BACKGROUND:Scarce data have investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and the possible peculiar phenotype and natural history of such an association.METHODS:Case-control study is based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a combined diagnosis of IBD and EoE were included. The overall prevalence and incidence in 2 periods, 2009 to 2015, and 2016 to 2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups.RESULTS:Eleven patients (age 11.2 ± 2.8 years, Males 91%) with EoE-IBD out of 3090 patients with IBD were identified, resulting in an overall prevalence of 0.35% and an incidence of 0.18% for 2009 to 2015 and 0.45% for 2016 to 2021. Treatment escalation rates for IBD were significantly higher in patients with IBD compared with EoE-IBD at 12- and 24-month follow-up (0% vs 30%, P = .04; and 9% vs 45.5%, P = .03, respectively). Furthermore, patients with IBD were at a significantly higher risk of hospitalization than both EoE-IBD and EoE patients (log rank P < .001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared with EoE ones.CONCLUSIONS:The incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in recent years. Having EoE appears to be associated with a milder IBD disease course, whereas having IBD does not seem to affect the natural history of EoE. More data are needed to better define the phenotype of such association.

The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFNγ) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing–remitting (RR) MS and 27 age- and sex-matched healthy controls. MS patients showed significantly higher MBP-induced IFNγ responses and PLP-induced IL-10 responses compared with healthy controls. Using the Multiple Sclerosis Functional Composite (MSFC), a new multifactorial measure of disability, MS patients showed a significant correlation between the IFNγ response to PLP peptides and MBP peptides, and disability. In contrast, in MS patients, there was no correlation between the MSFC and the response to unrelated control antigens or mitogens. These data show that myelin-specific T lymphocytes secreting the inflammatory cytokine IFNγ correlate with functional impairment in MS, supporting an antigen-specific link between the immune response to myelin and disability in MS.

BACKGROUND:Accurate measurements of mucosal eosinophil concentrations in gastrointestinal tracts of healthy children are necessary to differentiate health and disease states in general, and better define eosinophilic gastrointestinal diseases. STUDY:We retrospectively reviewed gastrointestinal biopsies from children with macroscopically normal endoscopies, who, after a minimal follow-up of one year, were not diagnosed with any organic disease. Peak eosinophil concentrations and distributions were assessed from each segment of the gastrointestinal tract. RESULTS:Three centers (Italy, United Kingdom, and Israel) contributed 202 patients (median age 13 years IQR 9.5-15.5, range 1-18 years). Median (IQR, range) eosinophil concentrations (eos/mm2) were: esophagus 0 (0-0, 0-84), stomach 0 (0-4, 0-84), duodenal bulb 20 (13-30, 7-67), second part of duodenum 20 (13-29, 0-105), terminal ileum 29 (14-51, 0-247), cecum 53 (37-89, 10-232), ascending colon 55 (25-84, 0-236), transverse colon 38 (21-67, 4-181), descending colon 29 (17-59, 0-114), sigmoid colon 25 (13-40, 0-215) and rectum 13 (4-28, 0-152). Significant geographical variance was present, however, no differences in eosinophil concentrations were identified between children with resolving symptoms vs. those with functional diagnoses, nor across age groups. CONCLUSIONS:Standardized eosinophil concentrations from the gastrointestinal tracts of children without organic disease will serve to better define both health and disease states. No differences were found between resolved symptoms vs. functional diagnoses nor between age groups in this pediatric cohort.

ABSTRACT Objectives: Retrospective, observational, single-center, cohort study investigating the safety profile of biological therapy in children with inflammatory bowel disease (IBD). Methods: Retrospective, observational, cohort study of pediatric patients with IBD, receiving infliximab, adalimumab, vedolizumab, or ustekinumab for at least 2 months. Data related to the immediate and delayed adverse events (AEs) were collected, focusing on the reaction type and severity, the time of onset, the outcome and the temporary or definitive therapy discontinuation secondary to the AE. Number of suspected and confirmed coronavirus disease-209 (COVID-19) cases and their outcomes, as well as flu vaccination coverage were collected. Results: One hundred eighty-five children were included (101 [55%] CD, 82 [44%] UC, and 2 [1%] IBDU): 149 received infliximab (IFX) (81%), 88 (48%) adalimumab (ADA), 18 (21%) vedolizumab, and 4 (2%) ustekinumab. The overall AE rates were 49%, 67% of whom likely medication-related. Eleven (6%) patients experienced more than 1 AE, 18 patients (10%) presented an immediate reaction, and 82 (45%) a delayed AE. Among the 90 patients experiencing at least 1 AE, 97% had mild-to-moderate AEs. Only 4 SAEs were reported (4%). Treatment discontinuation because of AE occurred in 25 patients (14%). Four COVID-19 cases were reported, all with a mild course. Conclusions: Our findings confirm a good safety profile of biologics. Infusion reactions to IFX administration remain one of the main issues, significantly linked to its immunogenicity and consequently with an impact on its efficacy and durability.

Eosinophilic esophagitis (EoE) is an immune-mediated condition characterized by symptoms of esophageal dysfunction and an eosinophilic inflammation of the esophagus.1 Swallowed topical steroids represent one of the possible strategies for inducing and maintaining remission in EoE.2 To date, a validated maintenance strategy has yet to be defined, especially in children. The available evidence suggests decreasing the dose after a successful induction therapy.3 No study has reported the efficacy of a continuous progressive dose reduction; thus, it is unknown if all patients need to use the same dosages and for how long.4,5.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder characterized by symptomatic esophageal dysfunction and an eosinophil-predominant inflammation of the esophagus. EoE arises from interaction between genetic and environmental factors. In pediatric patients, clinical manifestations vary depending on age, from a gastroesophageal reflux disease (GERD)-like condition to severe dysphagic symptoms. Upper endoscopy is considered the gold standard for diagnosis and monitoring of EoE; however, significant efforts are underway to identify noninvasive diagnostic tools and biomarkers to avoid repetitive invasive procedures. Therapeutic first-line options currently available for EoE are elimination diets, proton pump inhibitors (PPIs), and steroids. The aim of treatment is to improve clinical symptoms while obtaining mucosal healing and avoiding long-term complications. Dietary treatment options comprise different empiric diets or an exclusively amino acid formula. Despite the efficacy of diets, compliance is often challenging. PPIs and topical steroids represent the main pharmacological options for EoE, and both can induce and maintain remission. Topical steroids have been reported as more effective, but data on long-term safety remain insufficient for both these and PPIs. Endoscopic dilations are currently reserved for severe untreated fibrostenotic disease unresponsive to medical therapies. Several biologic agents are available but not yet approved for EoE.

BACKGROUND:Allergy to cow's milk is the most frequent allergy occurring in infants and young children. The dietary management of these patients consists of the elimination of any cow's milk proteins from the diet, and for formula-fed infants, the substitution of the usual infant formula with an adapted formula that is generally based on extensively hydrolyzed cow's milk proteins. The American Academy of Pediatrics has established specific criteria to confirm the hypoallergenicity of a formula intended for these children.AIM:To assess the hypoallergenicity of a new thickened extensively hydrolyzed casein-based formula (TeHCF) in children with cow's milk allergy (CMA).METHODS:Children diagnosed with CMA through a double-blind placebo-controlled food challenge (DBPCFC) were randomly administered increased doses of a placebo formula or the TeHCF [Allernova, new thickener including fibres (Novalac)] under double-blind conditions and medical surveillance on two separate days. Otherwise, both of these formulas and a cow's milk-based formula were randomly introduced to children who were highly suspected of having CMA on three separate days. Immediate and late reactions occurring after the introduction of any of these formulas were thoroughly recorded by the physician at the hospital and reported by parents to the physician after hospital discharge, respectively. If the children tolerated the TeHCF during the DBPCFC, they were exclusively fed this formula during a 3-mo period where potential allergic symptoms, anthropometric parameters, as secondary outcomes, and adverse events were registered. The Cow's Milk-related Symptoms Score (CoMiSSTM) was assessed and anthropometric parameters were compared to World Health Organization (WHO) reference data.RESULTS:Of the 30 children included in the study, the CMA diagnosis of 29 (mean age: 8.03 ± 7.43 mo) patients was confirmed by a DBPCFC. The children all tolerated the TeHCF during both the challenge and the subsequent 3-mo feeding period, which they all completed. During the latter period, the CoMiSSTM remained at a very low level, never exceeding its baseline value (1.4 ± 2.0), growth parameters were within WHO reference standards and no adverse event related to the TeHCF was reported. Over the first week of this period, the proportion of patients with digestive discomfort significantly decreased from 20.7% (6/29) to 3.4% (1/29), P = 0.025. The proportion of satisfaction with the overall effect of the formula reported by the parents and investigator was high, as was the formula acceptability by the child.CONCLUSION:The new TeHCF meets the hypoallergenicity criteria according to the American Academy of Pediatrics standards, confirming that the tested TeHCF is adapted to the dietary management of children with CMA. Moreover, growth was adequate in the included population.

Background: Topical steroids are effective in eosinophilic esophagitis (EoE), but patients often show different tendencies to relapse. We assessed whether gene expression is associated with a sort of steroid dependency in EoE children. Methods: Biopsy samples were prospectively collected on EoE children responding to topical steroids. Patients treated with viscous budesonide for 24 weeks were subsequently classified as early (6 months) or late (>6 months) relapsing. RNA was isolated from esophageal biopsies at the time of the relapse and analyzed by NGS for transcriptome profiling. Results: Of 40 patients, 22 patients were considered for mRNA expression profile. Thirteen were included in the early-relapse group, and 9 were in the late-relapse. No significant difference was observed in the two groups for clinical, endoscopic or histological features. Using the mRNA expression profile we performed supervised clustering using the 10 top differentially expressed genes between early and late relapsing patients. The heatmap and PCA show a proper segregation among patients. SERPINB12 is the only gene attaining a significant differential expression between the two groups (FDR < 0.05). Conclusions: Different tendencies to relapse in EoE children responding to topical steroids might be related to altered mRNA expressions. SERPINB12 presented a significantly higher expression in the late relapse group and it deserves further investigations. (C) 2019 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

A new prepared oral viscous budesonide (PVB) has been effective in inducing clinical and histological remission in pediatric eosinophilic esophagitis (EoE). To evaluate the efficacy of a 12-week maintenance therapy on clinical, endoscopic, and histological remission using half of the dose used in the induction therapy. We prospectively enrolled pediatric patients with active EoE. After 12 weeks of induction therapy with PVB (< 150 cm: 2 mg/day; ≥ 150 cm: 4 mg/day) patients received a maintenance dose of half of the dose used in the induction therapy (1 mg or 2 mg) for another 12 weeks. A 12-week follow-up was then performed in all patients after the end of therapy. Endoscopy was performed at weeks 0, 12, 24, and 36. Symptoms, endoscopy, and histology scores were also calculated. Serum cortisol was evaluated during the treatment period. We enrolled 20 children (15 males; median age 10 years; range 4–17). After the 12-week induction therapy 18 patients (90%) were in remission, with a significant decrease in the median peak of eosinophil count/HPF as well as a marked reduction in clinical, endoscopic, and histological scores (p < 0.01). At the end of the maintenance therapy (week 24), 17 patients (85%) were still in remission, while there were only 9 at week 36 (45%). No significant changes in cortisol levels were observed during the study period. The 12-week maintenance treatment with the half the dose of PVB was effective in sustaining remission at week 24; however, no reduction in the rate of relapse after suspension of treatment occurred.

Background: Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children. Aims: To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease. Methods: Patients were classified by age groups (A-C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages. Results: The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy. Conclusions: We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy. (c) 2018 Editrice Gastroenterologica Italiana S.r. l. Published by Elsevier Ltd. All rights reserved.

Background and aims: Enteral nutrition (EN) is an important aid for children with severe neurological impairment. This study aims to evaluate the effect of EN by gastrostomy tube on anthropometric parameters and quality of life (QoL). Moreover we evaluated, during EN, the efficacy of vitamin D3 supplementation on bone mineral density (BMD).

Objectives: Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single-centre, open-label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE.Methods: We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post-treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks.Results: At the end of PVB trial, endoscopy showed Macroscopic remission in 32 patients (88.9%), whereas at histology median pre- and post-treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15-100) to 2.9 (range: 0-30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance pH were treated also with proton pump inhibitors. No significant difference between pre-/post-treatment morning cortisol levels occurred.Conclusions: The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo controlled clinical trials would provide more information about dosing, efficacy, and long-term safety of this formulation, specifically designed for the oesophagus.

Background:Patients (pts) with eosinophilic esophagitis (EoE), a chronic immune‐mediated disorder, may exhibit symptoms of disturbed food transit (i.e. dysphagia, impaction) or mimicking gastro‐oesophageal reflux (GOR). We aimed at characterizing in EoE pts the intra‐esophageal pH pattern with 24‐h multichannel intraluminal impedance (MII‐pH) as well as the esophageal motility with high‐resolution manometry (EHRM)Methods:during a 30 month period we studied 57 patients (pts), median age 11 years (range: 7–16): 25 with EoE, diagnosed according to widely agreed criteria (JPGN 2014;58:107–18; ESPGHAN guidelines) and 32 with GOR disease (GORD). All underwent esophagogastro‐duodenoscopy, MII‐pH and EHRM. The pH‐MII and data analysis were done according to ESPGHAN EURO‐PIG protocol (JPGN 2012;55:230–4); variables analysed: reflux index, symptom index, number and type of liquid reflux, number of long lasting reflux episodes, correlation symptom‐reflux. The test was diagnostic of GORD if at least ≥ 2 of the previous variables were positive. The EHRM was performed with water perfused catheters and swallow contractile patterns categorized using criteria recently reported by a paediatric group (Am J Gastroenterol 2010;105:460–7). Several motility variables were analysed: esophago‐gastric junction (EGJ) morphology, end‐expiratory and end‐inspiratory EGJ pressure, distal contractile integral (DCI), pressurization front velocity (cm/s), peristaltic propagation pattern.Results:An abnormal MII‐pH profile was markedly more common in GORD pts (27; 84.37%) than in EoE pts (4; 16%; p < 0.001). On the contrary, EHRM irregularities were detected more commonly in EoE that the GORD pts: in particular, when motility tracing were analysed no significant difference for EGJ pressure and deglutitive EGJ relaxation was detected between the 2 groups; however, abnormalities such as peristaltic dysfunction (i.e. failed peristalsis, aperistalsis, and esophageal spasm features) and lower distal contractile integral adjusted for esophageal body length (DCIa) were more common in EoE (17; 68%) than in GORD pts (15; 46.8%) (p < 0.05)Conclusions:1) The great majority of EoE pts have a normal MII‐pH profile that doesn’t support the use of proton pump inhibitory therapy. 2) EoE pts exhibit higher prevalence of oesophageal motility abnormalities than GORD: this feature is likely sustained by the inflammatory infiltrate that characterizes the esophageal wall in EoE and accounts for the esophageal dysmotility complaints often detected in EoE pts.

Background: Oral Viscous Budesonide (OVB) is a recent therapeutic option for Eosinophilic Esophagitis (EoE) versus dietary restriction and inhaled steroids.

BACKGROUND:Lymphoid nodular hyperplasia (LNH) of the lower gastrointestinal tract is a common finding during paediatric colonoscopies, and its clinical significance has not yet been clearly established.OBJECTIVE:The purpose of this prospective, parallel multi-arm, randomized clinical trial was to study relationship between food allergy and LNH.METHODS:We recruited 268 children who had undergone a diagnostic colonoscopy between 1 January 2009 and 30 September 2011. The inclusion criteria were the following: (i) demonstration of LNH; (ii) no concomitant inflammatory or immune disease; (iii) no treatment since the clinical onset. The patients were assigned 1:1:1 to elimination diet (Group A), mesalamine (Group B) or symptomatic treatment with antispasmodics or antidiarrhoeal drugs (Group C) for an 8-wk period. Patients were followed for 24 months.RESULTS:We enrolled 72 of 97 children with intestinal LNH who were referred for haematochezia (76%), recurrent abdominal pain (68%) and/or chronic diarrhoea (32%). Clinical improvement was observed in 75%, 83% and 79% of the patients in Groups A, B and C, respectively. The difference in the response to treatment among the groups and the association to the clinical, endoscopic and allergic features of the patients were not statistically significant.CONCLUSIONS:Intestinal LNH should be considered a benign finding in children without red flags, because the symptoms are largely self-limiting. The use of mesalamine or elimination diet does not modify the clinical outcome compared to symptomatic therapy. The presence of food allergy was not predicted by allergy skin testing and was found in a minority of patients.