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BACKGROUND: This study aimed to assess the distribution of esophageal inflammation in patients with eosinophilic esophagitis (EoE) and its impact on diagnosis and outcome. AIMS AND METHODS: Data from consecutive adult EoE patients who were followed-up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected. RESULTS: One hundred forty-nine patients were included. Proximal EoE was observed in 8.1 % of patients; distal EoE in 27.5 %; and diffuse EoE in 64.4 %. Allergic rhinitis was more prevalent in distal and diffuse than proximal EoE (72.5 % vs. 61.5 % vs 33.3 %; P = 0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was not significantly different among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were more prevalent in proximal EoE (91.7 % vs. 53.8 % distal [P = 0.01] vs. 66 % diffuse[P = 0.05]). No significant differences in fibrotic features and esophageal stenoses were observed. The clinical and histological remission rates after first-line therapy were comparable in all groups. CONCLUSION: Esophageal inflammation in EoE more frequently involves the entire esophagus, followed by isolated distal and proximal involvement. No clear correlation was observed between the histological extent of EoE at diagnosis and comorbidities or treatment response.

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Objective The impact of Helicobacter pylori infection on gastric endoscopic findings in non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) remains unclear. This study investigated the influence of H. pylori infection on the prevalence and distribution of gastric lesions. Methods The details of 75 patients diagnosed with non-EoE EGIDs were retrospectively reviewed. Of the 56 patients with a definitive diagnosis according to the Japanese criteria (any GI tract; ≥20 eosinophils/high-power field), 25 patients with pathologic gastric eosinophil infiltration (gastric EI; ≥30 eosinophils/high-power field) were investigated in detail. The prevalence and distribution of gastric endoscopy findings were assessed according to the gastric mucosal atrophy status, an indicator of H. pylori infection. Results Erythema (76%) was the most common finding in the gastric EI-positive group, followed by erosions (36%), ulcers (28%), ulcer scars (28%), and edema (24%). None of these lesions differed significantly in frequency between the patients with and without gastric atrophy. When erosions, ulcers, and ulcer scars were unified, they were slightly more common in the gastric bodies of patients with gastric atrophy than those without gastric atrophy; however, no preferential site was found in those without gastric atrophy. We identified six patients with active gastric ulcers, and half had large, deep ulcers with marginal swelling/irregularity. Conclusion Gastric endoscopy findings in non-EoE EGIDs with gastric EI were evenly observed in the stomach, with no specific trend in frequency or distribution depending on atrophic gastritis, an indicator of H. pylori infection. Gastric ulcers in patients with non-EoE EGIDs should be considered in the differential diagnosis of idiopathic peptic ulcers.

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This position paper deals with an expert consensus on diagnosis and management of eosinophilic esophagitis and esophageal food impaction issued by the Austrian Eosinophilic Esophagitis Network, a working group under the patronage of the Austrian Society of Gastroenterology and Hepatology (ÖGGH). In need of a standardized approach on the management of EoE, recommendations were made based on international guidelines and landmark studies.

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Background: Food allergic (FA) conditions have been classified as immunoglobulin E (IgE) and non-IgE-mediated reactions that affect as many as 8% of young children and 2% of adults in Western countries, and their prevalence seems to be rising. Although the immunologic basis of IgE-mediated FA is well established, the mechanisms that govern non-IgE-mediated FA are not well understood and are marked by a paucity of comprehensive insights. Objective: The purpose of the present report is to examine the current classification and epidemiology of non-IgE-mediated FA, the latest immunologic mechanisms that underlie the three most commonly cited non-IgE FA conditions, viz., eosinophilic esophagitis, food protein-induced enterocolitis, and food protein-induced allergic proctocolitis, and explore what allergist/immunologists in practice should be aware of with regard to the condition. Methods: An extensive research was conducted in medical literature data bases by applying terms such as FA, non-IgE allergy, tolerance, unresponsiveness, cytokines, CD4+ T helper cell pathways, and key cytokine pathways involved in FA. Results: Current evidence now supports the view that immune dysregulation and cytokine-induced inflammation are the fundamental bases for both IgE- and non-IgE-mediated FA. The existing non-IgE-related FA literature is mostly characterized by a relative dearth of mechanistic information in contrast to IgE-mediated FA, in which the immunologic underpinnings as a T helper type 2 directed entity are well established. Although the need for future methodologic research and adherence to rigorous scientific protocols is essential, it is also necessary to acknowledge past contributions that have given much to our understanding of the condition. In the present report, a novel signature cytokine-based classification of IgE-mediated and non-IgE-mediated allergy is proposed that may offer a novel template for future research in the field of non-IgE-mediated FA. Conclusion: The present report provides an overview of the current classification and frequency of IgE- and non-IgE-mediated FAs, and offers insights and potential solutions to address lingering questions, particularly when concerning the latest immunologic mechanisms that underlie the pathogenesis of non-IgE-mediated FA. Although some progress has been made in recent years toward making diagnostic and treatment options available for these conditions, there still remain many lingering questions and concerns to be addressed, which can be fully understood by future research.

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Objectives: Dysphagia is a frequent symptom of active eosinophilic esophagitis (EoE), but at times it persists despite attaining histologic healing and lack of fibro-stenotic changes. We aimed to describe the manometric findings in this subset of patients. Methods: A retrospective review of charts between 2013 and 2023 at a tertiary pediatric gastroenterology center, treating roughly 1500 EoE patients per year. We included children with EoE referred to high-resolution impedance manometry (HRIM) for persistent dysphagia despite histologic healing (i.e., <15 eosinophils/high-power field [Eos/hpf]). Data including initial EoE diagnosis, endoscopy reports, esophageal biopsies, treatment regimens, and HRIM were retrospectively collected. Results: The estimated prevalence of post-remission dysphagia in our cohort was exceedingly rare (<0.05%). Four patients met the eligibility criteria of histologic remission and absence of fibro-stenotic features on endoscopic evaluation and thus, were included in this case series. Patients achieved remission with steroids, proton-pump inhibitor, or both within a median time of 5 months from diagnosis. Peak Eosinophil count at remission was ≤5 Eos/hpf in three patients and ≤10 Eos/hpf in one. On HRIM, all four patients had a hypomotile esophagus and abnormal bolus clearance. Lower esophageal sphincter integrated relaxation pressure values were normal in three patients and elevated in one. Two patients were diagnosed with ineffective esophageal motility, one with aperistalsis and one with achalasia type 1. Conclusions: Post-remission dysphagia is rare in EoE. Esophageal dysmotility with a hypomotile pattern may contribute to the persistent dysphagia in children with EoE. HRIM should be considered in patients with EoE in whom symptoms persist despite histologic remission.

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BACKGROUND: Nearly 80% of patients with eosinophilic esophagitis (EoE) have coexisting atopic disease, yet a subset do not. It is unclear if this lack of atopy impacts presentation or response to therapy. OBJECTIVES: To characterize the presentation and response to therapy in atopic versus nonatopic pediatric patients with EoE. METHODS: A case-control study of patients with EoE aged 6 months to 18 years (between 2018 and 2021) was performed. Patients were eligible if they had allergy testing, assessment of atopic history, and at least 1 endoscopy after initiation of treatment. Patients were considered nonatopic if they had negative allergy testing and no history of significant atopy. Response to therapy was classified as complete (peak eosinophils [eos] <15/high power field [hpf]), partial (≥15 eos/hpf but at least a 50% reduction in peak eos), or nonresponse. RESULTS: A total of 168 participants were enrolled. The majority were White (n = 141, 84%), male (n = 124, 74%), and non-Hispanic (n = 158, 95%). The mean age at diagnosis was 9.4 years (standard deviation: ±4.8 years). A total of 123 participants (73.2%) were atopic, and 45 (26.8%) were nonatopic. There was no significant difference between atopic and nonatopic for most demographics or presenting symptoms. Nonatopic participants were younger than atopic participants (8.14 vs 9.8 years, P = .046). Swallowed topical corticosteroids (STC) and food elimination diets (FED) were used at a similar rate. There were no differences in treatment response between atopic/nonatopic participants in regard to STC, FED, or STC+FED. CONCLUSIONS: Atopic status does not significantly impact presentation or response to treatment in pediatric EoE, but a lack of atopy may be a risk for earlier onset of disease.

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Eosinophilic oesophagitis is a long-term complication of oesophageal atresia (EA), an uncommon condition that affects approximately 1 in 3500 infants. An exploratory, open-label phase 2 clinical trial was conducted in paediatric eosinophilic oesophagitis after oesophageal atresia (EoE-EA) to assess the safety, pharmacokinetics, and efficacy of oral viscous budesonide (OVB). In total, eight patients were enrolled in the study and assigned to a twice-daily dosing regimen of either 0.8 or 1 mg OVB, depending on age and height, administered for 12 weeks. OVB was safe and effective in the treatment of EoE-EA. The current investigation focuses on the pharmacokinetics of budesonide and the impact of an oral viscous formulation on its absorption and bioavailability. Using a non-linear mixed effects approach, two distinct absorption profiles were identified, despite marked interindividual variability in drug concentrations. Budesonide exposure was higher than previously reported in children following oral inhalation. Even though no significant effect has been observed on serum cortisol levels, future studies should consider exploring different doses, schedules, and/or treatment durations, as there may be an opportunity to reduce the risk of cortisol suppression.

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Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.

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BACKGROUND: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. OBJECTIVE: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. METHODS: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. RESULTS: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden. CONCLUSION: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity.

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This chapter presents an overview of eosinophilic esophagitis (EoE) for the Primary Care Practitioner (PCP). The focus is on helping PCPs keep it in their differential diagnosis by discussing the spectrum of clinical presentations, how to screen for EoE in at-risk populations and subsequently manage the patient with this condition. The authors review epidemiology, risk factors and associated conditions, pathology, clinical presentation, diagnosis, and management options.

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Gastroesophageal reflux (GER) and eosinophilic esophagitis (EoE) are the most common inflammatory causes of pediatric dysphagia, but several other less prevalent conditions should be considered. These conditions can affect one or several aspects of the swallowing process. In some inflammatory conditions dysphagia may be an early symptom. Esophagoscopy and instrumental swallow studies are often needed to determine the underlying diagnosis and best treatment plan. In some inflammatory conditions dysphagia can portend a worse outcome and need for more aggressive treatment of the underlying condition. Consultations with speech language pathology, gastroenterology, dietetics, allergy/immunology and/or rheumatology are often needed to optimize management.

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Background: Eosinophilic esophagitis (EoE) is a disease that has been subcategorized into two endoscopic phenotypes: inflammatory and fibrostenotic. Moreover, studies have shown a link between EoE and immunoglobulin G4 (IgG4), a subclass of the immunoglobulin G (IgG) antibody. In this study, we aimed to evaluate the relationship between histologic IgG4 expression and endoscopic phenotypes in patients with EoE. Methods: This case-control study included patients diagnosed with EoE (n = 19) and patients with non-obstructive dysphagia without abnormal findings as controls (NOD; n = 12). The EoE group was further divided into three subgroups based on endoscopic phenotype: inflammatory, fibrostenotic, or combined. Retrospective examination of endoscopic findings and pathological slides was performed to analyze IgG4 staining. Results: Histological analysis revealed a significant difference in IgG4 cell count (15.00 vs. 0.58, p = 0.003) and eosinophil cell count (84.67 vs. 0.08, p < 0.001) between the EoE and NOD groups. Symptom manifestation and blood test results were similar across all three endoscopic EoE phenotypes. However, histological analysis revealed a significant difference in IgG4 cell count between the inflammatory, fibrostenotic, and combined phenotypes (4.13 vs. 17.6 vs. 59.7, p = 0.030). Conclusions: IgG4 expression was higher in EoE patients than in those with NOD, the highest being in the combined phenotype subgroup. These findings emphasize the important role of endoscopic and histological examination in diagnosing EoE and the need for further research in this area.

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The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

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Eosinophilic esophagitis (EoE) is an emerging chronic T helper type 2 (Th2)-associated, allergic, and immune-mediated disease, characterized histologically by eosinophil-predominant mucosal inflammation and clinically by esophageal dysfunction. Over the past years, the prevalence of EoE has dramatically increased globally. Until recently, most studies of EoE focused on using human biopsies, which are also used for diagnostic purposes, or esophageal epithelial cell lines, which led to major advances in the understanding of EoE. Despite this, a robust mouse model that mimics human disease is still crucial for both understanding disease pathogenesis and as a preclinical model for testing future therapeutics. Herein, we describe a highly reproducible and robust model of EoE that can be performed using wild-type mice by ear sensitization with oxazolone (OXA) followed by intraesophageal challenges. Experimental EoE elicited by OXA mimics the main histopathological features of human EoE, including intraepithelial eosinophilia, epithelial and lamina propria thickening, basal cell hyperplasia, and fibrosis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of EoE in mice using oxazolone Support Protocol 1: Preparing the mouse esophagus for histological analysis Support Protocol 2: Assessment of epithelial and lamina propria thickness using H&E staining Support Protocol 3: Assessment of eosinophilic infiltration using anti-MBP and basal cell proliferation using anti-Ki-67 staining Support Protocol 4: Flow cytometry of mouse esophageal samples Support Protocol 5: ELISA on protein lysates of esophageal samples.

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BACKGROUND AND AIMS: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. METHODS: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. RESULTS: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CONCLUSIONS: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

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Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

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