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Introduction: High levels of serum food‐specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics. Methods: This was a case–control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE‐negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels. Results: The analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p =.30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p =.24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p =.01) and the presence of sIgE to milk (OR 4.23; p =.008). Conclusion: Serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non‐EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study. [ABSTRACT FROM AUTHOR]

Summary: Background: Data on the role of the microbiome in adult patients with eosinophilic oesophagitis (EoE) are limited. Aims: To prospectively collect and characterise the salivary, oesophageal and gastric microbiome in patients with EoE, further correlating the findings with disease activity. Methods: Adult patients with symptoms of oesophageal dysfunction undergoing upper endoscopy were consecutively enrolled. Patients were classified as EoE patients, in case of more than 15 eosinophils per high‐power field, or non‐EoE controls, in case of lack of eosinophilic infiltration. Before and during endoscopy, saliva, oesophageal and gastric fundus biopsies were collected. Microbiota assessment was performed by 16 s rRNA analysis. A Sparse Partial Least Squares Discriminant Analysis (sPLS‐DA) was implemented to identify biomarkers. Results: Saliva samples were collected from 29 EoE patients and 20 non‐EoE controls;, biopsies from 25 EoE and 5 non‐EoE controls. In saliva samples, 23 Amplicon Sequence Variants (ASVs) were positively associated with EoE and 27 ASVs with controls, making it possible to discriminate between EoE and non‐EoE patients with a classification error (CE) of 24%. In a validation cohort, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of this model were 78.6%, 80%, 75%, 80% and 60%, respectively. Moreover, the analysis of oesophageal microbiota samples observed a clear microbial pattern able to discriminate between active and inactive EoE (CE = 8%). Conclusion: Our preliminary data suggest that salivary metabarcoding analysis in combination with machine learning approaches could become a valid, cheap, non‐invasive test to segregate between EoE and non‐EoE patients. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) involves a chronic immune‐mediated response to dietary antigens. Recent work identifies T‐cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food‐specific T‐cell repertoire. We sought to confirm T‐cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. Methods: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non‐EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V‐J‐CDR3s were assessed based on specific food triggers. Results: Active EoE biopsies from children but not adults displayed decreased unique TCRα/β clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non‐EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre‐diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). Conclusion: We confirmed relative clonality in children but not adults with active EoE and identified potential food‐specific TCRs, particularly for milk‐triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers. [ABSTRACT FROM AUTHOR]

Objective: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants. Design: Patients from six EoE‐centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro‐esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)‐histological, and molecular features were determined and compared with EoE, GERD, and healthy controls. Results: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE‐like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non‐specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed—in contrast to EoE—no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE‐typical Th2‐response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE‐like (characterized by eotaxin‐3 expression), non‐specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression). Conclusion: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype. [ABSTRACT FROM AUTHOR]

As seen, expression of non-fs EoE is intermediate between FS-EoE and controls in these examples regardless if statistically different between FS-EoE and non-fs EoE or not. Approximately 90% of the DEGs identified between FS-EoE versus control follow a pattern in which non-fs EoE has expression intermediate between controls and FS EoE. Eosinophilic Esophagitis (EoE) is a chronic inflammatory esophageal disease in which a subset of patients undergo pathologic tissue remodeling. [Extracted from the article]

Summary: Background: Eosinophilic oesophagitis (EoE) is associated with elevated IgG4 in oesophageal tissue and serum. Previously, we showed brush‐collected oesophageal secretions of EoE patients contained food antigen‐specific antibodies IgA and IgG4. It is unknown whether other food‐specific antibodies are present along the surface of the oesophagus in EoE. Aim: To identify whether immunoglobulins other than IgG4 and food‐specific antibodies are elevated along the oesophageal mucosal surface in oesophageal secretions in EoE patients Methods: Concentrations of total IgA, IgG1, IgG2, IgG3, IgG4, IgM and IgE were measured in oesophageal secretions from patients with active (n = 19) and inactive EoE (n = 9), and non‐EoE controls (n = 10). Food‐specific antibodies were measured using beads coupled to protein components from dairy, wheat and egg. Total immunoglobulin and cytokine and chemokine concentrations were measured in serum, saliva and oesophageal secretions of four patients with active EoE. Results: Oesophageal secretions have a unique immune profile. Patients with active EoE had elevated IgG2, IgG4 and IgM concentrations in oesophageal secretions compared to those with inactive EoE. Food‐specific IgG1, IgG2, IgG4 and IgM were significantly increased in patients with active EoE compared to inactive EoE and non‐EoE patients. Furthermore, active patients with a known dairy trigger display higher dairy‐specific IgG1, IgG2, IgG4, IgM, IgA and IgE. Conclusions: There is a distinct localised profile of immunoglobulins and food‐specific antibodies found within oesophageal secretions in EoE. These findings expand our knowledge about the currently identified immune responses in EoE and suggest possible roles for multiple immunoglobulins and food‐specific antibodies in the pathophysiology of EoE. [ABSTRACT FROM AUTHOR]

Background and Aim: Mental status such as anxiety and depression in patients with non‐esophageal eosinophilic gastrointestinal diseases (non‐EoE EGIDs) has not been studied. The aim of this study was to evaluate whether patients with non‐EoE EGIDs had mental disorders and decreased mental‐health‐related quality of life (QOL) similar to those in patients with disorders of gut–brain interaction (DGBI). Methods: We enrolled patients with non‐EoE EGIDs and DGBI visiting the Osaka Metropolitan University Hospital, and the measures listed below were compared between the groups. We collected data using the following questionnaires: hospital anxiety and depression scale, and short form (SF)‐8 including mental component summary (MCS)‐8. Results: We evaluated 21 and 17 patients with non‐EoE EGIDs and DGBI, respectively. The anxiety score was not significantly different between the groups. The proportion of patients with possible anxiety was not significantly different between the groups (19.0% vs 33.3%). These results show that patients with non‐EoE EGIDs had anxiety that might be equivalent to that of patients with DGBI. The depression score and proportion of patients with possible depression in the non‐EoE EGID group tended to be lower than those in the DGBI group. MCS‐8 scores were not significantly different between the non‐EoE EGID and DGBI groups, which might imply an equivalent decrease in mental‐health‐related QOL in both groups of patients. In patients with non‐EoE EGIDs, the anxiety score had a significant inverse association with the MCS‐8 score. Conclusions: Patients with non‐EoE EGIDs may have anxiety that correlates with decreased mental‐health‐related QOL. [ABSTRACT FROM AUTHOR]

Background and Aim: Little are known about differences in eosinophilic esophagitis (EoE) patients in the general population compared with patients treated at academic hospitals. This might affect the generalizability of study results. The aims of the study were to compare clinical features, and complications of EoE between patients from a population‐based cohort (DanEoE) and patients from an academic hospital cohort in Copenhagen (EoE‐Cph). Methods: The DanEoE cohort is a population‐ and register‐based cohort including all 236 adult EoE patients diagnosed in the North Denmark Region in 2007–2017 previously described in detail. The new EoE‐Cph cohort consists of 245 consecutively referred adult patients to a dedicated EoE center in an Academic Hospital in the Danish capital in 2013–2020. Data were collected from medical registries and medical files. Results: Patients in the academic cohort were at symptom debut 12 (SD 16) years younger (P = 0.001). At the time of diagnosis they were 5.4 (SD 15) years younger (P < 0.001). Where Gastro‐esophageal reflux disease (GORD) was present in one‐third of the population‐based cohort, this was only observed in 14% of the EoE‐Cph group (P < 0.05). Food bolus obstruction before diagnosis was 24% less common in the EoE‐Cph patients (P < 0.001). Conclusion: Results indicated that EoE patients referred to a Danish EoE center is a selected subgroup with disease debut at a younger age, less comorbid GORD, and rarely food bolus obstruction before diagnosis. This suggests that study results from academic hospitals might not have generalizability to the average EoE patient in a population. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a chronic non‐IgE‐mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq‐based transcriptomic analysis in paired samples was also carried out. Methods: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE‐specific mRNA panels (EDP and Eso‐EoE panel). Results: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA‐proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil‐related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso‐EoE, and corresponded with the most abundant proteins of the human esophageal proteome. Conclusions: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are the most commonly used first-line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are still unknown., Aims: To assess the effectiveness of PPI therapy for EoE in real-world practice., Methods: This cross-sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high-power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses., Results: Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30). PPI therapy achieved eosinophil density below 15 eosinophils per high-power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico-histological remission after PPI therapy (OR 3.7; 95% CI, 1.4-9.5); as well as those who prolonged treatment length from 8 to 12 weeks (OR 2.7; 95% CI, 1.3-5.3). After achieving clinico-histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype., Conclusions: Inflammatory EoE phenotype and treatment duration up to 12 weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term., (© 2020 John Wiley & Sons Ltd.)

Background Eosinophilic esophagitis (EoE) is a rapidly emerging, chronic inflammatory, genetically impacted disease of the esophagus, defined clinically by symptoms of esophageal dysfunction and, pathologically, by an eosinophil-predominant tissue infiltration. However, in four EoE families, we have identified patients presenting with EoE-typical and corticosteroid-responsive symptoms, but without tissue eosinophilia. The aim of this study was to clinically and immunologically characterize these patients with EoE-like disease. Methods Five patients suffering from an EoE-like disease were evaluated with endoscopic, histologic, functional, and quantitative immunohistological examinations, and mRNA expression determination. Results The frequency of first-generation offspring of patients affected by EoE or EoE-like disease was 40%. Immunofluorescence analysis confirmed an almost complete absence of eosinophils in the esophageal tissues of patients with EoE-like disease, but revealed a considerable T-cell infiltration, comparable to EoE. In contrast to EoE, eotaxin-3 mRNA and protein were markedly reduced in EoE-like disease ( P < 0.05). The mRNA expression levels of three selected EoE genes ( eotaxin-3, MUC4, and CDH26) allowed to discriminate between EoE-like disease, EoE, and normal epithelium. Conclusions Patients suffering from 'EoE without eosinophilia' do not fulfill formally the diagnostic criteria for EoE. However, their clinical manifestation, immunohistology, and gene expression pattern, plus the fact that they bequeath EoE to their offspring, suggest a uniform underlying pathogenesis. Conventional EoE, with its prominent eosinophilia, therefore appears to be only one phenotype of a broader 'inflammatory dysphagia syndrome' spectrum. In this light, the role of the eosinophils, the definition of EoE, and its diagnostic criteria must likely be reconsidered. [ABSTRACT FROM AUTHOR]

Background and Aim: Our primary aim was to describe the prevalence of immunoglobulin G (IgG) and its subclass IgG4 in immunohistochemistry staining in esophageal biopsy specimens of children with eosinophilic esophagitis (EoE) compared with that of specimens from children with gastroesophageal reflux disease (GERD). Methods: Esophageal biopsy specimens from children with EoE or GERD were stained prospectively for IgG and IgG4 antibodies. Subjects with EoE were divided into cohorts with either active EoE or EoE in remission. Active EoE cases were further divided into proton pump inhibitor responsive (PPI‐r) and PPI‐nonresponsive (PPI‐nr) subgroups. Demographic, clinical, and histologic data were compared among groups, including quantified IgG and IgG4 staining, peak eosinophil count, eosinophil‐derived neurotoxin levels, and EoE endoscopic reference score. Results: Seventy‐nine children (aged 10.6 ± 5.6 years; 68% male) were enrolled. IgG‐positive cell counts were significantly elevated in those with active EoE (n = 29, 3 [interquartile range, IQR: 2–6]/high‐powered field [HPF]), compared with those having EoE remission (n = 25, 1 [IQR: 0–2]/HPF; P = 0.002) and those with GERD (n = 25, 0 [IQR: 0–0.25]/HPF, P = <0.0001). IgG‐positive cell counts were significantly higher in the PPI‐r (n = 15, 5 [IQR: 2.5–11]/HPF) subgroup, compared with the PPI‐nr subgroup (n = 11, 3 [IQR: 1.5–3.5]/HPF; P = 0.041) at baseline endoscopy. Conclusion: Initial esophageal tissue biopsy specimens from pediatric subjects with active EoE showed a significant increase in IgG‐positive staining compared with tissue from subjects in EoE remission or with GERD. There was higher positivity of IgG‐stained cells in the PPI‐r subgroup compared with the PPI‐nr subgroup. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an atopic disease of the esophagus that has shown a significant increase in incidence and prevalence in the last 20 years. The etiology of EoE is unclear, and few studies explore the esophageal microbiota in EoE. The local microbiome has been implicated in the pathogenesis of several allergic and inflammatory diseases, such as asthma and eczema. In this study, we performed a systematic review to evaluate differences in the microbiota profile of patients with EoE compared with controls. MEDLINE, Embase, Cochrane Library, Scopus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched to identify studies investigating the microbiota composition in EoE. Three reviewers screened the articles for eligibility and quality. Seven articles underwent full‐text review, and a narrative synthesis was undertaken. The microbiota of the mouth and esophagus are correlated. Patients with active EoE present increased esophageal microbial load and increased abundance in particular species, such as Haemophilus and Aggregatibacter. On the other hand, EoE patients present a decrease in Firmicutes. High microbial load and abundance of Haemophilus are observed in EoE patients, but little evidence exists to demonstrate their influence on inflammation and disease. Understanding microbial signatures in EoE might contribute to the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background and Aim: The DanEoE is a previously described population‐ and register‐based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well‐defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. Methods: A retrospective cross‐sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. Results: At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis. Conclusion: In the population‐based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5‐year longer diagnostic delay. In the current study, the complication status did not predict the treatment response. This population‐based DanEOE cohort study indicates that the complicated eosinophilic esophagitis phenotype is a patient with a 5‐year longer diagnostic delay. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a T‐cell‐mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE‐causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen‐specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. Methods: We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E‐mediated milk allergy (n = 9). We measured total and milk‐specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4+ T helper (TH) cell proliferation and cytokine production after stimulation with endotoxin‐depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches. Results: Total and milk‐specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused TH lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL‐4+ of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk‐dependent memory TH‐cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL‐4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy. Conclusions: Peripheral markers of allergen‐specific immune activation may be useful in identifying EoE‐causal foods. Assaying milk‐dependent IL‐4 production by circulating memory TH lymphocytes most accurately predicts clinical EoE milk allergy. [ABSTRACT FROM AUTHOR]

Given the limited clinical effect of eosinophil-directed therapies in EoE to date, our data support exploring the clinical benefit of anti-MC agents in EoE. Pearson correlations performed with MC-specific protease carboxypeptidase A3 ( I CPA3 i ) demonstrated a strong correlation with eosinophil transcriptional signatures, including the eotaxin receptor I CCR3 i , the eosinophil granule lysophospholipase ( I CLC i ), and the eosinophil chemokines eotaxin-3 ( I CCL26 i ) and I IL5 i (Figures 1 and 2A). Abbreviations EoE eosinophilic esophagitis EDP eosinophilic esophagitis diagnostic panel MC mast cell PEC peak eosinophil count Eosinophilic esophagitis (EoE) is a type 2 inflammatory disorder characterized by esophageal inflammation, eosinophil infiltration, tissue remodeling, and stricture.[1] Currently, diagnosis of EoE is based on clinical assessments and a peak tissue eosinophil count (PEC) of >=15 eosinophils per high powered field, although PEC does not correlate well with symptom severity, and eosinophil reduction to normal levels does not correlate with symptomatic improvement in some studies.[1] Numerous studies have demonstrated that mast cells (MCs) are also present in significantly greater numbers in EoE than in normal esophageal biopsies. [Extracted from the article]

Background: Eosinophilic esophagitis (EoE) is a chronic, food‐driven allergic disease, characterized by eosinophil‐rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL‐4 and IL‐13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL‐4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL‐4 and IL‐13 and whether the type II IL‐4 receptor (comprised of the IL‐4Rα chain in association with IL‐13Rα1) mediates this effect has not been determined. Methods: Experimental EoE was induced in WT, Il13ra1−/−, and Krt14Cre/Il13ra1fl/fl mice by skin‐sensitized using 4‐ethoxymethylene‐2‐phenyl‐2‐oxazolin (OXA) followed by intraesophageal challenges. Esophageal histopathology was determined histologically. RNA was extracted and sequenced for transcriptome analysis and compared with human EoE RNAseq data. Results: Induction of experimental EoE in mice lacking Il13ra1 and in vivo IL‐13 antibody‐based neutralization experiments blocked antigen‐induced esophageal epithelial and lamina propria thickening, basal cell proliferation, eosinophilia, and tissue remodeling. In vivo targeted deletion of Il13ra1 in esophageal epithelial cells rendered mice protected from experimental EoE. Single‐cell RNA sequencing analysis of human EoE biopsies revealed predominant expression of IL‐13Rα1 in epithelial cells and that EoE signature genes correlated with IL‐13 expression compared with IL‐4. Conclusions: We demonstrate a definitive role for IL‐13 signaling via IL‐13Rα1 in EoE. These data provide mechanistic insights into the mode of action of current therapies in EoE and highlight the type II IL‐4R as a future therapeutic target. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence and incidence of eosinophilic esophagitis (EoE) has been increasing over recent years. However, the natural history remains incompletely understood particularly the differences in disease characteristics and progression of childhood‐onset and adult‐onset EoE. The aim of this study was to evaluate the disease characteristics and progression of childhood‐onset and adult‐onset EoE. Methods: A cross‐sectional, questionnaire‐based study, on 87 adults and 67 children from 2 major tertiary hospitals in South Australia was conducted. Data of those who were diagnosed with EoE between 1999 and 2018 were collected and correlated with medical records. Results: Of the 87 adults with EoE, 34 (39%) were diagnosed at the age of < 18 years (childhood‐onset EoE). Reflux symptoms were more common in childhood‐onset EoE, whereas asthma was more common in adult‐onset EoE. The median duration of symptoms prior to diagnosis of EoE was > 1–4 years in childhood‐onset disease (44%) and ≥ 10 years in adult‐onset disease (34%). Food impaction was significantly more common on initial presentation in those with adult‐onset EoE, whereas weight loss was more common in childhood‐onset EoE. At the time of questionnaire, regurgitation, abdominal pain, and bloating were more common in childhood‐onset EoE. Those with childhood‐onset EoE were more likely to have multiple symptoms at questionnaire when compared with their adult‐onset counterparts. In both groups, 15% (5/34 childhood‐onset EoE and 8/53 adult‐onset EoE) were asymptomatic at the time of questionnaire. Conclusion: Childhood‐onset EoE appears to be a progressive disease from childhood to adulthood, however with more inflammatory‐type symptoms post transition compared to those with adult‐onset EoE. [ABSTRACT FROM AUTHOR]

Background: Supernumerary sex chromosome aneuploidies (SCA) are common genetic conditions characterized by additional X or Y chromosome, affecting ~1/500 individuals, with the most frequent karyotypes of 47,XXY (Klinefelter syndrome), 47,XXX (Trisomy X), and 47,XYY (Jacob syndrome). Although there is considerable phenotypic variation among these diagnoses, these conditions are characterized by the presence of overlapping physical, medical, developmental, and psychological features. Our interdisciplinary clinic's experience anecdotally supports previous published findings of atopic conditions, feeding difficulties, and gastroesophageal reflux to be more prevalent in SCAs (Bardsley et al., Journal of Pediatrics, 2013, 163, 1085; Samango‐Sprouse et al., The Application of Clinical Genetics, 2019, 12, 191; Tartaglia et al., Acta Paediatrica, 2008, 100, 851). Furthermore, we observed that many of these patients have also been diagnosed with eosinophilic esophagitis (EoE), an association not currently reported in the literature. Methods: We conducted a retrospective chart review of all 667 patients with SCA seen at a large tertiary care center to investigate the prevalence and presenting features of EoE. Results: Four percent of children with SCAs had a biopsy‐confirmed diagnosis of EoE, which represents an odds ratio of 32 (95% CI 6–185) when compared to the prevalence rates reported in the general population. Conclusion: Routine screening for EoE symptoms may be warranted for individuals with SCA and atopic conditions. [ABSTRACT FROM AUTHOR]

Characterization of the esophageal microbiota in EoE subjects relative to non-EoE controls was performed by comparison of steroid-naïve subjects with active or inactive EoE to non-EoE controls. We aimed to characterize the bacterial and fungal communities in the esophageal mucosa of children with EoE and non-EoE controls and examine the effects of TSS on the microbiota in children with EoE. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by an eosinophil-predominant inflammation of the esophageal mucosa.1 We have previously characterized bacterial communities of the human esophagus in healthy children and adults.2 Our data and work from others suggest that the normal esophageal bacterial microbiota is dominated by I Firmicutes i species.2-4 Active inflammation in EoE is associated with bacterial dysbiosis, specifically with an increase in members of the I Proteobacteria i .2,3 However, while some have described the role of bacteria in atopic gastrointestinal diseases,5 little is known about the role of fungi in allergic esophageal inflammation or the role of topical swallowed steroids (TSS) in disease-associated dysbiosis. [Extracted from the article]

Background and Aim: The prevalence of eosinophilic esophagitis (EoE) is rising in the West. However, data from the Indian subcontinent is limited. In this prospective cross‐sectional study, we estimated the prevalence of EoE among children undergoing elective upper gastrointestinal endoscopy (UGIE). Methods: We enrolled 200 consecutive children (123 boys, median age 10.25 years [interquartile range 8.25–14.5]) between March 2020 and November 2022 at our center. Clinical characteristics, endoscopic findings, and laboratory parameters were noted. A total of 12 mucosal biopsies (3 each from the middle and lower third of the esophagus, stomach, and duodenum) were obtained. EoE was diagnosed if the peak eosinophil count was ≥15/high‐power field (HPF) in absence of gastric and duodenal eosinophilia. Results: The commonest indications for UGIE were gastroesophageal reflux disease‐like symptoms (29%), inflammatory bowel disease (22.5%), celiac disease (15%), and abdominal pain (13%). EoE was detected in seven children, suggesting an overall prevalence of 3.5%. Of the 20 children evaluated for dysphagia, 4 (20%) had EoE. Also, two of three (67%) children presented with food bolus impaction along with dysphagia had EoE. Of the seven children with EoE, three (43%) had bronchial asthma, two (28.5%) had peripheral eosinophilia, and one (14%) had elevated serum IgE. Trachealization and linear furrows were found in 57% and 71% cases, respectively. Four children received high‐dose proton pump inhibitor (PPI) for 12 weeks, two received PPI+ stricture dilatation, and one received systemic steroids. All achieved clinical, endoscopic, and histopathological remission. Conclusion: Hospital‐based prevalence of EoE among children undergoing elective UGIE was 3.5%. EoE patients had favorable outcomes with PPI. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic gastrointestinal disorders (EGIDs) are chronic allergic diseases categorized as eosinophilic esophagitis (EoE) and non‐EoE EGIDs. Few studies regarding the association between EGIDs and coronavirus disease 2019 (COVID‐19) have been reported. Although most Japanese individuals received the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine, the incidence of COVID‐19 remained high in 2022. This study examines the incidence of COVID‐19 in patients with EGIDs during the vaccination era. Methods: Patients with EGIDs who visited our department between October and December 2022 were enrolled in the study. The incidence and severity of COVID‐19 prior to October 1, 2022 were determined. Patients who reported having COVID‐19 also reported their hospitalization history, intensive care unit admissions, and EGID flares. The number of SARS‐CoV‐2 vaccinations received and treatment for EGIDs were obtained from the patients' medical records. Results: Of 111 patients with EGIDs (65 with EoE and 46 with non‐EoE EGIDs) included in this study, 31 (28%) patients reported having COVID‐19, including 14 (22%) with EoE and 17 (37%) with non‐EoE EGIDs. Fifty‐nine (84%) patients received two or more vaccinations, and 11 (16%) patients received no vaccinations. COVID‐19 was mild in all but one patient who had moderate symptoms. COVID‐19 was not associated with EGID flares. EGID treatments and an unvaccinated status were not associated with an increased risk of COVID‐19. Conclusion: COVID‐19 was mild in patients with EGIDs and not associated with EGIDs flares during the vaccination era. There was a relatively high incidence of COVID‐19 among patients with non‐EoE EGIDs. [ABSTRACT FROM AUTHOR]

Background: There is conflicting evidence about the association between eosinophilic esophagitis (EoE) and esophageal motility disorders. The aim of this study was to evaluate esophageal manometry findings in EoE. Methods: We conducted a systematic review using PubMed, EMBASE, and Web of Science. All articles from 1990 to 2021 with EoE patients who underwent esophageal manometry were eligible. We also included pertinent abstracts from national conferences from 2015 to 2020. The primary outcomes were the prevalence of specific Chicago 3 Classification (CCv3) diagnoses in EoE, as well as broader categories of non‐relaxing lower esophageal sphincter, and major and minor peristaltic disorders. When multiple studies reported a specific outcome, we performed random effects meta‐analysis to obtain pooled prevalence of each outcome. To reduce heterogeneity, we restricted meta‐analysis to high‐resolution manometry (HRM) studies only. Key Results: Of 763 publications identified, 27 original studies met criteria for inclusion, encompassing 706 EoE patients; 14 studies (425 patients) had HRM and underwent meta‐analysis. The pooled prevalence of any motility abnormality was 53% (95% CI: 43%–63%), largely comprised of minor motility disorders such as ineffective esophageal motility and fragmented peristalsis. Major motility disorders, classified by CCv3, were less common in EoE, with pooled prevalence of 2% (0%–7%), 10% (5%–16%), and 1% (0%–3%), for achalasia, esophagogastric‐junction outflow obstruction, and hypercontractile disorders, respectively. Conclusion and Inferences: Non‐specific motility disorders were common in patients with EoE, but major motility disorders were rare. Further studies are needed to determine the relationship between eosinophilic infiltration and the clinical relevance of abnormal esophageal motility findings in this population. [ABSTRACT FROM AUTHOR]

Background and Aim: Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) can be difficult to distinguish as many of their clinical and histological features overlap. Preliminary data suggest a potential association between EoE and immunoglobulin G4 (IgG4) but not GERD. This study aimed to examine the role of esophageal mucosal IgG4 staining when differentiating EoE from GERD. Methods: Esophageal biopsy specimens from patients with proven EoE and GERD were evaluated, and immunohistochemical staining for IgG4 was performed by an experienced gastrointestinal pathologist blinded to the clinical and endoscopic data. The results on IgG4 staining were then correlated with clinical, endoscopic, and histological features. Results: Sixty patients were included in the study, with 30 EoE (38.8 ± 12.8 years, 23 M:7 F) and 30 GERD (50.7 ± 14.3 years, 14 M:16 F) patients. The prevalence of a positive intercellular IgG4 stain was significantly higher in the EoE patients than those with GERD (23/29 vs 2/30; P < 0.0001). Positive IgG4 stain had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 77%, 93%, 92%, and 80% for predicting the diagnosis of EoE, respectively. In both EoE and GERD patients, correlation was found between positive IgG4 staining and food bolus obstruction, dysphagia to solids, reflux, fixed rings, Barrett's esophagus, hiatus hernia, and esophagitis. In EoE patients, positive IgG4 staining was not correlated with the type of symptoms, endoscopic findings, histological findings, proton pump inhibitor therapy, or history of allergy/atopy. Conclusion: Given the high specificity and PPV of positive IgG4 staining in esophageal biopsies for EoE, this can be a useful marker to distinguish the disease from GERD. [ABSTRACT FROM AUTHOR]

Background Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in which dietary antigens (in particular, milk) play a major role. EoE is most likely a mixed IgE and non-IgE food-mediated reaction in which overexpression of Th2 cytokines, particularly IL-13, play a major role; however, the cells responsible for IL-13 overexpression remain elusive. Th2-cytokines are secreted following the ligation of invariant natural killer T cell receptors to sphingolipids (SLs). Sphingolipids (SLs) are presented via the CD1d molecule on the INKTs surface. Cow's milk-derived SL has been shown to activate iNKTs from children with IgE-mediated food allergies to milk (FA-MA) to produce Th2 cytokines. The role of iNKTs and milk-SL in EoE pathogenesis is currently unknown. Objective The aim of this study was to investigate the role of iNKTs and milk-SL in EoE. Methods Peripheral blood mononuclear cells (PBMCs) from 10 children with active EoE (EoE-A), 10 children with controlled EoE (EoE-C) and 16 healthy controls (non-EoE) were measured ex vivo and then incubated with α-galactosylceramide (αGal) and milk-SL. INKTs from peripheral blood (PB) and oesophageal biopsies were studied. Results EoE-A children had significantly fewer peripheral blood iNKTs with a greater Th2-response to αGal and milk-SM compared with iNKTs of EoE-C and non-EoE children. Additionally, EoE-A children had increased iNKT levels in oesophageal biopsies compared with EoE-C children. Conclusion Milk-SLs are able to activate peripheral blood iNKTs in EoE-A children to produce Th2 cytokines. Additionally, iNKT levels are higher at the site of active oesophageal eosinophilic inflammation. Clinical Relevance This study suggests that sphingolipids (SLs) contained in milk may drive the development of EoE by promoting an iNKT-cell-mediated Th2-type cytokine response that facilitates eosinophil-mediated allergic inflammation. [ABSTRACT FROM AUTHOR]

This article provides a summary of a Cochrane review on the medical treatment of eosinophilic esophagitis (EoE). EoE is a chronic inflammatory condition of the esophagus that can affect individuals of all ages, but is more common in males and adults. The review evaluated the efficacy and safety of different medical interventions for EoE, including corticosteroids and biologics. The findings suggest that corticosteroids improve clinical and histological outcomes, while biologics may improve clinical outcomes. However, the cost and availability of biologics should be considered. Further research and cost-effectiveness analyses are needed to fully evaluate and compare these treatments. [Extracted from the article]

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3‐day food diaries. In this randomized controlled trial, diagnosed patients received either a four‐food elimination diet alone (FFED) or FFED with addition of an amino acid‐based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p <.05), while calcium (p =.058) and full‐fat cheese/curd (p =.056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p <.05), while ultra‐processed meals (p =.059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p =.058). Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High‐quality and anti‐inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE. [ABSTRACT FROM AUTHOR]

Abbreviations CCHMC Cincinnati Children's Hospital Medical Center CEGIR Consortium of Eosinophilic Gastrointestinal Disease Researchers EDP eosinophilic esophagitis diagnostic panel EoE eosinophilic esophagitis HPF high-power field MC Mast cells; PRO, Patient-reported outcome EEsAI eosinophilic esophagitis activity index PEESS Pediatric Eosinophilic Esophagitis Symptom Scores HSS EoE Histology Scoring System EREFS EoE endoscopic reference score CONFLICT OF INTEREST M.E.R. is a consultant for Pulm One, Spoon Guru, Allakos, ClostraBio, Serpin Pharm, Celgene, Shire, AstraZeneca, GlaxoSmithKline, Allakos, Adare, Regeneron, and Novartis and has an equity interest in the first five, as well as royalties from reslizumab (Teva Pharmaceuticals) and UpToDate. Mast cells (MCs) are involved in allergy, including EoE,2 and neuromodulation.3 MCs reside in peripheral tissue and communicate with nearby structures, including nerve endings. We divided active EoE into four quartiles by using I CPA3 i + I HPGDS i sum as a MC count surrogate marker; the highest and lowest quartiles represented MC-high and MC-low, respectively. [Extracted from the article]

Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and is clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia and esophageal food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation and alterations of the esophageal squamous epithelium, such as basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), are thought to contribute to esophageal dysfunction and disease symptoms. Corroborative clinical and discovery science‐based studies have established that EoE is characterized by an underlying allergic inflammatory response, in part, related to the IL‐13/CCL26/eosinophil axis driving dysregulation of several key epithelial barrier and proliferative regulatory genes including kallikrein (KLK) serine proteases, calpain 14 (CAPN14) and anoctamin 1 (ANO1). The contribution of these inflammatory and proliferative processes to the clinical and histological manifestations of disease are not fully elucidated. Herein, we discuss the immune molecules and cells that are thought to underlie the clinical and pathologic manifestations of EoE and the emerging therapeutics targeting these processes for the treatment of EoE. [ABSTRACT FROM AUTHOR]