Oleg Jadrešin

Compliance With Gluten-free Diet in Children With Coeliac Disease

Objectives: Coeliac disease (CD) is a lifelong disorder with gluten-induced manifestations in different organs. Gluten-free diet (GFD) is required to achieve remission and prevent complications; however, study reports on GFD growth effect are not consistent. Methods: Compliance with GFD was estimated according to current body mass and height; presence of anaemia and other signs and symptoms; and attitude toward GFD. Results: Seventy-one patients with CD (mean age = 12 years; mean age after CD diagnosis = 9 years) were examined and their blood sampled for determination of endomysial antibodies (EMA), haemoglobin, and red blood cell count. Questionnaire analysis revealed 42 (59.1%; 4 EMA positive) patients to be on strict GFD, 19 (26.8%; 5 EMA positive) were taking small amounts of gluten, and 10 (14.1%; all EMA positive) were not on a diet at all. The patients on strict GFD had greatest body height, yet the difference was not significant. These patients also had a higher mean body mass (P = 0.05) and significantly higher mean haemoglobin and mean cell haemoglobin levels (P = 0.05 and P < 0.05, respectively). Apart from chronic fatigue in patients on partial diet (P = 0.05), patient groups did not differ significantly in the frequency of symptoms. Anaemia and delayed puberty were recorded only in noncompliers (P < 0.01 and P < 0.05, respectively). Noncompliers often found the specific diet to pose a major life burden (P < 0.01) and did not visit a gastroenterologist on a regular basis (P < 0.01). Conclusions: Almost half of the coeliac patients were likely to abandon GFD without experiencing major symptoms, thus increasing the risk for developing complications later in life. An active attitude is required in the follow-up of patients with CD.

NOD2/CARD15 mutations in Croatian patients with Crohn's disease : prevalence and genotype-phenotype relationship

Background Crohns disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. Aims and methods As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohns patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohns disease was further assessed by logistic regression analysis. Results NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P=0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P=0.041, P=0.162, P=0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. Conclusions This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.

Gluten-Free Diet Has a Beneficial Effect on Chromosome Instability in Lymphocytes of Children With Coeliac Disease

Objectives. Children with coeliac disease (CD) have an increased number of chromosome aberrations in peripheral blood lymphocytes. Whether genetically determined or a secondary phenomenon in CD, chromosome abnormalities may be involved in the predisposition to cancer in CD patients. The aim of the study was to follow a group of children with CD in whom the initial frequency of chromosome aberrations at diagnosis was known and to measure the same variable after a minimum of 2 years on a gluten-free diet. Methods. Chromosome aberrations in peripheral blood lymphocytes were determined in 17 patients with CD, before and after at least 24 months of a gluten free diet (mean, 33 months), and in 15 healthy children. The differences in the frequency of aberrations were analyzed by Mann-Whitney U test and Wilcoxon matched-pairs signed-ranks test. Results. Twelve patients adhered to the diet and had a significantly lower frequency of chromosome aberrations than did 5 patients not following the diet (0.16%v 1.2%; P = 0.03), whereas at presentation there had been no difference (1.54%v 1.2%; P = 0.09). The frequency of aberrations at follow-up in patients who were diet adherent was significantly lower than at presentation (1.54% v 0.16%; P = 0.02) and remained unchanged in patients who were not diet adherent (1.2%v 1.2%; P = 1). After at least 24 months of a gluten-free diet, children with CD did not differ from healthy control subjects (0.16%v 0.27%; P = 0.54), whereas children not following the diet had an increased frequency of aberrations (1.2%v 0.27%; P = 0.05). Conclusions. The frequency of chromosome aberrations in peripheral blood lymphocytes of patients with CD decreased significantly on a gluten-free diet. We conclude that genomic instability is a secondary phenomenon, possibly caused by chronic intestinal inflammation.

Diagnosis of coeliac disease in children younger than 2 years.

Background and Aim: To diagnose coeliac disease (CD) in children younger than 2 years, the old ESPGHAN criteria based on 3 small bowel biopsies were recommended until recently. The aim of the present study was to investigate the applicability of only 1 small intestinal biopsy plus positive serology for the diagnosis of CD in children younger than 2 years. Methods: A prospective cohort study included 81 patients younger than 2 years with symptoms suggestive of CD, who all completed the diagnostic procedure based on 3 small bowel biopsies. According to the finding of the third biopsy, patients were divided into group A—CD confirmed (N = 44), and group B—CD not confirmed, after the gluten challenge (N = 37). Results: At the time of the first biopsy, total villous atrophy (Marsh IIIc) was found more often in group A than in group B (77% vs 27%, P < 0.01). Also, all of the studied antibodies were more frequently positive in group A than in group B (P < 0.01 for all of the tested antibodies). Positive anti-endomysial antibodies and Marsh IIIc finding were the best discriminators between the group A and the group B and considerably contributed to the prediction of CD. Conclusions: The second and the third biopsies (before and after the gluten challenge) may also be avoided when diagnosing CD in children younger than 2 years provided that the child, at the time of presentation, has positive anti-endomysial antibodies and Marsh IIIc on the small bowel biopsy. A gluten challenge should be still considered in all other children younger than 2 years.

Refeeding syndrome in children with different clinical aetiology.

Refeeding syndrome (RFS) is a well-described state of the series of metabolic and biochemical changes that can occur during the feeding of malnourished persons. The shifts in fluids and electrolytes can lead to complications during artificial feeding, which if not recognised and untreated can lead to death. Although the physiology and pathophysiology of RFS is well known, the circumstances under which the RFS appears, clinical manifestations and management of these patients are less clear. There are few published studies describing the occurrence of RFS in children. We describe two cases of RFS in children. The first case is a boy with unrecognised coeliac disease and second case is a girl with cerebral palsy. In both cases, the RFS has developed without clinical symptoms and it was shown only through laboratory findings. Electrolyte disturbances have been successfully corrected and treatment of the underlying disease continued.

Lactobacillus Reuteri DSM 17938 in the Treatment of Functional Abdominal Pain in Children - RCT Study.

Objectives: Beneficial therapeutic effect of probiotics has been reported in children with the irritable bowel syndrome (IBS) but not consistently in other functional abdominal pain-related disorders. The aim of the present study was to investigate the effect of Lactobacillus reuteri DSM 17938 in the treatment of functional abdominal pain (FAP) and IBS in children. Methods: Children (age 4–18 years) referred to pediatric gastroenterologist at Childrens Hospital Zagreb from May 2012 to December 2014, diagnosed as FAP or IBS, were randomized to receive L reuteri DSM 17938 108 CFU daily or placebo. The study was a prospective, randomized, double-blind, placebo-controlled parallel study. Symptoms were evaluated using Wong-Baker FACES pain rating scale for pain and Bristol scale for stool shape and consistence. Results: Data were analyzed for 55 children (26 in the intervention group and 29 in the placebo group). Children in the intervention group had significantly more days without pain (median 89.5 vs 51 days, P = 0.029). Abdominal pain was less severe in children taking probiotics during the second month (P < 0.05) and fourth month (P < 0.01). The 2 groups did not differ in the duration of abdominal pain, stool type, or absence from school. Both groups experienced significant reduction in the severity of abdominal pain from first to fourth month, with the reduction more prominent in the intervention group (P < 0.001 vs P = 0.004). Conclusions: Administration of L reuteri DSM 17938 was associated with a possible reduction of the intensity of pain and significantly more days without pain in children with FAP and IBS.

Methotrexate is an efficient therapeutic alternative in children with thiopurine-resistant Crohn’s disease

Abstract Objective. This study aimed to investigate the role of methotrexate (MTX) in the maintenance of clinical remission and mucosal healing in children with Crohn’s disease (CD), in whom azathioprine (AZA) treatment failed. Materials and methods. This was a retrospective, longitudinal cohort study which included all children who were diagnosed with CD during a period of 10 years and who received MTX for ≥12 months after failed AZA treatment. Remission was assessed clinically, defined by Pediatric Crohn’s Disease Activity Index as a score of ≤10 and no need for the reintroduction of the remission induction therapy. In the subset of patients with sustained clinical remission, the rate of mucosal healing was endoscopically assessed. Endoscopic lesions were assessed by Simple Endoscopic Score for CD. Each patient served as his or her own historical control. Results. Of the 32 included patients, 22 (68.7%) remained in the stable clinical remission after a period of 12 months and 14 (43.8%) did not experience relapse during the whole follow up (median duration 2.9 years; range 1–4.8 years). From all patients who were in clinical remission during the entire follow up (n = 14), endoscopy was performed in eight (57%) patients and showed complete mucosal healing macroscopically (Simple Endoscopic Score for CD score of 0) and microscopically in seven out of eight (87.5%) patients. Conclusion. MTX was found to be an efficient therapeutic alternative in the thiopurine-resistant patients, enabling the complete mucosal healing.