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Risk factors for relapse and surgery rate in children with Crohn’s disease

Abstract

The aim of this study was to evaluate risk factors associated with the relapse rate in the first year and the need for surgery in children with Crohn’s disease (CD). Data of all children (n = 74) diagnosed with CD from January 2004 to June 2011 were retrospectively analyzed. Multivariate Cox proportional hazards regression model was used to assess whether important clinical variables at diagnosis (age, presence of perianal disease, first induction therapy, first maintenance therapy, levels of Pediatric CD Activity Index (PCDAI), C-reactive protein (CRP), and standard deviation score (SDS) for height for weight) were associated with the risk of clinical recurrence in the first year and need for surgery during follow-up. Relapse occurred in 36 (48.6 %) patients in the first year from diagnosis. The only significant parameter associated with negative risk of relapse in the first year was exclusive enteral nutrition (EEN) used as induction therapy (hazard ratio (HR) 0.469, 95 % confidence interval (CI) 0.232–0.948). EEN induced remission in 84.2 % of patients. The only risk associated with EEN treatment failure was the involvement of the upper gastrointestinal tract. During the follow-up, 25 (33.7 %) patients underwent surgery. The multivariate Cox regression model failed to recognize significant risk factor for surgery. Conclusion: This study underlines the importance of early EEN in the treatment of CD; it is not only efficacious in the remission induction but could also prevent relapse in the first year.

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Fig. 1

Abbreviations

CD:

Crohn’s disease

CRP:

C-reactive protein

ECCO:

European Crohn’s and Colitis Organisation

EEN:

Exclusive enteral nutrition

ESPGHAN:

European Society of Paediatric Gastroenterology, Hepatology and Nutrition

HR:

Hazard ratio

IBD:

Inflammatory bowel disease

PCDAI:

Pediatric CD Activity Index

SDS:

Standard deviation score

References

  1. 1.

    Afzal NA, Davies S, Paintin M, Arnaud-Battandier F, Walker-Smith JA, Murch S, Heuschkel R, Fell J (2005) Colonic Crohn’s disease in children does not respond well to treatment with enteral nutrition if the ileum is not involved. Dig Dis Sci 50:1471–1475

  2. 2.

    Alhagamhmad MH, Day AS, Lemberg DA, Leach ST (2012) An update of the role of nutritional therapy in the management of Crohn’s disease. J Gastroenterol 47:872–882

  3. 3.

    Beattie RM, Schiffrin EJ, Donnet-Hughes A, Huggett AC, Domizio P, MacDonald TT, Walker-Smith JA (1994) Polymeric nutrition as the primary therapy in children with small bowel Crohn’s disease. Aliment Pharmacol Ther 8:609–615

  4. 4.

    Berni Canani R, Terrin G, Borrelli O, Romano MT, Manguso F, Coruzzo A, D’Armiento F, Romeo EF, Cucchiara S (2006) Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn’s disease. Dig Liver Dis 38:381–387

  5. 5.

    Borrelli O, Cordischi L, Cirulli M, Paganelli M, Labalestra V, Uccini S, Russo PM, Cucchiara S (2006) Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol 4:744–753

  6. 6.

    Breese EJ, Michie CA, Nicholls SW, Williams CB, Domizio P, Walker-Smith JA, MacDonald TT (1995) The effect of treatment on lymphokine-secreting cells in the intestinal mucosa of children with Crohn’s disease. Aliment Pharmacol Ther 9:547–552

  7. 7.

    Buchanan E, Gaunt WW, Cardigan T, Garrick V, McGrogan P, Russell RK (2009) The use of exclusive enteral nutrition for induction of remission in children with Crohn’s disease demonstrates that disease phenotype does not influence clinical remission. Aliment Pharmacol Ther 30:501–507

  8. 8.

    Day AS, Whitten KE, Lemberg DA, Clarkson C, Vitug-Sales M, Jackson R, Bohane TD (2006) Exclusive enteral feeding as primary therapy for Crohn’s disease in Australian children and adolescents: a feasible and effective approach. J Gastroenterol Hepatol 21:1609–1614

  9. 9.

    de Bie C, Kindermann A, Escher J (2013) Use of exclusive enteral nutrition in paediatric Crohn’s disease in the Netherlands. J Crohn’s Colitis 7:263–270

  10. 10.

    de Bie CI, Paerregaard A, Kolacek S, Ruemmele FM, Koletzko S, Fell JM, Escher JC (2013) Disease phenotype at diagnosis in pediatric Crohn’s disease: 5-year analyses of the EUROKIDS registry. Inflamm Bowel Dis 19:378–385

  11. 11.

    Dziechciarz P, Horvath A, Shamir R, Szajewska H (2007) Meta-analysis: enteral nutrition in active Crohn’s disease in children. Aliment Pharmacol Ther 26:795–806

  12. 12.

    Fell JM (2012) Update of the management of inflammatory bowel disease. Arch Dis Child 97:78–83

  13. 13.

    Fell JM, Paintin M, Arnaud-Battandier F, Beattie RM, Hollis A, Kitching P, Donnet-Hughes A, MacDonald TT, Walker-Smith JA (2000) Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn’s disease. Aliment Pharmacol Ther 14:281–289

  14. 14.

    Grover Z, Muir R, Lewindon P (2013) Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn’s disease. J Gastroenterol. doi:10.1007/s00535-013-0815-0

  15. 15.

    Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Grand RJ, Boyle JT (1991) Development and validation of a pediatric Crohn’s disease activity index. J Pediatr Gastroenterol Nutr 12:439–447

  16. 16.

    IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (2005) Inflammatory bowel disease in children and adolescents: recommendations for diagnosis—the Porto criteria. J Pediatr Gastroenterol Nutr 41:1–7

  17. 17.

    Jaspers GJ, Verkade HJ, Escher JC, de Ridder L, Taminiau JA, Rings EH (2006) Azathioprine maintains first remission in newly diagnosed pediatric Crohn’s disease. Inflamm Bowel Dis 12:831–836

  18. 18.

    Knight C, El-Matary W, Spray C, Sandhu BK (2005) Long-term outcome of nutritional therapy in paediatric Crohn’s disease. Clin Nutr 24:775–779

  19. 19.

    Kugathasan S, Werlin SL, Martinez A, Rivera MT, Heikenen JB, Binion DG (2000) Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol 95:3189–3194

  20. 20.

    Lambert B, Lemberg DA, Leach ST, Day AS (2012) Longer-term outcomes of nutritional management of Crohn’s disease in children. Dig Dis Sci 57:2171–2177

  21. 21.

    Leach ST, Mitchell HM, Eng WR, Zhang L, Day AS (2008) Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn’s disease. Aliment Pharmacol Ther 28:724–733

  22. 22.

    Levine A, de Bie CI, Turner D, Cucchiara S, Sladek M, Murphy MS, Escher JC (2013) Atypical disease phenotypes in pediatric ulcerative colitis: 5-year analyses of the EUROKIDS Registry. Inflamm Bowel Dis 19:370–377

  23. 23.

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

  24. 24.

    Punati J, Markowitz J, Lerer T, Hyams J, Kugathasan S, Griffiths A, Otley A, Rosh J, Pfefferkorn M, Mack D, Evans J, Bousvaros A, Moyer MS, Wyllie R, Oliva-Hemker M, Mezoff A, Leleiko N, Keljo D, Crandall W (2008) Effect of early immunomodulator use in moderate to severe pediatric Crohn disease. Inflamm Bowel Dis 14:949–954

  25. 25.

    Ravikumara M, Hinsberger A, Spray CH (2007) Role of methotrexate in the management of Crohn disease. J Pediatr Gastroenterol Nutr 44:427–430

  26. 26.

    Riello L, Talbotec C, Garnier-Lengline H, Pigneur B, Svahn J, Canioni D, Goulet O, Schmitz J, Ruemmele FM (2011) Tolerance and efficacy of azathioprine in pediatric Crohn’s disease. Inflamm Bowel Dis 17:2138–2143

  27. 27.

    Shanahan F (2002) Crohn’s disease. Lancet 359:62–69

  28. 28.

    Stephens MC, Shepanski MA, Mamula P, Markowitz JE, Brown KA, Baldassano RN (2003) Safety and steroid-sparing experience using infliximab for Crohn’s disease at a pediatric inflammatory bowel disease center. Am J Gastroenterol 98:104–111

  29. 29.

    Turner D, Grossman AB, Rosh J, Kugathasan S, Gilman AR, Baldassano R, Griffiths AM (2007) Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol 102:2804–12, quiz 3, 13

  30. 30.

    Van Assche G, Dignass A, Reinisch W, van der Woude CJ, Sturm A, De Vos M, Guslandi M, Oldenburg B, Dotan I, Marteau P, Ardizzone A, Baumgart DC, D’Haens G, Gionchetti P, Portela F, Vucelic B, Soderholm J, Escher J, Koletzko S, Kolho KL, Lukas M, Mottet C, Tilg H, Vermeire S, Carbonnel F, Cole A, Novacek G, Reinshagen M, Tsianos E, Herrlinger K, Bouhnik Y, Kiesslich R, Stange E, Travis S, Lindsay J (2010) The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: special situations. J Crohn’s Colitis 4:63–101

  31. 31.

    Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, Mouterde O, Merle V, Salomez JL, Branche J, Marti R, Lerebours E, Cortot A, Gower-Rousseau C, Colombel JF (2008) Natural history of pediatric Crohn’s disease: a population-based cohort study. Gastroenterology 135:1106–1113

  32. 32.

    Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T, Matsumoto K (2005) Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis 11:580–588

  33. 33.

    Zachos M, Tondeur M, Griffiths AM (2007) Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 1, CD000542

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Conflict of interest

All authors have stated that they have no conflict of interest.

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Correspondence to Iva Hojsak.

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Hojsak, I., Pavić, A.M., Mišak, Z. et al. Risk factors for relapse and surgery rate in children with Crohn’s disease. Eur J Pediatr 173, 617–621 (2014). https://doi.org/10.1007/s00431-013-2230-1

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Keywords

  • Crohn’s disease
  • Corticosteroids
  • Early treatment
  • Enteral nutrition
  • Surgery