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Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE. There is a discrepancy between symptoms and endoscopic and histologic features.Allergy testing is of no value in deciding which foods to eliminate.Eosinophilic esophagitis (EoE) may cause esophageal stenosis even in pediatric patients.Maintenance therapy after induction is necessary There is a discrepancy between symptoms and endoscopic and histologic features. Allergy testing is of no value in deciding which foods to eliminate. Eosinophilic esophagitis (EoE) may cause esophageal stenosis even in pediatric patients. Maintenance therapy after induction is necessary Validated tools are available for assessing symptoms and quality of life and should be incorporated in the management of children with EoE.Systemic steroids may be helpful in the treatment of severe esophageal strictures.A discrepancy between eosinophil depletion and symptomatic improvement requires reassessment of non-eosinophil-dependent inflammation.Implementation of programs for transition to adult care must be considered and started well before patients reach adulthood. Validated tools are available for assessing symptoms and quality of life and should be incorporated in the management of children with EoE. Systemic steroids may be helpful in the treatment of severe esophageal strictures. A discrepancy between eosinophil depletion and symptomatic improvement requires reassessment of non-eosinophil-dependent inflammation. Implementation of programs for transition to adult care must be considered and started well before patients reach adulthood.

Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (=15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7–17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3–16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7–2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children (P< 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children(P< 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria. This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data. We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P< 0.001). In group A, the prevalence of FGIDs and of functional constipation (FC) was significantly lower than in the previous study (P< 0.001), whereas in group B no significant difference was found. In both groups of age, the prevalence of abdominal migraine and irritable bowel syndrome decreased significantly (P< 0.001 and P< 0.001, respectively) using Rome IV versus Rome III criteria, conversely functional dyspepsia increased (P< 0.001). FGIDs are common in children and adolescents, their frequency increases with age, and there is a significant variation in the prevalence of some FGIDs among different European countries. The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs in children compared with Rome III criteria.

A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children. H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pyloriprevalence. H pyloriinfection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

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The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori(H. pylori) infected pediatric patients. Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry. Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj] = 3.44, 95% confidence interval [CI] 2.22–5.32, P< 0.001 and 2.62, 95% CI: 1.63–4.22, P< 0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadj= 3.81, 95% CI: 2.25–6.45, P< 0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility. Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.

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). Our study constituted 50 patients with CD at diagnosis before the initiation of a GFD (age 8.6?±?3.7 years, group A), 39 patients with CD on a GFD for at least 12 months (age 10.4?±?3.4 years, group B) and 38 healthy controls (age 7.7?±?3.8 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). At diagnosis, CD patients had higher scores in the CBCL for internalizing problems than healthy controls (55.7?±?10.3 vs 47.9?±?15.4, 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?±?0.49 vs 0.54?±?0.58, P?=?0.013). CD patients at diagnosis and their parents, had more mental health problems, including anxiety and depression, than healthy controls.

The aim of the study was to assess differences in the diagnosis and management of eosinophilic esophagitis (EoE) by European pediatric (PG) and adult gastroenterologists (AG), and their self-reported adherence to guidelines. A multiple-choice questionnaire gauged the diagnostic and management strategies of gastroenterologists treating children or adults in 14 European countries and the United Arab Emirates (UAE). Questionnaires were completed by 465 PG and 743 AG. PG were significantly more likely to take biopsies in patients with symptoms of esophageal dysfunction (86.2% PG vs 75.4% AG, P?

Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ± 33.5 months and age at diagnosis was 8.9 ± 4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. In this “real world” pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

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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. 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. 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). 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.

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Childhood functional gastrointestinal disorders (FGIDs) are common conditions associated with significant morbidity and high healthcare costs. This multicenter study aimed at assessing the clinical approach to infants (0–6 months) and children/adolescents (4–18 years) with suspected FGIDs by pediatricians from the Mediterranean Area. A survey evaluating the diagnostic approach, including the use of Rome II and III criteria, and the therapeutic management of some of the most prevalent FGIDs, such as irritable bowel syndrome (IBS), functional constipation (FC), and functional regurgitation (FR), was distributed to a sample of pediatricians. We collected 278 questionnaires from 9 countries (Croatia, Greece, Israel, Italy, Lebanon, Montenegro, Serbia, Slovenia, and Spain). Rome III criteria are used to diagnose FC by 28.8%. Treatment of FC is based on dietary modifications (97.5%) and osmotic laxatives (93.5%). Rome III criteria are used to diagnose FR by 22.3% of the responders, in contrast to 79.5% who rely on personal experience for diagnosis. Reported treatments mainly consist of reassurance (96.8%) and thickened feedings (77.3%). Nevertheless, 21.2% prescribe proton pump inhibitors or H2-blockers to infants with FR. Rome III criteria are used to diagnose IBS by only 25.9%. Moreover, 86% of the pediatricians base IBS therapy on the predominant symptom. The most prescribed treatments are analgesics (36.6%) for pain control, dietary advice (41.5%) for diarrhea-predominant IBS, and dietary advice (47.8%) for constipation-predominant IBS. Our data show that the use of Rome III diagnostic criteria is not sufficiently widespread among pediatricians, and that large variability remains in the management of FGIDs within the different Mediterranean countries surveyed.

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.

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. 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. 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 ?-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. The abnormality prevalences of aspartate transaminase, alanine transaminase, and ?-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.

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.

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. 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. Patients after 1 year of receiving GFD had higher BMD zscores compared with baseline (-1.45 ± 0.28 vs -0.61 ± 0.25, respectively, P= 0.004). BMD zscores 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 zscore 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 zscore (receiver operating characteristic curve analysis, all of the areas under the curve <0.66). 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.

The increasing number of pediatric patients infected with multiresistant Helicobacter pyloristrains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance. In this open multicentre trial, 62 children (<18 years, body weight >15 kg) infected with an H pyloristrain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin (~75 mg/kg/day), metronidazole (~25 mg/kg/day) and esomeprazole (~1.5 mg/kg/day) for 2 weeks. Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment. Primary outcome was a negative 13C-urea breath test after 6 weeks. Of 62 patients, 5 were lost to follow-up, 12 were nonadherent, and 45 treated per protocol. Eradication rates were 66% (41/62) [confidence interval 54–78] (intention to treat) and 73% (33/45) [confidence interval 60–86] (per protocol). Success of treatment was not related to dose per kilogram body weight. Mild to moderate adverse events were reported by 21 patients, including nausea (10.8%), diarrhoea (8.9%), vomiting (7.1%), abdominal pain (5.4%), and headache (3.6%), and led to discontinuation in 1 child. High-dose amoxicillin, metronidazole, and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pyloristrain.

The increasing number of pediatric patients infected with multiresistant Helicobacter pyloristrains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance.

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.

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. 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. 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. WD in children may be obscure and requires extensive investigation to establish the diagnosis. Genetic analysis is needed in equivocal cases.

Chronic constipation is one of the most common disorders in Western countries and despite numerous clinical, pathophysiologic, and epidemiologic studies its cause is still unclear. Several hypotheses have been proposed and according to experimental studies and clinical observation, fiber intake could play a role in its pathogenesis. The purpose of this case-control study was to examine the possible correlation of idiopathic chronic constipation in children and dietary intake, particularly fiber intake.

Chronic constipation is one of the most common disorders in Western countries and despite numerous clinical, pathophysiologic, and epidemiologic studies its cause is still unclear. Several hypotheses have been proposed and according to experimental studies and clinical observation, fiber intake could play a role in its pathogenesis. The purpose of this case‐control study was to examine the possible correlation of idiopathic chronic constipation in children and dietary intake, particularly fiber intake. A randomized sample of children (291 children with constipation and 1602 controls) aged 2 to 14 years was taken from three of the 52 counties of Greece. Stratification was performed on the basis of urban, rural, or suburban location and socioeconomic status. The nutritional data were obtained from a 3‐day dietary record and a dietary history. Statistical analysis was performed with multivariate tests, multivariate analysis of variance, discriminant analysis, and chi‐square analysis according to the characteristics of the correlated variables. Constipated children had a lower caloric and nutrient intake (p< 0.001), lower body weight/height (p< 0.001), and higher prevalence of reported anorexia (p< 0.001). Discriminant analysis indicated that dietary fiber alone was independently negatively correlated with chronic constipation, despite the age and the age of onset of constipation. Relative risk also had a negative correlation with fiber intake (p< 0.001). Of the main fiber fractions only cellulose and pentose were independently correlated with chronic constipation. Lack of fiber may play an important role in the etiology of chronic idiopathic constipation in children.