A novel pediatric Eosinophilic Esophagitis Symptoms and Adaptive Behavior Scale for different ages: GaziESAS v2.0.

BACKGROUND: High-quality scales (HQS) suitable that measure symptoms and adaptive behaviors (AB) with proven validity and reliability are needed for different age groups of children with eosinophilic esophagitis (EoE). OBJECTIVE: To develop a high-quality pediatric EoE symptoms and AB scale for different age groups. METHODS: Children (7-11 years), teens (12-18 years), and parents of 2-18-year-old children with EoE were included. A HQS should have encompassed: the identification of domain and item generation; content validity (CnV) and field test for construct validity (CsV) and reliability. Convergent validity (CgV) was examined for CsV. Correlations between the Pediatric Eosinophilic Esophagitis Symptom Score, version 2.0 (PEESS v2.0) and Gazi University Eosinophilic Esophagitis Symptoms and Adaptive Behavior Scale (GaziESAS) version 2.0 (v2.0) were examined for CgV. Reliability was determined through internal consistency (Cronbach-α) and test-retest reliability (intraclass correlation coefficients: ICC). RESULTS: Nineteen children, 42 teens, and 82 parents completed the study. GaziESAS v2.0 was composed of 20 items with two main domains: symptoms (subdomains: dysphagia and nondysphagia) and AB. CnV indexes were excellent for all items. The CgV varied from good to excellent correlation (r = 0.6 to r = 0.9). GaziESAS v2.0 showed good reliability (Cronbach-α >0.7 and ICC >0.6). CONCLUSION: GaziESAS v2.0 is the first pediatric HQS that measures the frequency of symptoms and AB in EoE within the last month with separate forms for children, teens, and parents.

New Findings of Immunodysregulation, Polyendocrinopathy, and Enteropathy X-linked Syndrome (IPEX); Granulomas in Lung and Duodenum.

Immune dysregulation, polyendocrinopathy and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by loss-of-function mutations in the gene forkhead box protein 3 (FOXP3). IPEX patients frequently show chronic diarrhea (enteropathy) associated with villous atrophies in the small intestine. Our case is different from this classical information in the literature, since he presented with neonatal onset inflammatory bowel disease within the first months of life accompanied by deep ulcers throughout colonic mucosa. Moreover, he developed chronic lung disease during follow-up and histopathological examinations showed granulomas in both gastrointestinal tract and lung parenchyma. Genetic analysis revealed the diagnosis of IPEX syndrome with a germline mutation in FOXP3. Thus, our study provides an unusual presentation of IPEX syndrome with colitis and granulomas presence in histopathological examinations.

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study.

BACKGROUND AND AIMS: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. METHODS: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. RESULTS: Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. CONCLUSIONS: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

Classification chaos in coeliac disease: Does it really matter?

The spectrum of mucosal pathology in coeliac disease (CD), initially defined by Marsh in 1992 has been subjected to several modifications in the following years by Oberhuber, then by Corazza and Villanaci, and finally by Ensari. The present study, aimed to end the ongoing confusion regarding the classification of mucosal pathology in CD by applying all the classifications proposed so far on a large series of cases. A total of 270 duodenal biopsies taken from the distal duodenum of patients with a diagnosis of CD were included in the study. All biopsies were classified according to Marsh, Oberhuber, Corazza Villanaci, and Ensari classification schemes. For statistical analyses cases were divided into three groups: Group 1 included type 1 lesions in Marsh, Ensari, and Oberhuber and grade A in Corazza Villanaci classifications. Group 2 comprised of type 2 lesions in Marsh and Ensari classifications together with type2, type 3a and 3b lesions in Oberhuber classification and grade B1 lesions in Corazza Villanaci classification. Group 3 included type 3 lesions in Marsh and Ensari classifications, and type 3c lesions in Oberhuber, and grade B2 lesions in Corazza Villanaci classifications. The kappa value was 1.00 (excellent) for group 1, 0.53 (fair) for group 2 and 0.78 (excellent) for group 3 (p<0.0001). These results suggest that any of the above classification system would serve similar purposes in the diagnosis of CD. Therefore, it is advisable that the pathologist should use the simplest reliable scheme.

Comparison of double balloon enteroscopy in adults and children.

AIM: To compare results of double balloon enteroscopy (DBE) procedures in pediatric and adult patients. METHODS: The medical files of patients who underwent DBE at Gazi University School of Medicine, Ankara, Turkey between 2009 and 2011 were examined retrospectively. Adult and pediatric patients were compared according to DBE indications, procedure duration, final diagnosis, and complications. DBE procedures were performed in an operating room under general anesthesia by two endoscopists. An oral or anal approach was preferred according to estimated lesion sites. Overnight fasting of at least 6 h prior to the start of the procedure was adequate for preprocedural preparation of oral DBE procedures. Bowel cleansing was performed by oral administration of sennosides A and B solution, 2 mL/kg, and anal saline laxative enema. The patients were followed up for 2 h after the procedure in terms of possible complications. RESULTS: DBE was performed in 35 patients (5 pediatric and 30 adult). DBE procedures were performed for abdominal pain, chronic diarrhea, bleeding, chronic vomiting, anemia, and postoperative evaluation of anastomosis. Final diagnosis was diffuse gastric angiodysplasia (n = 1); diffuse jejunal angiodysplasia (n = 1); ulceration in the bulbus (n = 1); celiac disease (n = 1); low differentiated metastatic carcinoma (n = 1); Peutz-Jeghers syndrome (n = 1); adenomatous polyp (n = 1) and stricture formation in anastomosis line (n = 1). During postprocedural follow-up, abdominal pain and elevated amylase levels were noted in three patients and one patient developed abdominal perforation. CONCLUSION: With the help of technological improvements, we may use enteroscopy as a safe modality more frequently in younger and smaller children.

Gastrointestinal mucosal involvement without amyloidosis in children with familial Mediterranean fever.

BACKGROUND AND OBJECTIVES: Familial Mediterranean fever (FMF) and inflammatory bowel disease togetherness is well described in the literature. Abdominal pain and various gastrointestinal manifestations may arise directly from FMF or secondary to FMF-associated diseases such as inflammatory bowel disease, vasculitidies, or amyloidosis. The aim of the study was to document gastrointestinal involvement in familial Mediterranean fever. METHODS: The medical files of the patients who were diagnosed as having FMF at the Department of Pediatric Gastroenterology, Gazi University School of Medicine between 2007 and 2012 were examined retrospectively. FMF diagnosis was made through performing clinical, laboratory, colonoscopy, endoscopy, and genetic analysis. RESULTS: Thirty-six patients were diagnosed as having FMF during this period. Among them, 11 patients were admitted with vomiting or diarrhea. Colonoscopy and upper gastrointestinal endoscopy were performed. Colonic inflammation and multiple gastric aphthous ulcerations were observed. CONCLUSIONS: In this report, we described 11 patients who presented with gastrointestinal symptoms and eventually diagnosed as having FMF. Gastrointestinal mucosal involvement without amyloidosis is documented by endoscopic and histopathologic investigations in these patients. We concluded that mucosal involvement of the gastrointestinal tract may be attack-related manifestations in these patients.

Relation between ghrelin level and treatment response in functional constipation.

BACKGROUND/AIMS: Ghrelin stimulates gastrointestinal motility. Although there are some experimental and clinical studies supporting the role of ghrelin for gastrointestinal motility disorders, limited research for constipation has been published. The purpose of this study was to evaluate the possible role of ghrelin in the pathophysiology of functional constipation in childhood. MATERIAL AND METHODS: Forty-three newly diagnosed constipated children aged 1-6 years and 25 healthy age-matched controls were included. Serum ghrelin levels were analyzed initially in both groups. Treatment protocol consisted of dietary modification, lactulose, and administration of pediatric enema. Ghrelin levels of children with functional constipation were reanalyzed after two monthsof treatment. RESULTS: Initial serum ghrelin levels of constipated patients were found to be lower than those of healthy children (p<0.001). Ghrelin levels increased during therapy. The differences between initial and second month serum ghrelin levels of constipated patients were found to be statistically significant (p<0.05). CONCLUSION: Our data supports the potential role of ghrelin in children with functional constipation. Observation of an increase in serum ghrelin levels with nonspecific treatment supports the hypothesis that low serum ghrelin levels might be a result rather than the cause of constipation.