Child and Parent Mental Health Problems in Pediatric Celiac Disease: A Prospective Study.

OBJECTIVES: The aim of our study was to estimate the levels of mental health problems in children with celiac disease (CD) along with their parents' mental health status, to compare these levels with those of healthy controls and to investigate how these problems are affected by a gluten-free diet (GFD). METHODS: Our study constituted 50 patients with CD at diagnosis before the initiation of a GFD (age 8.6 ±â€Š3.7 years, group A), 39 patients with CD on a GFD for at least 12 months (age 10.4 ±â€Š3.4 years, group B) and 38 healthy controls (age 7.7 ±â€Š3.8 years, group C), as well as their parents. One of the parents of each child completed the Child Behaviour Checklist (CBCL) and the Symptom Checklist 90 (SCL-90-R) to evaluate the children's and parents' mental health problems, respectively. Twenty patients in group A were reevaluated at least 12 months after initiation of a GFD (group D). RESULTS: At diagnosis, CD patients had higher scores in the CBCL for internalizing problems than healthy controls (55.7 ±â€Š10.3 vs 47.9 ±â€Š15.4, P = 0.007) and their parents demonstrated increased severity of mental health problems, including anxiety and depression, than the parents of healthy controls (0.72 ±â€Š0.49 vs 0.54 ±â€Š0.58, P = 0.013). CONCLUSIONS: CD patients at diagnosis and their parents, had more mental health problems, including anxiety and depression, than healthy controls.

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.

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.

Endoscopic tests for the diagnosis of Helicobacter pylori infection in children: Validation of rapid urease test.

BACKGROUND: Rapid urease test (CLO-test) is an inexpensive and quick method for diagnosis of Helicobacter pylori infection with controversial results in children. We evaluated the performance of CLO-test in relation to endoscopic and histological findings in children with H. pylori infection. MATERIALS AND METHODS: We studied the medical records of children with H. pylori infection who were diagnosed between 1989 and 2009. Noninfected children were used as controls. H. pylori infection was defined by positive culture or by two other positive tests (histology and CLO-test, or urea breath test when a single test was positive). All children had histology together with CLO-test. Tissue culture was performed whenever possible. RESULTS: Five hundred thirty infected children (10.4 +/- 3.0 years) and 1060 controls (7.3 +/- 4.4 years) were studied. Sensitivity of CLO-test was 83.4% (95% CI, 79.9-86.3%), of culture 84.6% (95% CI, 78.7-89.1%), of histology 93.2% (95% CI, 90.7-95.1%), and specificity 99% (95% CI, 98.2-99.4%), 100%, and 100% respectively. CLO-test positivity was correlated with higher bacterial density (p < .001), activity (p < .001) and severity of gastritis (p < .01), older age (p < .01), and the presence of antral nodularity (p < .001). When CLO-test was positive, the concordance with histology and culture was high (95.5 and 89.2% respectively), whereas low concordance was observed when CLO-test was negative (17.05 and 45.83% respectively). CONCLUSIONS: CLO-test had lower sensitivity and comparable specificity with histology. Both tests should be performed concurrently to accurately diagnose H. pylori infection in children.

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 Crohn's 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%, Crohn's 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.

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.

CagA and VacA polymorphisms do not correlate with severity of histopathological lesions in Helicobacter pylori-infected Greek children.

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.

Intrafamilial spread of Helicobacter pylori infection in Greece.

GOAL: To find out the role of family members in the Helicobacter pylori infection in childhood by investigating the incidence of infection within families of H. pylori-infected children. BACKGROUND: H. pylori infection is usually acquired in early childhood and possibly family members are the main source of infection. STUDY: One hundred consecutive children with upper gastrointestinal symptoms, without previous H. pylori eradication treatment were prospectively studied by gastroscopy and C-urea breath test. Simultaneously, all family members were studied by C-urea breath test regardless of earlier eradication treatment for H. pylori infection. The age of children and their parents, socioeconomic status, parents' education, and living conditions were recorded. RESULTS: Forty-four index symptomatic children were infected by H. pylori. No statistical difference was found concerning demographic factors, between H. pylori-positive and H. pylori-negative index children except age, which was higher in the H. pylori-infected children (P=0.009). In all H. pylori-positive and in 71.4% of the negative index children, at least 1 more family member was infected (P<0.001), always including a parent in the H. pylori-positive, compared with 69.6% in the H. pylori-negative group (P<0.001). The percentage of infected siblings, mothers and fathers was higher in H. pylori-infected index children (P<0.001, P=0.001, and P=0.035, respectively). CONCLUSIONS: The prevalence of H. pylori infection is significantly higher among families of infected index children. The presence of at least 1 infected family member in all H. pylori-positive index children suggests that the family could be the main source of H. pylori infection in children.

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. 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.