Pediatric Inflammatory Bowel Disease (IBD): Phenotypic, Genetic and Therapeutic Differences between Early-Onset and Adult-Onset IBD

Jeong Kee Seo

doi:10.5223/kjpgn.2011.14.1.1

Journal List > Korean J Pediatr Gastroenterol Nutr > v.14(1) > 1043495

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Seo: Pediatric Inflammatory Bowel Disease (IBD): Phenotypic, Genetic and Therapeutic Differences between Early-Onset and Adult-Onset IBD

Invited Review

Korean Journal of Pediatric Gastroenterology and Nutrition

Korean Journal of Pediatric Gastroenterology and Nutrition 2011; 14(1): 1-25.

Published online: 31 March 2011

DOI: https://doi.org/10.5223/kjpgn.2011.14.1.1

Pediatric Inflammatory Bowel Disease (IBD): Phenotypic, Genetic and Therapeutic Differences between Early-Onset and Adult-Onset IBD

Jeong Kee Seo, M.D.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

Corresponding author (jkseo@snu.ac.kr)

Received 2 March 2011 Revised 21 March 2011 Accepted 25 March 2011

Abstract

Inflammatory bowel disease (IBD) develops during childhood or adolescence in approximately 25% of patients with IBD. Recent studies on pediatric IBD have revealed that early-onset IBD has distinct phenotype differences compared to adult onset IBD. Pediatric early-onset IBD differs in many aspects including disease type, location of the lesions, disease behavior, gender preponderance and genetically attributable risks. This review examines the currently published data on the clinical, epidemiological and genetic differences between early-onset and adult-onset IBD. And finally, therapeutic considerations in the management of pediatric-onset IBD are also discussed.

Keywords: Pediatric inflammatory bowel disease, Crohn's disease, Ulcerative colitis, Early onset

Figures and Tables

Table 1

Montreal and Paris Classifications for CD19)

^*In both the Montreal and Paris Classification systems L4 and L4a/L4b may coexist with L1, L2, L3, respectively.

B1 = Nonstricturing, nonpenetrating disease: uncomplicated inflammatory disease without evidence of stricturing or penetrating disease; B2 = Stricturing disease: the occurrence of constant luminal narrowing demonstrated by radiologic, endoscopic, or surgical examination combinedwith prestenotic dilation and/or obstructive signs or symptoms but without evidence of penetrating disease; B3 = Penetrating disease: the occurrence of bowel perforation, intraabdominal fistulas, inflammatory masses and/or abscesses at any time in the course of the disease, and not secondary postoperative intra-abdominal complication (excludes isolated perianal or rectovaginal fistulae). B2B3 = Stricturing and penetrating disease: the presence of both B2 and B3 phenotypes in the same patient, either at the same moment in time, or separately over a period of time.

Table 2

Montreal and Paris Classifications for UC19)

^*Severe defined by Pediatric Ulcerative Colitis Activity index (PUCAI) ≥65.

Table 3

CD:UC Ratio in Pediatric IBD and Adult IBD

Table 4

Male Preponderance in Pediatric CD

Table 5

Pancolitis Predominance in Pediatric UC

Table 6

High Prevalence of Ileocolonic Disease in Pediatric CD

Table 7

Phenotypes and Disease Progression Behavior in Pediatric CD

Table 8

Pediatric Crohn's Disease Activity Index

Table 9

Pediatric Ulcerative Colitis Activity Index

Table 10

Suggested Classification Paradigm for Documenting Linear Growth Impairment in Pediatric Onset IBD

References

1. Seo JK, Yeon KM, Chi JG. Inflammatory bowel disease in children: clinical, endoscopic, radiologic and histopathologic investigation. J Korean Med Sci. 1992. 7:221–235.

2. Suh HA, Kim SE, Jang JY, Kim BJ, Kim JS, Lee SY, et al. Efficacy of nutritional therapy in children with crohn disease. Korean J Pediatr Gastroenterol Nutr. 2006. 9:210–217.

3. Lee NY, Park JH. Clinical features and course of crohn disease in children. Korean J Gastrointest Endosc. 2007. 34:193–199.

4. Lee JH, Lee HJ, Park SE, Choe YH. Infliximab: the benefit for refractory Crohn disease and top-down induction therapy in severe Crohn disease. Korean J Pediatr Gastroenterol Nutr. 2008. 11:28–35.

5. Abramson O, Durant M, Mow W, Finley A, Kodali P, Wong A, et al. Ncidence, prevalence, and time trends of pediatric inflammatory bowel disease in Northern California, 1996 to 2006. J Pediatr. 2010. 157:233–239.

6. Turunen P, Kolho KL, Auvinen A, Iltanen S, Huhtala H, Ashorn M. Incidence of inflammatory bowel disease in Finnish children, 1987-2003. Inflamm Bowel Dis. 2006. 12:677–683.

7. Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV, et al. Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis. 2009. 15:491–500.

8. Thompson N, Pounder R, Wakefield A, Montgomery S. Is measles vaccination a risk factor for inflammatory bowel disease? Lancet. 1995. 345:1071–1074.

9. Hafner S, Timmer A, Herfarth H, Rogler G, Scholmerich J, Schaffler A, et al. The role of domestic hygiene in inflammatory bowel diseases: hepatitis A and worm infestations. Eur J Gastroenterol Hepatol. 2008. 20:561–566.

10. Summers R, Elliott D, Urban J, Thompson R, Weinstock J. Trichuris suis therapy in Crohn's disease. Gut. 2005. 54:87.

11. Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy and protection against ulcerative colitis. N Engl J Med. 2001. 344:808–814.

12. Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy is followed by increased risk of Crohn's disease. Gastroenterology. 2003. 124:40–46.

13. Jowett S, Seal C, Pearce M, Phillips E, Gregory W, Barton J, et al. Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study. Gut. 2004. 53:1479–1484.

14. Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: a metaanalysis. Mayo Clin Proc. 2006. 81:1462–1471.

15. McGilligan VE, Wallace JM, Heavey PM, Ridley DL, Rowland IR. Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis. Inflamm Bowel Dis. 2007. 13:108–115.

16. Rubin DT, Hanauer SB. Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2000. 12:855–862.

17. Gasche C, Scholmerich J, Brynskov J, D'Haens G, Hanauer SB, Irvine EJ, et al. A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis. 2000. 6:8–15.

18. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. oward 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:Suppl A. 5–36.

19. Levine A, Griffiths A, Markowitz J, Wilson DC, Turner D, Russell RK, et al. Pediatric modification of the montreal classification for inflammatory bowel disease: the paris classification. Inflamm Bowel Dis. 2010. 11. 08. [Epub ahead of print].

20. Levine A, Kugathasan S, Annese V, Biank V, Leshinsky Silver E, Davidovich O, et al. Pediatric onset Crohn's colitis is characterized by genotype dependent age related susceptibility. Inflamm Bowel Dis. 2007. 13:1509–1515.

21. Meinzer U, Ideström M, Alberti C, Peuchmaur M, Belarbi N, Bellaïche M, et al. Ileal involvement is age dependent in pediatric Crohn's disease. Inflamm Bowel Dis. 2005. 11:639–644.

22. Markowitz J, Kugathasan S, Dubinsky M, Mei L, Crandall W, LeLeiko N, et al. Age of diagnosis influences serologic responses in children with Crohn's disease: a possible clue to etiology? Inflamm Bowel Dis. 2009. 15:714–719.

23. Ruemmele FM, El Khoury MG, Talbotec C, Maurage C, Mougenot JF, Schmitz J, et al. Characteristics of inflammatory bowel disease with onset during the first year of life. J Pediatr Gastroenterol Nutr. 2006. 43:603–609.

24. Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schäffer AA, Noyan F, et al. Inflammatory bowel disease and mutation affecting the interleukin-10 receptor. N Engl J Med. 2009. 361:2033–2045.

25. Van Limbergen J, Russell RK, Drummond HE, Aldhous MC, Round NK, Nimmo ER, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008. 135:1114–1122.

26. Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, Mouterde O, et al. Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology. 2008. 135:1106–1113.

27. Heyman MB, Kirschner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J Pediatr. 2005. 146:35–40.

28. Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, et al. The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007. 5:1424–1429.

29. Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr. 2003. 143:525–531.

30. Sawczenko A, Sandhu BK, Logan RF, Jenkins H, Taylor CJ, Mian S, et al. Prospective survey of childhood inflammatory bowel disease in the British isles. Lancet. 2001. 357:1093–1094.

31. Newby EA, Croft NM, Green M, Hassan K, Heuschkel RB, Jenkins H, et al. Natural history of paediatric inflammatory bowel diseases over a 5-year follow-up: a retrospective review of data from the register of paediatric inflammatory bowel diseases. J Pediatr Gastroenterol Nutr. 2008. 46:539.

32. Sagiv-Friedgut K, Karban A, Weiss B, Shaoul R, Shamir R, Bujanover Y, et al. Early-onset Crohn disease is associated with male sex and a polymorphism in the IL-6 promoter. J Pediatr Gastroenterol Nutr. 2010. 50:22–26.

33. Sauer CG, Kugathasan S. Pediatric inflammatory bowel disease: Highlighting pediatric differences in IBD. Med Clin North Am. 2010. 94:35–52.

34. Henriksen M, Jahnsen J, Lygren I, Sauar J, Kjellevold , Schulz T, et al. Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study). Inflamm Bowel Dis. 2006. 12:543–550.

35. 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. 4:1118–1123.

36. Gupta N, Bostrom AG, Kirschner BS, Cohen SA, Abramson O, Ferry GD, et al. Presentation and disease course in early-compared to later-onset pediatric Crohn's disease. Am J Gastroenterol. 2008. 103:2092–2098.

37. Keljo DJ, Markowitz J, Langton C, Lerer T, Bousvaros A, Carvalho R, et al. Course and treatment of perianal disease in children newly diagnosed with Crohn's disease. Inflamm Bowel Dis. 2009. 15:383–387.

38. Karban A, Itay M, Davidovich O, Leshinsky-Silver E, Kimmel G, Fidder H, et al. Risk factors for perianal Crohn's disease: the role of genotype, phenotype, and ethnicity. Am J Gastroenterol. 2007. 102:1702–1708.

39. Romano C, Famiani A, Gallizzi R, Comito D, Ferrau' V, Rossi P. Indeterminate colitis: a distinctive clinical pattern of inflammatory bowel disease in children. Pediatrics. 2008. 122:e1278–e1281.

40. Martland GT, Shepherd NA. Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity. Histopathology. 2007. 50:83–96.

41. Wells AD, McMillan I, Price AB, Ritchie JK, Nicholls RJ. Natural history of indeterminate colitis. Br J Surg. 1991. 78:179–181.

42. Moum B, Vatn MH, Ekbom A, Fausa O, Aadland E, Lygren I, et al. Incidence of inflammatory bowel disease in southeastern Norway: evaluation of methods after 1 year of registration. Southeastern Norway IBD Study Group of Gastroenterologists. Digestion. 1995. 56:377–381.

43. Farmer RG, Easley KA, Rankin GB. Clinical patterns, natural history, and progression of ulcerative colitis. A long-term follow-up of 1116 patients. Dig Dis Sci. 1993. 38:1137–1146.

44. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, 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:Suppl A. 5–36.

45. Cucchiara S, Iebba V, Conte MP, Schippa S. The microbiota in inflammatory bowel disease in different age groups. Dig Dis. 2009. 27:252–258.

46. Frank DN, Pace NR. Gastrointestinal microbiology enters the metagenomics era. Curr Opin Gastroenterol. 2008. 24:4–10.

47. Taurog JD, Richardson JA, Croft J, Simmons WA, Zhou M, Fernandez-Sueiro JL, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994. 180:2359–2364.

48. Fabia R, Ar'Rajab A, Johansson M, Andersson R, Willen R, Jeppsson B, et al. Impairment of bacterial flora in human ulcerative colitis and experimental colitis in the rat. Digestion. 1993. 54:248–255.

49. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002. 122:44–54.

50. Sartor RB. Review article: role of the enteric microflora in the pathogenesis of intestinal inflammation and arthritis. Aliment Pharmacol Ther. 1997. 11:Suppl 3. 17–22.

51. Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P, Marteau P, et al. Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut. 2003. 52:237–242.

52. Mylonaki M, Langmead L, Pantes A, Johnson F, Rampton DS. Enteric infection in relapse of inflammatory bowel disease: importance of microbiological examination of stool. Eur J Gastroenterol Hepatol. 2004. 16:775–778.

53. Meyer AM, Ramzan NN, Loftus EV Jr, Heigh RI, Leighton JA. The diagnostic yield of stool pathogen studies during relapses of inflammatory bowel disease. J Clin Gastroenterol. 2004. 38:772–775.

54. Swidsinski A, Loening-Baucke V, Vaneechoutte M, Doerffel Y. Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis. 2008. 14:147–161.

55. Conte MP, Schippa S, Zamboni I, Penta M, Chiarini F, Seganti L, et al. Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut. 2006. 55:1760–1767.

56. Schippa S, Conte MP, Borrelli O, Iebba V, Aleandri M, Seganti L, et al. Dominant genotypes in mucosa associated Escherichia coli strains from pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2009. 15:661–672.

57. Kirsner JB, Spencer JA. Family occurrences of ulcerative colitis, regional enteritis, and ileocolitis. Ann Intern Med. 1963. 59:133.

58. Yang H, McElree C, Roth M, Shanahan F, Targan S, Rotter J. Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews. Gut. 1993. 34:517–524.

59. Halme L, Paavola-Sakki P, Turunen U, Lappalainen M, Farkkila M, Kontula K. Family and twin studies in inflammatory bowel disease. World J Gastroenterol. 2006. 12:3668–3672.

60. Orholm M, Binder V, Sørensen TI, Rasmussen LP, Kyvik KO. Concordance of inflammatory bowel disease among Danish twins: results of a nationwide study. Scand J Gastroenterol. 2000. 35:1075–1081.

61. Abreu MT, Taylor KD, Lin YC, Hang T, Gaiennie J, Landers CJ, et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. Gastroenterology. 2002. 123:679–688.

62. Chamaillard M, Iacob R, Desreumaux P, Colombel JF. Advances and perspectives in the genetics of inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2006. 4:143–151.

63. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nuñez G, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005. 307:731–734.

64. Fiocchi C. Susceptibility genes and overall pathogenesis of inflammatory bowel disease: where do we stand? Dig Dis. 2009. 27:226–235.

65. Biank V, Broeckel U, Kugathasan S. Pediatric inflammatory bowel disease: clinical and molecular genetics. Inflamm Bowel Dis. 2007. 13:1430–1438.

66. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2006. 39:207–211.

67. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007. 39:596–604.

68. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet. 2007. 39:830–832.

69. Kugathasan S, Baldassano RN, Bradfield JP, Sleiman PM, Imielinski M, Guthery SL, et al. Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nat Genet. 2008. 40:1211–1215.

70. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006. 314:1461.

71. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007. 447:661–673.

72. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet. 2008. 40:955–962.

73. Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, et al. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008. 40:713–715.

74. Anderson CA, Massey DCO, Barrett JC, Prescott NJ, Tremelling M, Fisher SA, et al. Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology. 2009. 136:523–529.

75. Franke A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr G, et al. Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat Genet. 2008. 40:1319–1323.

76. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rious JD, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn disease. Nat Genet. 2008. 40:955–962.

77. McGovern DPB, Gardet A, Torkvist L, Goyette P, Essers J, Taylor KD, et al. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet. 2010. 42:332–337.

78. Latella G, Fiocchi C, Caprili R. News from the "5th international meeting on inflammatory bowel disease" CAPRI 2010. J Crohns Colitis. 2010. 4:690–702.

79. Peterson N, Guthery S, Denson L, Lee J, Saeed S, Prahalad S, et al. Genetic variants in the autophagy pathway contribute to paediatric Crohn's disease. Gut. 2008. 57:1336–1337.

80. Essers JB, Lee JJ, Kugathasan S, Stevens CR, Grand RJ, Daly MJ. Established genetic risk factors do not distinguish early and later onset Crohn's disease. Inflamm Bowel Dis. 2009. 15:1508–1514.

81. Scherr R, Essers J, Hakonarson H, Kugathasan S. Genetic determinants of pediatric inflammatory bowel disease: is age of onset genetically determined? Dig Dis. 2009. 27:236–239.

82. Ridder L, Weersma RK, Dijkstra G, Van der Steege G, Benninga MA, Nolte IM, et al. Genetic susceptibility has a more important role in pediatric onset Crohn disease than in adult-onset Crohn disease. Inflamm Bowel Dis. 2007. 13:1083–1092.

83. Imielinski M, Baldassano RN, Griffiths A, Russell RK, Annese V, Dubinsky M, et al. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet. 2009. 41:1335–1340.

84. Henderson P, Van Limbergen JE, Wilson DC, Satsangi J, Russell RK. Genetics of childhood-onset inflammatory bowel disease. Inflamm Bowel Dis. 2011. 17:346–361.

85. Sagiv-Friedgut K, Karban A, Weiss B, Shaoul R, Shamir R, Bujanover Y, et al. Early-onset Crohn disease is associated with male sex and a polymorphism in the IL-6 promoter. J Pediatr Gastroenterol Nutr. 2010. 50:22–26.

86. Akobeng AK, Gardener E. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease. Cochrane Database Syst Rev. 2005. (1):CD003715.

87. Sutherland L, MacDonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2003. (3):CD000543.

88. Turner D, Travis SPL, Griffiths AM, Ruemmele FM, Levine A, Benchimol EI, et al. Consensus for managing acute severe ulcerative colitis in children: A systemic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol. 2011. 01. 11. (in press).

89. Alfadhli AA, McDonald JW, Feagan BG. Methotrexate for induction of remission in refractory Crohn's disease. Cochrane Database Syst Rev. 2005. (1):CD003459.

90. Uhlen S, Belbouab R, Narebski K, Goulet O, Schmitz J, Cezard J, et al. Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study. Inflamm Bowel Dis. 2006. 12:1053–1057.

91. Turner D, Grossman AB, Rosh J, Kugathasan S, Gilman AR, Baldassano R, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's disease. Am J Gastroenterol. 2007. 102:2804–2812.

92. Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, Johanns J, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007. 132:863–873.

93. Hyams JS, Lerer T, Griffiths A, Pfefferkorn M, Kugathasan S, Evans J, et al. Long term outcome of maintenance infliximab therapy in children with Crohn's disease. Inflamm Bowel Dis. 2009. 15:816–822.

94. D'Haens G, Baert F, Van Assche G, Caenepeel P, Vergauwe P, Tuynman H, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008. 371:660–667.

95. Hyams JS. Risk/benefit Strategies must be employed pediatric Crohn's disease. Dig Dis. 2009. 27:291–296.

96. Thayu M, Markowitz JE, Mamula P, Russo PA, Muinos WI, Baldassano RN. Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. J Pediatr Gastroenterol Nutr. 2005. 40:220–222.

97. Drini M, Prichard PJ, Brown GJ, Macrae FA. Hepatosplenic T-cell lymphoma following infliximab therapy for Crohn's disease. Med J Aust. 2008. 189:464–465.

98. Sandborn W, Rutgeerts P, Reinisch W, Kornbluth A, Lichtiger S, D'Haens G, et al. SONIC: a randomized, double-blind, controlled trial comparing infliximab and infliximab plus azathioprine to azathioprine in patients with Crohn's disease naive to immunomodulators and biologic therapy. Am J Gastroenterol. 2008. 103:Suppl 1. S436.

99. Lichtenstein G, Diamond R, Wagner C, Olson A, Hegedus R, Bala M, et al. Infliximab administered as 3-dose induction followed by scheduled maintenance therapy in IBD: comparable clinical outcomes with or without concomitant immunomodulators. Gastroenterology. 2007. 132:Suppl 2. A146.

100. Van Assche G, Magdelaine-Beuzelin C, D'Haens G, Baert F, Noman M, Vermeire S, et al. Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology. 2008. 134:1861–1868.

101. Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, et al. Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr. 1991. 12:439–447.

102. Turner D, Otley AR, Mack D, Hyams J, de Bruijne J, Uusoue K, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007. 133:423–432.

103. Griffiths AM. Growth retardation in early-onset inflammatory bowel disease: should we monitor and treat these patients differently? Dig Dis. 2009. 27:404–411.

104. Walters TD, Griffiths AM. Mechanisms of growth impairment in pediatric Crohn's disease. Nat Rev Gastroenterol Hepatol. 2009. 6:513–523.

105. De Benedetti F, Meazza C, Oliveri M, Pignatti P, Vivarelli M, Alonzi T, et al. Effect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritis. Endocrinology. 2001. 142:4818–4826.

TOOLS

Similar articles