Joanna Panayiotou

Changing Pattern in the Clinical Presentation of Pediatric Celiac Disease: A 30-Year Study

Background/Aims: The incidence of celiac disease (CD) has increased in recent years due to the recognition of atypical forms and the identification of silent cases through serological screening. Our aim was to detect temporal trends in the presentation of pediatric CD in Greece. Methods: We reviewed the medical files of all children diagnosed with CD between 1978 and 2007 at a single academic pediatric center. Cases were classified according to the year of diagnosis. We examined demographic data, presenting symptoms, delay to diagnosis, and the prevalence of associated conditions. Results: During the study period, 284 new cases of CD were diagnosed. The incidence of CD was significantly increased in recent years (p < 0.05). We observed significant trends towards older age at diagnosis (p < 0.001), longer delay to diagnosis (p < 0.05) and decreased frequency of the classical and/or gastrointestinal predominant mode of presentation (p < 0.001). In recent years, diagnosis of CD was significantly more frequent due to testing of asymptomatic children with a positive family history for CD or personal history of associated conditions (p < 0.001). Conclusion: We report a changing pattern in the presentation of pediatric CD in Greece. CD is diagnosed more frequently in older children, oftentimes presents with atypical symptoms, and is increasingly detected through serological screening. CD should be considered in the presence of atypical presentations.

Intrafamilial spread of Helicobacter pylori: a genetic analysis.

Background. A high incidence of Helicobacter pylori among family members of children with H. pylori gastritis has previously been documented on biopsy material. The main objective of this study was the genetic clarification of H. pylori strains involved in intrafamilial dispersion.

CagA and VacA Polymorphisms Do Not Correlate with Severity of Histopathological Lesions in Helicobacter pylori-Infected Greek Children

ABSTRACT The presence of various numbers of EPIYA tyrosine phosphorylation motifs in the CagA protein of Helicobacter pylori has been suggested to contribute to pathogenesis in adults. In this prospective study, we characterized H. pylori isolates from symptomatic children, with reference to the diversity of functional EPIYA motifs in the CagA protein and vacA isotypes, and assessed the potential correlation with the histopathological manifestations of the infection. We analyzed 105 H. pylori isolates from 98 children and determined the diversity of EPIYA motifs in CagA by amplification and sequencing of the 3′ variable region of the cagA gene as well as vacA isotypes for the signal, middle, and intermediate regions. CagA phosphorylation and levels of secreted IL-8 were determined following in vitro infection of AGS gastric epithelial cells. Histopathological evaluation of H. pylori colonization, activity, and severity of the associated gastritis was performed according to the updated Sydney criteria. EPIYA A (GLKN[ST]EPIYAKVNKKK), EPIYA B (Q[V/A]ASPEPIY[A/T]QVAKKVNAKI), and EPIYA C (RS[V/A]SPEPIYATIDDLG) motifs were detected in the ABC (46.6%) and ABCC (17.1%) combinations. No isolates harboring more than two EPIYA C motifs in CagA were found. The presence of isogenic strains with variable numbers of CagA EPIYA C motifs within the same patient was detected in seven cases. Occurrence of increasing numbers of EPIYA C motifs correlated strongly with presence of a high-vacuolation (s1 or s2/i1/m1) phenotype and age. A weak positive correlation was observed between vacuolating vacA genotypes and presence of nodular gastritis. However, CagA- and VacA-dependent pathogenicities were not found to contribute to severity of histopathology manifestations in H. pylori-infected children.

Is peptic ulcer a common cause of upper gastrointestinal symptoms

Abstract The aim of the study was to investigate retrospectively a cohort of children with peptic ulcer disease during a period that covers the recent changes in diagnosis and management of the disease. Over a period of 9 years, 2550 children underwent upper gastrointestinal endoscopy for various reasons. All children, in whom a diagnosis of primary peptic ulcer was established, were included in the study. Previous and current medical history, family history, endoscopic and histological outcome were evaluated and the children were regularly followed-up on an out-patient basis. Primary peptic ulcer was diagnosed in 52 (10 gastric and 42 duodenal, 2%) out of 2550 children. The median age of children with gastric ulcer was 6.5 years, whereas of those with duodenal ulcer was 10.5 years (P=0.04). With regard to clinical symptoms no significant difference was found between children with and without ulcer. The prevalence of Helicobacter pylori infection was significantly higher in children with duodenal ulcer (62%) compared to those with gastric ulcer (20%; P<0.001). At first follow-up visit, 1 month after the end of treatment, 19 symptomatic children underwent a repeat endoscopy, which showed ulcer healing in 95% and failure in H. pylori eradication in 27%. During the long-term follow-up (median 3.5 years), six children became symptomatic. Two of them had duodenal ulcer associated with positive H. pylori. Conclusion Peptic ulcer disease is an uncommon disorder in childhood with non specific clinical features; it seems that efficient treatment and successful Helicobacter pylori eradication result in clinical improvement and cure as well as in long-term healing of ulcers.

Bone Health in Children With Celiac Disease Assessed By Dual X-ray Absorptiometry: Effect of Gluten-free Diet and Predictive Value of Serum Biochemical Indices

Objectives: In the present study, we aimed to assess bone status and the effect of gluten-free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances. Methods: Forty-five children at the time of diagnosis of CD (group A, 77.8% girls) and 36 children receiving GFD for >2 years (group B, 75% girls) were included. Sixteen children in group A were reexamined 12 months after initiation of GFD. Serum measurements of biochemical bone health indices and BMD, assessed by dual x-ray absorptiometry, were obtained. Results: Patients after 1 year of receiving GFD had higher BMD z scores compared with baseline (−1.45 ± 0.28 vs −0.61 ± 0.25, respectively, P = 0.004). BMD z scores were significantly lower than expected for the normal population, after 1 (P = 0.03) or at least 2 (P < 0.001) years of receiving GFD. In group B, BMD z score was positively correlated with 25-hydroxy vitamin D levels (P = 0.009). In the repeated measurements group, 25-hydroxy vitamin D differed between pre- and post-GFD (P = 0.018). No biochemical index was capable of predicting an abnormal BMD z score (receiver operating characteristic curve analysis, all of the areas under the curve <0.66). Conclusions: GFD has a beneficial effect on bone health. Two years receiving diet do not ensure normalization. Biochemical markers are not indicative of BMD disturbances. Dual x-ray absorptiometry should be included in the standard management of children with CD.

Inflammatory bowel disease in children: the role of a positive family history.

Objectives The aim of this study was to evaluate any potential influence of a family history of inflammatory bowel disease (IBD) on the clinical phenotypes and the course of IBD in children. Methods In this retrospective study, the notes of 411 children with the diagnosis of IBD, 244 (59.4%) with ulcerative colitis, 129 (31.4%) with Crohns disease and 38 (9.2%) with IBD unclassified, who were admitted to our department between 1 January 1981 and 31 December 2007 were reviewed. The aim was to assess the prevalence of familial IBD and its impact on the age of disease onset, clinical phenotypes according to the Montreal classification, course and outcome of disease. The control group consisted of IBD children without a family history of IBD, who were admitted to the hospital during the same time period. Results Thirty five (8.5%) children had a family history of IBD, (ulcerative colitis 6.6%, Crohns disease 10.9% and IBD unclassified 13.2%). Sixty-eight percent of the 22 pairs of first-degree relatives were concordant for the clinical phenotype of disease. Significantly, more children with familial IBD had symptom onset and/or disease diagnosis before 5 years of age compared with sporadic IBD (P = 0.01 and P = 0.014, respectively); however, no differences were seen in sex, clinical phenotypes, need for aggressive treatment and/or surgery. Conclusion Children with familial IBD had earlier onset of disease compared with those with sporadic IBD. However, this had no significant impact on the clinical phenotypes, the course and/or the outcome of disease.

HLA class II high-resolution genotyping in Greek children with celiac disease and impact on disease susceptibility.

Background:Celiac disease (CD) has been associated with HLA class II heterodimers. This study aimed at determining the HLA genotypic and allelic distribution in Greek children with CD as compared with the general population.Methods:A total of 118 children with CD and 120 healthy individuals serving as controls were included in the study.Results:Higher frequencies for HLA-DQB1*02:01 (40.25 vs. 9.58%, P < 0.001) and DQB1*02:02 (20.34 vs. 5.42%, P < 0.001) were observed in patients with CD, whereas HLA-DQB1*03:01 (16.53 vs. 30.42%, P < 0.001), DQB1*05:01 (0.85 vs. 10%, P < 0.001), and DQB1*05:02 (5.51 vs. 17.92%, P < 0.001) were significantly lower, as compared with the controls. DQA1*02:01 (patients with CD vs. controls: 20.76 vs. 6.67%, P < 0.001) and DQA1*05:01 (40.25 vs. 9.58%, P < 0.001) were significantly more frequent in patients. The frequencies of HLA-DQA1* 01:01, *01:02, *01:04, and *05:05 were significantly lower in patients (P < 0.001). The haplotype mainly associated with CD was DRB1*03-DQB1*02:01-DQA1*05:01; patients with CD vs. controls: 39.83 vs. 9.58%, P < 0.001. In total, 84.75% of patients carried DQ2 (vs. 21.67% in controls, P < 0.001), whereas 11.02% were DQ8 positive/DQ2 negative.Conclusion:This study confirms the existing data and provides additional evidence supporting a strong genetic predisposition for CD associated with the class II alleles DQB1*02 and DQA1*05 encoding the serological specificity DQ2.

DOES INTRAFAMILIAL SPREAD PLAY A ROLE FOR HELICOBACTER PYLORI INFECTION IN CHILDREN

INTRODUCTION: Acquisition of Helicobacter pylori (Hp) infection in children occurs mainly in those under 5 years of age. OBJECTIVE: Our aim was to investigate intrafamilial spread of Hp infection. METHODS: One hundred symptomatic children without previous eradication treatment were investigated by gastroscopy and the 13C-urea breath test (UBT). All family members of each index patient were investigated by using the UBT. Infected members were estimated according to UBT results, and for those members who were UBT-negative and had recently received eradication therapy after confirmation of infection by endoscopy, the previous positivity was taken into account. RESULTS: Ηp infection was identified in 44 (44%) of 100 symptomatic index children. There was no statistical difference between Ηp+ and Ηp− index children concerning demographic factors except age, which was higher in Ηp+ index children (P = .009). In all Ηp+ index children (100%) and in 71.4% of Ηp− children, at least 1 more family member was infected (P < .001); in all cases (100%) at least 1 parent in the group of Ηp+ index children, compared with 69.6% in Ηp− index children (P < .001), was infected. The rate of infected siblings of the Ηp+ index children was 43.2%, and that in the Ηp− group was 3.6% (P < .001). There were more infected mothers in the Ηp+ index children group (83.7% vs 50% in the Ηp− group; P = .001) and more infected fathers (76.7% vs 56.4%, respectively; P = .035). CONCLUSIONS: The identification of at least 1 more infected member in each family of Hp+ index patients, including a parent in all cases, strongly indicates family as the main source of infection for children and confirms the hypothesis of intrafamilial spread of Hp.

Serum Pepsinogen I(Pgi) in Children With Gastritis 64

Gastritis, associated or not by Helicobacter Pylori (HP) infection, consists a common cause of upper gastrointestinal symptomatology in children. The aim of the present study was to investigate a possible correlation of serum PGI levels to gastritis in children. The studv comprised 98 symptomatic and 41 asymptomatic children divided in 5 groups. A: 54(10.5±2yrs) with HP gastritis, B: 13(11±1.2yrs) after eradication of HP, C: 25 (10±2.2yrs) with gastritis without HP, D: 19 (9.4±2yrs) with normal gastric biopsy and E: 41 asymptomatic (9.1±1.5yrs). Children of groups A, B, C, D underwent upper endoscopy and HP detection by histology, CLO test and serum antibodies to HP. Serum PGI was estimated once in all groups, while it was repeated in group B. Statistics were performed by analysis of variance. Results are as follow:Table

INTRAFAMILIAL SPREAD OF HELICOBACTER PYLORI (HP): A GENETIC ANALYSIS

BACKGROUND A high incidence of Helicobacter pylori among family members of children with H. pylori gastritis has previously been documented on biopsy material. The main objective of this study was the genetic clarification of H. pylori strains involved in intrafamilial dispersion. MATERIALS AND METHODS Formalin-fixed, paraffin-embedded material of antral mucosa from 32 members of 11 families was studied for the presence of genetic homogeneity. To achieve this goal, the entire genome of H. pylori was studied by the polymerase chain reaction (PCR)-based random amplified polymorphic DNA (RAPD) fingerprinting method. Furthermore, the Urease A gene was analyzed using a multiplex PCR-assay and an alternative mutation detection method based on the Hydrolink trade mark analysis. RESULTS RAPD fingerprinting confirmed that closely related H. pylori strains were involved in the intrafamilial dispersion. Mutations and small deletions in Urease A gene were found in 22 out of 32 individuals. CONCLUSIONS The homology of the H. pylori genome in members of the same family strongly supports the hypothesis of transmission of H. pylori from person-to-person or from a common source.