Pathogenesis Of Eosinophilic Esophagitis Research Articles

Esophageal ILC2s mediate abnormal epithelial remodeling in eosinophilic esophagitis via Areg-EGFR signaling.

Eosinophilic esophagitis (EoE) is a chronic allergic disorder characterized by eosinophilia and epithelial thickening, resulting in dysphagia. While emerging evidence implicates increased frequencies of group 2 innate lymphoid cells (ILC2s) and increased interleukin (IL)-33 expression in EoE pathogenesis, the precise mechanisms remain unclear. In this study, we investigated the role of ILC2s in EoE pathogenesis. We observed an abundance of KLRG1+ ILC2s in the esophagi of healthy mice, with their numbers significantly increasing in murine EoE models and humans. Using a murine EoE model, we demonstrated the recapitulation of EoE-associated features, including basal-cell hyperproliferation, epithelial thickening, and eosinophilia. Notably, these characteristics are absent in ILC-deficient mice, whereas mice lacking IL-5 or eosinophils display epithelial defects, highlighting the pivotal role of ILC2s in EoE pathogenesis. Further investigations revealed increased amphiregulin (Areg) production by esophageal ILC2s in mice. The administration of Areg induced epithelial defects similar to those observed in EoE. Mechanistic studies using human esophageal cell lines revealed Areg-induced phosphorylation of epidermal growth factor receptor (EGFR). Significatntly, treatment with anti-Areg agents and EGFR inhibitors effectively attenuated EoE development, highlighting the therapeutic potential of targeting the Areg-EGFR axis.

Advances in omics data for eosinophilic esophagitis: moving towards multi-omics analyses.

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus characterized by eosinophil accumulation and has a growing global prevalence. EoE significantly impairs quality of life and poses a substantial burden on healthcare resources. Currently, only two FDA-approved medications exist for EoE, highlighting the need for broader research into its management and prevention. Recent advancements in omics technologies, such as genomics, epigenetics, transcriptomics, proteomics, and others, offer new insights into the genetic and immunologic mechanisms underlying EoE. Genomic studies have identified genetic loci and mutations associated with EoE, revealing predispositions that vary by ancestry and indicating EoE's complex genetic basis. Epigenetic studies have uncovered changes in DNA methylation and chromatin structure that affect gene expression, influencing EoE pathology. Transcriptomic analyses have revealed a distinct gene expression profile in EoE, dominated by genes involved in activated type 2 immunity and epithelial barrier function. Proteomic approaches have furthered the understanding of EoE mechanisms, identifying potential new biomarkers and therapeutic targets. However, challenges in integrating diverse omics data persist, largely due to their complexity and the need for advanced computational methods. Machine learning is emerging as a valuable tool for analyzing extensive and intricate datasets, potentially revealing new aspects of EoE pathogenesis. The integration of multi-omics data through sophisticated computational approaches promises significant advancements in our understanding of EoE, improving diagnostics, and enhancing treatment effectiveness. This review synthesizes current omics research and explores future directions for comprehensively understanding the disease mechanisms in EoE.

From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the "atopic march" picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.

Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model.

Eosinophilic esophagitis (EoE) is a chronic T helper type 2 (Th2)-associated inflammatory disorder triggered by food allergens, resulting in esophageal dysfunction through edema, fibrosis, and tissue remodeling. The role of epithelial remodeling in EoE pathogenesis is critical but not fully understood. To investigate the role of epithelial IKKβ/NFκB signaling in EoE pathogenesis using a mouse model with conditional Ikk β knockout in esophageal epithelial cells ( Ikk β EEC-KO ). EoE was induced in Ikkβ EEC-KO mice through skin sensitization with MC903/Ovalbumin (OVA) followed by intraesophageal OVA challenge. Histological and transcriptional analyses were performed to assess EoE features. Single-cell RNA sequencing (scRNA-seq) was used to profile esophageal mucosal cell populations and gene expression changes. Ikkβ EEC-KO /EoE mice exhibited hallmark EoE features, including eosinophil infiltration, intraepithelial eosinophils, microabscesses, basal cell hyperplasia, and lamina propria remodeling. RNA-seq revealed significant alterations in IKKβ/NFκB signaling pathways, with decreased expression of RELA and increased expression of IKKβ negative regulators. scRNA- seq analyses identified disrupted epithelial differentiation and barrier integrity, alongside increased type 2 immune responses and peptidase activity. Our study demonstrates that loss of epithelial IKKβ signaling exacerbates EoE pathogenesis, highlighting the critical role of this pathway in maintaining epithelial homeostasis and preventing allergic inflammation. The Ikkβ EEC-KO /EoE mouse model closely mirrors human EoE, providing a valuable tool for investigating disease mechanisms and therapeutic targets. This model can facilitate the development of strategies to prevent chronic inflammation and tissue remodeling in EoE. Critical Role of Epithelial IKKβ/NFκB Signaling: Loss of this signaling exacerbates EoE, causing eosinophil infiltration, basal cell hyperplasia, and tissue remodeling, highlighting its importance in esophageal health.Molecular Insights and Therapeutic Targets: scRNA-seq identified disrupted epithelial differentiation, barrier integrity, and enhanced type 2 immune responses, suggesting potential therapeutic targets for EoE. Relevance of the Ikkβ EEC-KO /EoE Mouse Model: This model replicates human EoE features, making it a valuable tool for studying EoE mechanisms and testing treatments, which can drive the development of effective therapies. This study reveals the crucial role of epithelial IKKβ/NFκB signaling in EoE, providing insights into disease mechanisms and potential therapeutic targets, highly relevant for advancing clinical management of EoE.

Causality of Helicobacter pylori infection on eosinophilic esophagitis and potential pathogenesis: a Mendelian randomization study.

Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE. Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.

Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis.

Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients. Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by "limma" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated. The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees. The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.

In Vivo Raman Spectroscopy Reveals Biochemical Composition of the Esophageal Tissue in Pediatric Eosinophilic Esophagitis.

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). 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. 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. 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.

Eosinophilic esophagitis as a side-effect of allergen immunotherapy: protocol for a systematic review and meta-analysis.

Background. Sensitization to food and airborne allergens is common in the majority of patients with eosinophilic esophagitis (EoE). Although there is not a direct cause-effect relationship of IgE-mediated allergy with the pathogenesis of EoE, there is a growing evidence that oral desensitization to food and sublingual immunotherapy (SLIT) may induce the development of EoE as an adverse effect. As part of the 'EoE and Allergen Immunotherapy (AIT)' Task Force funded by the European Academy of Allergy and Clinical Immunology (EAACI), a systematic approach will be followed to review the evidence from the published scientific literature on the development of EoE in children and adults under any type of AIT. Methods. This systematic review will be carried out following the PRISMA statement guidelines. Studies will be assessed for inclusion in the review according to the Population-Interventions-Comparators-Outcomes (PICO) criteria. Results. Expected outcomes will provide evidence on the AIT-EoE development connection. Conclusions. The findings from this review will be used as a reference to provide useful guidelines for physicians treating patients with EoE and/or are practicing AIT.

The role of dupilumab in the treatment of eosinophilic esophagitis.

Dupilumab has been approved to treat a variety of atopic disorders and was the first US FDA-approved medication for the treatment of eosinophilic esophagitis (EoE), initially approved in May 2022, with expansion in use to patients as young as 1year of age weighing at least 15 kg in January 2024. It is a fully human monoclonal antibody that inhibits both IL-4 and IL-13 signaling, suppressing TH2-mediated proinflammatory cytokines, chemokines and IgE implicated in EoE pathogenesis. Phase II and III trials in EoE have demonstrated histologic, endoscopic and symptomatic improvement in disease activity with an overall favorable safety profile. This article will review the available clinical trial data and real-world efficacy of dupilumab in EoE.

Changes in mucosal IgG4+- and IL-10+-cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet

Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variables were correlated with histologic measures of disease activity. Patients exhibited significant reduction in esophageal eosinophilia and overall histology. A significant decrease in IL-10+-cell frequencies correlated with histologic changes. In contrast, a decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10+-cell frequencies or histologic parameters. These results suggest a critical role of IL-10 in EoE pathogenesis. Conversely, IgG4 expression, while reflecting exposure to food antigens, is not obviously related to EoE histopathology or IL-10 expression.

Mechanistic Insights into Eosinophilic Esophagitis: Therapies Targeting Pathophysiological Mechanisms.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies.

A Practical Update on Pediatric Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emerging atopic disease of unknown etiology limited to the esophagus. The pathogenesis is still understood and is likely characterized by type 2 inflammation. Food allergens are the primary triggers of EoE that stimulate inflammatory cells through an impaired esophageal barrier. In children and adolescents, clinical presentation varies with age and mainly includes food refusal, recurrent vomiting, failure to thrive, abdominal/epigastric pain, dysphagia, and food impaction. Upper-gastrointestinal endoscopy is the gold standard for diagnosing and monitoring EoE. EoE therapy aims to achieve clinical, endoscopic, and histological ("deep") remission; prevent esophageal fibrosis; and improve quality of life. In pediatrics, the cornerstones of therapy are proton pump inhibitors, topical steroids (swallowed fluticasone and viscous budesonide), and food elimination diets. In recent years, much progress has been made in understanding EoE pathogenesis, characterizing the clinical and molecular heterogeneity, and identifying new therapeutic approaches. Notably, clinical, molecular, endoscopic, and histological features reflect and influence the evolution of inflammation over time and the response to currently available treatments. Therefore, different EoE phenotypes and endotypes have recently been recognized. Dupilumab recently was approved by FDA and EMA as the first biological therapy for adolescents (≥12 years) and adults with active EoE, but other biologics are still under consideration. Due to its chronic course, EoE management requires long-term therapy, a multidisciplinary approach, and regular follow-ups.

TSLP shapes the pathogenic responses of memory CD4+ T cells in eosinophilic esophagitis.

The cytokine thymic stromal lymphopoietin (TSLP) mediates type 2 immune responses, and treatments that interfere with TSLP activity are in clinical use for asthma. Here, we investigated whether TSLP contributes to allergic inflammation by directly stimulating human CD4+ T cells and whether this process is operational in eosinophilic esophagitis (EoE), a disease linked to variants in TSLP. We showed that about 10% of esophageal-derived memory CD4+ T cells from individuals with EoE and less than 3% of cells from control individuals expressed the receptor for TSLP and directly responded to TSLP, as determined by measuring the phosphorylation of STAT5, a transcription factor activated downstream of TSLP stimulation. Accordingly, increased numbers of TSLP-responsive memory CD4+ T cells were present in the circulation of individuals with EoE. TSLP increased the proliferation of CD4+ T cells, enhanced type 2 cytokine production, induced the increased abundance of its own receptor, and modified the expression of 212 genes. The epigenetic response to TSLP was associated with an enrichment in BATF and IRF4 chromatin-binding sites, and these transcription factors were induced by TSLP, providing a feed-forward loop. The numbers of circulating and esophageal CD4+ T cells responsive to TSLP correlated with the numbers of esophageal eosinophils, supporting a potential functional role for TSLP in driving the pathogenesis of EoE and providing the basis for a blood-based diagnostic test based on the extent of TSLP-induced STAT5 phosphorylation in circulating CD4+ T cells. These findings highlight the potential therapeutic value of TSLP inhibitors for the treatment of EoE.

Eosinophilic esophagitis and esophageal microbiota.

Eosinophilic esophagitis (EoE) is an antigen-mediated chronic inflammatory disease of the esophagus, the prevalence of which has steadily increased in recent years. The pathogenesis of EoE is not yet well-defined; however, recent studies have demonstrated that the esophageal microbiota is an essential regulator of physiological and pathological processes of EoE. Currently, research on EoE and microbiota is an emerging field of study that is receiving increasing attention. Here, we review existing EoE-related esophageal microbiota studies to explore the potential mechanisms underlying esophageal microbiota-mediated EoE. The esophageal microbiome is altered in patients with EoE. Although α diversity is usually not significantly different, an increase in Haemophilus and a decrease in Firmicutes were observed in EoE patients. The role of microbiota in initiating and perpetuating inflammation is not fully understood. Current evidence suggests that the penetration of microbiota leads to the activation of epithelial cells as well as innate and adaptive immune cells, with the subsequent release of cytokines, leading to immune responses and inflammation. The involvement of toll-like receptors in EoE also supports the potential role of the microbiota in the progression of this disease. While EoE-induced inflammation can also lead to alterations in the local microbiome. Moreover, dietary modifications, proton pump inhibitors, and corticosteroids can modulate the esophageal microbiota; however, definitive conclusions about the alterations of microbes after treatment cannot be drawn. These findings provide promising avenues for future studies.

Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis

The current report describes a stepwise mechanistic pathway of NLRP3/caspase1/IL-18-regulated immune responses operational in eosinophilic esophagitis (EoE). We show that esophageal epithelial cells and macrophage-derived NLRP3 regulated IL-18 initiate the disease and induced IL-5 facilitates eosinophil growth and survival. We also found that A. fumigatus-exposed IL-18−/− mice or IL-18-neutralized mice are protected from EoE induction. Most importantly, we present that intravascular rIL-18 delivery to ΔdblGATA mice and CD2-IL-5 mice show the development of EoE characteristics feature like degranulated and intraepithelial eosinophils, basal cell hyperplasia, remodeling and fibrosis. Similarly, we show an induced NLRP3-caspase1-regulated IL-18 pathway is also operational in human EoE. Lastly, we present the evidence that inhibitors of NLRP3 and caspase-1 (MCC950, BHB, and VX-765) protect A. fumigatus- and corn-extract-induced EoE pathogenesis. In conclusion, the current study provides a new understanding by implicating NLRP3/caspase1-regulated IL-18 pathway in EoE pathogenesis. The study has the clinical significance and novel therapeutic strategy, which depletes only IL-18-responsive pathogenic eosinophils, not naïve IL-5-generated eosinophils critical for maintaining innate immunity.

Food allergy: cause or consequence of pediatric eosinophilic esophagitis? Potential implications of ultraprocessed foods in prevention and management.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by eosinophilic infiltration, leading to esophageal dysfunction, inflammation, and fibrotic remodeling. In the last few decades, there has been an increased prevalence of EoE at an alarming rate in the pediatric age. The pathogenesis of EoE is still largely undefined, and this limits the definition of effective strategies for the prevention and management of this condition. EoE is considered a multifactorial disease arising from a negative interaction between environmental factors and genetic background, causing an impaired esophageal epithelial barrier with subsequent abnormal allergen exposure activating type 2 (Th2) inflammation. Food antigens have been suggested as key players in Th2 inflammation in pediatric patients with EoE, but emerging evidence suggests a potential role of other dietary factors, including ultraprocessed foods, as possible triggers for the occurrence of EoE. In this paper, we discuss the potential role of these dietary factors in the development of the disease, and we propose a new approach for the management of pediatric patients with EoE.

Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology.

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. 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). 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. 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.

The role of biologics in the pathogenesis and treatment of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder characterized by inflammation, and intraepithelial infiltration of eosinophils in the esophageal epithelium. It is associated with unbearable symptoms, such as dysphagia, and bolus impaction which affect the nutritional status, and quality of life of the patients. It is diagnosed from a thorough medical history, and confirmed by endoscopy and esophageal biopsy. Traditionally, it has been treated with elimination diet, proton pump inhibitors, and swallowed topical corticosteroids. However, several of the patients with EoE are refractory to the treatment. Eosinophilic esophagitis like eosinophilic asthma is a T helper type 2 lymphocyte (Th2)-mediated allergic disease. During an allergic inflammation Th2 cells secrete cytokines, such as interleukin-5 (IL-5). IL-4, and IL-13 which play a key role in the pathogenesis of EoE. Th2 cytokines promote eosinophilopoiesis, differentiation, proliferation, maturation and activation of eosinophils. Activated eosinophils liberate several cytotoxic cationic proteins, and reactive oxygen species which cause epithelial injury, inflammation, and remodeling, which later progresses to esophageal fibrosis. Dupilumab (dupixent®)is a monoclonal antibody which target the IL-4 receptor (IL-4Rα) which signals for both IL-4 and IL-13. Dupilumab is the only biologic which is effective, and approved for the treatment of EoE in adults and children 12 years and older. Treatment with dupixent® has been shown to improve dysphagia, dilate and relax the gullet, and allow patients to enjoy their cherished dish. Biologics such as dupilumab should be administered early in patients with EoE in order to prevent the menacing complications of the disease, such as esophageal stricture, and esophageal perforation, which necessitate surgical esophageal dilatation, and repair.

Oral detergent exposure alters the esophageal microbiome and induces eosinophilic inflammation

Detergent exposure is a possible environmental factor recently implicated in the pathogenesis of eosinophilic esophagitis (EoE). We have shown the detergent sodium dodecyl sulfate (SDS) induces epithelial barrier dysfunction and eosinophilic inflammation in mice. We aimed to examine changes in the mouse esophageal microbiome following SDS exposure.

Эозинофильные заболевания желудочно-кишечного тракта. Эозинофильный энтерит у детей

Aim. To analyze current data on epidemiology, pathophysiology of eosinophilic gastrointestinal diseases (EGID) in children with focus on small intestinal affection. Key points. EGID are inflammatory conditions of the gastrointestinal tract, characterized by tissue eosinophilia with a depth of organ damage from the mucous layer to the muscular and serous layer, resulting in severe damage to their structure and function. Importance of food allergy is still underestimated, although it affects about 5% of children and up to 3–4% of adults. Eosinophilic diseases of the digestive tract are receiving close attention from experts all over the world. A few decades ago, these diseases were described as rare and articles presented isolated clinical cases, but nowadays the publications have increased by several times. There is increasing evidence of the role of aeroallergens and food allergens in the pathogenesis of eosinophilic esophagitis, gastritis, and enteritis, as children and adults with EGID are often found to have positive skin tests for food allergens and/or a family history of allergic diseases. Keywords: eosinophilic disorders of the gastrointestinal tract, eosinophilic gastrointestinal diseases, eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, food allergy, atopy