Korean J Pediatr Gastroenterol Nutr.  2011 Mar;14(1):1-25. 10.5223/kjpgn.2011.14.1.1.

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

Affiliations
  • 1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea. jkseo@snu.ac.kr

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.

Keyword

Pediatric inflammatory bowel disease; Crohn's disease; Ulcerative colitis; Early onset

MeSH Terms

Adolescent
Adult
Colitis, Ulcerative
Crohn Disease
Humans
Inflammatory Bowel Diseases
Phenotype

Cited by  6 articles

Biological Therapy for Inflammatory Bowel Disease in Children
So Young Na, Jung Ok Shim
Pediatr Gastroenterol Hepatol Nutr. 2012;15(1):13-18.    doi: 10.5223/pghn.2012.15.1.13.

Gut Microbiota in Inflammatory Bowel Disease
Jung Ok Shim
Pediatr Gastroenterol Hepatol Nutr. 2013;16(1):17-21.    doi: 10.5223/pghn.2013.16.1.17.

Higher Morbidity of Monogenic Inflammatory Bowel Disease Compared to the Adolescent Onset Inflammatory Bowel Disease
Kwang Yeon Kim, Eun Joo Lee, Ju Whi Kim, Jin Soo Moon, Ju Young Jang, Hye Ran Yang, Jae Sung Ko
Pediatr Gastroenterol Hepatol Nutr. 2018;21(1):34-42.    doi: 10.5223/pghn.2018.21.1.34.

Recent Advance in Very Early Onset Inflammatory Bowel Disease
Jung Ok Shim
Pediatr Gastroenterol Hepatol Nutr. 2019;22(1):41-49.    doi: 10.5223/pghn.2019.22.1.41.

Nutritional Problems and Management in Children with Inflammatory Bowel Disease
Jae Hong Park
Hanyang Med Rev. 2011;31(4):240-245.    doi: 10.7599/hmr.2011.31.4.240.

Recent advance in very early-onset inflammatory bowel disease
Jung Ok Shim
Intest Res. 2019;17(1):9-16.    doi: 10.5217/ir.2018.00130.


Reference

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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
8. Thompson N, Pounder R, Wakefield A, Montgomery S. Is measles vaccination a risk factor for inflammatory bowel disease? Lancet. 1995. 345:1071–1074.
Article
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.
Article
10. Summers R, Elliott D, Urban J, Thompson R, Weinstock J. Trichuris suis therapy in Crohn's disease. Gut. 2005. 54:87.
Article
11. Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy and protection against ulcerative colitis. N Engl J Med. 2001. 344:808–814.
Article
12. Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy is followed by increased risk of Crohn's disease. Gastroenterology. 2003. 124:40–46.
Article
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.
Article
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.
Article
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.
Article
16. Rubin DT, Hanauer SB. Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2000. 12:855–862.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
33. Sauer CG, Kugathasan S. Pediatric inflammatory bowel disease: Highlighting pediatric differences in IBD. Med Clin North Am. 2010. 94:35–52.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
40. Martland GT, Shepherd NA. Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity. Histopathology. 2007. 50:83–96.
Article
41. Wells AD, McMillan I, Price AB, Ritchie JK, Nicholls RJ. Natural history of indeterminate colitis. Br J Surg. 1991. 78:179–181.
Article
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.
Article
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.
Article
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.
Article
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.
Article
46. Frank DN, Pace NR. Gastrointestinal microbiology enters the metagenomics era. Curr Opin Gastroenterol. 2008. 24:4–10.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
57. Kirsner JB, Spencer JA. Family occurrences of ulcerative colitis, regional enteritis, and ileocolitis. Ann Intern Med. 1963. 59:133.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
64. Fiocchi C. Susceptibility genes and overall pathogenesis of inflammatory bowel disease: where do we stand? Dig Dis. 2009. 27:226–235.
Article
65. Biank V, Broeckel U, Kugathasan S. Pediatric inflammatory bowel disease: clinical and molecular genetics. Inflamm Bowel Dis. 2007. 13:1430–1438.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
87. Sutherland L, MacDonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2003. (3):CD000543.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
104. Walters TD, Griffiths AM. Mechanisms of growth impairment in pediatric Crohn's disease. Nat Rev Gastroenterol Hepatol. 2009. 6:513–523.
Article
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.
Article
Full Text Links
  • KJPGN
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr