Clinical Indices for Pediatric Inflammatory Bowel Disease Research

  • Dan TurnerEmail author
  • Oren Ledder


There is a large array of measurable parameters in inflammatory bowel disease (IBD), including symptoms and signs as well as endoscopic, serologic, and radiological findings. Therefore, generation of standardized multi-item outcome measure which accurately reflects disease state and response to interventions is critical for clinical research. Multiple instruments have been developed to assess various concepts of IBD both in Crohn’s disease and ulcerative colitis (UC) including clinical disease activity; patient-reported signs and symptoms; endoscopic, radiographic, and histologic appearance; and quality of life. These need to be modified, or often newly constructed, to more accurately reflect specific issues in the pediatric population. To be considered accurate, these measures must be evaluated for validity, reliability, responsiveness, and feasibility. This chapter provides an overview of the main instruments used in research and clinical practice, with an emphasis on assessing the specific utility of each.


Crohn’s disease Ulcerative colitis Inflammatory bowel disease Pediatric Clinical indices Clinical research Outcome measure Activity index Endoscopic measurement Patient-reported outcome Quality of life 


  1. 1.
    Kirshner B, Guyatt G. A methodological framework for assessing health indices. J Chronic Dis. 1985;38(1):27–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Wright JG, Feinstein AR. A comparative contrast of clinimetric and psychometric methods for constructing indexes and rating scales. J Clin Epidemiol. 1992;45(11):1201–18.PubMedCrossRefGoogle Scholar
  3. 3.
    Marx RG, Bombardier C, Hogg-Johnson S, Wright JG. Clinimetric and psychometric strategies for development of a health measurement scale. J Clin Epidemiol. 1999;52(2):105–11.PubMedCrossRefGoogle Scholar
  4. 4.
    Aaronson N, Alonso J, Burnam A, Lohr KN, Patrick DL, Perrin E, Stein RE. Assessing health status and quality-of-life instruments: attributes and review criteria. Qual Life Res. 2002;11(3):193–205.PubMedCrossRefGoogle Scholar
  5. 5.
    Irvine EJ, Feagan B, Rochon J, Archambault A, Fedorak RN, Groll A, et al. Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group. Gastroenterology. 1994;106(2):287–96.PubMedCrossRefGoogle Scholar
  6. 6.
    Yoshida EM. The Crohn’s Disease Activity Index, its derivatives and the Inflammatory Bowel Disease Questionnaire: a review of instruments to assess Crohn’s disease. Can J Gastroenterol (Journal canadien de gastroenterologie). 1999;13(1):65–73.CrossRefGoogle Scholar
  7. 7.
    Streiner DLN, Geoffrey R. Health measurement scales: a practical guide to their development and use. 2nd ed. Toronto: Oxford University Press; 1995.Google Scholar
  8. 8.
    Portney LW, Watkins MP. Foundations of clinical research applications to practice. 2nd ed. Upper Saddle River: Prentice Hall; 2000. p. 557–86.Google Scholar
  9. 9.
    Liang MH. Evaluating measurement responsiveness. J Rheumatol. 1995;22(6):1191–2.PubMedGoogle Scholar
  10. 10.
    Deyo RA, Centor RM. Assessing the responsiveness of functional scales to clinical change: an analogy to diagnostic test performance. J Chronic Dis. 1986;39(11):897–906.PubMedCrossRefGoogle Scholar
  11. 11.
    Beaton DE. Understanding the relevance of measured change through studies of responsiveness. Spine. 2000;25(24):3192–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Beaton DE, Bombardier C, Katz JN, Wright JG. A taxonomy for responsiveness. J Clin Epidemiol. 2001;54(12):1204–17.PubMedCrossRefGoogle Scholar
  13. 13.
    Best WR, Becktel JM, Singleton JW, Kern Jr F. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70(3):439–44.PubMedGoogle Scholar
  14. 14.
    de Dombal FT, Softley A. IOIBD report no 1: observer variation in calculating indices of severity and activity in Crohn’s disease. International Organisation for the Study of Inflammatory Bowel Disease. Gut. 1987;28(4):474–81.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Sands BE, Ooi CJ. A survey of methodological variation in the Crohn’s disease activity index. Inflamm Bowel Dis. 2005;11(2):133–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Regueiro MKK, Schraut W, et al. Crohn’s disease activity index does not correlate with endoscopic recurrence one year after ileocolonic resection. Inflamm Bowel Dis. 2011;17:118–26.PubMedCrossRefGoogle Scholar
  17. 17.
    Schoepfer AMBC, Straumann A, et al. Fecal calprotectin correlates more closely with the simple endoscopic score for Crohn’s disease (SES-CD) than CRP, blood leukocytes and the CDAI. Am J Gastroenterol. 2010;105:162–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1(8167):514.PubMedCrossRefGoogle Scholar
  19. 19.
    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(4):895–902.PubMedCrossRefGoogle Scholar
  20. 20.
    Escher JC. Budesonide versus prednisolone for the treatment of active Crohn’s disease in children: a randomized, double-blind, controlled, multicentre trial. Eur J Gastroenterol Hepatol. 2004;16(1):47–54.PubMedCrossRefGoogle Scholar
  21. 21.
    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(4):439–47.PubMedCrossRefGoogle Scholar
  22. 22.
    Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr. 1985;107(3):317–29.PubMedCrossRefGoogle Scholar
  23. 23.
    Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. II. Arch Dis Child. 1966;41(220):613–35.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Otley A, Loonen H, Parekh N, Corey M, Sherman PM, Griffiths AM. Assessing activity of pediatric Crohn’s disease: which index to use? Gastroenterology. 1999;116(3):527–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Kundhal PS, Critch JN, Zachos M, Otley AR, Stephens D, Griffiths AM. Pediatric Crohn Disease Activity Index: responsive to short-term change. J Pediatr Gastroenterol Nutr. 2003;36(1):83–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Hyams J, Markowitz J, Otley A, Rosh J, Mack D, Bousvaros A, et al. Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience. J Pediatr Gastroenterol Nutr. 2005;41(4):416–21.PubMedCrossRefGoogle Scholar
  27. 27.
    Turner DGA, Walters TD, et al. Appraisal of the pediatric Crohn disease activity index on four prospectively collected datasets: recommended cutoff values and clinimetric properties. Am J Gastroenterol. 2010;105:2085–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Turner D, Hyams J, Markowitz J, Lerer T, Mack DR, Evans J, et al. Appraisal of the pediatric ulcerative colitis activity index (PUCAI). Inflamm Bowel Dis. 2009;15(8):1218–23.PubMedCrossRefGoogle Scholar
  29. 29.
    Kappelman MD, Crandall WV, Colletti RB, Goudie A, Leibowitz IH, Duffy L, Milov DE, Kim SC, Schoen BT, Patel AS, Grunow J, Larry E, Fairbrother G, Margolis P. Short pediatric Crohn disease activity index for quality improvement and observational research. Inflamm Bowel Dis. 2011;17(4):112–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Turner D, Griffiths AM, Steinhart AH, Otley AR, Beaton DE. Mathematical weighting of a clinimetric index (Pediatric Ulcerative Colitis Activity Index) was superior to the judgmental approach. J Clin Epidemiol. 2009;62(7):738–44.PubMedCrossRefGoogle Scholar
  31. 31.
    Cozijnsen MDV, Kokke F, et al. Adalimumab therapy in children with Crohn disease previously treated with Infliximab. J Pediatr Gastroenterol Nutr. 2015;60:205–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Frivolt KST, Werkstetter KJ, et al. Repeated exclusive enteral nutrition in the treatment of pediatric Crohn’s disease: predictors of efficacy and outcome. Aliment Pharmacol Ther. 2014;39:1398–407.PubMedCrossRefGoogle Scholar
  33. 33.
    Loonen HJ, Griffiths AM, Merkus MP, Derkx HH. A critical assessment of items on the Pediatric Crohn’s Disease Activity Index. J Pediatr Gastroenterol Nutr. 2003;36(1):90–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Shepanski MA, Markowitz JE, Mamula P, Hurd LB, Baldassano RN. Is an abbreviated Pediatric Crohn’s Disease Activity Index better than the original? J Pediatr Gastroenterol Nutr. 2004;39(1):68–72.PubMedCrossRefGoogle Scholar
  35. 35.
    Turner D, Levine A, Walters TD, et al.. Which PCDAI version best reflects intestinal inflammation in pediatric Crohn’s disease. J Pediatr Gastroenterol Nutr. 2016. PMID: 27050050. [Epub ahead of print].Google Scholar
  36. 36.
    Leach STNL, Tilakaratne S, et al. Journal of pediatric gastroenterology and nutrition. Aug;51(2):232–673Development and assessment of a modified pediatric Crohn disease activity index. J Pediatr Gastroenterol Nutr. 2010;51(2):232–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Ruemmele FM. Mucosal healing for pediatric Crohn’s disease: is it really worth the effort or just much ado about nothing? J Crohns Colitis. 2016;10(1):1–2.PubMedCrossRefGoogle Scholar
  38. 38.
    Shah SCCJ, Sands BE, et al. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn’s disease. Aliment Pharmacol Ther. 2015;43(3):317–33.PubMedCrossRefGoogle Scholar
  39. 39.
    Baert FML, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Schnitzler FFH, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–301.PubMedCrossRefGoogle Scholar
  41. 41.
    Zubin GLP. Predicting endoscopic Crohn’s disease activity before and after induction therapy in children: a comprehensive assessment of PCDAI, CRP, and fecal calprotectin. Inflamm Bowel Dis. 2015;21:1386–91.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Sun HPE, Hyams JS, et al. Well-defined and reliable clinical outcome assessments for pediatric Crohn’s disease: a critical need for drug development. J Pediatr Gastroenterol Nutr. 2015;60:729–36.PubMedCrossRefGoogle Scholar
  43. 43.
    Gecse KBBW, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut. 2014;63:1381–92.PubMedCrossRefGoogle Scholar
  44. 44.
    Irvine EJ. Usual therapy improves perianal Crohn’s disease as measured by a new disease activity index. McMaster IBD Study Group. J Clin Gastroenterol. 1995;20(1):27–32.PubMedCrossRefGoogle Scholar
  45. 45.
    Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340(18):1398–405.PubMedCrossRefGoogle Scholar
  46. 46.
    Dejaco C, Harrer M, Waldhoer T, Miehsler W, Vogelsang H, Reinisch W. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn’s disease. Aliment Pharmacol Ther. 2003;18(11–12):1113–20.PubMedCrossRefGoogle Scholar
  47. 47.
    West RL, van der Woude CJ, Hansen BE, Felt-Bersma RJ, van Tilburg AJ, Drapers JA, et al. Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn’s disease with infliximab: a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2004;20(11–12):1329–36.PubMedCrossRefGoogle Scholar
  48. 48.
    Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65.PubMedCrossRefGoogle Scholar
  49. 49.
    Tozer PNS, Siddiqui MR, et al. Long-term MRI-guided combined anti-TNF-alpha and thiopurine therapy for Crohn’s perianal fistulas. Inflamm Bowel Dis. 2012;18:1825–34.PubMedCrossRefGoogle Scholar
  50. 50.
    Horsthuis KZM, Bipat S, et al. Evaluation of an MRI-based score of disease activity in perianal fistulizing Crohn’s disease. Clin Imaging. 2011;35:360–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Van Assche GVD, Bielen D, et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn’s disease. Am J Gastroenterol. 2003;98:332–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Savoye-Collet CSG, Koning E, et al. Fistulizing perianal Crohn’s disease: contrast-enhanced magnetic resonance imaging assessment at 1 year on maintenance anti-TNF-alpha therapy. Inflamm Bowel Dis. 2011;17:1751–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Shenoy-Bhangle ANK, Goldner D, et al. MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults. Pediatr Radiol. 2014;44:23–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2(4947):1041–8.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Powell-Tuck J, Bown RL, Lennard-Jones JE. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. Scand J Gastroenterol. 1978;13(7):833–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Sutherland LR, Martin F, Greer S, Robinson M, Greenberger N, Saibil F, et al. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology. 1987;92(6):1894–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298(6666):82.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Lichtiger S, Present DH. Preliminary report: cyclosporin in treatment of severe active ulcerative colitis. Lancet. 1990;336(8706):16–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Seo M, Okada M, Yao T, Ueki M, Arima S, Okumura M. An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol. 1992;87(8):971–6.PubMedGoogle Scholar
  60. 60.
    Seo M, Okada M, Yao T, Okabe N, Maeda K, Oh K. Evaluation of disease activity in patients with moderately active ulcerative colitis: comparisons between a new activity index and Truelove and Witts’ classification. Am J Gastroenterol. 1995;90(10):1759–63.PubMedGoogle Scholar
  61. 61.
    Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998;43(1):29–32.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Azzolini F, Pagnini C, Camellini L, Scarcelli A, Merighi A, Primerano AM, et al. Proposal of a new clinical index predictive of endoscopic severity in ulcerative colitis. Dig Dis Sci. 2005;50(2):246–51.PubMedCrossRefGoogle Scholar
  63. 63.
    Turner D, Seow CH, Greenberg GR, Griffiths AM, Silverberg MS, Steinhart AH. A systematic prospective comparison of noninvasive disease activity indices in ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7(10):1081–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Turner D, Levine A, Escher JC, et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr. 2012;55(3):340–61.PubMedCrossRefGoogle Scholar
  65. 65.
    Travis SPLSD, Krzeski P, et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012;61:535–42.PubMedCrossRefGoogle Scholar
  66. 66.
    Beattie RMNS, Domizio P, Williams CB, Walker-Smith JA. Endoscopic assessment of the colonic response to corticosteroids in children with ulcerative colitis. J Pediatr Gastroenterol Nutr. 1996;22(4):373–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Colombel JFRP, Reinisch W, Esser D, Wang Y, Lang Y, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141(4):1194–201.PubMedCrossRefGoogle Scholar
  68. 68.
    Gustavsson AJG, Hertervig E, Friis-Liby I, Blomquist L, Karlén P, et al. Clinical trial: colectomy after rescue therapy in ulcerative colitis – 3-year follow-up of the Swedish-Danish controlled infliximab study. Aliment Pharmacol Ther. 2010;32(8):984–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Froslie KFJJ, Moum BA, Vatn MH. Mucosal Healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–22.PubMedCrossRefGoogle Scholar
  70. 70.
    Turner D, Otley A, deBruijne J, Mack D, Uusoue K, Zachos M, Mamula P, Hyams J, Griffiths AM. Development of a pediatric ulcerative colitis activity index (PUCAI). J Pediatr Gastroenterol Nutr. 2006;43(4):E47.CrossRefGoogle Scholar
  71. 71.
    Dotson JL, Crandall WV, Zhang P, et al. Feasibility and validity of the pediatric ulcerative colitis activity index in routine clinical practice. J Pediatr Gastroenterol Nutr. 2014;60(2):200–4.CrossRefGoogle Scholar
  72. 72.
    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(2):423–32.PubMedCrossRefGoogle Scholar
  73. 73.
    Turner D, Griffiths AM, Veerman G, Johanns J, Damaraju L, Blank M, et al. Endoscopic and clinical variables that predict sustained remission in children with ulcerative colitis treated with infliximab. Clin Gastroenterol Hepatol. 2013;11(11):1460–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Schechter A, Griffiths C, Gana JC, Shaoul R, Shamir R, Shteyer E, et al. Early endoscopic, laboratory and clinical predictors of poor disease course in paediatric ulcerative colitis. Gut. 2014;64(4):580–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Gray FL, Turner CG, Zurakowski D, Bousvaros A, Linden BC, Shamberger RC, et al. Predictive value of the pediatric ulcerative colitis activity index in the surgical management of ulcerative colitis. J Pediatr Surg. 2013;48(7):1540–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Turner D, Mack D, Leleiko N, Walters TD, Uusoue K, Leach ST, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology. 2010;138(7):2282–91.PubMedCrossRefGoogle Scholar
  77. 77.
    Turner D, Walsh CM, Benchimol EI, Mann EH, Thomas KE, Chow C, et al. Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy. Gut. 2008;57(3):331–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Sylvester FA, Turner D, Draghi 2nd A, Uuosoe K, McLernon R, Koproske K, et al. Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis. Inflamm Bowel Dis. 2011;17(8):1726–30.PubMedCrossRefGoogle Scholar
  79. 79.
    Turner D, Hyams J, Markowitz J, Lerer T, Mack DR, Evans J, et al. Appraisal of the pediatric ulcerative colitis activity index (PUCAI). Inflamm Bowel Dis. 2009;15(8):1218–23.PubMedCrossRefGoogle Scholar
  80. 80.
    Hyams J, Damaraju L, Blank M, Johanns J, Guzzo C, Winter HS, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2012;10(4):391–9. e1PubMedCrossRefGoogle Scholar
  81. 81.
    Romano C, Famiani A, Comito D, Rossi P, Raffa V, Fries W. Oral beclomethasone dipropionate in pediatric active ulcerative colitis: a comparison trial with mesalazine. J Pediatr Gastroenterol Nutr. 2010;50(4):385–9.PubMedGoogle Scholar
  82. 82.
    Civitelli F, Di Nardo G, Oliva S, Nuti F, Ferrari F, Dilillo A, et al. Ultrasonography of the colon in pediatric ulcerative colitis: a prospective, blind, comparative study with colonoscopy. J Pediatr. 2014;165(1):78–84.e2.PubMedCrossRefGoogle Scholar
  83. 83.
    Teitelbaum JERR, Jaeger J, et al. Correlation of health-related quality of life in children with inflammatory bowel disease, their parents, and physician as measured by a visual analog scale. J Pediatr Gastroenterol Nutr. 2013;57(5):594–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Koslowe ORJ. Taking full measure of the pediatric ulcerative colitis activity index. J Pediatr Gastroenterol Nutr. 2015;60(2):148–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Travis SP, Stange EF, Lemann M, Oresland T, Chowers Y, Forbes A, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut. 2006;55(Suppl 1):i16–35.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    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(10):1179–207.PubMedCrossRefGoogle Scholar
  87. 87.
    Reproducibility of colonoscopic findings in Crohn’s disease: a prospective multicenter study of interobserver variation. Groupe d’Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Dig Dis Sci. 1987;32(12):1370–9.Google Scholar
  88. 88.
    Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn’s disease: a prospective multicentre study. Groupe d’Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30(7):983–9.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Rutgeerts P, Diamond RH, Bala M, Olson A, Lichtenstein GR, Bao W, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn’s disease. Gastrointest Endosc. 2006;63(3):433–42. quiz 64.PubMedCrossRefGoogle Scholar
  90. 90.
    D’Haens G, Van Deventer S, Van Hogezand R, Chalmers D, Kothe C, Baert F, et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology. 1999;116(5):1029–34.PubMedCrossRefGoogle Scholar
  91. 91.
    Bauditz J, Haemling J, Ortner M, Lochs H, Raedler A, Schreiber S. Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn’s disease. Gut. 1997;40(4):470–4.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505–12.PubMedCrossRefGoogle Scholar
  93. 93.
    Crocco S, Martelossi S, Giurici N, Villanacci V, Ventura A. Upper gastrointestinal involvement in paediatric onset Crohn’s disease: prevalence and clinical implications. J Crohns Colitis. 2012;6(1):51–5.PubMedCrossRefGoogle Scholar
  94. 94.
    Ledder OCP, Griffiths A, et al. Utility of proposed modified simple endoscopic score in upper gastrointestinal Crohn’s disease. United European Gastroenterol J. 2015;3(5S):A597.Google Scholar
  95. 95.
    Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99(4):956–63.PubMedCrossRefGoogle Scholar
  96. 96.
    Bayart P DN, Nachury M, et al. Rate of postoperative clinical recurrence in Crohn’s disease patients classified i2 on Rutgeerts score with lesions confimed to the ileocolonic anastomosis is not different compared to patients with moderate lesions on the terminal ileum. United European Gastroenterol J. 2015;3(5S):A3.Google Scholar
  97. 97.
    Gralnek IM, Defranchis R, Seidman E, Leighton JA, Legnani P, Lewis BS. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther. 2007;27(2):146–54.PubMedCrossRefGoogle Scholar
  98. 98.
    Cotter J, Dias de Castro F, Magalhães J, Moreira MJ, Rosa B. Validation of the Lewis score for the evaluation of small-bowel Crohn’s disease activity. Endoscopy. 2015;47(4):330–5.PubMedGoogle Scholar
  99. 99.
    Höög CM, Bark LÅ, Broström O, Sjöqvist U. Capsule endoscopic findings correlate with fecal calprotectin and C-reactive protein in patients with suspected small-bowel Crohn’s disease. Scand J Gastroenterol. 2014;49:1084–90.PubMedCrossRefGoogle Scholar
  100. 100.
    Rosa B, Moreira MJ, Rebelo A, Cotter J. Lewis Score: a useful clinical tool for patients with suspected Crohn’s Disease submitted to capsule endoscopy. J Crohns Colitis. 2012;6(6):692–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Uri Kopylov DY, Lahat A, Neuman S, Levhar N, Greener T, Klang E, Rozendorn N, Amitai MM, Ben-Horin S, Eliakim R. Detection of small bowel mucosal healing and deep remission in patients with known small bowel Crohn’s disease using biomarkers, capsule endoscopy, and imaging. Am J Gastroenterol. 2015;110:1316–23.PubMedCrossRefGoogle Scholar
  102. 102.
    Baron JH, Connell AM, Lennard-Jones JE. Variation between observers in describing mucosal appearances in proctocolitis. Br Med J. 1964;1(5375):89–92.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Orlandi F, Brunelli E, Feliciangeli G, Svegliati-Baroni G, Di Sario A, Benedetti A, et al. Observer agreement in endoscopic assessment of ulcerative colitis. Ital J Gastroenterol Hepatol. 1998;30(5):539–41.PubMedGoogle Scholar
  104. 104.
    Schroeder KWTW, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Travis SPLSD, Krzeski P, et al. Reliability and initial validation of the Ulcerative Colitis Endoscopic Index of Severity. Gastroenterology. 2013;145:987–95.PubMedCrossRefGoogle Scholar
  106. 106.
    Lobaton TBT, De Hertogh G, et al. The Modified Mayo Endoscopic Score (MMES): a new index for the assessment of extension and severity of endoscopic activity in ulcerative colitis patients. J Crohns Colitis. 2015;9(10):846–52.PubMedCrossRefGoogle Scholar
  107. 107.
    Food and Drug Administration. Guideline for industry – Patient-reported outcome measures: use in medical product development to support labelling claims. Silver Spring: Food and Drug Administration; 2009.Google Scholar
  108. 108.
    Kelstrup AMJP, Korzenik J. The accuracy of self-reported medical history: a preliminary analysis of the promise of internet-based research in Inflammatory Bowel Diseases. J Crohns Colitis. 2014;8(5):349–56.PubMedCrossRefGoogle Scholar
  109. 109.
    Bewtra MBC, Tomov VT, et al. An optimized patient-reported ulcerative colitis disease activity measure has been derived from the Mayo score and the simple clinical colitis activity index. Inflamm Bowel Dis. 2014;20(6):1070–8.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Khanna RZG, D’Haens G, et al. A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn’s disease activity. Aliment Pharmacol Ther. 2015;41:77–86.PubMedCrossRefGoogle Scholar
  111. 111.
    Matza LSPD, Riley AW, et al. Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force. Value Health. 2013;16:461–79.PubMedCrossRefGoogle Scholar
  112. 112.
    Marcovitch LNA, Mack D, et al. Item generation and reduction of the “TUMMY” index, a newly derived patient reporting outcome for pediatric ulcerative colitis (Abstract). United European Gastroenterol J. 2015;3(5S):A438.Google Scholar
  113. 113.
    Mackner LM, Crandall WV, Szigethy EM. Psychosocial functioning in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(3):239–44.PubMedCrossRefGoogle Scholar
  114. 114.
    Sainsbury A, Heatley RV. Review article: psychosocial factors in the quality of life of patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2005;21(5):499–508.PubMedCrossRefGoogle Scholar
  115. 115.
    Kucharzik TPF, Maaser C. Bowel Ultrasonography in Inflammatory Bowel Disease. Dig Dis Sci. 2015;33(1):17–25.CrossRefGoogle Scholar
  116. 116.
    Rimola JRS, García-Bosch O, Ordás I, Ayala E, Aceituno M, Pellisé M, Ayuso C, Ricart E, Donoso L, Panés J. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease. Gut. 2009;58(8):1113–20.PubMedCrossRefGoogle Scholar
  117. 117.
    Rimola JOI, Rodriguez S, García-Bosch O, Aceituno M, Llach J, Ayuso C, Ricart E, Panés J. Magnetic resonance imaging for evaluation of Crohn’s disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis. 2011;17(8):1759–68.PubMedCrossRefGoogle Scholar
  118. 118.
    Pariente BCJ, Danese S, Sandborn WJ, Lewin M, Fletcher JG, Chowers Y, D’Haens G, Feagan BG, Hibi T, Hommes DW, Irvine EJ, Kamm MA, Loftus Jr EV, Louis E, Michetti P, Munkholm P, Oresland T, Panés J, Peyrin-Biroulet L, Reinisch W, Sands BE, Schoelmerich J, Schreiber S, Tilg H, Travis S, van Assche G, Vecchi M, Mary JY, Colombel JF, Lémann M. Development of the Crohn’s disease digestive damage score, the Lémann score. Inflamm Bowel Dis. 2011;17(6):1415–22.PubMedCrossRefGoogle Scholar
  119. 119.
    Focht G, Traub T, Church P, Walters TD, Greer ML, Amitai M, Cytter R, Castro D, Otley A, O’Brien K, Mack D, Davila J, Griffiths AM, Turner D. Damage and inflammatory activity in pediatric Crohn’s disease (CD) based on radiologist and gastroenterologist physician global assessment. J Crohns Colitis. 2014;8(S2):S410.CrossRefGoogle Scholar
  120. 120.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–76.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, The Hebrew University of Jerusalem, Shaare Zedek Medical CenterJerusalemIsrael

Personalised recommendations