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To assess the short- and long-term efficacy of proton pump inhibitor (PPI) therapy for pediatric eosinophilic esophagitis (EoE) in real-world practice with a step-down strategy, and to evaluate factors predictive of PPI responsiveness.We collected data regarding the efficacy of PPIs during this cross-sectional analysis of the prospective nationwide RENESE registry. Children with EoE treated with PPI monotherapy were included. Histological remission was defined as a peak eosinophilic count of15 eosinophils (eos)/high-power field (hpf). Factors associated with PPI responsiveness were identified using multivariate logistic regression analysis.After induction therapy, histological and clinico-histological remission were observed in 51.4% (n=346) and 46.5% of children, respectively. Normal endoscopic appearance of the esophagus was associated with a higher possibility (odds ratio [OR], 9.20; 95% confidence interval [CI], 2.10-40.16), and fibrostenotic phenotype was associated with a lower possibility (OR, 0.36; 95% CI, 0.18-0.74) of histological remission. Long-term therapy with a step-down strategy effectively maintained histological remission in 68.5% and 85.3% of children at 7 months (n=108) and 16 months (n=34), respectively. Complete initial histological remission (≤5 eos/hpf) was associated with a higher possibility of sustained histological remission (OR, 5.08; 95% CI, 1.75-14.68). Adverse events were infrequent and mild.We confirmed the efficacy of PPIs for a large cohort of children with EoE with sustained histological remission using a step-down strategy. Children with fibrostenotic phenotypes are less likely to respond to induction therapy. Furthermore, patients with complete initial histological remission are more likely to experience long-term histological remission.

Based on previous studies that demonstrate an increase in cases of eosinophilic esophagitis among patients undergoing oral food immunotherapy, we aimed to establish the importance of close monitoring of these patients to detect the disease and to determine if medical treatment can be effective without the need to withdraw the food involved in OIT.

OBJECTIVES The rate of eosinophilic esophagitis (EoE) diagnosis is increasing. This study aims to determine the incidence of EoE in the pediatric population residing in the southwestern Madrid and to analyze whether absolute monthly pollen counts, modified or not by the principal atmospheric pollutants, are associated with it. METHODS A cross-sectional study on prospectively recruited patients was designed to calculate the incidence of EoE in children aged under 15 years who were diagnosed between September 2014 and August 2016 in twelve hospitals. We collected demographic and symptoms data, date of onset of symptoms, date of medical consultation, and date of endoscopic diagnosis of each included patient. Relative risk estimation was performed to assess the association between the incidence of diagnosis and monthly pollen counts and levels of atmospheric pollutants. All these models were adjusted for the number of total patients that underwent endoscopy at first time. RESULTS One hundred forty-eight patients were included. The most frequent symptoms were abdominal pain [42.57%], dysphagia [42.57%], and impaction [39%-86%]. The median overall monthly incidence was 1.13 [interquartile rank: 0.97-1.43] cases/100,000 children, and the annual mean was 15.2. The overall analysis of the relationship between incidence and absolute monthly counts, corrected for the number of first-time endoscopies performed, revealed no statistically significant association with pollen and air pollutants. There was a higher frequency of diagnosis during the pollination period of Cupressaceae [relative risk 1.647; 95% CI (1.192-2.276) p

Objectives: Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy. Methods: This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum. Results: We found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein (P

BackgroundDirect comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce.AimTo compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages.MethodsCross-sectional analysis of the EoE CONNECT registry.ResultsThe adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood‐onset cohort (patients diagnosed at ConclusionsChildhood‐onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment.

Diagnostic delay; Endoscopy; Eosinophilic esophagitis Retraso en el diagnóstico; Endoscopia; Esofagitis eosinofílica Retard diagnòstic; Endoscòpia; Esofagitis eosinofílica Background: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. Objective: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. Methods: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. Results: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). Conclusion: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.

Objectives To perform long-term celiac disease (CD) screening in an HLA-DQ2 (+) cohort from the general population and to assess the influence of risk genotypes on its development. Methods In 2004, an HLA-DQ2 (+) cohort was selected. After the first CD screening at age 2 to 3 years, we performed a follow-up screening 8 to 10 years later. Antitransglutaminase 2 antibodies were determined using a rapid test kit. Results were confirmed by serum IgA antitransglutaminase 2 and IgA endomysial antibody determination. CD diagnosis was carried out by intestinal biopsies. Four HLA-DQ2 genotypic groups were used: G1: DQ2.5/DQ2.5 (G1A) or DQ2.5/ DQ2.2 (G1B); G2: DQ2.2/DQ7.5 (DQ2.5 trans); G3: DQ2.5/ X; G4: DQ2.2/X. Results CD prevalence after 10 years of follow-up was 5.8% (95% confidence interval 3.8-8.7). One of every 3 HLA-DQ2(+) children carried at least 1 haplotype DQ2.2 or DQ7. The homozygous genotype DQ2.5/DQ2.5 and the HLA-DQ2.5 trans genotype increased CD risk 4- and 3-fold, respectively. The homozygous genotype DQ2.5/ DQ2.2 did not increase the CD risk. Children carrying G1 or G2 genotypes were diagnosed with CD earlier and more frequently during the follow-up compare with those carrying G3 or G4 genotypes. Approximately 81% of children with spontaneous antibody negativization after the first screening maintained negative antibodies. Conclusions A repeated screening of at-risk children during their follow-up allowed us to diagnose new CD cases. In our cohort, HLA- DQ2.5 trans genotype conferred a higher risk in the development of CD than HLA- DQ2.5/DQ2.2. The majority of children with potential CD and CD autoimmunity at 10 years of age remained healthy.

Vedolizumab is a humanised monoclonal antibody that binds to integrin alpha 4 beta 7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease; however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-alpha) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with UC and 75% of those with UC; p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC; p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively; p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively; p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were uncommon and mild. Three patients (7.1%) presented headaches, 1 presented alopecia, 1 presented anaemia and 1 presented dermatitis. Conclusion: The results show that treatment with vedolizumab is a safe and effective option for achieving clinical remission in paediatric patients with inflammatory bowel disease with primary failure or loss of response to other treatments, especially in UC. What is Known: Vedolizumab is effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. Most studies and clinical trials have been performed on adult populations, and there is currently no indication for paediatric populations. What is New: Children with inflammatory bowel disease refractory to anti-TNF presented higher clinical emission rates than those published for adults. There are few publications of this magnitude on paediatric populations treated with vedolizumab and with long-term follow-up (52 weeks).

Background and objectives: Based on previous studies revealing acid-suppression medication as a risk factor for food allergy tolerance induction, we aimed to establish the importance of those findings in patients undergoing oral immunotherapy (OIT).Materials and methods, results: We describe a case series of four patients who underwent milk OIT with a concomitant use of proton pump inhibitor (PPI) medication and who developed anaphylaxis after a known, previously tolerated dose of milk.Conclusions: PPIs may act as a cofactor in patients undergoing OIT, triggering adverse reac-tions, irrespective of the PPI used or the dosage. It would be necessary to separate the admin-istration of drug from food intake.Since OIT is a new form of treatment, long-term adverse events arising from PPI treatment and other possible triggers are still uncertain. Consequently, monitoring of patient must be prolonged over time. Additional investigations on the influence of different drugs in OIT main-tenance phase are required.

Proton pump inhibitor (PPI)-responsive eosinophilic esophagitis (EoE) is frequently observed in children, but data on long-term treatment are scarce. The objective of this study is to evaluate the long-term efficacy and safety of PPIs in children with EoE.This prospective study enrolled children with EoE and histological remission to an 8-week esomeprazole trial (1 mg/kg/dose, twice daily). Esomeprazole was maintained at 1 mg/kg/day for 1 year. Symptom recurrence and adverse events were monitored and a follow-up endoscopy was performed at 12 months. Complete histological remission was defined as ≤5 eosinophils/high-power field (eos/hpf), and partial histological remission as5 and15 eos/hpf. Patients had no concomitant dietary restrictions or topical steroid.Fifty-seven children were included. Histological remission on maintenance PPI therapy was present in 40 children (70.1%; 95% CI 56.5-81.5). Long-term remission rate was higher in children with initial complete histological remission than in those with partial remission (81% vs 50%, P = 0.014). Forty-nine children (86%) remained asymptomatic. Pretreatment clinical and histological findings and median PPI dose/kg/day were similar between relapsers and nonrelapsers. Eleven out of 12 children (91.6%) receiving esomeprazole 0.5 mg · kg · day for 12 additional months remained in remission. Mild and transient side effects without requiring PPI avoidance were observed in 5 children.Up to 70% of children with PPI-responsive EoE remain in histological and clinical remission on a low-dose maintenance treatment at 1-year follow-up, with adequate safety profile. Complete histological remission to an 8-week PPI trial was associated with higher probability of histological remission on maintenance therapy.

Supplemental Digital Content is available in the text, Objective: Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). Methods: Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. Results: Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C19∗17 (P = 0.35). In children who received a PPI dose between ≥1.54 and ≤2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C19∗17 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C19∗17 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C19∗17 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023). Conclusions: Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.

Eosinophilic esophagitis (EoE) is a chronic, local, immune-mediated disorder characterized by symptoms of esophageal dysfunction and the presence of a dense eosinophilic infiltrate in the esophageal mucosa. Consensus diagnostic recommendations for EoE diagnosis included absence of histological response to a proton-pump inhibitor (PPI) trial, to exclude gastro-oesophageal reflux disease (GERD)-associated esophagitis. This recommendation exposed an entity known as "proton pump inhibitor-responsive esophageal eosinophilia" (PPI-REE), which refers to patients with EoE phenotype who are PPI-responsive and do not present GERD. In recent years, there is evidence which indicates that PPI-REE is a sub-phenotype of EoE with similar clinical, endoscopic, histological and genetic characteristics, as well as Th2-related inflammatory response. As a result, PPIs should be considered another treatment for EoE and not a diagnostic tool. PPI-REE was originally described in a case series which included two children and in two retrospective pediatric series. Later, a prospective pediatric study showed a high rate of response to PPIs at high doses with long-term maintenance at lower doses. PPI monotherapy in children with esophageal eosinophilia (EE) has been observed to reduce eotaxin-3 expression in epithelial cells and to practically reverse the allergy and inflammatory transcriptome. These data reveal that PPIs are also an effective treatment for EoE in pediatric patients, although more studies are necessary in order to define the best induction and maintenance treatment regimen, the long-term safety profile and their influence on the occurrence of fibrosis and esophageal remodeling.

Proton-pump inhibitor-responsive esophageal eosinophilia is a newly recognized entity with an unclear prevalence in children, as only retrospective data are available. The aim of this study was to determine the prevalence and clinical features of proton-pump inhibitor-responsive esophageal eosinophilia in children.This prospective study enrolled patients with esophageal symptoms and esophageal eosinophilic counts as 15 or more than 15 eos/hpf (eosinophils per high-power field). Children received treatment with esomeprazole 1 mg · kg per dose twice daily for 8 weeks and the endoscopy was repeated. Complete response to proton-pump inhibitor (PPI) was defined as 5 or less than 5 eos/hpf, and a partial response as5 and15 eos/hpf in post-treatment biopsies.Fifty-one children (74.5% boys) were included. Histological response was observed in 35 children (68.6%): 24 children (47%) had a complete response and 11 children (21.6%) had a partial response. Only 16 children (31.4%) were diagnosed with eosinophilic esophagitis (EoE). There were no differences in history of atopy, allergy tests, pH study results, and endoscopic scores. Clinical symptoms were similar, with the exception of food impaction, which was more frequent in children with EoE (56.2% vs 20%, P = 0.01). The mean pretreatment peak eosinophil count was higher in patients with EoE (74.8 ± 36.2 vs 46.3 ± 30.7, P = 0.007). Eleven of the 14 patients (78.6%) on a lower PPI treatment maintenance dose remained in clinicopathologic remission at 1-year follow-up.A significant proportion of children with esophageal eosinophilia responded to high dose PPI treatment. Clinical, endoscopic, and pH study results were similar, with exception of patients with EoE, who were more likely to experience food impaction and have higher esophageal eosinophil counts.

OBJECTIVES To assess the prevalence and clinical presentation of celiac disease (CD) in a cohort of children with HLA-DQ2 positive and evaluate the risk factors in the development of CD. METHODS Between July 2004 and July 2005, parents of all healthy full-term newborns in our hospital were invited to participate. HLA-DQ2 was tested in blood sample of the umbilical cord. A point of contact serological test was performed on children between 2 and 3 years of age. Positive results were confirmed by serum anti-transglutaminase 2 and endomysial antibodies. Children with high autoantibody titers underwent an intestinal biopsy. Children of the cohort diagnosed with CD before the screening study were included. Sex, mode of delivery, breast-feeding duration, and age of gluten introduction were studied. RESULTS Of 1291 children, 362 were HLA-DQ2 positive and 262 participated in the study. CD was diagnosed in 4.1% (95% confidence interval (CI) 1.9-6.3). In the whole cohort, 60% had gastrointestinal symptoms, 7% poor weight gain, and 33% were asymptomatic. Five children with potential CD and 6 with CD autoimmunity became negative (42.3%) and are still negative after 5 to 7 years. Female sex was at-risk factor odds ratio 5.7 (95% CI 1.5-20.9), whereas breast-feeding during gluten introduction had a protective effect odds ratio 0.1 (95% CI 0.01-0.8). CONCLUSIONS Prevalence of CD in this cohort was 4%, half of whom had digestive symptoms. Because a high proportion of children showed a spontaneous disappearance of antibodies, prevalence studies of CD in young children should be based on intestinal damage so as not to overestimate results.

The morning glory disc anomaly is a not very frequent congenital alteration of the optic papilla associated with a retinal vascular dysgenesia. Several cases of association have been described between this disc anomaly and the presence of Moyamoya vessels. We report the case of a boy with this association.A 5 year-old boy was evaluated for several episodes of disconnection, some of them preceded by intense headaches and associated to incoherent language, and in other occasions with hypotonia and unmotivated laugh of variable duration. The physical and neurological exploration was normal, except for the optic disc papilla of the right eye that was very big and dug, compatible with Morning glory disc anomaly. No alterations were found at cranial CT and EEG. In the magnetic resonance imaging were visualized multiple small round low intensity areas in the basal ganglia, because of the high number of collateral vessels. The angioRM showed stenosis of the supraclinoid portions of both internal carotids as well as the proximal segments of the anterior cerebral artery and the left middle cerebral artery with abnormal network of collateral vessels at the base of the brain like a puff of smoke . This is a typical imaging for Moyamoya disease.In all patient with Morning glory disc anomaly, mainly if they presents neurological clinical features, the realization of angioRM studies will be evaluated, to discard the existence of Moyamoya disease.