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Infections Requiring Hospitalization as Predictors of Pediatric-Onset Crohn's Disease and Ulcerative Colitis.

ABSTRACT: Objectives. To assess the relationship between infections and the risk of pediatric-onset inflammatory bowel disease (IBD). Methods. We conducted a nested case-control study of 501 incident cases aged ?17 years and 9,442 controls who were members of Kaiser Permanente Northern California for at least one consecutive year between 1996 and 2006. IBD was confirmed and the incidence date was adjudicated by pediatric gastroenterologists. Hospitalized infections were identified from the principal diagnosis code of electronic inpatient records. Medications to treat infections were identified during the hospitalization. Conditional logistic regression was used to assess the associations between hospitalized infections, medications, and Crohn's disease and ulcerative colitis. Results. In the year prior to diagnosis, both hospitalized infection of any system (OR 6.3; 95% CI 1.6-23.9) and hospitalized intestinal infection (OR 19.4; 95% CI 2.6-143.2) were associated with CD. Hospitalized infections of any system were inversely associated with UC after excluding the year prior to diagnosis (OR 0.4; 95% CI 0.2-0.9). No UC case had a hospitalized gastrointestinal infection prior to diagnosis. Conclusion. Infections appear to play opposite roles prior to the diagnosis of CD and UC. Infections may be associated with an increased risk of CD and a decreased risk of UC.

SUBMITTER: Hutfless S

PROVIDER: S-EPMC4446489 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Infections Requiring Hospitalization as Predictors of Pediatric-Onset Crohn's Disease and Ulcerative Colitis.

Hutfless Susan S Abramson Oren O Heyman Melvin B MB Bayless Theodore M TM Li De-Kun DK Winthrop Kevin K Herrinton Lisa J LJ

Gastroenterology research and practice 20150514

Objectives. To assess the relationship between infections and the risk of pediatric-onset inflammatory bowel disease (IBD). Methods. We conducted a nested case-control study of 501 incident cases aged ≤17 years and 9,442 controls who were members of Kaiser Permanente Northern California for at least one consecutive year between 1996 and 2006. IBD was confirmed and the incidence date was adjudicated by pediatric gastroenterologists. Hospitalized infections were identified from the principal diagn ...[more]

PMID: 26074957

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Project description:BackgroundThe genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59).MethodTo study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array. SNP2HLA was used to impute classical HLA alleles and their corresponding amino acids, and the results are compared with adult onset UC.ResultsHLA explained the almost entire association signal, dominated with 191 single nucleotide polymorphisms (SNPs) (p = 5 x 10-8 to 5 x 10-10). Although very small effects, established SNPs in adult onset UC loci had similar direction and magnitude in pediatric onset UC. SNP2HLA imputation identified HLA-DRB1*0103 (odds ratio [OR] = 6.941, p = 1.92*10-13) as the most significant association for pediatric UC compared with adult onset UC (OR = 3.59). Further conditioning showed independent effects for HLA-DRB1*1301 (OR = 2.25, p = 7.92*10-9) and another SNP rs17188113 (OR = 0.48, p = 7.56*10-9). Two HLA-DRB1 causal alleles are shared with adult onset UC, while at least 2 signals are unique to pediatric UC. Subsequent stratified analyses indicated that HLA-DRB1*0103 has stronger association for extensive disease (E4: OR = 8.28, p = 4.66x10-10) and female gender (OR = 8.85, p = 4.82x10-13).ConclusionIn pediatric onset UC, the HLA explains almost the entire genetic associations. In addition, the HLA association is approximately twice as strong in pediatric UC compared with adults, due to a combination of novel and shared effects. We speculate the paramount importance of antigenic stimulation either by infectious or noninfectious stimuli as a causal event in pediatric UC onset.

Project description:Ulcerative colitis in children can have a negative effect on quality of life (QOL).We included 16 of 31 patients who underwent colectomy for ulcerative colitis before 20 years of age between 1980 and 2005 at University of California in San Francisco Benioff Children's Hospital. A disease-specific QOL questionnaire (Inflammatory Bowel Disease Questionnaire-32), validated for adults, was used to determine QOL and an additional questionnaire addressing bowel function and reproductive health in long-term follow-up of these patients.Median age at the time of survey was 20.3 years (17.9-25.3), and time postcolectomy was 6.9 years (4.8-9.0). Mean total score was 159.7 ± 43.3 (58-210). Two patients (12.5%) had scores of ? 200, 12 (75.0%) had 101 to 199, and 2 (12.5%) had ? 100. Patients ages 18 years or younger at the time of survey showed higher QOL, particularly in emotional health (P=0.020), social function (P=0.014), and overall QOL (P=0.009). Social function scored highest of all of the systems (median 7; interquartile range 4-7). Patients with scores ? 100 had repeated episodes of pouchitis (16-30) compared with the other 14 patients (0-3). Children who were diagnosed ages 12 years or younger tended to have higher QOL (p=0.072). Years postcolectomy did not correlate to QOL. Eleven patients were sexually active. Two males had feelings of impotence and decreased libido, and 6 females experienced dyspareunia. Three women tried unsuccessfully to conceive after colectomy. One woman became pregnant 4 times, each leading to miscarriage.Younger age at time of colectomy, diagnosis, and survey show higher QOL. Highest satisfaction was found in ability to attend school, work, and social engagements. Pouchitis continued to be an issue for a small number of the patients, with 2 patients having recurring episodes that severely affected QOL. Patients reported decreased sexual activity and fertility at the time of survey due to colectomy, especially for females.

Dataset Information

Infections Requiring Hospitalization as Predictors of Pediatric-Onset Crohn's Disease and Ulcerative Colitis.

Publications

Infections Requiring Hospitalization as Predictors of Pediatric-Onset Crohn's Disease and Ulcerative Colitis.

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