Eleftheria Roma

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.

Wilson disease in children: analysis of 57 cases.

Objectives: Wilson disease (WD) has a wide spectrum of clinical manifestations. Affected children may be entirely asymptomatic and the diagnosis problematic. Herein we present the clinical and laboratory characteristics of 57 children with WD and point out the diagnostic difficulties in a pediatric population. Patients and Methods: Clinical and laboratory data were collected from 57 consecutive children with WD. Evaluation included detailed physical examination, conventional laboratory testing, genetic analysis, and liver biopsy. Results: The mean age at diagnosis was 9.27 ± 3.62 years (range 4 months–18 years). Twenty patients were symptomatic, 19 were referred because of abnormal liver function test results and/or hepatomegaly, and 18 received their diagnoses after family screening. Twenty-two patients had both Kayser-Fleischer ring and decreased serum ceruloplasmin levels, 13 had urinary copper excretion after penicillamine challenge >1600 μg/24 hours, and 3 had liver copper content >250 μg/g dry weight. Of the remaining 19 patients, 17 had both low serum ceruloplasmin ≤20 mg/dL and increased urinary copper excretion, >75 μg/24 hours before, or >1000 μg/24 hours after penicillamine challenge. In 2 patients with equivocal cases who had serum ceruloplasmin 26 mg/dL, the diagnosis was confirmed by genetic analysis. No correlation was found between specific mutations and the disease phenotypic expression. Chelating therapy was well tolerated, and the outcome was satisfactory. Conclusions: WD in children may be obscure and requires extensive investigation to establish the diagnosis. Genetic analysis is needed in equivocal cases.

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.

Prevalence and characterization of class 1 integrons in Escherichia coli of poultry and human origin.

A prospective study was conducted to determine the prevalence and the gene-cassette content of class 1 integrons in Escherichia coli of poultry and human origin. A total of 235 E. coli isolates were examined; 65 were derived from farm poultry, 80 from hospitalized, and 90 from nonhospitalized patients. Susceptibilities to a range of antimicrobial agents were determined by disk diffusion. Int1-specific polymerase chain reaction, conserved-segment polymerase chain reaction, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis of XbaI digests of genomic DNA. The integron carriage rate for poultry isolates was 49.2%, whereas the carriage rate for hospital isolates was 26.2% and for community 11.1%. Multidrug resistance (resistance to three or more classes of antibiotics) phenotypes were observed in 96.8% of the integron-positive isolates, whereas only 34.9% of nonintegron-carrying organisms were multidrug resistant (p < 0.001). Seven integron types ranging in size from 663 to 2674 bp were identified; six types were observed in poultry isolates, five in hospital, and three in community isolates. Each integron type carried a distinct gene-cassette combination. The most prevalent gene cassettes belonged to the aad and dfr families. Identical integrons were detected in E. coli of human and poultry origin. A large reservoir of integrons exists in E. coli of poultry origin. The horizontal transfer of class 1 integrons among bacteria of poultry and human origins may contribute in the dissemination of antimicrobial resistance.

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.

Investigative MR Cholangiopancreatography for Primary Sclerosing Cholangitis-type Lesions in Children With IBD

Objectives: The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)–type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand. Methods: Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis. Results: Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and &ggr;-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD. Conclusions: The abnormality prevalences of aspartate transaminase, alanine transaminase, and &ggr;-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.

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.

Circulating leptin and adiponectin and their relation to glucose metabolism in children with Crohn’s disease and ulcerative colitis

Background:Crohn’s disease (CD) and ulcerative colitis (UC) result in metabolic consequences. We assessed circulating leptin and adiponectin concentrations and examined their relations to glucose metabolism in children with CD and UC.Methods:Circulating morning fasting concentrations of leptin, adiponectin, glucose, and insulin were measured in 32 children with CD and 18 children with UC. Insulin resistance (IR) and β-cell function were evaluated by the updated homeostatic model assessments (HOMA2-IR and HOMA2-B).Results:Leptin was positively related to BMI z-scores overall and in the CD and the UC subgroups (P < 0.001). A negative correlation between leptin and disease activity was observed in the entire population (P = 0.034) and in the UC (P = 0.03) group. None of the assessed parameters was related to adiponectin. Fourteen percent of the participants were insulin resistant (15.6% in the CD group and 11.1% in the UC group), significantly more than expected (P < 0.001). Leptin was associated with HOMA2-IR (overall: r = 0.29, P = 0.045). Pathway analysis suggested that, overall, disease activity and BMI significantly affect leptin, which in turn is the only correlate of HOMA2-IR.Conclusion:Disease activity was significantly and inversely related to leptin in children with inflammatory bowel disease (IBD). A significant proportion of the patients had increased IR, which is positively related to circulating leptin.

Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment

Objectives: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. Methods: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing–driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters. Results: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P < 0.001). A statistically significant decrease of the proportion of cases with negative FLG and positive POSTN staining was observed from the first (pretreatment) to the second (post-treatment) biopsy in the subgroup of patients with EoE (P < 0.001 in both correlations). Conclusions: FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.