КЛИНИЧЕСКАЯ КАРТИНА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЯЗВЕННОГО КОЛИТА У ДЕТЕЙ: РОССИЙСКИЙ ПЕДИАТРИЧЕСКИЙ КОНСЕНСУС

(Авторы: А.С. Потапов, Э.И. Алиева, Т.В. Габрузская, А.В. Горелов, И.Н. Захарова, Е.А. Корниенко, В.Н. Панфилова, Д.В. Печкуров, М.А. Ратникова, М.О. Ревнова, Е.П. Ситникова, Н.И. Урсова, Э.Н. Федулова, Е.Г. Цимбалова, П.В. Шумилов, О.В. Щербакова, Н.Е. Щиголева)

Язвенный колит — хроническое рецидивирующее воспалительное заболевание толстой кишки с распространением поражения непрерывно, от прямой кишки в проксимальном направлении. Язвенный колит у детей, несмотря на имеющиеся сходные признаки с таковым у взрослых больных, имеет ряд особенностей и отличий по характеру течения и ответу на терапию, в связи с чем в подходах к ведению детей нужно также учитывать эти особенности. В 2012 г. Европейской организацией по изучению болезни Крона и язвенного колита и Европейским обществом педиатрической гастроэнтерологии, гепатологии и питания на основе принципов доказательной медицины были разработаны совместные рекомендации по диагностике и лечению язвенного колита у детей. На основе Европейских рекомендаций группой ведущих детских гастроэнтерологов, занимающихся проблемой воспалительных заболеваний кишечника, с учетом российских особенностей и опыта ведения детей с язвенным колитом, был разработан и 15.02.2013 г. принят на Экспертном совете по разработке Российского консенсуса, прошедшем в рамках работы XVII съезда педиатров России, Российский консенсус по язвенному колиту у детей. В рекомендациях предложены стандартизированные протоколы, которые позволят проводить своевременную и эффективную диагностику, лечение и наблюдение детей с язвенным колитом. В то же время необходимо отметить, что данный консенсус не является догмой, и всегда следует учитывать индивидуальные особенности больного, а также новые научно обоснованные данные.а.

1. Benchimol E. I., Fortinsky K. J., Gozdyra P. et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm. Bowel. Dis. 2011; 17: 423–439.

2. Henderson P., Hansen R., Cameron F. L. et al. Rising incidence of pediatric inflammatory bowel disease in Scotland. Inflamm. Bowel. Dis. 2012; 18: 999–1005.

3. Heyman M. B., Kirschner B. S., Gold B. D. et al. Children with earlyonset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J. Pediatr. 2005; 146: 35–40.

4. Van Limbergen J., Russell R. K., Drummond H. E. et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008; 135: 1114–1122.

5. Gower-Rousseau C., Dauchet L., Vernier-Massouille G. et al. The natural history of pediatric ulcerative colitis: a population-based cohort study. Am. J. Gastroenterol. 2009; 104: 2080–2088.

6. Travis S. P. L., Stange E. F., Leґmann M. et al. European evidencebased consensus on the management of ulcerative colitis: current management. J. Crohn Colitis. 2008; 2: 24–62.

7. Turner D., Travis S. P., Griffiths A. M. et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBDWorking Group of ESPGHAN. Am. J. Gastroenterol. 2011; 106: 574–588.

8. Glickman J. N., Bousvaros A., Farraye F. A. et al. Pediatric patients with untreated ulcerative colitis may present initially with unusual morphologic findings. Am. J. Surg. Pathol. 2004; 28: 190–197.

9. Levine A., de Bie C. L., Turner D. et al. Atypical disease phenotypes in paediatric ulcerative colitis: 5-year analyses of the EUROKIDS registry. Inflamm. Bowel. Dis. 2012 [Epub ahead of print].

10. Robert M. E., Tang L., Hao L. M. et al. Patterns of inflammation in mucosal biopsies of ulcerative colitis: perceived differences in pediatric populations are limited to children younger than 10 years. Am. J. Surg. Pathol. 2004; 28: 183–189.

11. Haskell H., Andrews C. W., Jr., Reddy S. I. et al. Pathologic features and clinical significance of «backwash» ileitis in ulcerative colitis. Am. J. Surg. Pathol. 2005; 29: 1472–1481.

12. de Bie C. I., Buderus S., Sandhu B. K. et al. Diagnostic workup of paediatric patients with inflammatory bowel disease in Europe: results of a 5-year audit of the EUROKIDS registry. J. Pediatr. Gastroenterol. Nutr. 2012; 54: 374–380.

13. Koletzko S., Niggemann B., Arato A. et al. Diagnostic approach and management of cow’s milk protein allergy in infants and children: a practical guideline of the GI-committee of ESPGHAN. J Pediatr Gastroenterol Nutr. 2012; 55: 221–229.

14. Glocker E. O., Frede N., Perro M. et al. Infant colitis — it’s in the genes. Lancet. 2010; 376: 1272. 15. Glocker E. O., Kotlarz D., Boztug K. et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 2009; 361: 2033–2045.

15. Begue B., Verdier J., Rieux-Laucat F. et al. Defective IL10 signaling defining a subgroup of patients with inflammatory bowel disease. Am. J. Gastroenterol. 2011; 106: 1544–1555.

16. Beattie R. M., Nicholls S. W., Domizio P. et al. Endoscopic assessment of the colonic response to corticosteroids in children with ulcerative colitis. J. Pediatr. Gastroenterol. Nutr. 1996; 22: 373–379.

17. Mack D. R., Langton C., Markowitz J. et al. Laboratory values for children with newly diagnosed inflammatory bowel disease. Pediatrics. 2007; 119: 1113–1119.

18. Weinstein T. A., Levine M., Pettei M. J. et al. Age and family history at presentation of pediatric inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 2003; 37: 609–613.

19. Henderson P., Casey A., Lawrence S. J. et al. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease. Am. J. Gastroenterol. 2012; 107: 941–949.

20. Venediktova M. M., Tsimbalova E. G., Potapov A. S., Mayanskii N. A. Voprosi diagnostiki v pediatrii — Diagnostics in pediatrics. 2011; 3 (6): 23–26.

21. Turner D., Leach S. T., Mack D. et al. Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response. Gut. 2010; 59: 1207–1212.

22. Sylvester F. A., Turner D., Draghi A., 2nd et al. Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis. Inflamm. Bowel. Dis. 2011; 17: 1726–1730.

23. Harris M. S., Lichtenstein G. R. Review article: delivery and efficacy of topical 5-aminosalicylic acid (mesalazine) therapy in the treatment of ulcerative colitis. Aliment. Pharmacol. Ther. 2011; 33: 996–1009.

24. Lichtenstein G. R., Kamm M. A. Review article: 5-aminosalicylate formulations for the treatment of ulcerative colitis — methods of comparing release rates and delivery of 5-aminosalicylate to the colonic mucosa. Aliment. Pharmacol. Ther. 2008; 28: 663–673.

25. Sutherland L., Macdonald J. K. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochr. Database Syst. Rev. 2006: CD000543.

26. Sutherland L., Macdonald J. K. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochr. Database Syst. Rev. 2006: CD000544.

27. Odera G., Giuliani B., Santini B. et al. Topical treatment with 5-SA and hydrocortisone. Riv. Ital. Pediatr. 1986; 12: 674–678.

28. Ford A. C., Khan K. J., Sandborn W. J. et al. Efficacy of topical 5-aminosalicylates in preventing relapse of quiescent ulcerative colitis: a meta-analysis. Clin. Gastroenterol. Hepatol. 2012; 10: 513–519.

29. Kolho K. L., Raivio T., Lindahl H. et al. Fecal calprotectin remains high during glucocorticoid therapy in children with inflammatory bowel disease. Scand. J. Gastroenterol. 2006; 41: 720–725.

30. Powell-Tuck J., Bown R. L., Lennard-Jones J. E. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. Scand. J. Gastroenterol. 1978; 13: 833–837.

31. Uchida K., Araki T., Toiyama Y. et al. Preoperative steroid-related complications in Japanese pediatric patients with ulcerative colitis. Dis. Colon Rectum. 2006; 49: 74–79.

32. Gionchetti P., Rizzello F., Ferrieri A. et al. Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroidtreatment: a double-blind, placebo-controlled trial. Dig. Dis. Sci. 1999; 44: 1220–1221.

33. Ohkusa T., Kato K., Terao S. et al. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am. J. Gastroenterol. 2010; 105: 1820–1829.

34. Timmer A., McDonald J. W., Macdonald J. K. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochr. Database Syst. Rev. 2007: CD000478.

35. Gisbert J. P., Linares P. M., McNicholl A. G. et al. Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis. Aliment. Pharmacol. Ther. 2009; 30: 126–137.

36. Khan K. J., Dubinsky M. C., Ford A. C. et al. Efficacy of immunosuppressive therapy for inflammatory bowel disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 2011; 106: 630–642.

37. Barabino A., Torrente F., Ventura A. et al. Azathioprine in paediatric inflammatory bowel disease: an Italian multicentre survey. Aliment. Pharmacol. Ther. 2002; 16: 1125–1130.

38. Kader H. A., Mascarenhas M. R., Piccoli D. A. et al. Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis. J. Pediatr. Gastroenterol. Nutr. 1999; 28: 54–58.

39. Verhave M., Winter H. S., Grand R. J. Azathioprine in the treatment of children with inflammatory bowel disease. J. Pediatr. 1990; 117: 809–814.

40. Pozler O., Chladek J., Maly J. et al. Steady-state of azathioprine during initiation treatment of pediatric inflammatory bowel disease. J. Crohns Colitis. 2010; 4: 623–628.

41. Sandborn W. J. A review of immune modifier therapy for inflam matory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am. J. Gastroenterol. 1996; 91: 423–433.

42. De Greef E., Vandenplas Y., Veereman-Wauters G. Opportunistic infections in paediatric inflammatory bowel disease patients. Arch. Dis. Child. 2011; 91: 5–7.

43. Russell R. K., Wilson M. L., Loganathan S. et al. A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease. Aliment. Pharmacol. Ther. 2011; 33: 946–953.

44. Turner D., Griffiths A. M. Acute severe ulcerative colitis in children: a systematic review. Inflamm. Bowel. Dis. 2011; 17: 40–449.

45. Lawson M. M., Thomas A. G., Akobeng A. K. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochr. Database Syst. Rev. 2006: CD005112.

46. Rutgeerts P., Sandborn W. J., Feagan B. G. et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2005; 353: 2462–2476.

47. Hyams J., Damaraju L., Blank M. et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin. Gastroenterol. Hepatol. 2012; 10: 391–399.

48. Baranov A. A., Potapov A. S., Tsimbalova E. G. Vestnik Rossiiskoi akademii meditsinskikh nauk — Annals of the Russian Academy of Medical Sciences. 2011; 6: 36–41.

49. Hyams J. S., Lerer T., Griffiths A. et al. Outcome following infliximab therapy in children with ulcerative colitis. Am. J. Gastroenterol. 2010; 105: 1430–1436.

50. Panaccione R., Ghosh S., Middleton S. et al. Infliximab, azathioprine or infliximabюazathioprine for treatment of moderate to severe ulcerative colitis. The UC SUCCESS trial. J. Crohns Colitis. 2011; 5: 13.

51. Lichtenstein G. R., Diamond R. H., Wagner C. L. et al. Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment. Pharmacol. Ther. 2009; 30: 210–226.

52. Chaparro M., Guerra I., Munoz-Linares P. et al. Systematic review: antibodies and anti-TNF-alpha levels in inflammatory bowel disease. Aliment. Pharmacol. Ther. 2012; 35: 971–986.

53. Bernstein C. N., Fried M., Krabshuis J. H. et al. World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010. Inflamm. Bowel. Dis. 2010; 16: 112–124.

54. Gonzalez-Huix F., Fernandez-Banares F., Esteve-Comas M. et al. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis. Am. J. Gastroenterol. 1993; 88: 227–232.

55. McIntyre P. B., Powell-Tuck J., Wood S. R. et al. Controlled trial of bowel rest in the treatment of severe acute colitis. Gut. 1986; 27: 481–485.

56. Dickinson R. J., Ashton M. G., Axon A. T. et al. Controlled trial of intravenous hyperalimentation and total bowel rest as an adjunct to the routine therapy of acute colitis. Gastroenterology. 1980; 79: 1199–1204.

57. Barabino A., Tegaldo L., Castellano E. et al. Severe attack of ulcerative colitis in children: retrospective clinical survey. Dig. Liver Dis. 2002; 34: 44–49.

58. Bechtold S., Alberer M., Arenz T. et al. Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease. Inflamm. Bowel Dis. 2010; 16: 216–225.

59. Werkstetter K. J., Pozza S. B., Filipiak-Pittroff B. et al. Long-term development of bone geometry and muscle in pediatric inflammatory bowel disease. Am. J. Gastroenterol. 2011; 106: 988–998.

60. Gokhale R., Favus M. J., Karrison T. et al. Bone mineral density assessment in children with inflammatory bowel disease. Gastroenterology. 1998; 114: 902–911.

61. Sylvester F. A., Wyzga N., Hyams J. S. et al. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm. Bowel. Dis. 2007; 13: 42–50.

62. Walther F., Fusch C., Radke M. et al. Osteoporosis in pediatric patients suffering from chronic inflammatory bowel disease with and without steroid treatment. J. Pediatr. Gastroenterol. Nutr. 2006; 43: 42–51.

63. Pappa H., Thayu M., Sylvester F. et al. Skeletal health of children and adolescents with inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 2011; 53: 11–25.

64. Greenley R. N., Stephens M., Doughty A. et al. Barriers to adherence among adolescents with inflammatory bowel disease. Inflamm. Bowel. Dis. 2010; 16: 36–41.

65. Hommel K. A., Denson L. A., Baldassano R. N. Oral medication adherence and disease severity in pediatric inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol. 2011; 23: 250–254.

66. Hommel K. A., Baldassano R. N. Barriers to treatment adherence in pediatric inflammatory bowel disease. J. Pediatr. Psychol. 2010; 35: 1005–1010.

67. Reed-Knight B., Lewis J. D., Blount R. L. Association of disease, adolescent, and family factors with medication adherence in pediatric inflammatory bowel disease. J. Pediatr. Psychol. 2011; 36: 308–317.

68. Cassinotti A., Actis G. C., Duca P. et al. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal. Am. J. Gastroenterol. 2009; 104: 2760–2767.

69. Actis G. C., Fadda M., Pellicano R. et al. The 17-year singlecenter experience with the use of azathioprine to maintain remission in ulcerative colitis. Biomed. Pharmacother. 2009; 63: 362–365.

70. Turner D., Otley A. R., Mack D. et al. Development and evaluation of a Pediatric Ulcerative Colitis Activity Index (PUCAI): a prospective multicenter study. Gastroenterology. 2007; 133: 423–432.