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

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. [Display omitted] Shook et al. developed and applied a massively parallel reporter assay for the allergic disease eosinophilic esophagitis (EoE). They identified common polymorphisms associated with EoE risk that also impacted transcriptional regulation. This study is an important step toward understanding how EoE genetic risk variants lead to genotype-dependent biology. [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]

Background: First-line treatment of eosinophilic esophagitis (EoE) includes monotherapy with proton-pump inhibitors (PPIs), food elimination diet (FED), or topical corticosteroids. Current guidelines suggest patients with EoE should continue any responsive first-line monotherapies. However, the efficacy of FED monotherapy in patients with EoE responsive to PPI monotherapy has not been well studied. Our study aimed to investigate how attempting FED monotherapy after experiencing remission of EoE after PPI monotherapy influenced long-term EoE management. Methods: We retrospectively identified patients with EoE responsive to PPI monotherapy who trialed FED monotherapy. We then employed a mixed method approach to a prospective cohort. Selected patients were observed long term for quantitative outcomes, while qualitative results were obtained from patient surveys regarding their perspectives on the trial of FED monotherapy. Results: We identified 22 patients who trialed FED monotherapy after experiencing remission of EoE following PPI monotherapy. Of these 22 patients, 13 had remission of EoE with FED monotherapy, while 9 had re-activation of EoE. Out of 22 patients, 15 were enrolled in a cohort for observation. No exacerbations of EoE occurred while on maintenance treatment. Most patients stated that they would recommend this process to others with EoE (93.33%) and that trial of FED monotherapy helped them identify a treatment plan that aligned with their lifestyle (80%). Conclusion: Our work shows that FED monotherapy can be an effective alternative for patients with EoE responsive to PPI monotherapy that may improve patient quality of life, suggesting alternative treatment options should be considered for monotherapy-responsive EoE. [ABSTRACT FROM AUTHOR]

Résumé: Autrefois considérée comme une maladie rare, l'œsophagite à éosinophiles (EoE) suscite depuis une vingtaine d'années un intérêt croissant et est devenue l'une des affections les plus couramment diagnostiquées au cours de l'endoscopie digestive haute pour dysphagie chez l'enfant et l'adulte. La physiopathologie de cette affection est complexe et regroupe plusieurs mécanismes, notamment une réponse immunitaire anormale vis-à-vis d'antigènes environnementaux, une altération et fibrose de la muqueuse œsophagienne. Le diagnostic d'EoE est à la fois clinique avec dysfonction œsophagienne et histologique avec une infiltration de la muqueuse œsophagienne par les polynucléaires éosinophiles. L'arsenal thérapeutique pour traiter cette maladie est relativement large : règles hygiéno-diététiques, traitements pharmacologiques tels que les inhibiteurs de la pompe à protons et corticoïdes topiques, mais aussi les anticorps monoclonaux, en cours d'étude. L'endoscopie occupe également une place de choix dans la prise en charge thérapeutique avec une innocuité bien établie, notamment dans les formes fibro-sténosantes où l'efficacité des traitements pharmacologiques est souvent mise en défaut. Enfin, l'endoscopie a également un intérêt dans le suivi de la maladie avec un score de référence endoscopique « EREFS » (pour Exsudats, Anneaux, Œdèmes, Sillons et Sténoses) utilisé comme outil standardisé pour mieux évaluer et surveiller la maladie. Nous nous intéresserons ici particulièrement au rôle de l'endoscopie dans le diagnostic, le traitement et le suivi de l'EoE. Previously considered as a rare disease, eosinophilic esophagitis (EoE) has aroused growing interest over the past twenty years and has become one of the most currently diagnosed disease during upper digestive endoscopy in the context of dysphagia in children and adults. The pathophysiology of esophagitis is complex and involves several mechanisms, including, an abnormal immune response to environmental antigens, alteration of the esophageal mucosa, and the development of fibrosis. The diagnosis of EoE is both clinical with esophageal dysfunction and histological with infiltration of the esophageal mucosa by eosinophilic polynuclei. The therapeutic arsenal to treat this pathology is relatively broad and calls upon hygienic-dietary rules, pharmacological treatments such as proton pump inhibitors and topical corticoids, and also monoclonal antibodies currently under studies. Endoscopy also occupies an important role in therapeutic management, particularly in fibro-stenosing forms of EoE where the efficacy of pharmacological treatments is often challenged, with well-established safety. Finally, endoscopy also has an interest in the follow-up of the disease with an endoscopic reference score which is EREFS (exudates, rings, oedemas, furrows and stenoses) used as a standardized tool to better evaluate and monitor EoE. Here we will focus on the role of endoscopy in the diagnosis, treatment and follow-up of EoE. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. Methods: Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. Results: There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE‐positive (N = 12) and EoE‐negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. Conclusions: Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum‐specific IgE suggest that other inflammatory mechanisms, besides type I, IgE‐mediated, allergen‐specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE‐mediated and non‒IgE‐mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a chronic disease characterized histologically by > 15 eosinophils per high-power field (eos/hpf). Esophageal mucosal mast cells have been implicated in EoE pathogenesis. The association of atopy with EoE has been established but has not been correlated with levels of serum tryptase. The lack of concurrent atopy in some patients suggests the possibility that atopy may either be the related subtype of EoE or may be a sign of comorbidities. No study has looked at whether patients present with different phenotypes/comorbid disease when they have evidence of elevated serum tryptase. We hypothesized that these patients differ with respect to presentation and comorbidities with more refractory GI disease.Aims: To examine whether elevations of serum tryptase associate with different, more severe clinical presentations in EoE patients which may be explained via mast cell activation.Materials and Methods: Retrospective chart review identified 72 patients with EoE with results for serum tryptase between 2015 and 2016. Patients were classified as TryptaseHI (tryptase > 10.9 µg/l) and TryptaseLO (< 10.9 µg/l). Clinical characteristics and treatment response were compared using univariate analysis and multivariate regression between the groups.Results: Out of 72 patients, 12 were tested as TryptaseHI (16.7%, 95% CI 8.1-25.3%). TryptaseHI was associated frequently with asthma (P = 0.0003), urticaria (P = 0.002), arthralgia (P = 0.005), sinusitis (P = 0.03), nausea/vomiting (P = 0.046), and eosinophilic gastrointestinal disease (P = 0.001). Asthma and arthralgia were found to be significantly associated with TryptaseHI (P = 0.0013, P = 0.0098, respectively). Mucosal eosinophil counts and tryptase levels were not correlated (R2 0.095, P = 0.77). Tryptase did not resolve with resolution of esophageal eosinophilia.Conclusions: We found that EoE patients with elevated tryptase levels more commonly presented with asthma, urticaria, arthralgia, nausea/vomiting, sinusitis, and more distal eosinophilia. This indicates that atopy in EoE patients warrants further exploration. The lack of correlation between histologic remission and reduction of serum tryptase levels post-treatment suggests that mast cell activation may be an independent, yet associated disease. More study into this unique association is warranted. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of eosinophilic esophagitis (EoE) is currently unknown, but evidence suggests that allergic sensitization to food and airborne allergens may play a key role. This retrospective study examines the rate of sensitization to both food and airborne allergens in EoE patients, and compares their sensitivity patterns to control groups. Methods: We identified 103 patients with a diagnosis of EoE via esophageal eosinophilia (≥15 eosinophils/high‐power field [hpf]), who had undergone comprehensive food and/or airborne allergen testing through either skin or in vitro methods. Food and airborne allergen sensitization was defined as positive testing in at least 1 food subgroup (milk, peanut, tree nut, seafood/fish, soy, grain, egg) or airborne subgroup (tree, grass, weed, mite/cockroach, animal, mold), respectively. The same sensitization criterion was applied to allergic rhinitis (AR) patients, with and without a clinical suspicion of food allergy (FA), in order to create control groups. Results: Sensitization in the EoE group to at least 1 subgroup of food allergen and airborne allergen was seen in 77.1% (64/83) and 71.7% (38/53), respectively (p = 0.82). There were significant differences in sensitization between EoE and control groups for tree nut, soy, grain, and egg, but no differences noted in any of the other food or airborne allergen subgroups, even after accounting for age and gender. Conclusion: EoE and control groups had similar airborne allergen sensitization patterns, yet dissimilar food allergen sensitization patterns, suggesting that specific allergens may play a more prominent role in the pathogenesis of EoE. The EoE group had a more uniform distribution pattern for food allergens, compared to controls. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis is a relatively recently discovered disease of increasing incidence and prevalence and is a common cause of dysphagia and food bolus impaction. The definition of eosinophilic esophagitis continues to evolve, most recently with the characterization of proton pump inhibitor-responsive esophageal eosinophilia. The number of high-quality prospective, controlled trials guiding therapeutic decisions in eosinophilic esophagitis has increased steadily over the past several years. Treatment options at present focus on dietary therapy, particularly implementation of a 6-food elimination diet, and medical therapy, primarily the use of swallowed, topical corticosteroids. Proton pump inhibitors play an important role in current management. Conservative esophageal dilation is effective at ameliorating dysphagia in symptomatic patients with esophageal strictures. We conducted an evidence-based review of the diagnosis and treatment options in adults with eosinophilic esophagitis. The understanding of eosinophilic esophagitis continues to be refined. Continued validation of appropriate endpoints, however, is essential to establish the efficacy of existing and novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

IL-18 is induced in food allergy and EoE is food allergen-induced disease. Therefore, we tested the hypothesis whether IL-18 is involved in food allergen-induced EoE pathogenesis. Accordingly, we examined normal SPT + and SPT − EoE patient blood and biopsy samples for IL-18, IL-18Rα, ICAM and VCAM expression. Herein, we show increased IL-18 level is highly significant in food allergen SPT + compared to SPT − EoE patients. We also report that IL-18Rα + cells and mRNA levels are induced in the esophageal biopsies of EoE patients and blood IL-18 levels correlate with esophageal eosinophilia (P < 0.01). Additionally, we report that the levels of esophageal eosinophil and mast cells correlate with ICAM expression in human EoE. Mechanistically, we show that IL-18 in vitro stimulates iNKT cells and endothelial cells and induce eosinophil active cytokines IL-5 and IL-13. We provide the evidence that IL-18 is critical cytokine involved in activation of iNKT cells and ICAM in promoting human EoE. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is often misdiagnosed as GERD; therefore, the goal of the current study is to establish a non-invasive diagnostic and monitoring biomarker that differentiated GERD from EoE. Reports indicates that IL-15 responsive iNKT cells and tissue specific IgE have a critical in EoE pathogenesis, not in GERD. Therefore, we tested the hypothesis that the panel of IL-15-responsive T cell and IgE receptors may be novel non-invasive biomarkers for EoE. Accordingly, the receptors of IL-15 responsive T cells (Vα24, Jα18, γδT, αβT) and IgE (FcεRI & FcεRII) were examined. The data indicates that blood mRNA levels of Vα24, Jα18, γδ T, αβ T and FcεRI are significantly reduced in EoE compared to the GERD patients and normal individuals. The ROC curve analysis indicated FcεRII, Jα18 and δ TCR are the positive predictors that discriminate EoE from GERD. Thus, these molecules will be a novel non-invasive diagnostic biomarker for EoE. • Decreased blood IL-15Rα mRNA levels differentiate EoE and GERD patient.. • Decreased blood mRNA levels of IL-15 responsive γδ T cells receptors differentiate EoE and GERD patient. • Decreased blood mRNA levels of IL-15 responsive iNKT cell receptors and IgE receptors differentiate EoE and GERD patient. • The levels of blood T cell receptors mRNA in EoE & GERD with perfect ROC curves establishes non-invasive biomarker for EoE. [ABSTRACT FROM AUTHOR]