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Patients with non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) are prone to nutritional deficiencies due to food-avoidant behaviors, malabsorption, and high nutrition impact symptoms. Nutrient deficiencies correspond to the segment, depth, and extent of the gastrointestinal tract involved and can impact organs distant from the gut. Patients with non-EoE EGIDs are often atopic, and some appear to respond to dietary avoidance of specific food allergens. Tests to identify food triggers other than response to elimination diets are lacking. Dietary restriction therapy should be considered in such patients and is best implemented through a multidisciplinary approach to avoid nutritional complications., Competing Interests: Disclosure M. Chehade is currently serving or has served as consultant for Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Nexstone Immunology, Allakos, Shire/Takeda, and Phathom, and is currently receiving or has received research funding from Regeneron, United States, Allakos, Shire/Takeda, AstraZeneca, United Kingdom, Adare/Ellodi, Bristol-Myers Squibb, United States, Danone, v. B. Doerfler has served on speakers bureaus for Nutricia North America, on advisory boards for Trellus Health LLC, and received honoraria from PRIMED CME and ACHL Healthcare. D. Atkins has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Background: Endoscopic confocal laser endomicroscopy (eCLE) is an established technique that allows clinical evaluation of mucosal integrity by fluorescein leaking through the mucosa upon duodenal food challenge (DFC). Analysis of eCLE with DFC in eosinophilic esophagitis (EoE) would be interesting to evaluate epithelial barrier dysfunction also in other regions of the gastrointestinal tract and to characterize potential individual food allergens that trigger the esophageal inflammation., Methods: In an observational and proof of concept study we evaluated 9 patients with histologically proven EoE by eCLE and DFC. Severity of symptoms were graduated according to the validated symptom-based EoE activity index. The endoscopic appearance of the esophagus was described according to the Endoscopic Reference Score System (ERERS). Spontaneous and food induced transfer of fluorescein into duodenal lumen were detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. Food allergens were yeast, egg, soy, milk, and wheat, respectively. Local application of sodium chloride solution 10 % to the duodenal mucosa before DFC served as a control. Patients responding to DFC received a dietary exclusion therapy according to the results of DFC., Results: We investigated 9 patients with EoE (8 men, 49.7±13.8, 36-76 years). Symptom-based EoE activity index was 79±27.4, 33-100. In all patients EoE was confirmed by histology with number of esophageal mucosal eosinophilic granulocytes > 15/HPF, (91.4±77.4, 42-263). Mean ERERS score was 4.5±1.3, 3-7. None of the patients was aware of any food intolerance. eCLE revealed one patient with spontaneous transfer of i. v. fluorescein into duodenal lumen before DFC ("leaky gut"). 40 DFC were performed in the remaining 8 patients of whom 5 patients (61 %) responded to DFC. Rank order of fluorescein leakage upon DFC was wheat and milk in 37.5 % each, soy in 25 %, and egg in 12.5 %. The patients were treated by PPI (n=9), esophageal bouginage (n=5) and/or local corticoid therapy (n=3). The 5 patients responding to DFC received an additional food exclusion dietary advice focussed on the results of DFC. All patients reported a reduction of their symptoms. EoE activity indexes of patients with positive DFC were 73.7+28.6, 33-100 before and 22.7+37.9, 0-79 four weeks after food exclusion., Conclusion: The findings of our proof of concept study suggest that eCLE with DFC may be an interesting tool to further evaluate patients with EoE. This technique has the potential to identify patients who may benefit from an additional individual dietary therapy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood, and chronic EoE-directed therapy is therefore required to prevent long-term sequelae., Objective: We investigated whether EoE patients in histologic remission have persistent dysregulation of esophageal gene expression., Methods: Esophageal biopsy samples from 51 pediatric and 52 adult subjects with EoE in histopathologic remission (<15 eosinophils per high-power field [eos/hpf]) and control (48 pediatric and 167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE diagnostic panel, which comprises a set of 94 esophageal transcripts differentially expressed in active EoE., Results: Defining remission as <15 eos/hpf, we identified 51 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (false discovery rate < 0.05). Using the stringent definition of remission (0 eos/hpf), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (false discovery rate < 0.05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the endoscopic reference system score (Spearman r = 0.35, P = .011), specifically correlating with the rings' endoscopic reference system subscore (r = 0.53, P = .004)., Conclusion: We have identified persistent EoE-associated esophageal gene expression in patients with disease in deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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 VIP s 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.

Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10 -8 ) and 27 additional loci of suggestive significance (5 × 10 -8  < p < 1 × 10 -5 ). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal. To systematically interrogate the gene regulatory activity of these variants, we designed a massively parallel reporter assay (MPRA) containing the alleles of each variant within their genomic sequence context cloned into a GFP reporter library. Analysis of reporter gene expression in TE-7, HaCaT, and Jurkat cells revealed cell-type-specific gene regulation. We identify 32 allelic enhancer variants, representing 6 genome-wide significant EoE loci and 7 suggestive EoE loci, that regulate reporter gene expression in a genotype-dependent manner in at least one cellular context. By annotating these variants with expression quantitative trait loci (eQTL) and chromatin looping data in related tissues and cell types, we identify putative target genes affected by genetic variation in individuals with EoE. Transcription factor enrichment analyses reveal possible roles for cell-type-specific regulators, including GATA3. Our approach reduces the large set of EoE-associated variants to a set of 32 with allelic regulatory activity, providing functional insights into the effects of genetic variation in this disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Eosinophilic colitis (EC) is the rarest among primary eosinophilic gastrointestinal disorders (EGID). EC is underdiagnosed due to its blurred and proteiform clinical manifestations. To explore the clinical and atopic characteristic of EC adult patients, the diagnostic delay, and relapse-associated factors, by comparison with patients with eosinophilic esophagitis (EoE) and irritable bowel syndrome (IBS). EC patients followed-up at four clinics were included, and clinical, histopathological, and laboratory data were retrieved. As control groups, age-matched patients with EoE and IBS were recruited. Allergy tests included skin prick test and serum specific IgE. Diagnostic delay was assessed. Overall, data from 73 patients were retrieved, including 40 with EC (median age 39 years IQR 22.5-59, F:M 2.1:1), 12 with EoE (F:M ratio: 1:5), and 21 with IBS (F:M ratio: 1:0.9). The most common features in EC patients were female sex (67.5%), atopy (77.5%), abdominal pain/distention (70%), diarrhoea (77.5%), and faecal calprotectin elevation (22.5%). Blood eosinophils were elevated in EoE, but not in EC (p < 0.001), while ECP did not differ across the three groups (p = 0.4). The frequency of allergen sensitization reached 25% of patients. Several frequent pan-allergens for this region were present. The overall diagnostic delay was 10 months (IQR 4-15). Factors contributing to a greater diagnostic delay were atopy, weight loss, and a previous misdiagnosis. EC is mostly a diagnosis of exclusion, burdened by a substantial diagnostic delay. In female patients the presence of allergen sensitization, abdominal symptoms and faecal calprotectin elevation should raise the suspicion of EC., (© 2024. The Author(s).)

Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs., Competing Interests: Disclosure statement Supported by the National Institutes of Health (grant K99/R00 AI158660 [to T.S.] and grants R01 AI045898, R01 AI124355, and U19 AI070235 [to M.E.R.]); the Digestive Health Center (Pilot and Feasibility Program; grant P30 DK078392 [to T.S.]); Cincinnati Children's Trustee Award (to T.S.); the Campaign Urging Research for Eosinophilic Disease (CURED) (to M.E.R.); the Sunshine Charitable Foundation and its supporters Denise A. Bunning and David G. Bunning (to M.E.R.); and CEGIR (U54 AI117804 to M.E.R.), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, NCATS. CEGIR is also supported by patient advocacy groups including the Campaign Urging Research for Eosinophilic Diseases (CURED), American Partnership for Eosinophilic Disorders (APFED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by the National Center for Advancing Translational Sciences (NCATS) and the National Institute of Neurological Disorders and Stroke (NINDS). Disclosure of potential conflict of interest: M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Celldex, Uniquitybio, Santa Ana Bio, EnZen Therapeutics, Bristol Myers Squibb, AstraZeneca, Pfizer, GlaxoSmith Kline, Regeneron/Sanofi, and Guidepoint and has an equity interest in the first 8 listed plus Allakos and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate. In addition, T. Shoda and M. E. Rothenberg are inventors of patents owned by Cincinnati Children’s Hospital. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Purpose of Review: This review seeks to understand novel avenues for eosinophilic GI disease management. Biomarkers offer a unique and non-invasive approach to tracking EoE disease progression. While no biomarkers have definitively met the diagnostic criteria for eosinophilic GI diseases, some biomarkers have been shown to be associated with disease activity. Here, we examine the potential of recently studied biomarkers., Recent Findings: Current research shows advancements in blood, luminal fluid, and breath testing. Particular areas of interest include mRNA analyses, protein fingerprinting, amplicon sequence variants (ASVs), T cells and IgE receptors, eosinophilic cationic proteins, cytokines, and nitric oxide exhalation. Preliminary results showed that mucosal biomarkers, directly captured from the esophagus, may reflect the best representation of biopsy-based results, in contrast to biomarkers obtained from indirect or peripheral (blood, breath) methods. However, this is based on limited clinical studies without sufficient numbers to evaluate true diagnostic accuracy. Large-scale randomized trials are needed to fully ascertain both the optimal sampling technique and the specific biomarkers that reflect diagnostic status of the disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The diagnosis of eosinophilic esophagitis (EoE) is based on clinical symptoms of esophageal dysfunction and eosinophil predominant esophageal inflammation. Clinical symptoms in children with EoE vary based on age and may be nonspecific. EoE has a male predominance with the majority having comorbid atopic disorders. At present, treatment options include medications (proton pump inhibition, swallowed topical steroids), dietary therapy or biologic therapy (dupilumab, approved for those ≥12 years of age). Outside of EoE in the context of oral immunotherapy, EoE is typically chronic requiring lifelong therapy. Long-term complications including feeding difficulties, malnutrition, and fibrostenotic disease., Competing Interests: Disclosure M. Bauer, has served as a consult for Sanofi. N. Nguyen, has served as a consultant for Regeneron/Sanofi and is on the advisory board for EvoEndo. C.A. Liacouras, has served a speaker and consultant for Abbott; a speaker for Regeneron and a speaker for Sanofi., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Adult patients with eosinophilic esophagitis (EoE) typically present with a history of dysphagia for solids, sometimes with additional reflux-like pain and a history of prior food impactions. In contrast to these alarming symptoms, the general appearance and physical examination of adult patients with EoE is in line with apparently healthy individuals. Therefore, the diagnosis is based on a history of solid-food dysphagia and eosinophilic tissue infiltration. Importantly, the increasing prevalence of EoE variants, that is, typical EoE symptoms in the absence of a relevant eosinophilia, and several studies with eosinophil-targeting drugs, call the pathogenic role of eosinophils into question., Competing Interests: Disclosure L. Biedermann has consulting contracts with Abbvie, BMS, MSD, Vifor, Falk, Esocap, Calypso, Ferring, Pfizer, Takeda, Janssen, Sanofi. A. Straumann has consulting contracts with Astra-Zeneca, BMS, Calypso, EsoCap, Falk Pharma, GSK and Sanofi., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The clinical presentation of eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis (non-EoE EGIDs) varies depending on the gastrointestinal segments affected by the eosinophilic inflammation, the extent of eosinophilic inflammation within the gastrointestinal tract and its depth through the bowel wall. Non-EoE EGIDs with mucosal involvement tend to present with diarrhea, malabsorption, and sometimes bleeding, those with muscular involvement may present with symptoms of obstruction or pseudo-obstruction, intussusception, and even perforation, whereas those with serosal involvement may present with eosinophilic ascites. Here we describe the differences in symptoms experienced by children with non-EoE EGIDs with varying degrees of eosinophilic inflammation through the bowel wall., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets., Competing Interests: Disclosure E.S. Dellon: Research funding: Adare/Ellodi, Allakos, ARENA, United States/Pfizer, AstraZeneca, United Kingdom, Eupraxia, Canada, GSK, Meritage, Miraca, Nutricia, United States, Celgene, United States/Receptos/BMS, Regeneron, United States, Revolo, Shire/Takeda. Consultant: Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio; Educational grant: Allakos, Aqilion, Holoclara, Invea. S.K. Gupta: Research funding: Adare/Ellodi, Allakos, Regeneron, Shire/Takeda. Consultant: Adare/Ellodi, Allakos, Celgene/Receptos/BMS, PeerViewRegeneron, Shire/Takeda., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Eosinophilic gastrointestinal diseases (EGIDs) including eosinophilic esophagitis (EoE) are rare diseases in which eosinophils abnormally infiltrate the gastrointestinal tract. Because these are rare diseases, there is limited information regarding race and ethnicity in EGIDs and even less is known about the impact of socioeconomic factors. There is some evidence that access to care in rural settings may be affecting epidemiologic understanding of EGIDs in the pediatric populations. Future work should try to evaluate bias in research and strive for representation in clinical trials and medicine., Competing Interests: Disclosures A.B. Muir serves on medical advisory board for Nexstone immunology, Bristol Meyers Squibb, Regeneron/Sanofi; Receives research support from Allakos and Morphic., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microscopic examination of esophageal biopsies is essential to diagnose eosinophilic esophagitis (EoE). Eosinophil inflammation is the basis for the diagnosis, but additional abnormalities may contribute to persistent symptoms and epithelial barrier dysfunction. Both peak eosinophil count and assessments of additional features should be included in pre-therapy and post-therapy pathology reports. Pathologic abnormalities identified in esophageal biopsies of EoE are reversible in contrast to esophageal strictures., Competing Interests: Disclosures M.H. Collins is a consultant for Allakos, Arena/Pfizer, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc./Alimentiv, Inc. and Shire, a Takeda company. M. Pletneva is a consultant for Allakos. N.C. Arva, A. Bernieh, O. Lopez-Nunez and G.-Y. Yang do not have conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Vitamin D deficiency is associated with atopic and immune-mediated diseases but has not been extensively assessed in eosinophilic esophagitis (EoE). We aimed to assess if vitamin D levels in newly diagnosed EoE patients were lower than in non-EoE controls and examine levels in relation to EoE clinical features., Methods: This secondary analysis of a prospective cohort study used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained and stored at -80 o C. Serum 25-hydroxy-vitamin D 3 (25(OH)D 3 ) was measured by ELISA. Levels for cases and controls were compared at baseline. Within cases, 25(OH)D 3 levels were compared for clinical, endoscopic, and histologic measures., Results: We analyzed 40 EoE and 40 non-EoE controls. Mean serum 25(OH)D 3 level was slightly lower in EoE patients than controls (30.9 ± 15.3 ng/mL vs. 35.9 ± 15.4; p = 0.15). After controlling for age, sex, and race, adjusted levels were 10.8 ng/mL lower in EoE patients (95% CI: -19.0, -2.5), but 25(OH)D 3 deficiency (< 20ng/mL) was similar in cases and controls (20% vs. 15%; p = 0.56). Levels of 25(OH)D 3 were not associated with differences in clinical or endoscopic features of EoE, and EREFS and eosinophil counts did not significantly correlate with 25(OH)D 3 levels (R of -0.28 [p = 0.08] and - 0.01 [p = 0.93], respectively). 25(OH)D 3 levels were lower in EoE cases with lamina propria fibrosis (23.2 ± 9.6 vs. 45.0 ± 17.7; p = 0.03)., Conclusions: After adjusting for age, sex, and race, 25(OH)D 3 levels were lower in EoE cases than controls, but deficiency was not common. 25(OH)D 3 levels were generally similar across most EoE disease features., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue., Methods: The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177., Results: The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70)., Discussion: Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers., Conclusion: Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background and Aims: The evaluation provided by functional lumen imaging probe (FLIP) panometry includes esophageal distensibility/compliance (mechanics) of the esophageal body and esophagogastric junction (EGJ) and esophageal motility (secondary peristalsis). We developed a composite score using these parameters to characterize physiomechanical function in patients with eosinophilic esophagitis (EoE)., Methods: Two hundred fifteen adult patients with EoE who completed FLIP panometry during sedated endoscopy with esophageal biopsy sampling were included. FLIP metrics of esophageal body Compliance, Contractile response, Distensibility plateau, and maximum EGJ Diameter (C2D2) were scored as 0 for normal versus 1 or 2 for increasing degree of abnormality. Scores were summed to calculate the composite C2D2 score., Results: The C2D2 score had a significant positive correlation with mucosal eosinophil count (ρ = .241) and total Endoscopic EoE Reference Score (ρ = .467). Among 46 patients off treatment at the baseline evaluation, future proton pump inhibitor (PPI) responders (ie, achieved mucosal eosinophil count <15 per high-powered field after PPI treatment) had lower C2D2 scores than PPI nonresponders (median, 2 [interquartile range, 1-3] vs 4 [interquartile range, 2-6], respectively; P = .003). A regression model (that controlled for age, sex, and baseline eosinophil count) showed a C2D2 score ≤3 had an odds ratio of 14.5 (95% confidence interval, 2.6-85) to predict future PPI response. However, total Endoscopic EoE Reference Scores (P = .142) and baseline eosinophil count (P = .480) did not differ between PPI responders and PPI nonresponders., Conclusions: This composite score of FLIP panometry metrics, the C2D2 score, may facilitate characterizing physiomechanical function in EoE and serve as an objective outcome measure., Competing Interests: Disclosure The following authors disclosed financial relationships: D. A. Carlson: Consultant for Medtronic, Phathom Pharmaceuticals, Braintree, and Medpace; speaker for Medtronic; licensing agreement with Medtronic. I. Hirano: Consultant for Adare/Ellodi, Allakos, AstraZeneca, Celgene/Receptos/Bristol Meyers Squibb, Sanofi/Regeneron, Shire/Takeda, Amgen, Arena, Eli Lilly, EsoCap, Gossamer Bio, and Parexel/Calyx; research support from Adare/Ellodi, Allakos, AstraZeneca, Celgene/Receptos/Bristol Meyers Squibb, Sanofi/Regeneron, Shire/Takeda, and Arena; speaker for Sanofi/Regeneron and Shire/Takeda. N. Gonsalves: Consultant for Allakos, AstraZeneca, Abbvie, Sanofi-Regeneron, Nutricia, Knopp Pharma, and BMS; speaker for Takeda and Sanofi-Regeneron. P. J. Kahrilas: Consultant for Reckitt and Ironwood; licensing agreement with Medtronic. J. E. Pandolfino: Consultant for Sandhill Scientific/Diversatek, Medtronic, Torax/Ethicon, EndoGastric Solutions, Ironwood, and Phathom Pharmaceuticals; speaker for Sandhill Scientific/Diversatek, Takeda, AstraZeneca, Medtronic, Torax/Ethicon, and EndoGastric Solutions; research support from Sandhill Scientific/Diversatek; licensing agreement with Medtronic. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Recurrent upper endoscopies are essential for monitoring therapy response and disease activity in patients with eosinophilic esophagitis (EoE), leading to increased costs, procedural complications, and anesthesia exposure. The aim of this study was to examine an office-based model using serial sedation-free blind esophageal epithelial brushing (BEEB) to monitor therapy response through eosinophil-derived neurotoxin (EDN) levels and guide therapy plans in pediatric EoE patients., Methods: EoE patients (≤21 years of age) were enrolled in this prospective study. Subjects were placed on dietary, pharmacologic, or combination therapy with the goal of inducing or maintaining remission. To assess response to sequential interventions, subjects underwent sequential sedation-free BEEBs through nasogastric tubes to measure EDN levels. Based on serial brushings, an individual plan of diet, medications, or a combination of both was created for each subject, and a final endoscopy was then performed to validate the accuracy of the individual plans., Results: Twenty-four subjects completed the study. The average peak eosinophil count in patients with active EoE was 58.1 ± 30.8 eosinophils per high-power field and mean EDN level was 165.2 ± 191.3 μg/mL. A total of 42 BEEBs were completed. Individual therapy plans based on sequential BEEB were accurate in 19 out of the 24 patients (79%) and specifically nine out of 10 patients (90%) treated with elimination diets., Conclusion: This study suggests that office-based sedation-free BEEBs can be used to monitor therapy response and disease activity in pediatric EoE patients., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Goals: We aimed to examine the response rate to proton pump inhibitors (PPIs) and potassium-competitive acid blockers and the prevalence of topical corticosteroid (TCS) therapy as the second-line treatment for eosinophilic esophagitis (EoE)., Background: Acid-suppressive drugs such as PPIs and potassium-competitive acid blockers are often used to treat EoE. Treatment response is based on outcomes including symptoms, endoscopy, and histology; however, the detailed response rate to PPI/P-CAB is unknown., Study: In total, 236 patients with histologically confirmed EoE who received PPI/P-CAB as the first-line treatment were included. We assessed the symptoms, endoscopic reference score (EREFS), and histology [eosinophils per high-power field (eos/hpf)] 8 weeks after PPI/P-CAB administration. Complete normalization was defined as the disappearance of symptoms, EREFS score 0, or 0-1 eos/hpf, and response as disappearance or improvement of symptoms, EREFS score ≤2, or <15 eos/hpf. The prevalence of TCS therapy in each response group was assessed., Results: Complete normalization was achieved in 25%, 50%, 36%, and 8% of patients for symptoms, endoscopy, histology, and all 3 outcomes, respectively. The response rates were 81%, 87%, 87%, 75%, and 60% for symptoms, endoscopy, histology, and all 3 outcomes, respectively. TCS use was significantly lower (8%) in patients who achieved response of all 3 outcomes than in other groups and was dependent on the number of outcomes with nonresponse., Conclusions: Complete normalization of symptoms, endoscopy, and histology using PPI/P-CAB is uncommon. Based on treatment efficacy by response/nonresponse, TCS was the secondary treatment in cases with an increase in the number of nonresponse outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: The Index of Severity for Eosinophilic Esophagitis (I-SEE) was recently developed. We aimed to understand I-SEE scores in a longitudinal pediatric cohort and to determine the relationship between I-SEE and clinical features in children., Methods: We performed a retrospective analysis on a prospectively enrolled cohort of children at a single center who were treated as part of routine clinical care. I-SEE was calculated at the diagnostic and follow-up endoscopies over a mean of 6.6 years. Scoring was 0 for inactive, 1-6 for mild, 7-14 for moderate, and ≥15 for severe eosinophilic esophagitis (EoE). We analyzed clinical, endoscopic, and histologic features at each instance. Symptoms were analyzed at the baseline, first follow-up, and last endoscopic instance., Results: Of 67 children who met study criteria of at least 3 endoscopies over at least 2 years of follow-up time, 43%, 36%, and 21% had mild, moderate, and severe I-SEE scores at baseline, respectively. Between the first and second endoscopic instances, there was a decrease in the group mean I-SEE from 9.7 ± 7.2 to 6.1 ± 5.9 (P < .001). By the last instance, the overall I-SEE score dropped to 3.9 (P < .001). Body mass index <5% and poor feeding were more common in the children with severe I-SEE scores at baseline, and both improved by the last instance. Fibrosis was improved by the last instance biopsy (P < .01)., Conclusions: I-SEE is a responsive severity metric in children treated long term during routine clinical care. Baseline low body mass index and poor feeding were more common in children with severe I-SEE scores., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE., Methods: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE)., Results: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE., Conclusion: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 ( STAT6 ), CYP2C19 , CYP3A4 , CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.

Background: To assess the efficacy of applying the endoscopic reference score for EoE (EREFS) in children with symptoms of esophageal dysfunction naïve to proton pump inhibitor (PPI) therapy., Methods: An observational cross-sectional study was conducted by reviewing reports and photographs of upper gastrointestinal endoscopies (UGE) and esophageal biopsies of patients with symptoms of esophageal dysfunction. Patients who were treated with PPI or had other conditions that may cause esophageal eosinophilia were excluded., Results: Of the 2,036 patients evaluated, endoscopic findings of EoE were identified in 248 (12.2%) and more than one abnormality was observed in 167 (8.2%). Among all patients, 154 (7.6%) presented esophageal eosinophilia (≥15 eosinophils per high power field) (P<0.01). In this group, 30 patients (19.5%) had normal endoscopy. In patients with EoE, edema (74% vs 6.5%, P<0.01) and furrows (66.2% vs 2.4%, P<0.01) were more prevalent than in the control group. Association of edema and furrows was more frequent in patients with EoE than in the control group (29.2% vs 1.6%, P<0.01, OR=24.7, CI=15.0-40.5). The presence of more than one endoscopic finding had sensitivity of 80.5%, specificity of 93.4%, positive predictive value (PPV) of 50%, negative predictive value (NPV) of 98.3%, and accuracy of 92.4%., Conclusion: In conclusion, this study showed that endoscopic features suggestive of EoE had high specificity and NPV for diagnosing EoE in children naïve to PPI therapy. These findings highlight the importance of the EREFS in contributing to early identification of inflammatory and fibrostenosing characteristics of EoE, making it possible to identify and to avoid progression of the disease., Background: • The EoE endoscopic reference score (EREFS) was developed and validated in adults and has been demonstrated to be an adequate tool for diagnosing and assessing treatment response in children., Background: • The presence of more than one endoscopic finding stronglysuggests EoE., Background: • The EoE endoscopic reference score presents high specificity and negative predictive value for diagnosing EoE in children naïve to proton pump inhibitor (PPI) therapy., Background: • Endoscopic findings suggestive of EoE in patients naïve to treatment may be useful to characterize disease phenotype and individualize treatment according to the initial clinical presentation.

Background: Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood., Objective: We sought to gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE., Methods: Bulk RNA sequencing was performed on esophageal biopsy specimens from adult patients with EoE (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsy specimens from control subjects without EoE (n = 5) were also included., Results: At baseline, the transcriptome of the patients with EoE showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its costimulatory effect on T cells, was the most dysregulated early EoE gene, showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by costimulating esophageal epithelial cells with the EoE-relevant cytokines IL-13 and TNF-α., Conclusions: Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE and suggest that TNFSF18 may be an important effector molecule in this response., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Goals: To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE)., Background: PPI leads to histologic remission in ~50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in ~50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear., Study: This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable)., Results: One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037)., Conclusions: Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The incidence of eosinophilic esophagitis (EoE) is 3-5 times greater in patients with inflammatory bowel disease (IBD) compared with the general population. This study aimed to differentiate true EoE from esophageal eosinophilia in IBD patients by evaluating expression of major basic protein (MBP) and interleukin-13 (IL-13) in esophageal biopsies., Methods: This retrospective study included subjects who had an esophagogastroduodenoscopy with esophageal biopsies for IBD work up or suspicion for EoE. Patients were classified into 5 groups: EoE with ≥15 eosinophils per high power field (eos/hpf), EoE-IBD with ≥15 eos/hpf, IBD eosinophilia with 1-14 eos/hpf, IBD and control groups. Biopsies were stained with MBP and IL-13 antibodies and the results (% staining/total tissue area), demographic, and clinical findings were compared among the groups., Results: The median for MBP staining levels in EoE-IBD was 3.8 (interquartile range 1.3-23), significantly lower than in EoE at 52.8 (8.3-113.2), but higher than in IBD eosinophilia at 0.2 (0-0.9; p < 0.001) and negligible in the IBD and control groups. IL-13 expression in EoE was significantly higher only compared with IBD and controls not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity while IL-13 had 83% sensitivity and 90% specificity using cutoff point from the cohort without EoE-IBD patients. Based on MBP cutoff point that distinguished EoE from non EoE, 56% in EoE-IBD were MBP-positive whereas 100% in EoE group (p < 0.05)., Conclusions: MBP may be an excellent marker in distinguishing true EoE from eosinophilia caused by IBD. Our data implied that MBP together with endoscopic and histologic changes can assist EoE diagnosis in IBD patients., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background & Aims: Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP)., Methods: Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay)., Results: A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho = -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060)., Conclusions: Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Eosinophil-derived neurotoxin (EDN) is a viable marker of eosinophilic esophagitis (EoE) disease activity. We studied the utility of measuring EDN from esophageal epithelial brushings for diagnosing EoE, focusing on two scenarios: (1) cases of exclusive distal eosinophilia and (2) cases of discrepancy between endoscopy and histology., Methods: Records of patients who underwent esophagogastroduodenoscopy (EGD) with EDN measured via esophageal brushings at Arnold Palmer Hospital for Children in Orlando, Florida from January 2014 to October 2018 were retrospectively reviewed. Demographics, clinical, endoscopic, and histologic data were collected., Results: We reviewed 231 patient records (66.7% male, mean age 10.3 years, range 1-22 years). EDN values correlated with endoscopic reference score (EREFS) and peak eosinophil count (PEC) (Spearman's rho = 0.756 (p < 0.001) and 0.824 (p < 0.001) respectively). Average PEC, EREFS, and EDN concentrations were higher in patients with active EoE than in controls or patients with EoE in remission (inactive). When grouping patients based on esophageal eosinophilia distribution, EDN mirrored PEC, and EREFS. Patients with exclusive distal eosinophilia had lower EDN concentrations than those with eosinophilia in >1 level of the esophagus (23.8 ± 46.1 mcg/mL vs. 171.3 ± 205.8 mcg/mL respectively, p < 0.001). EDN values were more consistent with EREFS in cases of discrepancies between endoscopic findings and pathology (p < 0.001)., Conclusion: EDN measured in esophageal brushing samples reflects disease activity objectively and accurately. It also offers significant value in cases of exclusive distal esophageal eosinophilia and when discrepancies exist between endoscopy and histology., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: The incidence of eosinophilic esophagitis (EoE) is increasing in some regions of the world. Retrospective studies have found an inverse association with Helicobacter pylori infection (H. pylori). A recent prospective study has questioned this relationship. We aimed to evaluate this relationship in Mexican patients., Patients and Methods: We evaluated adult patients without prior eradication of H. pylori. Cases were defined by the presence of esophageal symptoms and >15 eosinophils/high power field (HPF) in the esophageal biopsy. Controls were defined by the presence of <15 eosinophils/HPF in esophageal biopsy. H. pylori infection was defined by histology. Patients were matched by age and gender assigning four controls per case., Results: We included 190 patients: 38 cases and 152 controls. Cases had higher frequency of atopy, dysphagia, food impaction, peripheral eosinophilia, and endoscopic EoE abnormalities. The overall prevalence of H. pylori was 63.6%. Cases had significantly lower prevalence of H. pylori than controls (36.8% vs. 70.4%, OR 0.21 95% CI 0.08-0.69, p = 0.001). Atopic patients had lower prevalence of H. pylori than non-atopic: 13.1% vs. 50.5% (OR 0.20, 95% CI 0.06-0.69, p < 0.001), particularly allergic rhinitis and food allergy., Conclusions: We observed an inverse relationship between H. pylori and EoE as well as atopy. Studies in experimental models of EoE that clarify the role of H. pylori in this interaction are required, as well as robust studies that include other factors (socioeconomic, cultural, microbiota, etc.) in order to clarify this relationship., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Introduction: Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment., Methods: This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites., Results: Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87)., Discussion: Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS., (Copyright © 2023 by The American College of Gastroenterology.)

Background: The presentation of eosinophilic esophagitis (EoE) is heterogeneous, but trends over time are not known., Aim: To determine whether clinical and endoscopic phenotypes at EoE diagnosis have changed over the past 2 decades., Methods: In this retrospective cohort study, adults and children with newly diagnosed EoE were phenotyped as follows: (1) inflammatory vs fibrostenotic vs mixed on endoscopy; (2) atopic vs non-atopic; (3) age at symptom onset; (4) age at diagnosis; (5) presence of autoimmune or connective tissue disease; and (6) responsive to steroids. The prevalence of different phenotypes was categorized by 5-year intervals. Multivariate analysis was performed to assess for changes in patient features over time., Results: Of 1187 EoE patients, age at diagnosis increased over time (from 22.0 years in 2002-2006 to 31.8 years in 2017-2021; p < 0.001) as did the frequency of dysphagia (67% to 92%; p < 0.001). Endoscopic phenotypes were increasingly mixed (26% vs 68%; p < 0.001) and an increasing proportion of patients had later onset of EoE. However, there were no significant trends for concomitant autoimmune/connective tissue disease or steroid responder phenotypes. On multivariate analysis, after accounting for age, dysphagia, and food impaction, the increase in the mixed endoscopic phenotype persisted (aOR 1.51 per each 5-year interval, 95% CI 1.31-1.73)., Conclusion: EoE phenotypes have changed over the past two decades, with increasing age at diagnosis and age at symptom onset. The mixed endoscopic phenotype also increased, even after controlling for age and symptomatology. Whether this reflects changes in provider recognition or disease pathophysiology is yet to be elucidated., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Several studies have reported large increases in the incidence of eosinophilic oesophagitis (EoE) in the last 20 years. We aimed to systematically review the incidence and prevalence of EoE, focused on all European countries., Methods: Systematic review and meta-analysis up to 31 December 2022, based on PubMed, CINAHL and extensive hand searching of reference lists. Twenty-five eligible studies were identified and included., Results: For both adults and children, the highest EoE incidence and prevalence have been reported from regional studies in Spain. EoE incidence for both adults and children was significantly lower (p < 0.001) in nationwide studies (meta-analysis = 3.64 per 100,000 person-years overall) compared with regional or centre-based studies (7.16). EoE incidence and prevalence were significantly higher (p < 0.001) in adults than children. All studies that reported on longitudinal trends in EoE incidence showed increases over time, more markedly during more recent years. Larger increases in incidence tend to refer to regional rather than nationwide studies; from Spain, Switzerland and Denmark, both for paediatric and adult age groups. Increases in EoE incidence 100,000 person-years were larger than for incidence per number of diagnostic endoscopies. The most frequently reported co-morbidities in adults were rhinitis, followed by asthma, food allergy and gastroesophageal reflux disease, and in children, erosive oesophagitis, asthma, food allergy and rhinitis., Conclusions: The incidence of EoE has increased in Europe over the last 30 years, exceeding increases in the volume of oesophago-gastro-duodenoscopies performed. The patchy and low incidence and prevalence of EoE generally in Europe and compared with North America, may reflect a lack of clinical awareness and research focus rather than a genuinely low incidence of EoE. A co-ordinated Europe-wide study that uses standardised methodology is urgently needed to provide a comprehensive picture of EoE incidence and prevalence across Europe., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: Biochemical alterations in the esophagus of patients with eosinophilic esophagitis (EoE) are poorly understood. We used Raman spectroscopy through a pediatric endoscope to identify key Raman features reflective of the esophageal biochemical composition to differentiate between children with EoE from non-EoE controls and between children with active (aEoE) and inactive EoE (iEoE)., Methods: Spectral measurements were obtained using a customized pediatric endoscope-compatible fiber-optic Raman probe in real time during an esophagogastroduodenoscopy. Chemometric analysis was performed to identify key Raman features associated with EoE. Pearson correlation analysis was used to assess relationship between the key Raman features and EoE activity indices. Their diagnostic utility was ascertained using the receiver operator characteristic curve analysis., Results: Forty-three children were included in the study (EoE = 32 [74%] and non-EoE control = 11 [26%]; aEoE = 20 [63%] and iEoE = 12 [37%]). Raman intensities assigned to lipids, proteins, and glycogen:protein ratio accurately distinguished children with EoE from those without EoE and aEoE from iEoE. They significantly correlated with EoE activity indices. The Raman peak ratio for lipids had 90.6% sensitivity, 100% specificity, and an area under the curve of 0.95 to differentiate children with EoE from non-EoE controls. The glycogen:protein ratio had 70% sensitivity, 91.7% specificity, and an area under the curve of 0.75 to distinguish children with aEoE from iEoE., Discussion: Real-time intraendoscopy Raman spectroscopy is an effective method for identifying spectral markers reflective of the esophageal biochemical composition in children with EoE. This technique may aid in the diagnosis and monitoring of EoE and help to elucidate EoE pathogenesis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Introduction: Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4 + T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing., Methods: In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus., Results: Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4 + T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4 + and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4 + T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE., Discussion: Herein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gruden, Kienzl, Ristic, Kindler, Kaspret, Schmid, Kargl, Sturm, Doyle, Wright, Baumann-Durchschein, Konrad, Blesl, Schlager and Schicho.)

Background/aims: Asymptomatic esophageal eosinophilia (aEE) is considered to be a potential precursor of eosinophilic esophagitis (EoE). However, there are few clinical parameters that can be used to evaluate the disease. Therefore, we aimed to clarify the factors involved in the symptoms of EoE by examining the clinicopathological differences between aEE and EoE., Methods: We reviewed 41 patients with esophageal eosinophilia who underwent endoscopic ultrasonography and high-resolution manometry. They were divided into the aEE group (n=16) and the EoE group (n=25) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score. The patients' clinicopathological findings were collected and examined., Results: The median Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score was 3.0 in the aEE group and 10.0 in the EoE group. There was no significant difference in patient characteristics, endoscopic findings and pathological findings. The cutoff value for wall thickening was 3.13 mm for the total esophageal wall thickness and 2.30 mm for the thickness from the surface to the muscular layer (total esophageal wall thickness: 84.0% sensitivity, 75.0% specificity; thickness from the surface to the muscular layer: 84.0% sensitivity, 68.7% specificity). The high-resolution manometry study was abnormal in seven patients (43.8%) in the aEE group and in 12 (48.0%) in the EoE group. The contractile front velocity was slower in the EoE group (p=0.026)., Conclusions: The esophageal wall thickening in the lower portion of the esophagus is an important clinical factors related to the symptoms in patients with EoE.

Background: Celiac disease (CD) is an immune-mediated enteropathy that has been associated with other immune-related gastrointestinal disorders, such as eosinophilic esophagitis (EoE) and lymphocytic gastritis (LG). To our knowledge, this is the first study in Saudi Arabia that has described such an association., Aim: To evaluate the prevalence of EoE and LG in children and adolescents with CD., Methods: This was a retrospective cross-sectional study of all pediatric patients (aged 0-18 years) with CD following up at King Abdulaziz University Hospital, between January, 2014, and December, 2021. The study examined clinical, demographic, endoscopic, and histopathological data., Results: Seventy-five patients with CD were included in the analysis. The median age was 12 years (range, 2-18 years). Male constituted 54.7% of the overall cohort ( n  = 41). The most common clinical symptoms were short stature (54.7%), weight loss (34.7%), abdominal pain (33.3%), abdominal distension (29.3%), anorexia (29.3%), diarrhea (24%), and vomiting (21.3%). The esophageal biopsy results reported were basal cell hyperplasia in 24 patients (32.9%), esophageal eosinophilia in 23 patients (31.5%), and EoE in 3 patients (4.1%). The gastric biopsy results were normal in 40 patients (53.3%). The most common abnormality was chronic inactive gastritis with no Helicobacter pylori (HP) infection (16%). LG was found in 3 patients (4%)., Conclusions: The prevalence of EoE in this cohort of patients with CD was lower than the prevalence recorded in a number of other studies. Further studies are needed to determine the effects of a gluten-free diet (GFD) on EOE and LG., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Meshari A. Alaifan et al.)

Introduction: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs., Methods: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment., Results: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed., Conclusion: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Noneosinophilic esophagitis eosinophilic gastrointestinal disorders (non-EoE-EGIDs) have limited treatment options to induce histologic and clinical remission. Dupilumab is a human monoclonal antibody against the interleukin-4 receptor ɑ subunit, which has been reported to induce improvement in pediatric patients with non-EoE-EGIDs., Methods: We conducted a retrospective chart review to identify if patients with eosinophilic gastritis (EoG) and/or eosinophilic duodenitis (EoD) experience clinical and histologic remission with dupilumab., Results: Twelve patients were included (2 patients with EoG and EoD, 3 patients with EoG only, and 7 patients with EoD only). All patients experienced improvement of at least 1 symptom on dupilumab, 3 patients (25%) had no change in severity of 1 or more of their symptoms, and no patients had worsening symptoms. On dupilumab, 2 patients with EoG (40%) and 3 patients with EoD (33.3%) were completely asymptomatic. Histologic changes were investigated in a subanalysis including 8 patients (2 patients with EoG and EoD, 2 patients with EoG only, and 4 patients with EoD only). Median peak gastric eosinophil counts in patients with EoG reduced from 80.5 eos/hpf (min-max 32-150, Q1-Q3 45.5-111) to 7.5 eos/hpf (min-max 0-28, Q1-Q3 1.5-16.8). Median peak duodenal eosinophil counts in patients with EoD reduced from 39 eos/hpf (min-max 30-50, Q1-Q3 37.3-46.3) to 16.5 eos/hpf (min-max 0-50, Q1-Q3 8-38.5). All 4 patients (100%) with EoG and 4 patients (66.6%) with EoD had histologic remission on dupilumab., Discussion: In this retrospective case series, we showed preliminary evidence that dupilumab may be effective in inducing histologic and symptomatic remission in patients with non-EoE-EGIDs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease., Methods: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications., Results: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p &lt; 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia., Conclusion: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype., (© 2023 S. Karger AG, Basel.)

Summary: Background: Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune‐mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil‐predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia. Aims: To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non‐EoE EGIDs, and discuss key remaining knowledge gaps. Methods: We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta‐analyses. Results: Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non‐EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies. Conclusions: Unmet needs for research are dramatically different for EoE and non‐EoE EGIDs. In EoE, non‐invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non‐EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders. [ABSTRACT FROM AUTHOR]

Background: A low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007–2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease. Objective: The aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN). Methods: This retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007 and 2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected. Results: In 32% of the children with EoE in the NDR, first-line treatment corresponded with the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Histologic evaluation within 12 weeks as recommended was performed in 13% of the children. Conclusions: In Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline. [ABSTRACT FROM AUTHOR]

Background/Aims: Asymptomatic esophageal eosinophilia (aEE) is considered to be a potential precursor of eosinophilic esophagitis (EoE). However, there are few clinical parameters that can be used to evaluate the disease. Therefore, we aimed to clarify the factors involved in the symptoms of EoE by examining the clinicopathological differences between aEE and EoE. Methods: We reviewed 41 patients with esophageal eosinophilia who underwent endoscopic ultrasonography and high-resolution manometry. They were divided into the aEE group (n=16) and the EoE group (n=25) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score. The patients’ clinicopathological findings were collected and examined. Results: The median Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score was 3.0 in the aEE group and 10.0 in the EoE group. There was no significant difference in patient characteristics, endoscopic findings and pathological findings. The cutoff value for wall thickening was 3.13 mm for the total esophageal wall thickness and 2.30 mm for the thickness from the surface to the muscular layer (total esophageal wall thickness: 84.0% sensitivity, 75.0% specificity; thickness from the surface to the muscular layer: 84.0% sensitivity, 68.7% specificity). The high-resolution manometry study was abnormal in seven patients (43.8%) in the aEE group and in 12 (48.0%) in the EoE group. The contractile front velocity was slower in the EoE group (p=0.026). Conclusions: The esophageal wall thickening in the lower portion of the esophagus is an important clinical factors related to the symptoms in patients with EoE. [ABSTRACT FROM AUTHOR]

Abstract Background A low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007–2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease. Objective The aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN). Methods This retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007 and 2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected. Results In 32% of the children with EoE in the NDR, first-line treatment corresponded with the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Histologic evaluation within 12 weeks as recommended was performed in 13% of the children. Conclusions In Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline.

This article, published in the journal Endoscopy, examines the clinical presentation and endoscopic-histological features of patients with eosinophilic esophagitis (EoE) who were diagnosed with food impaction (FI) compared to those without FI (NFI). The study found that patients with FI had a less frequent occurrence of gastroesophageal reflux-like symptoms before EoE diagnosis compared to NFI patients. Additionally, FI patients had a higher EREFS score, indicating a more severe disease presentation, and a higher eosinophilic peak. The findings suggest that EoE patients with FI may have a less symptomatic disease course before diagnosis, potentially leading to a delay in diagnosis. [Extracted from the article]