avkАрхивъ внутренней медициныThe Russian Archives of Internal Medicine2226-67042411-6564“SINAPS” LLC10.20514/2226-6704-2017-7-4-252-259avk-676Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESСОВРЕМЕННЫЙ ВЗГЛЯД НА ПАТОГЕНЕЗ И ЛАБОРАТОРНУЮ ДИАГНОСТИКУ ЯЗВЕННОГО КОЛИТА (ОБЗОР ЛИТЕРАТУРЫ)THE MODERN VIEW OF THE PATHOGENESIS AND LABORATORY DIAGNOSTICS OF ULCERATIVE COLITIS (LITERATURE REVIEW)СовалкинВ. И.SovalkinV. I.

кафедра госпитальной терапии, эндокринологии

БикбавоваГ. Р.BikbavovaG. R.

кафедра госпитальной терапии, эндокринологии

ЕмельяноваЮ. А.Emel’yanovaYu. A.

кафедра госпитальной терапии, эндокринологии

neganova.y@mail.ruГБОУ ВПО ОмГМУРоссияOmsk State Medical UniversityRussian Federation20170408201774252259Copyright © Совалкин В.И., Бикбавова Г.Р., Емельянова Ю.А., 20172017Совалкин В.И., Бикбавова Г.Р., Емельянова Ю.А.Sovalkin V.I., Bikbavova G.R., Emel’yanova Y.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medarhive.ru/jour/article/view/676

Основной теорией патогенеза воспалительных заболеваний кишечника в настоящее время считается активация иммунного ответа к антигенам собственной кишечной микрофлоры у генетически предрасположенных лиц. «Золотым стандартом» диагностики язвенного колитаявляется колоноскопия с морфологическим исследованием биоптата. В связи с инвазивностью, сложностью в подготовке и проведении, высокой стоимостью эндоскопического исследования, существует потребность в применении лабораторных биомаркеров язвенного колита, с помощью которых можно выделить группу лиц, подлежащих углубленному инструментальному обследованию. В обзоре освещается современный взгляд на патогенез заболевания, специфические лабораторные биомаркеры в диагностике язвенного колита, для мониторинга эффективности проводимой терапии, в качестве предикторов тяжелого течения язвенного колита, прогнозирования терапевтического ответа и раннего выявления рецидива.

The basic theory of the pathogenesis of inflammatory bowel disease (IBD) is currently considered a violation of immune activation and immune response against its own antigens to the intestinal flora in genetically predisposed individuals. “The gold standard” diagnosis of UC is colonoscopy with biopsy morphological study. Due to the invasiveness, complexity in the preparing and conducting, the high cost of endoscopy there is a need in the application of laboratory biomarkers UC, with which you can select a group of persons subject to an in-depth examination of the instrumental. Thereview highlights the modern view of the pathogenesis of the disease, the ability to use a variety of laboratory biomarkers in the diagnosis of UC, for monitoring the effectiveness of the therapy, as predictors of severe course of UC, therapeutic response prediction and early detection of recurrence

язвенный колитлабораторные маркерыulcerative colitislaboratory markersReferencesАлешина Г.М., Кокряков В.Н., Шамова О.В., и др. Современная концепция об антимикробных пептидах как молекулярных факторах иммунитета. Медицинский академический журнал. 2010; 4:149-160. Aleshina, G.M., Kokryakov V.N., Shamova O.V., et al. The modern concept of antimicrobial peptides as molecular factors of immunity. Medical academic journal. 2010; 4: 149-160 [In Russian].Atreya R., Öst A., Admyre C., et al. OP002 Histopathological response and remission after dual topical application of the Tolllike receptor 9 agonist DIMS0150 in patients with moderate-tosevere ulcerative colitis. Gastroenterology. April 2016; 150(Issue 4, Suppl. 1): S775.Баулина, Н.М., Кулакова О.Г., Фаворова О.О. МикроРНК: роль в развитии аутоиммунного воспаления . Aсta naturae. 2016; 8(1/28):23-36. Baulina, N.M., Kulakova O.G., Favorova O.O. MicroRNAs: role in the development of autoimmune inflammation. Asta naturae. 2016; 8 (1/28): 23-36 [In Russian].Bellavia M., Tomasello G., Romeo M. et al. Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis. Medical Microbiology and Immunology. 2013; 202(6): 393–406.Ильяшенко М.Г. Клинико-диагностическое значение антимикробных пептидов у больных язвенным колитом, диссертация к.м.н. 2014 год. Ilyashenko M.G. Clinical and diagnostic value of antimicrobial peptides in patients with ulcerative colitis, the thesis D.M., 2014 [In Russian].Belousova E.A. Epidemiology of inflammatory bowel disease in Russia. Falk Symposium. 2006: 31.Конович Е.А., Халиф И.Л., Шапина М.В. Иммунопатогенез воспалительных заболеваний кишечника. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2013; 4: 69-78. Konovich E.A., Halif I.L., Shapina M.V. The immunopathogenesis of inflammatory bowel disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2013; 4: 69-78 [In Russian] .Bernstein CN, Rawsthorne P, Cheang M, et al. A population-based case control study of potential risk factors for IBD. Am. J. Gastroenterol. 2006; 101: 993–100.Лазебник Л.Б., Гусей н-Заде М.Г., Ефремов Л.И., и др. Фекальный кальпроктеин как биомаркер эффективности различных медицинских вмешательств у больных воспалительными заболеваниями кишечника. Эксперементальная и клиническая гастроэнтерология. 2013; 8: 11-16. Lazebnik L.B., Guseyn- Zade M G., Efremov L.I. et al. Fecal kalproktein as a biomarker of the effectiveness of various medical interventions in patients with inflammatory bowel disease. Of experimental and clinical gastroenterology. 2013; 8: 11-16 [In Russian].Campieri M., Gionchetti P. Review Bacteria as the cause of ulcerative colitis. Gut. 2001; 48: 132-135 doi:10.1136/gut.48.1.132.Фиокки К. Современные патогенетические аспекты воспалительных заболеваний кишечника. Бай кальский форум по проблемам воспалительных заболеваний толстой кишки. 2012: 3–70. Fiokki K. Modern aspects of pathogenesis of inflammatory bowel disease. Baikal Forum on inflammatory diseases of the colon. 2012: 3-70 [In Russian].Darlington G.J., Wilson D.R., Lachman L.B. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J. Cell. Biol. 1986; 103: 787–793.Харитонов А.Г., Кондрашина Э.А., Барановский А.Ю., и др. Клинико-иммунологически особенности различных вариантов течения язвенного колита. Клиническая лабораторная диагностика. 2013; 3: 22-26. Haritonov A.G., Kondrashina E.A., Baranovskii A.Yu., et al. Clinical and immunological features of different variants of the ulcerative colitis. Clinical Laboratory diagnostika. 2013; 3: 22-26 [In Russian].De Cruz P., Prideaux L., Wagner J., et al. Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. Inflamm. Bowel. Dis. 2012; 18: 372.Хомутова Е.Ю., Игнатьев Ю.Т., Скрипкин Д.А., и др. Виртуальная колоноскопия: методика проведения. Радиология — практика. 2009; 2: 21-27. Homutova E.Yu., Ignatev Yu.T., Skripkin D.A., et all. Virtual colonoscopy: Methodology. Radiologiya — practice. 2009; 2: 21-27 [In Russian].Di Martino M.T., Campani V., Misso G. et al. In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma. PloS One. 2014; 9(2): e90005.Duffy M., O’Mahony L., Coffey J.C., Collins J.K., Shanahan F., Redmond H.P., and Kirwan W.O. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis. Dis. Colon. Rectum. 2002; 45: 384–388.Duffy M., O’Mahony L., Coffey J.C., Collins J.K., Shanahan F., Redmond H.P., and Kirwan W.O. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis. Dis. Colon. Rectum. 2002; 45: 384–388.Edmond L.M., Hopkins M.J., Magee E.A., and Cummings J.H. The effect of 5-aminosalicylic acid-containing drugs on sulfide production by sulfate-reducing and amino acid-fermenting bacteria. Inflamm Bowel Dis. 2003; 9: 10–17.Edmond L.M., Hopkins M.J., Magee E.A., and Cummings J.H. The effect of 5-aminosalicylic acid-containing drugs on sulfide production by sulfate-reducing and amino acid-fermenting bacteria. Inflamm Bowel Dis. 2003; 9: 10–17.Fujita H., Eishi Y., Ishige I., et al. Quantitative analysis of bacterial DNA from Mycobacteria spp., Bacteroides vulgatus, and Escherichia coli in tissue samples from patients with inflammatory bowel diseases. J. Gastroenterol. 2002; 37: 509-516.Fujita H., Eishi Y., Ishige I., et al. Quantitative analysis of bacterial DNA from Mycobacteria spp., Bacteroides vulgatus, and Escherichia coli in tissue samples from patients with inflammatory bowel diseases. J. Gastroenterol. 2002; 37: 509-516.George P. . p53 How crucial is its role in cancer? Int. J. Curr. Pharm. Res. 2011; 3: 19—25.George P. . p53 How crucial is its role in cancer? Int. J. Curr. Pharm. Res. 2011; 3: 19—25.Gheorghe C., Pascu O., Gheorghe L., et al. Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study. Eur. J. Gastroenterol. Hepatol. 004; 16: 1153–1159.Gheorghe C., Pascu O., Gheorghe L., et al. Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study. Eur. J. Gastroenterol. Hepatol. 004; 16: 1153–1159.Gosiewski T., Strus M., Fyderek K. et al. Horizontal distribution of the fecal microbiota in adolescents with inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutri- tion.2012; 54(1): 20–27.Gosiewski T., Strus M., Fyderek K. et al. Horizontal distribution of the fecal microbiota in adolescents with inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutri- tion.2012; 54(1): 20–27.Gross V., Andus T., Caesar I., et al. Evidence for continuous stimulation of interleukin-6 production in Crohn’s disease. Gastroenterology. 1992; 102: 514–519.Gross V., Andus T., Caesar I., et al. Evidence for continuous stimulation of interleukin-6 production in Crohn’s disease. Gastroenterology. 1992; 102: 514–519.Iborra M., Bernuzzi F., Correale C. et al. Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease Clinical & Experemental immunology. 2013; 173(Issue 2): 250–258.Iborra M., Bernuzzi F., Correale C. et al. Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease Clinical & Experemental immunology. 2013; 173(Issue 2): 250–258.Kapsoritakis A.N., Koukourakis M.I., Sfiridaki A. et al. Mean platelet volume: a useful marker of inflammatory bowel disease activity. Am. J. Gastroenterol. 2001; 96: 776–781.Kapsoritakis A.N., Koukourakis M.I., Sfiridaki A. et al. Mean platelet volume: a useful marker of inflammatory bowel disease activity. Am. J. Gastroenterol. 2001; 96: 776–781.Khan M.W., Kale A.A., Bere P., Vajjala S., Gounaris E., and Pakanati K.C. Microbes, intestinal inflammation and probiotics. Expert Review of Gastroenterology and Hepatology. 2012; 6 (1): 81–94.Khan M.W., Kale A.A., Bere P., Vajjala S., Gounaris E., and Pakanati K.C. Microbes, intestinal inflammation and probiotics. Expert Review of Gastroenterology and Hepatology. 2012; 6 (1): 81–94.Kruis W. et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004; 53(11): 1617–1623.Kruis W. et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004; 53(11): 1617–1623.Lapidus A. Crohn’s disease in Stockholm County during 1990–2001: an epidemiological update; World J. Gastroenterol. 2006; 12: 75–81.Lapidus A. Crohn’s disease in Stockholm County during 1990–2001: an epidemiological update; World J. Gastroenterol. 2006; 12: 75–81.Ling H., Fabbri M., Calin G.A. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat. Rev. Drug Discov. 2013; 12(11): 847–65.Ling H., Fabbri M., Calin G.A. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat. Rev. Drug Discov. 2013; 12(11): 847–65.Loftus C.G., Loftus E.V., Harmsen W.S. et al. Update on the incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota, 1940–2000 Inflamm. Bowel. Dis. 2007; 13: 254–261.Loftus C.G., Loftus E.V., Harmsen W.S. et al. Update on the incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota, 1940–2000 Inflamm. Bowel. Dis. 2007; 13: 254–261.Mack, D. R. et al. Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am. J. Physiol.1999; 276 (4 /1): G941–950.Mack, D. R. et al. Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am. J. Physiol.1999; 276 (4 /1): G941–950.Magdalena Pilarczyk-Zurek, Agnieszka Chmielarczyk, Possible role of Escherichia coli in propagation and perpetuation of chronic inflammation in ulcerative colitis. BMC Gastroenterology 2013; 13(1): 61, DOI: 10.1186/1471-230X-13-61.Magdalena Pilarczyk-Zurek, Agnieszka Chmielarczyk, Possible role of Escherichia coli in propagation and perpetuation of chronic inflammation in ulcerative colitis. BMC Gastroenterology 2013; 13(1): 61, DOI: 10.1186/1471-230X-13-61.Mallolas J., Esteve M., Rius E. et al. Gut. 2000; 47(1): 74–78.Mallolas J., Esteve M., Rius E. et al. Gut. 2000; 47(1): 74–78.Mallon P. et al. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst. Rev. 2007; 4: CD005573.Mallon P. et al. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst. Rev. 2007; 4: CD005573.Marchal J., Hilsden R. Environment and epidemiology of inflammatory bowel disease. In Inflammatory bowel disease. Ed. Satsangi J., Sutherland L. Churchill-Livingstone. 2003: 17-28.Marchal J., Hilsden R. Environment and epidemiology of inflammatory bowel disease. In Inflammatory bowel disease. Ed. Satsangi J., Sutherland L. Churchill-Livingstone. 2003: 17-28.McMullen L., Leach S.T., Lemberg D.A. Day A.S. Current roles of specific bacteria in the pathogenesis of inflammatory bowel disease. Microbiology. 2015; 1(1): 82-91.McMullen L., Leach S.T., Lemberg D.A. Day A.S. Current roles of specific bacteria in the pathogenesis of inflammatory bowel disease. Microbiology. 2015; 1(1): 82-91.Mendoza J.L., Abreu M.T. Biological markers in inflammatory bowel disease: practical consideration for clinicians. Gastroenterol. Clin. Biol. 2009; 33 Suppl 3: S158–S173.Mendoza J.L., Abreu M.T. Biological markers in inflammatory bowel disease: practical consideration for clinicians. Gastroenterol. Clin. Biol. 2009; 33 Suppl 3: S158–S173.Naves J.E., Manye J., Loren V., et al. P021 Differential plasma microRNA expression profile in ulcerative colitis patients according to their response to corticosteroids. Abstracts of the 10th Congrress of ECCO:S87.Naves J.E., Manye J., Loren V., et al. P021 Differential plasma microRNA expression profile in ulcerative colitis patients according to their response to corticosteroids. Abstracts of the 10th Congrress of ECCO:S87.Ordás I, Eckmann L., Talamini M. et al. Ulcerative colitis. Lancet. 2012; 380: 1606–1619.Ordás I, Eckmann L., Talamini M. et al. Ulcerative colitis. Lancet. 2012; 380: 1606–1619.Papp M., Norman G.L., Altorjay I. et al. Utility of serological markers in inflammatory bowel diseases: gadget or magic? World J. Gastroenterol. 2007; 13: 2028–2036. Архивъ внутренней медицины • № 4 • 2017 ОБЗОРНЫЕ СТАТЬИ 259Papp M., Norman G.L., Altorjay I. et al. Utility of serological markers in inflammatory bowel diseases: gadget or magic? World J. Gastroenterol. 2007; 13: 2028–2036. Архивъ внутренней медицины • № 4 • 2017 ОБЗОРНЫЕ СТАТЬИ 259Pathak S., Grillo A.R, Scarpa M. et al. MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis. Experimental & Molecular Medicine. 2015; 47: e164.Pathak S., Grillo A.R, Scarpa M. et al. MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis. Experimental & Molecular Medicine. 2015; 47: e164.Pitcher M.C.L., Cummings J.H. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut . 1996; 39: 1–4.Pitcher M.C.L., Cummings J.H. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut . 1996; 39: 1–4.Qiu Z., Dai Y. Roadmap of miR-122-related clinical application from bench to bedside. Expert Opin. Invest. Drugs. 2014; 23(3): 347–355.Qiu Z., Dai Y. Roadmap of miR-122-related clinical application from bench to bedside. Expert Opin. Invest. Drugs. 2014; 23(3): 347–355.Rhodes J.M. The role of Escherichia coli in inflammatory bowel disease. Gut. 2007 May; 56(5): 610-612.Rhodes J.M. The role of Escherichia coli in inflammatory bowel disease. Gut. 2007 May; 56(5): 610-612.Rubin G.P., Hungin a P., Kelly P.J. et al. Inflammatory bowel disease: epidemiology and management in an English general practice population Aliment Pharmacol Ther. 2000; 14: 1553–1559.Rubin G.P., Hungin a P., Kelly P.J. et al. Inflammatory bowel disease: epidemiology and management in an English general practice population Aliment Pharmacol Ther. 2000; 14: 1553–1559.Shepherd B., Schwartz D.A. Inflammatory bowel disease: diagnostic and treatment options. Hosp. Physician. 2005; 41(10): 11–19.Shepherd B., Schwartz D.A. Inflammatory bowel disease: diagnostic and treatment options. Hosp. Physician. 2005; 41(10): 11–19.Silverberg M.S., Satsangi J., Ahmad T., Arnott I.D., Bernstein C.N., Toward 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: 5A–36A.Silverberg M.S., Satsangi J., Ahmad T., Arnott I.D., Bernstein C.N., Toward 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: 5A–36A.Singh R.P., Massachi I., Manickavel S. et al. Autoimmun. Rev. 2013; 12: 1160–1165.Singh R.P., Massachi I., Manickavel S. et al. Autoimmun. Rev. 2013; 12: 1160–1165.Solberg I.C., Lygren I., Cvancarova M. et al. Inflamm. bowel dis. 2009; 15(3): 406–414.Solberg I.C., Lygren I., Cvancarova M. et al. Inflamm. bowel dis. 2009; 15(3): 406–414.Sood A. et al. The probiotic preparation, VSL #3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin. Gastroenterol. Hepatol. 2009; 7(11): 1202–1209, 1209 e1.Sood A. et al. The probiotic preparation, VSL #3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin. Gastroenterol. Hepatol. 2009; 7(11): 1202–1209, 1209 e1.Strober W., Fuss I.J. Pro-Inflammatory Cytokines in the Pathogenesis of IBD, Gastroenterology. 2011; 140(6): 1756-1767.Strober W., Fuss I.J. Pro-Inflammatory Cytokines in the Pathogenesis of IBD, Gastroenterology. 2011; 140(6): 1756-1767.Takagi T., Naito Y., Mizushima K. et al. Increased expression of micro-RNA in the inflamed colonic mucosa of patients with active ulcerative colitis. J. Gastroenterol. Hepatol. 2010; 25 (Suppl. 1): S129–133.Takagi T., Naito Y., Mizushima K. et al. Increased expression of micro-RNA in the inflamed colonic mucosa of patients with active ulcerative colitis. J. Gastroenterol. Hepatol. 2010; 25 (Suppl. 1): S129–133.Tomankova T., Petrek M., Gallo J. et al. MicroRNAs: emerging regulators of immune-mediated diseases. Scand. J. Immunol. 2011. doi: 10.1111/j.1365-3083.2011.02650.x.Tomankova T., Petrek M., Gallo J. et al. MicroRNAs: emerging regulators of immune-mediated diseases. Scand. J. Immunol. 2011. doi: 10.1111/j.1365-3083.2011.02650.x.Tursi A. et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebocontrolled study. Am. J. Gastroenterol. 2010; 105 (10): 2218–2227.Tursi A. et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebocontrolled study. Am. J. Gastroenterol. 2010; 105 (10): 2218–2227.Van Assche G., Vermeire S., Rutgeerts P. Inflimab therapy for patients with inflammatory bowel disease: 10 years on. Eur. J. Pharmacol. 2009; 623 Suppl 1: S17–S25.Van Assche G., Vermeire S., Rutgeerts P. Inflimab therapy for patients with inflammatory bowel disease: 10 years on. Eur. J. Pharmacol. 2009; 623 Suppl 1: S17–S25.Vasiliauskas E. Recent advances in the diagnosis and classification of inflammatory bowel disease. Curr. Gastroenterol. Rep. 2003; 5: 493-500.Vasiliauskas E. Recent advances in the diagnosis and classification of inflammatory bowel disease. Curr. Gastroenterol. Rep. 2003; 5: 493-500.Vergara Т., Cofré P., Cifuentes S. et al. Rev. med. chil. 2006; 134(8): 960–964.Vergara Т., Cofré P., Cifuentes S. et al. Rev. med. chil. 2006; 134(8): 960–964.Vermeire S., Van Assche G., Rutgeerts P. C-reactive protein as a marker for inflammatory bowel disease. Inflamm. Bowel. Dis. 2004; 10: 661–665.Vermeire S., Van Assche G., Rutgeerts P. C-reactive protein as a marker for inflammatory bowel disease. Inflamm. Bowel. Dis. 2004; 10: 661–665.Vidal A., Gómez-Gil E., Sans M., Portella M.J., Salamero M., Piqué J.M., Panés J. Life events and inflammatory bowel disease relapse: a prospective study of patients enrolled in remission. Am. J. Gastroenterol. 2006; 101: 775–781.Vidal A., Gómez-Gil E., Sans M., Portella M.J., Salamero M., Piqué J.M., Panés J. Life events and inflammatory bowel disease relapse: a prospective study of patients enrolled in remission. Am. J. Gastroenterol. 2006; 101: 775–781.

The authors declare that there are no conflicts of interest present.