The Natural History of Crohn Disease in Children

Chapter

Abstract

The natural history of Crohn disease (CD) and ulcerative colitis (UC) is characterized by recurrent exacerbations interspersed with periods of inactive disease. The goal of therapy should be to induce and maintain clinical remission and strive for endoscopic healing of the intestinal mucosa in order to improve the quality of life. Common complications include failure to thrive and impaired psychosocial development. The advent of infliximab has been very beneficial for pediatric patients suffering from CD and UC. In children and young adolescents, the short-term response and remission rates are high. Infliximab in children with IBD has shown to be steroid sparing and restores growth, two most important goals of therapy in this patient group. Systematic maintenance dosing with infliximab infusions (5 mg/kg) every 8 weeks is superior to episodic therapy or infusions every 12 weeks in maintaining response and remission. The safety profile of infliximab is overall favorable although continued vigilance remains necessary for the occurrence of infrequent but serious events, including opportunistic infection and malignancies, especially in patients with concomitant immunosuppressive treatment.

Keywords

Placebo Lymphoma Adenocarcinoma Corticosteroid Prednisone 

References

  1. 1.
    Summers RW, Switz DM, Sessions Jr JT, et al. National Cooperative Crohn’s Disease Study: results of drug treatment. Gastroenterology. 1979;77(4 Pt 2):847–69.PubMedGoogle Scholar
  2. 2.
    Malchow H, Ewe K, Brandes JW, et al. European Cooperative Crohn’s Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984;86(2):249–66.PubMedGoogle Scholar
  3. 3.
    Markowitz J, Grancher K, Kohn N, et al. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119:895–902.PubMedCrossRefGoogle Scholar
  4. 4.
    Romano C, Cucchiara S, Barabino A, et al. Usefulness of ω-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn’s disease: a double-blind, randomized, placebo-controlled study. World J Gastroenterol. 2005;11(45):7118–21.PubMedGoogle Scholar
  5. 5.
    Langholz E, Munkholm P, Krasilnikoff PA, et al. Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort. Scand J Gastroenterol. 1997;32:139–47.PubMedCrossRefGoogle Scholar
  6. 6.
    Munkholm P, Langholz E, Davidsen M, et al. Disease activity courses in a regional cohort of Crohn’s disease patients. Scand J Gastroenterol. 1995;30(7):699–706.PubMedCrossRefGoogle Scholar
  7. 7.
    Loftus Jr EV, Schoenfeld P, Sandborn WJ. The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review. Aliment Pharmacol Ther. 2002;16(1):51–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:5A–36.Google Scholar
  9. 9.
    Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008;135:1114–22.PubMedCrossRefGoogle Scholar
  10. 10.
    Dubinsky MC, Kugathasan S, Mei L, et al. Increased immune reactivity predicts aggressive complicating Crohn’s disease in children. Clin Gastroenterol Hepatol. 2008;6:1105–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8(4):244–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Tarrant KM, Barclay ML, Frampton CMA, Gearry RB. Perianal disease predicts changes in Crohn’s disease phenotype—results of a population-based study of inflammatory bowel disease phenotype. Am J Gastroenterol. 2008;103:3082–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Eidelwein AP, Thompson R, Fiorino K, et al. Disease presentation and clinical course in black and white children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44:555–60.PubMedCrossRefGoogle Scholar
  14. 14.
    Kugathasan S, Collins N, Maresso K, et al. CARD15 gene mutations and the risk for early surgery in pediatric-onset Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2:1003–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Russell RK, Drummond HE, Nimmo EE, et al. Genotype-phenotype analysis in childhood-onset Crohn’s disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease. Inflamm Bowel Dis. 2005;11(11):955–64.PubMedCrossRefGoogle Scholar
  16. 16.
    Vermeire S, Pierik M, Hlavaty T, et al. Association of organic cation transporter risk haplotype with perianal penetrating Crohn’s disease but not with susceptibility to IBD. Gastroenterology. 2005;129(6):1845–53.PubMedCrossRefGoogle Scholar
  17. 17.
    Dubinsky MC, Lin Y-C, Dutridge D, et al. Serum immune responses predict rapid disease progression among children with Crohn’s disease: immune responses predict disease progression. Am J Gastroenterol. 2006;101:360–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Kirschner BS. Growth and development in chronic inflammatory bowel disease. Acta Paediatr Scand Suppl. 1990;366:98–104.PubMedCrossRefGoogle Scholar
  19. 19.
    Markowitz J, Grancher K, Rosa J, et al. Growth failure in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1993;16(4):373–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn’s disease. Gastroenterology. 1988;95(6):1523–7.PubMedGoogle Scholar
  21. 21.
    Sanderson IR, Udeen S, Davies PS, et al. Remission induced by an elemental diet in small bowel Crohn’s disease. Arch Dis Child. 1987;62:123–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132:863–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Malik S, Wong SC, Bishop J, Hassan K, McGrogan P, Ahmed SF, et al. Improvement in growth of children with Crohn disease following anti-TNF-α therapy can be independent of pubertal progress and glucocorticoid reduction. J Pediatr Gastroenterol Nutr. 2011;52:32–7.CrossRefGoogle Scholar
  24. 24.
    Faubion Jr WA, Loftus Jr EV, Harmsen WS, et al. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121(2):255–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Munkholm P, Langholz E, Davidsen M, et al. Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut. 1994;35(3):360–2.PubMedCrossRefGoogle Scholar
  26. 26.
    Markowitz J, Hyams J, Mack D, et al. Corticosteroid therapy in the age of infliximab: acute and 1 year outcomes in newly diagnosed children with Crohn disease. Clin Gastroenterol Hepatol. 2006;4(9):1124–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Farmer RG, Michener WM. Prognosis of Crohn’s disease with onset in childhood or adolescence. Dig Dis Sci. 1979;24(10):752–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Ferguson A, Sedgwick DM. Juvenile-onset inflammatory bowel disease: predictors of morbidity and health status in early adult life. J R Coll Physicians Lond. 1994;28(3):220–7.PubMedGoogle Scholar
  29. 29.
    Griffiths AM. Factors that influence the postoperative recurrence of Crohn’s disease in childhood. In: Hadziselimovic F, Herzog B, Burgin-Wolff A, editors. Inflammatory bowel disease and coeliac disease in children. Boston: Kluwer Academic; 1990. p. 131–6.CrossRefGoogle Scholar
  30. 30.
    Besnard M, Jaby O, Mougenot JF, et al. Postoperative outcome of Crohn’s disease in 30 children. Gut. 1998;43(5):634–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Gupta N, Cohen SA, Bostrom AG, et al. Risk factors for initial surgery in pediatric patients with Crohn’s disease. Gastroenterology. 2006;130(4):1069–77.PubMedCrossRefGoogle Scholar
  32. 32.
    Cosnes J, Nion-Larmurier I, Beaugerie L, et al. Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery. Gut. 2005;54:237–41.PubMedCrossRefGoogle Scholar
  33. 33.
    Ramadas AV, Gunesh S, Thomas GAO, et al. Natural history of Crohn’s disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates. Gut. 2010;59:1200–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Domènech E, Zabana Y, Garcia-Planella E, López San Román A, Nos P, Ginard D, et al. Clinical outcome of newly diagnosed Crohn’s disease: a comparative, retrospective study before and after infliximab availability. Aliment Pharmacol Ther. 2010;31(2):233–9.PubMedGoogle Scholar
  35. 35.
    Pedersen N, Duricova D, Lenicek M, Elkjaer M, Bortlik M, Andersen PS, et al. Infliximab dependency is related to decreased surgical rates in adult Crohn’s disease patients. Eur J Gastroenterol Hepatol. 2010;22(10):1196–203.PubMedCrossRefGoogle Scholar
  36. 36.
    Duricova D, Pedersen N, Lenicek M, Hradsky O, Bronsky J, Adamcova M, et al. Infliximab dependency in children with Crohn’s disease. Aliment Pharmacol Ther. 2009;29(7):792–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Becker JM. Surgical therapy for ulcerative colitis and Crohn’s disease. Gastroenterol Clin North Am. 1999;28(2):371–90, viii–ix.Google Scholar
  38. 38.
    Chardavoyne R, Flint GW, Pollack S, et al. Factors affecting recurrence following resection for Crohn’s disease. Dis Colon Rectum. 1986;29(8):495–502.PubMedCrossRefGoogle Scholar
  39. 39.
    Brignola C, Cottone M, Pera A, et al. Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn’s disease. Italian Cooperative Study Group. Gastroenterology. 1995;108:345–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Caprilli R, Andreoli A, Capurso L, et al. Oral mesalazine (5-­aminosalicylic acid: Asacol) for the prevention of post-operative recurrence of Crohn disease. Gruppo Italiano per lo Studio del Colon e del Retto (GISC). Aliment Pharmacol Ther. 1994;8:35–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Rutgeerts P, Heile M, Geboes K, et al. Controlled trial of metronidazole treatment for prevention of Crohn’s recurrence after ileal resection. Gastroenterology. 1995;108:1617–21.PubMedCrossRefGoogle Scholar
  42. 42.
    Rutgeerts P, Van Assche G, Vermeire S, et al. Ornidazole for prophylaxis of postoperative Crohn’s disease recurrence: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2005;128(4):856–61.PubMedCrossRefGoogle Scholar
  43. 43.
    Hanauer SB, Korelitz BI, Rutgeerts P, et al. Postoperative maintenance of Crohn’s disease remissions with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Gastroenterology. 2004;127:723–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Baldassano RN, Han PD, Jeshion WC, et al. Pediatric Crohn’s disease: risk factors for postoperative recurrence. Am J Gastroenterol. 2001;96(7):2169–76.PubMedCrossRefGoogle Scholar
  45. 45.
    Markowitz J, Markowitz JE, Bousvaros A, et al. Workshop report: prevention of postoperative recurrence in Crohn’s disease. J Pediatr Gastroenterol Nutr. 2005;41(2):145–51.PubMedCrossRefGoogle Scholar
  46. 46.
    Ekbom A, Helmick C, Zack M, et al. Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement. Lancet. 1990;336:357–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Mellemkjaer L, Johansen C, Gridley G, et al. Crohn’s disease and cancer risk (Denmark). Cancer Causes Control. 2000;11:145–50.PubMedCrossRefGoogle Scholar
  48. 48.
    Jess T, Loftus EV, Velayos FS, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota. Gastroenterology. 2006;130:1039–46.PubMedCrossRefGoogle Scholar
  49. 49.
    Loftus Jr EV, Tremaine WJ, Habermann TM, et al. Risk of lymphoma in inflammatory bowel disease. Am J Gastroenterol. 2000;95:2308–12.PubMedCrossRefGoogle Scholar
  50. 50.
    Kandiel A, Fraser AG, Korelitz BI, et al. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut. 2005;54(8):1121–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Thayu M, Markowitz JE, Mamula P, et al. Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. J Pediatr Gastroenterol Nutr. 2005;40:220–2.PubMedCrossRefGoogle Scholar
  52. 52.
    Otley A, Smith C, Nicholas D, et al. The IMPACT questionnaire: a valid measure of health-related quality of life in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2002;35:557–63.PubMedCrossRefGoogle Scholar
  53. 53.
    Otley A, Griffiths AM, Hyams J, et al. Health-related quality of life in the first year following a diagnosis of pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(8):684–91.PubMedCrossRefGoogle Scholar
  54. 54.
    Rabbett H, Elbadri A, Thwaites R, et al. Quality of life in children with Crohn disease. J Pediatr Gastroenterol Nutr. 1996;23:528–33.PubMedCrossRefGoogle Scholar
  55. 55.
    Akobeng AK, Suresh-Babu MV, Firth D, et al. Quality of life in children with Crohn’s disease: a pilot study. J Pediatr Gastroenterol Nutr. 1999;28:S37–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Moody G, Eaden JA, Mayberry JF. Social implications of childhood Crohn’s disease. J Pediatr Gastroenterol Nutr. 1999;28:S43–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Ferguson A, Sedgwick DM, Drummond J, et al. Morbidity of juvenile onset inflammatory bowel disease: effects on education and employment in early adult life. Gut. 1994;35:665–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Pediatric Gastroenterology and NutritionSteven and Alexandra Cohen Children’s Medical Center of New YorkNew Hyde ParkUSA

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