Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review.

Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed's own filter of: 'child: birth-18 years'. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H2 receptor antagonists (H2 RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H2 RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use.

Clustering of (auto)immune diseases with early-onset and complicated inflammatory bowel disease.

Studies in adult inflammatory bowel disease (IBD) patients have highlighted associations with genetic and serologic markers and suggest an association with disease location, behaviour and natural history. Data on patients with Crohn's disease (CD, n=80), ulcerative colitis (UC, n=15) and indeterminate colitis (n=4) were collected. All individuals were analysed for CARD15 R702W, G908R and L1007fs for toll-like receptor 4 (TLR4) Asp299Gly and for anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmatic antibodies (pANCA). After a mean of 10.7 years of follow up, the disease behaviour changed in 45% of CD patients, in contrast to disease location, where only 12.5% had a change (p<0.001). The younger the age at diagnosis, the more patients presented with colonic disease (p=0.021). Also, more TLR4 Asp299 Gly variants were found when the age at onset was younger (p=0.018). A large number of concomitant diseases were observed. There was no difference in the prevalence of TLR4 variants nor ASCA or pANCA between the patients with or without concomitant diseases. Patients who progressed more often needed surgery as compared to patients who remained free of stenosing or fistulising disease (27/32 or 84% versus 3/35 or 8.6%, respectively, p<0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA.

Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD.

BACKGROUND & AIMS: Three years after the identification of NOD2/CARD15, 2 more genes for inflammatory bowel diseases (IBDs) were reported. The carnitine/organic cation transporter (OCTN) on 5q31 (IBD5) is associated with Crohn's disease (CD) and DLG5 (10q23), a member of membrane-associated guanylate kinase (MAGUK) family, with IBD. We studied mutation prevalence, assessed phenotypic expression, and performed conditional analysis to examine evidence for gene-gene interactions. METHODS: A cohort of 2032 individuals was genotyped for disease-associated OCTN and DLG5 variants, including 981 patients with IBD (CD, n = 769; ulcerative colitis, n = 186; indeterminate colitis, n = 26) followed up at a tertiary IBD center. For 373 patients, DNA from both parents was available (cohort 1) for transmission disequilibrium testing analysis; case-control analysis was performed in 608 patients and 305 controls (cohort 2). RESULTS: There was no distortion of transmission toward affected offspring for any of the variant alleles. Case-control analysis also failed to shown an association. A higher frequency of DLG5 113A was observed in CARD15-positive patients (12.2%) compared with CARD15-negative patients (8.7%; P = .033). The OCTN-TC risk haplotype was associated with penetrating disease (odds ratio, 1.474; 95% confidence interval, 1.028-2.114; P = .035). For DLG5, there were no associations with a particular phenotype. CONCLUSIONS: DLG5 and OCTN do not play a role in the susceptibility to IBD, CD, or ulcerative colitis in the Flemish population but play a role in the phenotypic expression of the disease. OCTN variants were associated with perianal and penetrating CD. More studies in independent populations are urgently needed to assess the validity of DLG5 and OCTN in the pathogenesis of IBD.

Inflammation of the gastric cardia in children with symptoms of acid peptic disease.

OBJECTIVES: To assess the severity and causes of inflammation of the gastric cardia in children undergoing endoscopy for symptoms of acid peptic disease. STUDY DESIGN: Patients undergoing upper gastrointestinal endoscopy for symptoms of acid peptic disease had biopsies from gastric cardia, gastric, and esophageal sites, and 24-hour intraesophageal pH monitoring. Gastric cardia was defined at endoscopy as the anatomic zone from the squamocolumnar junction to 0.5 cm below it. Severity of gastric cardia inflammation was scored 0 to 9 according to densities of inflammatory cells and epithelial abnormalities in surface and pit epithelium. A score > or =2 was considered positive. RESULTS: Forty-seven children (median age, 6.5 years; range, 3-15) had Helicobacter pylori infection, gastroesophageal reflux disease (GERD), or both. In 22 patients, H pylori was detected in cardiac biopsies by rapid urease test and histology; it was detected also in the corpus and antrum in only seven of the 22. No patient had H pylori in gastric corpus/antrum without having the organism at the cardia as well. In 12 H pylori-positive patients, GERD was also diagnosed. Twenty-five patients had GERD and no H. pylori infection. Severity score was 3.8+/-0.8 in the H pylori group and 2.08+/-0.9 in the GERD alone group (P<.001); however, there was no difference in reflux index (24-hour % of gastroesophageal reflux) between the two groups. In neither group was correlation found between reflux index and severity score (H pylori, r=0.22; GERD alone, r=0.31; NS) nor between cardia inflammation and esophagitis grade (H pylori, r=0.37; GERD alone, r=0.22; NS). CONCLUSIONS: In children with symptoms of acid peptic disease, inflammation of the gastric cardia does occur. It is more severe when the cardiac zone is infected with H pylori than in its absence. Of major practical significance is the finding that the gastric cardia is a highly sensitive site for the detection of H pylori infection.