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Inflammatory Bowel Disease-Unclassified in Children: Diagnosis and Pharmacological Management

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Abstract

Inflammatory bowel diseases are chronic disorders of the gastrointestinal tract that include Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBDU). The latter defines a subgroup of patients with clinical and endoscopic evidence of chronic colitis, without specific features of either CD or UC. These patients will possibly be re-classified as having UC or CD during the follow-up, although a significant percentage of them will keep the diagnosis of IBDU. IBDU is the rarest subtype of IBD, both in children and in adults, although it is twice as common among the pediatric population, especially in the younger ages. The diagnosis can only be made after a comprehensive diagnostic work-up, combining clinical history, physical and laboratory examination, upper and lower gastrointestinal endoscopy, with histology and imaging of the small bowel. The therapeutic strategy is borrowed from that of UC and CD, although recent data suggest that IBDU has a lower therapeutic burden with a generally mild disease course and a good response to mesalamine. Since there are only few published data on pediatric IBDU, and no guidelines on its management are available, this review aims at summarizing the most recent evidence for the diagnostic work-up with a specific focus on medical and surgical options in the treatment of IBDU.

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References

  1. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Towards 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  Google Scholar 

  2. Levine A, de Bie CI, Turner D, Cucchiara S, Sladek M, Murphy MS, et al. Atypical disease phenotypes in pediatric ulcerative colitis: 5-year analyses of the EUROKIDS Registry. Inflamm Bowel Dis. 2013;12:370–7.

    Article  Google Scholar 

  3. Romano C, Famiani A, Gallizzi R, Comito R, Ferrau V, Rossi P. Indeterminate colitis: a distinctive clinical pattern of inflammatory bowel disease in children. Pediatrics. 2008;122:e1278–81.

    Article  PubMed  Google Scholar 

  4. Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, 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  PubMed  Google Scholar 

  5. Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014;8:1179–207.

    Article  CAS  PubMed  Google Scholar 

  6. Turner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr. 2012;55:340–61.

    Article  CAS  PubMed  Google Scholar 

  7. Prenzel F. Uhlig HH Frequency of indeterminate colitis in children and adults with IBD—a metaanalysis. J Crohns Colitis. 2009;3:277–81.

    Article  PubMed  Google Scholar 

  8. Winter DA, Karolewska-Bochenek K, Lazowska-Przeorek I, Lionetti P, Mearin ML, Chong SK, et al. Pediatric IBD-unclassified is less common than previously reported; results of an 8-year audit of the EUROKIDS registry. Inflamm Bowel Dis. 2015;21:2145–53.

    Article  PubMed  Google Scholar 

  9. Auvin S, Molinié F, Gower-Rousseau C, Brazier F, Merle V, Grandbastien B, et al. Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988–1999). J Pediatr Gastroenterol Nutr. 2005;41:49–55.

    Article  PubMed  Google Scholar 

  10. Castro M, Papadatou B, Baldassare M, Balli F, Barabino A, Barbera C, et al. Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996–2003). Inflamm Bowel Dis. 2008;14:1246–52.

    Article  CAS  PubMed  Google Scholar 

  11. Müller KE, Lakatos PL, Arató A, Kovács JB, Várkonyi Á, Szűcs D, et al. Incidence, Paris classification, and follow-up in a nationwide incident cohort of pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2013;57:576–82.

    Article  PubMed  Google Scholar 

  12. Carvalho RS, Abadom V, Dilworth HP, Thompson R, Oliva-Hemker M, Cuffari C. Indeterminate colitis: a significant subgroup of pediatric IBD. Inflamm Bowel Dis. 2006;12:258–62.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  14. Oliva-Hemker M, Hutfless S, Al Kazzi ES, Lerer T, Mack D, LeLeiko N, et al. Clinical presentation and five-year therapeutic management of very early-onset inflammatory bowel disease in a large north American cohort. J Pediatr. 2015;167:527–32.

    Article  PubMed  Google Scholar 

  15. Kammermeier J, Dziubak R, Pescarin M, Drury S, Godwin H, Reeve K, et al. Phenotypic and genotypic characterisation of inflammatory bowel disease presenting before the age of 2 years. J Crohns Colitis. 2017;11:60-69.

    Article  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. 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;12:677–83.

    Article  PubMed  Google Scholar 

  18. Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. Differential diagnosis in inflammatory bowel disease colitis: state of the art and future perspectives. World J Gastroenterol. 2015;7(21):21–46.

    Article  Google Scholar 

  19. Alexander F, Sarigol S, DiFiore J, Stallion A, Cotman K, Clark H, et al. Fate of the pouch in 151 pediatric patients after ileal pouch anal anastomosis. J Pediatr Surg. 2003;38:78–82.

    Article  PubMed  Google Scholar 

  20. Mamula P, Telega GW, Markowitz JE, Brown KA, Russo PA, Piccoli DA, et al. Inflammatory bowel disease in children 5 years of age and younger. Am J Gastroenterol. 2002;97:2005–10.

    Article  PubMed  Google Scholar 

  21. Annese V, Andreoli A, Astegiano M, Campieri M, Caprilli R, Cucchiara S, et al. Clinical features in familial cases of Crohn’s disease and ulcerative colitis in Italy: a GISC study. Italian Study Group for the Disease of Colon and Rectum. Am J Gastroenterol. 2001;96:2939–45.

    CAS  PubMed  Google Scholar 

  22. Aloi M, Birimberg-Schwartz L, Buderus S, Hojsak I, Fell JM, Bronsky J, 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.

    Article  PubMed  Google Scholar 

  23. Rimola J, Ordás I, Rodriguez S, García-Bosch O, Aceituno M, Llach J, et al. Magnetic resonance imaging for evaluation of Crohn’s disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis. 2011;17:1759–68.

    Article  PubMed  Google Scholar 

  24. Ruemmele FM, Hyams JS, Otley A, Griffiths A, Kolho KL, Dias JA, et al. Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. Gut. 2015;64:438–46.

    Article  PubMed  Google Scholar 

  25. Subramanian S, Ekbom A, Rhodes JM. Recent advances in clinical practice: a systematic review of isolated colonic Crohn’s disease: the third IBD? Gut. 2017;66:362-381.

  26. Ruemmele FM, Targan SR, Levy G, Dubinsky M, Braun J, Seidman EG. Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterology. 1998;115:822–9.

    Article  CAS  PubMed  Google Scholar 

  27. Vandewalle-El Khoury P, Colombel JF, Joossens S, Standaert-Vitse A, Collot M, Halfvarson J, et al. Detection of antisynthetic mannoside antibodies (ASigmaMA) reveals heterogeneity in the ASCA response of Crohn’s disease patients and contributes to differential diagnosis, stratification, and prediction. Am J Gastroenterol. 2008;103:949–57.

    Article  PubMed  Google Scholar 

  28. Lakatos PL, Papp M, Rieder F. Serologic antiglycan antibodies in inflammatory bowel disease. Am J Gastroenterol. 2011;106:406–12.

    Article  PubMed  Google Scholar 

  29. Reese GE, Constantinides VA, Simillis C, Darzi AW, Orchard TR, Fazio VW, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006;101:2410–22.

    Article  CAS  PubMed  Google Scholar 

  30. Birimberg-Schwartz L, Wilson DC, Kolho KL, Karolewska-Bochenek K, Afzal NA, Spray C, 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.

    Article  PubMed  Google Scholar 

  31. Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D, Peeters M, et al. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology. 2002;122:1242–7.

    Article  PubMed  Google Scholar 

  32. Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2012;18:1340–55.

    Article  PubMed  Google Scholar 

  33. von Stein P, Lofberg R, Kuznetsov NV, Gielen AW, Persson JO, Sundberg R, et al. Multigene analysis can discriminate between ulcerative colitis, Crohn’s disease, and irritable bowel syndrome. Gastroenterology. 2008;134:1869–81.

    Article  Google Scholar 

  34. Janczewska I, Kapraali M, Saboonchi F, Nekzada Q, Wessulv Å, Khoshkar J, et al. Clinical application of the multigene analysis test in discriminating between ulcerative colitis and Crohn’s disease: a retrospective study. Scand J Gastroenterol. 2012;47:162–9.

    Article  CAS  PubMed  Google Scholar 

  35. Bjerrum JT, Nyberg C, Olsen J, Nielsen OH. Assessment of the validity of a multigene analysis in the diagnostics of inflammatory bowel disease. J Intern Med. 2014;275:484–93.

    Article  CAS  PubMed  Google Scholar 

  36. Manguso F, Bennato R, Lombardi G, Riccio E, Costantino G, Fries W. Efficacy and Safety of Oral Beclomethasone Dipropionate in Ulcerative Colitis: A Systematic Review and Meta-Analysis. PLoS One. 2016;15(11):e0166455.

    Article  Google Scholar 

  37. Mossop H, Davies P, Murphy MS. Predicting the need for azathioprine at first presentation in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2008;47:123–9.

    Article  CAS  PubMed  Google Scholar 

  38. Willot S, Noble A, Deslandres C. Methotrexate in the treatment of inflammatory bowel disease: an 8-year retrospective study in a Canadian pediatric IBD center. Inflamm Bowel Dis. 2011;17:2521–6.

    Article  PubMed  Google Scholar 

  39. Kelsen JR, Grossman AB, Pauly-Hubbard H, Gupta K, Baldassano RN, Mamula P. Infliximab therapy in pediatric patients 7 years of age and younger. J Pediatr Gastroenterol Nutr. 2014;59:758–62.

    Article  CAS  PubMed  Google Scholar 

  40. Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, et al. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Aliment Pharmacol Ther. 2003;15(18):175–81.

    Article  Google Scholar 

  41. Papadakis KA, Treyzon L, Abreu MT, Fleshner PR, Targan SR, Vasiliauskas EA. Infliximab in the treatment of medically refractory indeterminate colitis. Aliment Pharmacol Ther. 2003;1(18):741–7.

    Article  Google Scholar 

  42. Caspersen S, Elkjaer M, Riis L, Pedersen N, Mortensen C, Jess T, Sarto P, et al. Infliximab for inflammatory bowel disease in Denmark 1999–2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol. 2008;6:1212–7.

    Article  PubMed  Google Scholar 

  43. Brown CJ, Maclean AR, Cohen Z, Macrae HM, O’Connor BI, McLeod RS. Crohn’s disease and indeterminate colitis and the ileal pouch-anal anastomosis: outcomes and patterns of failure. Dis Colon Rectum. 2005;48:1542–9.

    Article  PubMed  Google Scholar 

  44. Dayton MT, Larsen KR, Christiansen DD. Similar functional results and complications after ileal pouch-anal anastomosis in patients with indeterminate vs ulcerative colitis. Arch Surg. 2002;137:690–4.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Giulia D’Arcangelo & Marina Aloi

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  1. Giulia D’Arcangelo
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  2. Marina Aloi
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Correspondence to Marina Aloi.

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G. D’Arcangelo and M. Aloi declare no financial relationships with a commercial entity producing health-related products and or services related to this article. No honorarium, grant, or other form of payment was given to anyone to write and produce the manuscript.

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D’Arcangelo, G., Aloi, M. Inflammatory Bowel Disease-Unclassified in Children: Diagnosis and Pharmacological Management. Pediatr Drugs 19, 113–120 (2017). https://doi.org/10.1007/s40272-017-0213-9

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