Eosinophil-predominant Inflammation Research Articles

A Mouse Model for Eosinophilic Esophagitis (EoE).

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

Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.

Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases.

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

Novel corticosteroid formulations in the treatment of eosinophilic esophagitis: what is the evidence?

Eosinophilic esophagitis (EoE) is a food allergen-induced disease of the esophagus. Chronic, eosinophil-predominant inflammation eventually leads to fibrosis, esophageal dysfunction and severe morbidity. Swallowed topical corticosteroids (STCs) are a mainstay of anti-inflammatory therapy in the treatment of active EoE. Data on the efficacy of novel corticosteroid formulations, developed specifically for esophageal delivery, have recently become available. A comprehensive review was performed aiming to summarize evidence on the role of STCs in the treatment of EoE. Two biomedical bibliographic databases (PubMED, EMBASE) were searched for articles providing original information on the efficacy and safety of STCs in adult EoE patients. Budesonide orodispersible tablet (BOT) and budesonide oral suspension (BOS) both surpassed placebo formulations regarding the efficacy of inducing and maintaining histologic, symptomatic and endoscopic remission. Overall, BOT displayed the highest grade of efficacy with clinico-histologic remission rates up to 75% after 1 year. Fluticasone propionate (APT-1011) achieved and maintained histologic and endoscopic responses in the majority of patients, whereas only a positive trend was demonstrated for symptomatic improvement. Mometasone and ciclesonide were studied in a limited number of smaller-scale trials and placebo-controlled data are required to substantiate the promising findings. All STCs displayed a similar side effects profile and were generally considered safe and well-tolerated. Current evidence supports long-term treatment with novel corticosteroid formulations, challenging the established treatment paradigm of EoE. BOT appears to be the most effective steroid therapy, although head-to-head comparative trials between STCs are needed.

An interesting case of dysphagia- eosinophilic esophagitis

Eosinophilic esophagitis (EE) is an atopic condition of the esophagus that has become increasingly recognized over the last decade. It is associated with a variety of esophageal symptoms such as dysphagia, food impaction and chest pain. It has a predilection for white males between the age of 30 and 40 years of age. EE is diagnosed based on the combination of typical esophageal symptoms and esophageal mucosal biopsies demonstrating squamous epithelial eosinophil-predominant inflammation. Hereby we present a case of 65-year-old female who presented with dysphagia and gastritis for 12 months duration.

Endotyping of nasal polyps in a multiracial Asian population

Background: Chronic rhinosinusitis is a heterogenous disease with variation in the endotypes of nasal polyps, with type 2 inflammation being more prevalent in Caucasian populations whereas Chinese populations are more heterogenous. We aim to describe the variation in endotypes for patients with chronic rhinosinusitis with nasal polyposis in our unique multiracial population. Methodology: Demographic, clinical and structured histopathological data of 66 patients who underwent sinus surgery for nasal polyposis were evaluated retrospectively. Results: 54.6% had eosinophilic disease, and 45.4% had non-eosinophilic disease with no significant demographic differences between the 2 populations. There were significantly higher peripheral eosinophil levels in patients with eosinophil-predominant inflammation on tissue histology (mean absolute eosinophil count 0.59 ± 0.18 x 109) compared with non-eosinophilic disease (mean absolute eosinophil count 0.24 ± 0.11 x 109). Structured histopathological reporting revealed that patients with eosinophilic disease had higher degree of inflammation and eosinophil aggregates. Conclusions: Our population is shown to have a slight preponderance toward eosinophilic disease, however the Chinese majority tended to have non-eosinophilic disease. Serum eosinophilia and the presence of asthma seems to correlate well with tissue eosinophilia, which can potentially be utilised as markers of type 2 inflammatory disease.

S2371 Ripped by Chips: A Case Report of Esophageal Perforation After Consumption of Chips

Introduction: Eosinophilic esophagitis (EoE) is an uncommon condition defined as a chronic, immune-mediated, esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.1 Patients typically present with esophageal dysphagia and food impaction. We present a unique and rare case presentation of a young male patient who presents with pneumomediastinum in the setting of undiagnosed EoE. Case Description/Methods: A 31-year-old male with no significant past medical history presents to the emergency department with lower neck pain. He reports sudden onset of pain after consuming a sandwich containing potato chips. This was followed by 2 immediate episodes of hematemesis. Vital signs were within normal limits. Physical exam was significant for bilateral crepitus on exam. CT Chest with contrast was significant for extensive pneumomediastinum around the esophagus suggestive of an esophageal perforation. CT neck was significant for extensive emphysema in the neck and pneumomediastinum with esophageal wall emphysema suggestive of esophageal rupture (Figure). An esophagram revealed no evidence of gross esophageal leak suggesting a contained micro perforation, so he was managed conservatively with IV pain medications, initial period of nil by mouth followed by slow escalation to a liquid diet. His diet was slowly escalated, and he was discharged home in stable condition. Two months later at an outpatient gastroenterology follow up, an esophagogastroduodenoscopy was significant for ringed esophagus, longitudinal furrows, white plaques and white specks throughout the entire esophagus. Biopsies were consistent with eosinophilic esophagitis with increase eosinophil count in the proximal esophagus. He was started on a daily proton pump inhibitor with ongoing follow up. Discussion: The incidence of EoE appears to be increasing, in part due to rising recognition of the disorder. It is important for physicians to identify its features early to prevent further complications. Esophageal perforation is a rare but serious complication of eosinophilic esophagitis, occurring in ∼2% of cases.2 Ongoing inflammation from longstanding untreated EoE has previously been reported to have led to esophageal perforation but rarely in such a dramatic fashion.3Figure 1.: 1. Significant emphysema in the neck and pneumomediastinum with thinning of the posterolateral aspect of esophagus concerning for esophageal rupture.

171. DELAYED DIAGNOSIS OF EOSINOPHILIC ESOPHAGITIS IN THOSE PRESENTING TO THE EMERGENCY DEPARTMENT WITH FOOD BOLUS IMPACTION

Abstract Food bolus impaction can be a manifestation of chronic untreated inflammation in those with underlying eosinophilic esophagitis (EoE). The eosinophil predominant inflammation of the esophagus is associated with a higher prevalence of fibrosis when it remains undetected and untreated. Non-malignant food bolus impaction is strongly associated with an underlying diagnosis of EoE, but outside of gastroenterology and other esophageal interested specialists there remains poor understanding of how to diagnose and manage this condition. We conducted a retrospective study of patients presenting to a tertiary emergency unit with esophageal food bolus impaction between November 2018 and May 2021. Electronic attendance records and the endoscopy database were examined to determine the associations between demographics, comorbidities, endoscopic findings, biopsy findings and follow up. We also evaluated the effect of the pandemic on food bolus management with statistical analysis undertaken using IBM SPSS software. Of the 938 patients who presented to the emergency department with food bolus impaction, 83.6% were sent home with no follow up. Only 7.2% went on to have an endoscopy. In those with macroscopic evidence of inflammation, only 35.8% of patients had the correct number of biopsies taken to establish a histological cause for their symptoms. 1.6% of patients demonstrated histological evidence of EoE, of whom 80% were male and 20% female. The COVID-19 lockdown did not negatively impact access to endoscopy with mean wait time improving from 121-days prior to lockdown compared to 69-days during lockdown, p < 0.01. Our findings highlight significant shortcomings in the management of those presenting emergently with food bolus impaction and possible undiagnosed EoE. There remains a need for clear management pathways to aid risk-stratification, discharge planning and endoscopic practices in the diagnosis of EoE. We therefore propose an algorithm for food bolus management to facilitate early endoscopy, effective diagnosis, and appropriate follow-up, ensuring optimal management for patients with non-malignant dysphagia requiring emergency admission for resolution of food impaction.

Current and emerging therapies for eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a Type-2 chronic inflammatory food antigen-driven disease of the esophagus, characterized by eosinophilic predominant inflammation and a constellation of symptoms. The incidence and prevalence of EoE has increased over the past 2 decades. There is an unmet need for approved less burdensome treatment options. Objective: To describe the underlying pathophysiology and diagnosis of EoE and discuss the currently available treatment options. We also aim to review the new and emerging therapies for EoE. Methods: A search of a medical literature data base was performed for articles that discuss treatment for EoE. Results: A comparison of current therapies showed that dietary elimination, swallowed topical corticosteroids, and proton-pump inhibitor therapy are all effective for different populations. Emerging therapies that were reviewed include new topical corticosteroids and biologics directed against Type 2 inflammation. Conclusion: EoE is a chronic inflammatory disorder that can be debilitating, with long-term sequelae. There are no current approved therapies in the United States. Numerous new treatments are on the horizon. Increasing amounts of data are helping to tailor treatment for each patient. Ultimately, shared decision-making is the best approach to guide treatment choices with patients to manage the ever-increasing burden of this disease.

Murine model of steroid-resistant neutrophilic bronchial asthma as an attempt to simulate human pathology

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, which is associated with neutrophilic inflammation and resistant to conventional corticosteroid therapy. Contrary to eosinophil-predominant airway inflammation neutrophilic BA is developed through Th1- and Th17-immune responses. However, the etiology of corticoid insensitive neutrophilic BA is still remains unclear. Therefore, in the current study we developed a mouse model of BA with predominant neutrophilic rather than eosinophilic pulmonary inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund's adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed the main BA manifestations: production of allergen specific IgE, development of airway hyperreactivity, airway remodeling and pulmonary neutrophilic inflammation. Moreover, this pathology developed through Th1- and Th17-dependent mechanisms and mice with induced neutrophilic BA phenotype responded poorly to dexamethasone treatment, that coincide to clinical observations. The established mouse model could be useful both for studying the pathogenesis and for testing novel approaches to control neutrophilic BA.

Diagnosis and Treatment of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. The diagnostic criteria for EoE have changed with our growing knowledge over the past two decades. Esophageal eosinophilia, which responds histologically to a proton pump inhibitor (PPI) is not a distinct disease but a subset of EoE. An endoscopic scoring system that relies on the assessment of exudates, rings, edema, furrows, and strictures is a useful tool for assessing endoscopic severity. PPIs are regarded as safe and effective first-line treatments for EoE. Oral topical corticosteroids or dietary therapy are also options for first-line treatment. Endoscopic dilation is effective for relieving the dysphagia symptoms of a patient with an esophageal stricture.

Synergistic effect of roflumilast with dexamethasone in a neutrophilic asthma mouse model.

Asthma is a chronic airway inflammatory disease with heterogeneous features. Most cases of asthma are steroid sensitive, but 5%-10% are unresponsive to steroids, leading to challenges in treatment. Neutrophilic asthma is steroid-resistant and characterized by the absence or suppression of the T-helper type II (TH 2) process and an increase in the TH 1 and/or TH 17 process. Roflumilast (ROF) has anti-inflammatory effects and has been used to treat chronic inflammatory airway diseases, such as chronic pulmonary obstructive disease. It is unclear whether ROF may have a therapeutic role in neutrophilic asthma. In this study, we investigated the synergistic effect of ROF with dexamethasone (DEX) in a neutrophilic asthma mouse model. C57BL/6 female mice sensitized to ovalbumin (OVA) were exposed to five intranasal OVA treatments and three intranasal lipopolysaccharide (LPS) treatments for an additional 10days. During the intranasal OVA challenge, ROF was administrated orally, and DEX was injected intraperitoneally. Protein, pro-inflammatory cytokines, inflammatory cytokines and other suspected markers were identified by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and western blot. Following exposure to LPS in OVA-induced asthmatic mice, neutrophil predominant airway inflammation rather than eosinophil predominant inflammation was observed, with increases in airway hyperresponsiveness (AHR). The lungs of animals treated with ROF exhibited less airway inflammation and hyperresponsiveness. To investigate the mechanism underlying this effect, we examined the expression of proinflammatory cytokines suspected to be involved in inflammatory cytokines and proteins. Roflumilast reduced total protein in bronchioalveolar lavage fluid; levels of interleukin (IL)-17A, IL-1β messenger RNA, interferon γ and tumour necrosis factor α; and recovered histone deacetylase-2 (HDAC2) activity. Combination therapy with ROF and DEX further reduced the levels of IL-17, IL-22 and IL-1β mRNA and proinflammatory cytokines. The combination of ROF and DEX reduced lung inflammation and AHR much more than one of them alone. Roflumilast reduces AHR and lung inflammation in the neutrophilic asthma mouse model. Furthermore, additive effects were observed when DEX was added to ROF treatment, possibly because of recovery of HDAC2/β-actin activity. This study demonstrates the anti-inflammatory properties of ROF in a neutrophilic asthma mouse model.

A128 PATIENT CHARACTERIZATION AND ASSESSMENT OF REMISSION RATES IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS AFTER INITIAL TREATMENT AND 1-YEAR POST-DIAGNOSIS

BackgroundEosinophilic esophagitis (EoE) is a chronic immune- or antigen-mediated esophageal disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. With incidence rates rapidly increasing, EoE is the leading cause of food bolus impaction and the second leading cause of chronic esophagitis. The treatment of EoE includes both induction and maintenance therapy to prevent complications including esophageal fibrosis and strictures. Despite significant advances in the diagnosis and treatment of EoE, the natural history and long-term management of the disease remains poorly understood.AimsTo describe the clinical characterization of children with EoE, and to assess remission rates after initial treatment and 1-year post-diagnosis.MethodsIn this ongoing, single-center retrospective study, the electronic medical charts of children newly diagnosed with EoE between January 2017-March 2021 participating in the EoE-AHEAD Registry study were reviewed. Children aged 6 months-18 years with a confirmed diagnosis of EoE based on consensus guidelines and receiving outpatient care at the SickKids EoE clinic were included.ResultsA total of 37 children with a median age of 11 years (IQR: 4.5, 12.5) were included, the majority of which were male (86.5%). Demographic and clinical characteristics are shown in Table 1. On initial treatment, 2.7% of children were on an elemental diet, 18.9% on a food elimination diet, 40.5% on proton-pump inhibitor (PPI) therapy, 16.2% on topical steroids, 8.1% on systemic steroids, and 13.5% on a combination therapy. Of the 30 children with a second endoscopy (mean interval since diagnosis of 6.1 months (3.9)), 30% achieved histological remission after the initial treatment (see Figure 1). Of the 14 children with a one-year follow-up endoscopy, 14.2% were in remission, 3 of which had relapsed. No significant differences in treatment modality were found between those who achieved remission and those who did not.ConclusionsThis is the first Canadian registry study to examine the longitudinal outcomes of EoE in a pediatric setting. Our preliminary results show that only 30% of children achieved histological remission following first-line treatment. The choice of initial therapy varied, although the majority of patients (62.2%) were prescribed a PPI and/or a topical steroid. Our findings highlight the importance of identifying different disease phenotypes to develop personalized therapeutic approaches for the management of EoE.Demographic and clinical characterization (n=37)Age, year (median, IQR)11 (4.5, 12.5)Sex (% Male)86.5%Ethnicity (% Caucasian)40.9%Personal history of atopy91.9%Family history of atopy73.0% Funding AgenciesSickKids start-up funds (JM Hulst) and the Comprehensive Research Experience for Medical Students (CREMS) Program

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis.

To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109 /liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (-3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (-1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77-91%) and the specificity was 99% (95% CI 98-100%). The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research.

GATA-3 and T-bet as diagnostic markers of non-esophageal eosinophilic gastrointestinal disease

Eosinophilic gastrointestinal diseases (EGID) represent a spectrum of disorders classically defined by eosinophil-predominant inflammation. Currently, there are no consensus diagnostic criteria for non-esophageal EGIDs. In contrast to the esophagus, eosinophils are resident cells in the gastrointestinal mucosa; therefore, establishing histologic thresholds indicative of pathology is more challenging. EGID are associated with Th2 inflammation. The master transcriptional regulators of Th1 and Th2 inflammation are T-bet and GATA-3, respectively.

Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort.

Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field (P = 0.0002). Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.

Evidence-based treatments for eosinophilic esophagitis: insights for the clinician.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients’ age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE.

High-Resolution Esophageal Manometric Features in Eosinophilic Esophagitis Patients: A Retrospective Study

<h3>Background and Aims</h3> Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disease characterized by symptoms related to esophageal dysfunction and eosinophil-predominant inflammation. The aims of our study included (1) to assess esophageal motility patterns of EoE by topographic analysis of high-resolution manometry (HRM) and (2) to establish a relationship between symptoms of EoE and motility abnormalities seen on HRM. <h3>Methods</h3> A retrospective study in which all adult patients over 18 years of age with EoE diagnosed by endoscopy and histology and who underwent HRM were included in the study during the study period. Motility patterns in patients with EoE under HRM were analyzed. Data were presented as frequencies and percentages with inference by Pearson's chi-square test or Fisher's exact test. <h3>Results</h3> Seven hundred patients diagnosed with EoE were noted, and of these, 38 patients had undergone esophageal HRM. Fifty-eight percent of these patients were noted to have an esophageal motility abnormality on HRM. Thirty-seven percent of the patients showed absent peristalsis with pan-esophageal pressurization but normal integrate relaxation pressure; 21% of the patients showed peristaltic dysfunction; and 42% of the patients had a normal HRM. Seventy-one percent of the patients with pan-esophageal pressurization presented with food impaction requiring endoscopy for disimpaction and esophageal dilation (<i>P</i> = .015). <h3>Conclusion</h3> The most common abnormality noted was aperistalsis with pan-esophageal pressurization. This abnormality correlated with the clinical presentation of bolus impaction requiring an endoscopic intervention (<i>P</i> = .015).

Molecular Mechanisms of Eosinophilic Esophagitis.

Food hypersensitivity is a group of diseases arising from a specific immune response that reproduces on exposure to a given food. The current understanding of molecular mechanisms and immunopathology of non-IgE-mediated/mixed food hypersensitivity, e.g., eosinophilic esophagitis, contains many gaps in knowledge. This review aims to provide a modern classification and identify the primary diseases of non-IgE-mediated/mixed food hypersensitivity reactions, delineate the distinctive molecular features, and discuss recent findings in the immunopathology of eosinophilic esophagitis that may become a basis to develop valid biomarkers and novel therapies for this disease. Eosinophilic esophagitis is a recently recognized allergic-mediated disease with eosinophil-predominant esophagus inflammation. Its pathogenesis is a complicated network of interactions and signaling between epithelial, mesenchymal, and immune cells on molecular and intercellular levels. Alterations produced by overactivation of some cytokine signaling pathways, e.g., IL-13 or thymic stromal lymphopoietin (TSLP), were evolved and observed in this review from the viewpoints of molecular, genetic, epigenetic, and transcriptomic changes. Despite substantial experimental data, the reliable and representative mechanism of eosinophilic esophagitis pathogenesis has yet to show itself. So, the place of esophagitis between mixed and non-IgE-mediated allergic disorders and between eosinophilic gastrointestinal disorders currently seems vague and unclear.