Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

AIM:To investigated the molecular cause of very early-onset ulcerative colitis(UC)in an 18-mo-old affected child.METHODS:We analysed the interleukin-10(IL10)receptor genes at the DNA and RNA level in the proband and his relatives.Beta catenin and tumor necrosis factor-α(TNFα)receptors were analysed in the proteins extracted from peripheral blood cells of the proband,his relatives and familial adenomatous polyposis(FAP)and PTEN hamartoma tumor syndrome(PHTS)patients.Samples were also collected from the proband’s inflamed colorectal mucosa and compared to healthy and tumour mucosa collected from a FAP patient and patients affected by sporadic colorectal cancer(CRC).Finally,we examined mesalazine and azathioprine effects on primary fibroblasts stabilised from UC and FAP patients.RESULTS:Our patient was a compound heterozygote for the IL10RB E47K polymorphism,inherited from his father,and for a novel point mutation within the IL10RA promoter(the-413G->T),inherited from his mother.Beta catenin and tumour necrosis factorαreceptors-Ⅰ(TNFRI)protein were both over-expressed in peripheral blood cells of the proband’s relatives more than the proband.However,TNFRII was over-expressed only in the proband.Finally,both TNFα-receptors were shown to be under-expressed in the inflamed colon mucosa and colorectal cancer tissue compared to healthy colon mucosa.Consistent with this observation,mesalazine and azathioprine induced,in primary fibroblasts,IL10RB and TNFRII over-expression and TNFRI and TNFαunder-expression.We suggest thatβ-catenin and TNFRI protein expression in peripheral blood cells could represent molecular markers of sub-clinical disease in apparently healthy relatives of patients with early-onset UC.CONCLUSION:A synergistic effect of several variant alleles of the IL10 receptor genes,inherited in a Mende-lian manner,is involved in UC onset in this young child.

Italian survey on non-steroidal anti-inflammatory drugsand gastrointestinal bleeding in children

AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in

Prevalence of functional gastrointestinal disorders in children with celiac disease on different types of gluten-free diets

BACKGROUND Functional gastrointestinal disorders(FGIDs)are common during the pediatric age.FGIDs are not related to biochemical or structural abnormalities.However,since they have a high prevalence,several studies have evaluated an overlap between FGIDs and organic diseases.Individuals with celiac disease(CD)have been shown to be at an increased risk for functional abdominal pain,even if they adhere well to a gluten-free diet(GFD).Little information is available for the pediatric age group.The aims of our study were to evaluate the prevalence of FGIDS in CD children 1 year after diagnosis and to compare the prevalence of FGIDs in CD children on a GFD with processed foods compared with those on a GFD with natural products.AIM To assess the prevalence of FGIDs in children with CD after 1 year of follow-up and to compare the prevalence of FGIDs in children with CD on a GFD with processed foods and in children on a GFD with natural products.METHODS We recruited pediatric patients aged 1-18 years with a new CD diagnosis.Participants were randomized to two groups:Group A on a GFD with processed foods(diet 1);and group B on a GFD with natural products(diet 2).Clinical monitoring,diet assessment and the questionnaire on pediatric gastrointestinal symptoms-Rome IV version were performed at diagnosis(T0)and after 12 mo of follow-up(T1).Dietary intake was assessed using a 3-d food diary record.Data from the diaries were evaluated using WinFood nutrient analysis software.We assessed the prevalence of FGIDs at T1 and the correlation with the type of GFD.RESULTS We registered 104 CD children,with 55 patients in group A(53.0%)and 49 patients in group B(47.0%).Initially,30 of the 55(54.5%)CD children were symptomatic in group A,while 25 of 49(51.0%)were symptomatic in group B.At T1,in spite of a low or negative serology for CD,FGIDs prevalence was 10/55(18.0%)in group A and 8/49(16.3%)in group B,with no statistically significant difference between the two groups(P=0.780).At T1 the macro-and micronutrient intake was similar across the two groups with no significant differences in nutrient analysis.However,in both groups at T1 we found that a lower prevalence of FGIDs(P=0.055)was associated with an inferior caloric(odds ratio=0.99,95%confidence interval:0.99-1.00)and fat(odds ratio=0.33,95%confidence interval:0.65-0.95)intake.CONCLUSION Our results showed that CD children on a GFD have gastrointestinal symptoms with an elevated prevalence of FGIDs.Our study suggests that developing FGIDs may be linked to caloric intake and percentage of food fat,but it does not change between a GFD with processed foods or a GFD with natural products.However,long-term monitoring is required to evaluate a correlation between FGIDs and various types of GFDs.