, Hellemans HP, Hakvoort RJ, et al. Genetic markers in clinically well defined patients with ulcerative colitis (UC). Clin Exp Immunol. 1999;115(2):294–300.PubMedCrossRefGoogle Scholar
  43. 43.
    Trachtenberg EA, Yang H, Hayes E, Vinson M, Lin C, Targan SR, et al. HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish caucasian populations. Hum Immunol. 2000;61(3):326–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Ahmad T, Armuzzi A, Neville M, Bunce M, Ling KL, Welsh KI, et al. The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis. Tissue Antigens. 2003;62(6):527–35.PubMedCrossRefGoogle Scholar
  45. 45.
    de la Concha EG, Fernandez-Arquero M, Lopez-Nava G, Martin E, Allcock RJ, Conejero L, et al. Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL. Gastroenterology. 2000;119(6):1491–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Haritunians T, Taylor KD, Targan SR, Dubinsky M, Ippoliti A, Kwon S, et al. Genetic predictors of medically refractory ulcerative colitis. Inflamm Bowel Dis. 2010;16(11):1830–40.PubMedCrossRefGoogle Scholar
  47. 47.
    Arijs I, Li K, Toedter G, Quintens R, Van Lommel L, Van Steen K, et al. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. Gut. 2009;58(12):1612–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Sylvester FA, Turner D, Draghi II A, Uuosoe K, McLernon R, Koproske K, et al. Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis. Inflamm Bowel Dis. 2011;17(8):1726–30.PubMedCrossRefGoogle Scholar
  49. 49.
    Ardizzone S, Cassinotti A, Duca P, Mazzali C, Penati C, Manes G, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9(6):483–9.e3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Digestive Diseases, Hepatology & NutritionConnecticut Children’s Medical CenterHartfordUSA

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