Skip to main content
SpringerLink
Log in

Crohn’s Disease

  • Chapter
  • First Online:
Textbook of Pediatric Gastroenterology, Hepatology and Nutrition

Abstract

Crohn’s disease (CD), together with ulcerative colitis (CD) and inflammatory bowel disease-unclassified (IBD-U), belongs to the group of inflammatory bowel diseases (IBDs), that are chronic, idiopathic, and detrimental disorders of the gastrointestinal (GI) tract. CD manifests during childhood or adolescence in up to 25% of patients, and the incidence has been increasing over the last four decades. The etiology and the mechanisms of CD are still unknown. Recent data suggest that it is the result of altered immune homeostasis within the intestinal mucosa in genetically predisposed individuals: this may evolve into an uncontrolled inflammatory response, probably triggered by the intestinal microbiota and/or other environmental factors. Presenting symptoms and therapeutic armamentarium are similar in adults and children, however, there are significant peculiarities characterizing pediatric-onset CD. Children with CD are at particular risk for extraintestinal manifestations, including growth failure, delayed puberty, weight loss, and anemia, which may be more harmful than in adults. The therapy itself can adversely impact normal growth and development. Other issues unique to pediatric patients are the paucity of controlled clinical trials and the psychological issues related to this specific age group.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ye Y, Manne S, Treem WR, Bennett D. Prevalence of inflammatory bowel disease in pediatric and adult populations: recent estimates from large National Databases in the United States, 2007-2016. Inflamm Bowel Dis. 2020;26:619–25.

    Google Scholar 

  2. Kaplan GG, Bernstein CN, Coward S, Bitton A, Murthy SK, et al. The impact of inflammatory bowel disease in Canada 2018: epidemiology. J Can Assoc Gastroenterol. 2019;2:S6–S16.

    Google Scholar 

  3. Carroll MW, Kuenzig ME, Mack DR, Otley AR, Griffiths AM, et al. The impact of inflammatory bowel disease in Canada 2018: children and adolescents with IBD. J Can Assoc Gastroenterol. 2019;2:S49–67.

    Google Scholar 

  4. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018;390:2769–78.

    Google Scholar 

  5. Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, et al. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol. 2018;15:39–49.

    Google Scholar 

  6. de Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017;14:739–49.

    Google Scholar 

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

    CAS  Google Scholar 

  8. Kugathasan S, Denson LA, Walters TD, Kim MO, Marigorta UM, et al. Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study. Lancet. 2017;389:1710–8.

    Google Scholar 

  9. Kugathasan S, Cohen S. Searching for new clues in inflammatory bowel disease: tell tales from pediatric IBD natural history studies. Gastroenterology. 2008;135:1038–41.

    Google Scholar 

  10. Ghione S, Sarter H, Fumery M, Armengol-Debeir L, Savoye G, et al. Dramatic increase in incidence of ulcerative colitis and Crohn's disease (1988-2011): a population-based study of French adolescents. Am J Gastroenterol. 2018;113:265–72.

    Google Scholar 

  11. Baumgart DC, Bernstein CN, Abbas Z, Colombel JF, Day AS, et al. IBD around the world: comparing the epidemiology, diagnosis, and treatment: proceedings of the World Digestive Health Day 2010--inflammatory bowel disease task force meeting. Inflamm Bowel Dis. 2011;17:639–44.

    Google Scholar 

  12. Windsor JW, Kaplan GG. Evolving epidemiology of IBD. Curr Gastroenterol Rep. 2019;21:40.

    Google Scholar 

  13. Mokhtar NM, Nawawi KNM, Verasingam J, Zhiqin W, Sagap I, et al. A four-decade analysis of the incidence trends, sociodemographic and clinical characteristics of inflammatory bowel disease patients at single tertiary centre, Kuala Lumpur, Malaysia. BMC Public Health. 2019;19:550.

    Google Scholar 

  14. Park SH, Kim YJ, Rhee KH, Kim YH, Hong SN, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong District of Seoul, Korea in 1986-2015. J Crohns Colitis. 2019;13:1410–7.

    Google Scholar 

  15. Vegh Z, Kurti Z, Lakatos PL. Epidemiology of inflammatory bowel diseases from west to east. J Dig Dis. 2017;18:92–8.

    Google Scholar 

  16. Van Limbergen J, Russell RK, Drummond HE, Aldhous MC, Round NK, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008;135:1114–22.

    Google Scholar 

  17. Aloi M, Lionetti P, Barabino A, Guariso G, Costa S, et al. Phenotype and disease course of early-onset pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2014;20:597–605.

    Google Scholar 

  18. Fumery M, Pariente B, Sarter H, Savoye G, Spyckerelle C, et al. Long-term outcome of pediatric-onset Crohn's disease: a population-based cohort study. Dig Liver Dis. 2019;51:496–502.

    Google Scholar 

  19. Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, et al. Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology. 2008;135:1106–13.

    Google Scholar 

  20. Peyrin-Biroulet L, Loftus EV, Colombel JF, Sandborn WJ. Long-term complications, extraintestinal manifestations, and mortality in adult Crohn's disease in population-based cohorts. Inflamm Bowel Dis. 2011;17:471–8.

    Google Scholar 

  21. Nazareth N, Magro F, Machado E, Ribeiro TG, Martinho A, et al. Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease. Med Microbiol Immunol. 2015;204:681–92.

    CAS  Google Scholar 

  22. Larabi A, Barnich N, Nguyen HTT. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD. Autophagy. 2020;16:38–51.

    CAS  Google Scholar 

  23. Lee JG, Han DS, Jo SV, Lee AR, Park CH, et al. Characteristics and pathogenic role of adherent-invasive Escherichia coli in inflammatory bowel disease: potential impact on clinical outcomes. PLoS One. 2019;14:e0216165.

    CAS  Google Scholar 

  24. Negroni A, Costanzo M, Vitali R, Superti F, Bertuccini L, et al. Characterization of adherent-invasive Escherichia coli isolated from pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:913–24.

    Google Scholar 

  25. Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology. 2004;127:412–21.

    Google Scholar 

  26. Graham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature. 2020;578:527–39.

    CAS  Google Scholar 

  27. Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Front Immunol. 2015;6:551.

    Google Scholar 

  28. Ng SC, Woodrow S, Patel N, Subhani J, Harbord M. Role of genetic and environmental factors in British twins with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:725–36.

    Google Scholar 

  29. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411:599–603.

    CAS  Google Scholar 

  30. Duerr RHTK, Brant SR, et al. A genome wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–46.

    CAS  Google Scholar 

  31. Imhann F, Vich Vila A, Bonder MJ, Fu J, Gevers D, et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut. 2018;67:108–19.

    CAS  Google Scholar 

  32. Latiano A, Palmieri O, Corritore G, Valvano MR, Bossa F, et al. Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16:1108–17.

    Google Scholar 

  33. Hu S, Vich Vila A, Gacesa R, Collij V, Stevens C, et al. Whole exome sequencing analyses reveal gene-microbiota interactions in the context of IBD. Gut. 2020;70:285.

    Google Scholar 

  34. de Lange KMML, Lee JC, et al. Genome-Wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet. 2017;49:256–61.

    Google Scholar 

  35. Glocker EOKD, Boztug K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009;361:2033–45.

    CAS  Google Scholar 

  36. Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, et al. The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology. 2014;147:990–1007.e3.

    Google Scholar 

  37. Kotlarz D, Beier R, Murugan D, Diestelhorst J, Jensen O, et al. Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. Gastroenterology. 2012;143:347–55.

    CAS  Google Scholar 

  38. Uhlig HH. Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease. Gut. 2013;62:1795–805.

    CAS  Google Scholar 

  39. Muise AM, Snapper SB, Kugathasan S. The age of gene discovery in very early onset inflammatory bowel disease. Gastroenterology. 2012;143:285–8.

    Google Scholar 

  40. Ho SM, Lewis JD, Mayer EA, Plevy SE, Chuang E, et al. Challenges in IBD research: environmental triggers. Inflamm Bowel Dis. 2019;25:S13–23.

    Google Scholar 

  41. Khalili H, Chan SSM, Lochhead P, Ananthakrishnan AN, Hart AR, et al. The role of diet in the aetiopathogenesis of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2018;15:525–35.

    CAS  Google Scholar 

  42. Abraham BP, Mehta S, El-Serag HB. Natural history of pediatric-onset inflammatory bowel disease: a systematic review. J Clin Gastroenterol. 2012;46:581–9.

    Google Scholar 

  43. Sanderson IR. Growth problems in children with IBD. Nat Rev Gastroenterol Hepatol. 2014;11:601–10.

    CAS  Google Scholar 

  44. Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJ. Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis. Gut. 2000;46:694–700.

    CAS  Google Scholar 

  45. Aloi MB-SL, Buderus S, et al. Treatment options and outcomes of pediatric IBDU compared with other IBD subtypes: a retrospective multicenter study from the IBD Porto group of ESPGHAN. Inflamm Bowel Dis. 2016;22:1378–83.

    Google Scholar 

  46. Levine AKS, Turner D, et al. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr. 2014;58:795–806.

    CAS  Google Scholar 

  47. Solem CA, Loftus EV, Tremaine WJ, Harmsen WS, Zinsmeister AR, et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:707–12.

    Google Scholar 

  48. Willot S, Vermeire S, Ohresser M, Rutgeerts P, Paintaud G, et al. No association between C-reactive protein gene polymorphisms and decrease of C-reactive protein serum concentration after infliximab treatment in Crohn's disease. Pharmacogenet Genomics. 2006;16:37–42.

    CAS  Google Scholar 

  49. Denis MA, Reenaers C, Fontaine F, Belaïche J, Louis E. Assessment of endoscopic activity index and biological inflammatory markers in clinically active Crohn's disease with normal C-reactive protein serum level. Inflamm Bowel Dis. 2007;13:1100–5.

    Google Scholar 

  50. De Cruz P, Kamm MA, Hamilton AL, Ritchie KJ, Krejany EO, et al. Crohn's disease management after intestinal resection: a randomised trial. Lancet. 2015;385:1406–17.

    Google Scholar 

  51. Colombel JF, Panaccione R, Bossuyt P, Lukas M, Baert F, et al. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet. 2018;390:2779–89.

    Google Scholar 

  52. Mow WS, Vasiliauskas EA, Lin YC, Fleshner PR, Papadakis KA, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology. 2004;126:414–24.

    CAS  Google Scholar 

  53. Dubinsky M. Can serologic markers help determine prognosis and guide therapy? Dig Dis. 2010;28:424–8.

    Google Scholar 

  54. Birimberg-Schwartz LWD, Kolho KL, et al. pANCA and ASCA in children with IBD-unclassified, Crohn's colitis, and ulcerative Colitis-A longitudinal report from the IBD Porto Group of ESPGHAN. Inflamm Bowel Dis. 2016;22:1908–14.

    Google Scholar 

  55. Birimberg-Schwartz L, Wilson DC, Kolho KL, Karolewska-Bochenek K, Afzal NA, et al. pANCA and ASCA in children with IBD-unclassified, Crohn's colitis, and ulcerative colitis-A longitudinal report from the IBD Porto Group of ESPGHAN. Inflamm Bowel Dis. 2016;22:1908–14.

    Google Scholar 

  56. D'Arcangelo G, Aloi M. Inflammatory bowel disease-unclassified in children: diagnosis and pharmacological management. Paediatr Drugs. 2017;19:113–20.

    Google Scholar 

  57. Smids C, Horjus Talabur Horje CS, Groenen MJM, van Koolwijk EHM, Wahab PJ, et al. The value of serum antibodies in differentiating inflammatory bowel disease, predicting disease activity and disease course in the newly diagnosed patient. Scand J Gastroenterol. 2017;52:1104–12.

    CAS  Google Scholar 

  58. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341:c3369.

    Google Scholar 

  59. Cucchiara S, D'Arcangelo G, Isoldi S, Aloi M, Stronati L. Mucosal healing in Crohn's disease: new insights. Expert Rev Gastroenterol Hepatol. 2020;14:335–45.

    CAS  Google Scholar 

  60. Däbritz J, Langhorst J, Lügering A, Heidemann J, Mohr M, et al. Improving relapse prediction in inflammatory bowel disease by neutrophil-derived S100A12. Inflamm Bowel Dis. 2013;19:1130–8.

    Google Scholar 

  61. Vitali R, Stronati L, Negroni A, Di Nardo G, Pierdomenico M, et al. Fecal HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011;106:2029–40.

    CAS  Google Scholar 

  62. de Ridder L, Turner D, Wilson DC, Koletzko S, Martin-de-Carpi J, et al. Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group. Inflamm Bowel Dis. 2014;20:291–300.

    Google Scholar 

  63. Aloi M, Di Nardo G, Romano G, Casciani E, Civitelli F, et al. Magnetic resonance enterography, small-intestine contrast US, and capsule endoscopy to evaluate the small bowel in pediatric Crohn's disease: a prospective, blinded, comparison study. Gastrointest Endosc. 2015;81:420–7.

    Google Scholar 

  64. Di Nardo G, Aloi M, Oliva S, Civitelli F, Casciani E, et al. Investigation of small bowel in pediatric Crohn's disease. Inflamm Bowel Dis. 2012;18:1760–76.

    Google Scholar 

  65. Horsthuis K, Bipat S, Stokkers PC, Stoker J. Magnetic resonance imaging for evaluation of disease activity in Crohn's disease: a systematic review. Eur Radiol. 2009;19:1450–60.

    Google Scholar 

  66. Horsthuis K, Ziech ML, Bipat S, Spijkerboer AM, de Bruine-Dobben AC, et al. Evaluation of an MRI-based score of disease activity in perianal fistulizing Crohn's disease. Clin Imaging. 2011;35:360–5.

    Google Scholar 

  67. Ruemmele FMVG, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014;8:1179–207.

    Google Scholar 

  68. Pallotta N, Civitelli F, Di Nardo G, Vincoli G, Aloi M, et al. Small intestine contrast ultrasonography in pediatric Crohn's disease. J Pediatr. 2013;163:778–84.e1.

    Google Scholar 

  69. Allocca M, Fiorino G, Bonifacio C, Furfaro F, Gilardi D, et al. Comparative accuracy of bowel ultrasound versus magnetic resonance enterography in combination with colonoscopy in assessing Crohn's disease and guiding clinical decision-making. J Crohns Colitis. 2018;12:1280–7.

    Google Scholar 

  70. Bots S, Nylund K, Löwenberg M, Gecse K, Gilja OH, et al. Ultrasound for assessing disease activity in IBD patients: a systematic review of activity scores. J Crohns Colitis. 2018;12:920–9.

    CAS  Google Scholar 

  71. Di Nardo G, Oliva S, Ferrari F, Riccioni ME, Staiano A, et al. Usefulness of wireless capsule endoscopy in paediatric inflammatory bowel disease. Dig Liver Dis. 2011;43:220–4.

    Google Scholar 

  72. Dulai PS, Levesque BG, Feagan BG, D'Haens G, Sandborn WJ. Assessment of mucosal healing in inflammatory bowel disease: review. Gastrointest Endosc. 2015;82:246–55.

    Google Scholar 

  73. Yamamoto H, Kita H, Sunada K, Hayashi Y, Sato H, et al. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases. Clin Gastroenterol Hepatol. 2004;2:1010–6.

    Google Scholar 

  74. Heine GD, Hadithi M, Groenen MJ, Kuipers EJ, Jacobs MA, et al. Double-balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease. Endoscopy. 2006;38:42–8.

    CAS  Google Scholar 

  75. Di Nardo G, Oliva S, Aloi M, Rossi P, Casciani E, et al. Usefulness of single-balloon enteroscopy in pediatric Crohn's disease. Gastrointest Endosc. 2012;75:80–6.

    Google Scholar 

  76. Colombel JF, D'haens G, Lee WJ, Petersson J, Panaccione R. Outcomes and strategies to support a treat-to-target approach in inflammatory bowel disease: a systematic review. J Crohns Colitis. 2020;14:254–66.

    Google Scholar 

  77. Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–38.

    CAS  Google Scholar 

  78. Aloi M, Nuti F, Stronati L, Cucchiara S. Advances in the medical management of paediatric IBD. Nat Rev Gastroenterol Hepatol. 2014;11:99–108.

    CAS  Google Scholar 

  79. Danese S, Fiorino G, Peyrin-Biroulet L. Early intervention in Crohn's disease: towards disease modification trials. Gut. 2017;66:2179–87.

    CAS  Google Scholar 

  80. Levine A, Chanchlani N, Hussey S, Ziv-Baran T, Escher JC, et al. Complicated disease and response to initial therapy predicts early surgery in Paediatric Crohn's disease: results from the Porto group GROWTH study. J Crohns Colitis. 2020;14:71–8.

    Google Scholar 

  81. Cohen SA, Aloi M, Arumugam R, Baker R, Bax K, et al. Enteric-coated budesonide for the induction and maintenance of remission of Crohn's disease in children. Curr Med Res Opin. 2017;33:1261–8.

    CAS  Google Scholar 

  82. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology. 2000;119:895–902.

    CAS  Google Scholar 

  83. Punati J, Markowitz J, Lerer T, Hyams J, Kugathasan S, et al. Effect of early immunomodulator use in moderate to severe pediatric Crohn disease. Inflamm Bowel Dis. 2008;14:949–54.

    Google Scholar 

  84. Hanauer SB, Sandborn WJ, Lichtenstein GR. Evolving considerations for Thiopurine therapy for inflammatory bowel diseases-a clinical practice update: commentary. Gastroenterology. 2019;156:36–42.

    Google Scholar 

  85. Herfarth HH, Kappelman MD, Long MD, Isaacs KL. Use of methotrexate in the treatment of inflammatory bowel diseases. Inflamm Bowel Dis. 2016;22:224–33.

    Google Scholar 

  86. Colman RJ, Lawton RC, Dubinsky MC, Rubin DT. Methotrexate for the treatment of pediatric Crohn's disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2018;24:2135–41.

    Google Scholar 

  87. Ruemmele FM. Immunomodulation with methotrexate: underused and undervalued? Dig Dis. 2009;27:312–4.

    Google Scholar 

  88. Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007;132:863–73; quiz 1165–6.

    CAS  Google Scholar 

  89. Civitelli F, Nuti F, Oliva S, Messina L, La Torre G, et al. Looking beyond mucosal healing: effect of biologic therapy on transmural healing in pediatric Crohn's disease. Inflamm Bowel Dis. 2016;22:2418–24.

    Google Scholar 

  90. Cucchiara S, D'Arcangelo G, Isoldi S, Aloi M, Stronati L. Mucosal healing in Crohn's disease: new insights. Expert Rev Gastroenterol Hepatol. 2020:1–11.

    Google Scholar 

  91. Klenske E, Bojarski C, Waldner M, Rath T, Neurath MF, et al. Targeting mucosal healing in Crohn's disease: what the clinician needs to know. Ther Adv Gastroenterol. 2019;12:1756284819856865.

    Google Scholar 

  92. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362:1383–95.

    CAS  Google Scholar 

  93. Papamichael K, Cheifetz AS, Melmed GY, Irving PM, Vande Casteele N, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019;17:1655–68.e3.

    Google Scholar 

  94. Ricciuto A, Dhaliwal J, Walters TD, Griffiths AM, Church PC. Clinical outcomes with therapeutic drug monitoring in inflammatory bowel disease: a systematic review with meta-analysis. J Crohns Colitis. 2018;12:1302–15.

    Google Scholar 

  95. Vande Casteele N, Ferrante M, Van Assche G, Ballet V, Compernolle G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148:1320–9.e3.

    Google Scholar 

  96. Papamichael K, Chachu KA, Vajravelu RK, Vaughn BP, Ni J, et al. Improved long-term outcomes of patients with inflammatory bowel disease receiving proactive compared with reactive monitoring of serum concentrations of infliximab. Clin Gastroenterol Hepatol. 2017;15:1580–8.e3.

    Google Scholar 

  97. Vaughn BP, Martinez-Vazquez M, Patwardhan VR, Moss AC, Sandborn WJ, et al. Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study. Inflamm Bowel Dis. 2014;20:1996–2003.

    Google Scholar 

  98. D'Haens G, Vermeire S, Lambrecht G, Baert F, Bossuyt P, et al. Increasing infliximab dose based on symptoms, biomarkers, and serum drug concentrations does not increase clinical, endoscopic, and corticosteroid-free remission in patients with active Luminal Crohn's disease. Gastroenterology. 2018;154:1343–51.e1.

    Google Scholar 

  99. Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA, et al. Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology. 2012;143:365–74.e2.

    CAS  Google Scholar 

  100. Ananthakrishnan AN, Cagan A, Cai T, Gainer VS, Shaw SY, et al. Comparative effectiveness of infliximab and adalimumab in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis. 2016;22:880–5.

    Google Scholar 

  101. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007;132:52–65.

    CAS  Google Scholar 

  102. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323–33; quiz 591.

    CAS  Google Scholar 

  103. Sandborn WJ, Hanauer SB, Rutgeerts P, Fedorak RN, Lukas M, et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut. 2007;56:1232–9.

    CAS  Google Scholar 

  104. Faubion WA, Dubinsky M, Ruemmele FM, Escher J, Rosh J, et al. Long-term efficacy and safety of adalimumab in pediatric patients with Crohn's disease. Inflamm Bowel Dis. 2017;23:453–60.

    Google Scholar 

  105. Papamichael K, Cheifetz AS. Therapeutic drug monitoring in inflammatory bowel disease: for every patient and every drug? Curr Opin Gastroenterol. 2019;35:302.

    Google Scholar 

  106. Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, et al. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014;147:618–27.e3.

    Google Scholar 

  107. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, et al. Ustekinumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2016;375:1946–60.

    CAS  Google Scholar 

  108. Grover Z, Burgess C, Muir R, Reilly C, Lewindon PJ. Early mucosal healing with exclusive enteral nutrition is associated with improved outcomes in newly diagnosed children with Luminal Crohn’s disease. J Crohns Colitis. 2016;10:1159–64.

    CAS  Google Scholar 

  109. Narula N, Dhillon A, Zhang D, Sherlock ME, Tondeur M, et al. Enteral nutritional therapy for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2018;4:CD000542.

    Google Scholar 

  110. Connors J, Basseri S, Grant A, Giffin N, Mahdi G, et al. Exclusive enteral nutrition therapy in paediatric Crohn's disease results in long-term avoidance of corticosteroids: results of a propensity-score matched Cohort analysis. J Crohns Colitis. 2017;11:1063–70.

    Google Scholar 

  111. Yu Y, Chen KC, Chen J. Exclusive enteral nutrition versus corticosteroids for treatment of pediatric Crohn's disease: a meta-analysis. World J Pediatr. 2019;15:26–36.

    CAS  Google Scholar 

  112. Quince C, Ijaz UZ, Loman N, Eren AM, Saulnier D, et al. Extensive modulation of the fecal metagenome in children with Crohn's disease during exclusive enteral nutrition. Am J Gastroenterol. 2015;110:1718–29; quiz 30.

    CAS  Google Scholar 

  113. Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut. 2018;67:1726–38.

    CAS  Google Scholar 

  114. Sigall Boneh R, Van Limbergen J, Wine E, Assa A, Shaoul R, et al. Dietary therapies induce rapid response and remission in pediatric patients with active Crohn's disease. Clin Gastroenterol Hepatol. 2020;19:752.

    Google Scholar 

  115. Levine A, Wine E, Assa A, Sigall Boneh R, Shaoul R, et al. Crohn's disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology. 2019;157:440–50.e8.

    Google Scholar 

  116. Svolos V, Hansen R, Nichols B, Quince C, Ijaz UZ, et al. Treatment of active Crohn's disease with an ordinary food-based diet that replicates exclusive enteral nutrition. Gastroenterology. 2019;156:1354–67.e6.

    Google Scholar 

  117. Amil-Dias J, Kolacek S, Turner D, Pærregaard A, Rintala R, et al. Surgical management of Crohn disease in children: guidelines from the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2017;64:818–35.

    Google Scholar 

  118. Limmer AM, Koh HC, Gilmore A. Stricturoplasty-a bowel-sparing option for long segment small bowel Crohn's disease. J Surg Case Rep. 2017;2017:rjx163.

    Google Scholar 

  119. Maguire LH, Alavi K, Sudan R, Wise PE, Kaiser AM, et al. Surgical considerations in the treatment of small bowel Crohn's disease. J Gastrointest Surg. 2017;21:398–411.

    Google Scholar 

  120. Kantor N, Wayne C, Nasr A. What is the optimal surgical strategy for complex perianal fistulous disease in pediatric Crohn's disease? A systematic review. Pediatr Surg Int. 2017;33:551–7.

    Google Scholar 

  121. Haennig A, Staumont G, Lepage B, Faure P, Alric L, et al. The results of seton drainage combined with anti-TNFα therapy for anal fistula in Crohn's disease. Color Dis. 2015;17:311–9.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Gastroenterology and Liver Unit, Department of Women’s and Children’s Health, Sapienza University of Rome, Rome, Italy

    Marina Aloi & Salvatore Cucchiara

Authors
  1. Marina Aloi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salvatore Cucchiara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salvatore Cucchiara .

Editor information

Editors and Affiliations

  1. Section of Pediatric Gastroenterology Hepatology and Nutrition, University of Chicago, Chicago, IL, USA

    Stefano Guandalini

  2. Pediatric Liver, GI and Nutrition Center, Child Health, King’s College Hospital, London, UK

    Anil Dhawan

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Aloi, M., Cucchiara, S. (2022). Crohn’s Disease. In: Guandalini, S., Dhawan, A. (eds) Textbook of Pediatric Gastroenterology, Hepatology and Nutrition. Springer, Cham. https://doi.org/10.1007/978-3-030-80068-0_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-80068-0_28

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-80067-3

  • Online ISBN: 978-3-030-80068-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation