P. Munkholm

Environmental factors and risk of developing paediatric inflammatory bowel disease — A population based study 2007–2009

BACKGROUND AND AIMSnTo identify environmental risk factors for developing inflammatory bowel disease (IBD) in children <15 years of age.nnnMETHODSnIBD patients and randomly selected healthy controls from a well defined geographical area in Denmark were prospectively recruited in the period 1.1.2007-31.12.2009. Data regarding socioeconomic status, area of residence, living conditions, infections and diet were obtained by a questionnaire.nnnRESULTSnA total of 118 IBD patients (59 Crohns disease (CD), 56 ulcerative colitis (UC) and 3 IBD unclassified (IBDU)) and 477 healthy controls filled out the questionnaire. The response rates were 91% in patients and 45% in controls, respectively. Several risk factors for IBD were identified: IBD in first degree relatives (IBD: OR (odds ratio): 6.1 (95%CI: 2.5-15.0), CD (OR: 6.8 (2.3-20.2)) and UC (OR: 6.1 (2.3-16.0))); bedroom sharing (IBD: OR: 2.1 (1.0-4.3), CD (OR: 3.6 (1.3-9.4))); high sugar intake (IBD: OR: 2.5 (1.0-6.2), CD (OR: 2.9 (1.0-8.5))); prior admission to a hospital for gastrointestinal infections (IBD: 7.7 (3.1-19.1), CD (7.9 (2.5-24.9)) and UC (7.4 (2.5-21.6))); stressful events (IBD: 1.7 (1.0-2.9)). Protective factors were daily vs. less than daily vegetable consumption (CD: 0.3 (0.1-1.0), UC (0.3 (0.1-0.8))) and whole meal bread consumption (IBD: OR: 0.5 (0.3-0.9), CD (0.4 (0.2-0.9))). An increased risk of diagnosis of CD compared to UC was shown for patients living in more urban areas (OR: 1.3 (1.1-1.6)).nnnCONCLUSIONnWe identified several risk and protective factors for developing IBD. Studies on the influence of environmental factors are important in our understanding of aetiology and phenotypes of paediatric IBD.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMSnThe incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more westernised standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients.nnnMETHODSnThe EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors.nnnRESULTSnA total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohns disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01).nnnCONCLUSIONSnIn this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia: Results of the 2011 ECCO-EpiCom inception cohort

BACKGROUND AND AIMSnThe aim of the present study was to validate the IBD (inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom (European Crohns and Colitis Organization-Epidemiological Committee) inception cohort by including a second independent inception cohort from participating centers in 2011 and an Australian center to investigate whether there is a difference in the incidence of IBD between Eastern and Western European countries and Australia.nnnMETHODSnFourteen centers from 5 Eastern and 9 Western European countries and one center from Australia participated in the ECCO-EpiCom 2011 inception cohort. Patients data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu.nnnRESULTSnA total of 711 adult patients were diagnosed during the inclusion year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72 (10%) from Australia; 259 (37%) patients were diagnosed with Crohns disease, 380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000 in Western Europe and 30.3/100,000 in Australia. Significantly more patients were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (43% vs. 27%, p=0.02).nnnCONCLUSIONnIncidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different from that reported in the 2010 cohort.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with Inflammatory Bowel Disease — An ECCO-EpiCom study☆

BACKGROUND & AIMSnHealth-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe.nnnMETHODSnThe EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up.nnnRESULTSnIn total, 1079 patients were included in this study. Crohns disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population.nnnCONCLUSIONnMedical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: An ECCO-EpiCom study

BACKGROUND AND AIMSnThe EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD).nnnMETHODSnA quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers.nnnRESULTSnOf 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05).nnnCONCLUSIONnHealth care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

Genetic susceptibility and genotype–phenotype association in 588 Danish children with inflammatory bowel disease

AIMnTo investigate the association between known inflammatory bowel disease (IBD)-associated genetic variants and development of paediatric IBD, and specific clinical sub-phenotypes.nnnMATERIAL AND METHODSnIn this case-control study we included IBD patients <18 years of age at diagnosis from the Danish National Patient Registry and healthy children <18 years of age were randomly selected from the Danish Central Office of Civil Registration. The latter had filled out a questionnaire regarding health status, and DNA was obtained from blood samples and the buccal mucosa. Patient files were retrieved and clinical information was extracted. DNA was obtained from Guthrie cards from the Danish National Neonatal Screening Biobank (PKU-biobanken) at Statens Serum Institut and from blood samples.nnnRESULTSnA total of 588 IBD patients (244 Crohns disease (CD), 318 ulcerative colitis (UC) and 26 IBD-unclassified (IBDU)) and 543 healthy controls were included. We found an association between CD and rs22411880 (ATG16L1, odds ratio (OR)=1.7 [1.1-1.7], p=0.003), rs5743289 (NOD2, OR=1.4 [1.1-1.9], p=0.009) and the paediatric specific rs1250550 (ZMIZ1, OR=0.7 [0.5-0.9], p=0.01). None of the investigated 41 SNPs were associated with disease localisation, medical treatment or surgery after correcting for multiple analyses.nnnCONCLUSIONnWe found an association between CD and three previously published genetic variants and replicated the association with the paediatric specific ZMIZ1 gene. No Bonferroni corrected significant genotype-phenotype associations were found. For future studies aimed at finding predictors for disease course in (paediatric) IBD, it will be worthwhile to include a combination of genetic, clinical and serological markers.

Genetic and Environmental Factors in Monozygotic Twins with Crohn’s Disease and Their First-Degree Relatives: A Case Report

Background/Aims: Familial Crohn’s disease has shown concordance concerning location and clinical type of the disease especially among monozygotic twins. Susceptibility to Crohn’s disease is both based on genetic and environmental factors. We investigated polymorphisms of CARD15, TLR4, and OCTN, and environmental factors in a monozygotic twin pair with Crohn’s disease and their first-degree relatives. Methods: 22-year-old monozygotic female twins with ileocolonic Crohn’s disease and their healthy brother and parents were examined. DNA samples from patients and relatives were genotyped for CARD15, TLR4,and OCTN polymorphisms. ASCA and p-ANCA analyses were performed. Additionally, patients and relatives filled out a questionnaire concerning multiple environmental factors. Results: Both twins presented in the same year with identical Vienna Classification phenotypes: stenotic behavior (B2) and localization in terminal ileum and colon (L3). Both carried a CARD15 R702W variant, but had normal alleles in TLR4 and OCTN. They were smokers since the age of 15, used oral contraceptives and had undergone appendectomy. The healthy father and brother were CARD15 R702W positive, were non-smokers and had not undergone appendectomy. Conclusion: This case report is the first to describe complete concordance in CARD15 status, phenotypic appearance, and smoking, appendectomy and oral contraceptive use in a pair of monozygotic twins with CD.

P222 - Overall and cause-specific mortality in Crohn's disease: a meta-analysis of population-based studies

P221 Lack of association of previously identified disease loci 10q12, 11p15, and 20q13 in IBD A. Latiano1 *, E. Colombo1, O. Palmieri1, M.R. Valvano1, T. Latiano1, G. Corritore1, R. D’Inca2, M. Vecchi3, R. Caprilli4, S. Ardizzone5, S. Nobile6, D. De Venuto7, C. Sferlazzas8, A. Staiano9, V. Lodde10, G. Iacono11, C. Bascietto12, B. Papadatou13, A. Marseglia14, M. Castro13, S. Cucchiara12, V. Annese1. 1Unit of Gastroenterology, San Giovanni Rotondo, Italy, 2Unit of Gastroenterology, Padova, Italy, 3Unit of Gastroenterology, San Donato Milanese, Milano, Italy, 4Unit of Gastroenterology, “La Sapienza”, Roma, Italy, 5Unit of Gastroenterology, “Sacco”, Milano, Italy, 6Unit of Pediatrics of SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition), Ancona, Italy, 7SIGENP, Bari, Italy, 8SIGENP, Messina, Italy, 9SIGENP, Napoli, Italy, 10SIGENP, Padova, Italy, 11SIGENP, Palermo, Italy, 12SIGENP, “La Sapienza”, Roma, Italy, 13SIGENP, “Bambino Gesu”, Roma, Italy, 14SIGENP, San Giovanni Rotondo, Italy

Disease course during the first five years following diagnosis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort

Disease course during the first five years following diagnosis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort

P433 Is e-Health, web-based monitoring and treatment, useful for children and adolescents with inflammatory bowel disease? – a paediatric clinical trial

Background: Cholangiocarcinoma (CC) complicates in 10 20% of the patients with dominant stricture (DS) in patients with primary sclerosing cholangitis (PSC) related with inflammatory bowel diseases (IBD). Methods: We investigated 2200 patients with IBD for PSC with DS. Results: PSC was diagnosed in 41 pts (1.6%). Of the 41 pts with PSC, DS was diagnosed in 14 (34%); 64% were male, and followed for a mean of 4.86 yrs (0 13 yrs). Main finding was pruritis alone in 64% pts with DS as in 15% without DS (p = 0.003). The diagnose date of both IBD and PSC was younger in pts with DS than without DS (36.9 yrs vs. 38.1 and 40.2 yrs vs. 41.1 yrs; p > 0.05, respectively). Only current ALP and GGT levels were differ between the groups (p: 0.003 and p: 0.001, respectively). In this study, ERCP performed in 22 pts with PSC and was the main diagnostic tool for the questioning the occurence of DS (p = 0.011), besides CT, MRI and liver bx. ERCP usually performed more than once. EST and baloon dilation performed in all pts with stenting in 9 pts. Brush cytology performed only in 3 pts with strong suspicious for CC and benign pathology reported. IBD disease duration was longer in pts without DS than with DS (10.4 yrs vs. 8.1 yrs, p > 0.05). During the follow-up, 2 patients dead due to the causes other than CC; one due to endstage liver disease, and one had back wash ileitis complicated with colon malignancy and later died. Liver transplantation performed twice in one patient and still alive and in a good condition. At the same time, we evaluated our last 5-years pathology records for CC in a different study, and found 19 cases. None was related with our IBD or PSC-IBD group. Of the 19, colonoscopy performed in 5, and showed no IBD on biopsy. Conclusions: In our series, dominant strictures with PSC related with IBD showed a relatively benign nature differently from the current literature.