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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: There is likely variation in approach and management of patient with EoE due to lack of standardized care and variation in guidelines. We aimed to identify current practices regarding diagnosis and treatment in children with eosinophillic esophagitis (EoE) in Australia and New Zealand (ANZ). Methods: Information on current diagnostic and management approaches for pediatric EoE was collected via an online survey sent to pediatric gastroenterologists (pGE) in ANZ. We performed a cross-sectional study of pGE using a 49-question instrument regarding evaluation, diagnostic, and therapeutic aspects of EoE between October 2019 and December 2019. Results: Eighty-five percent of the survey responders were from Australia, and 66% were academic. 30% pGE perform > 3 esophageal biopsies for diagnosis of EoE, 40% involve an allergist, 30% use a twice daily PPI trial, and 70% do not exclude other cause of esophageal eosinophilia. For management, only 3% use dietary elimination as an initial therapy, and 24% use less than the recommended doses of swallowed fluticasone. Forty-nine percent were likely to stop treatment in after remission is achieved for 12 months. The EoE endoscopic reference score (EREFS) was not routinely used (49%). Two-thirds of pGE are concerned about long-term effects of recurrent need of general anesthesia. Conclusions: Diagnostic and management strategies for EoE differed widely among pGE in ANZ, including in diagnostic biopsies, assessing competing causes of esophageal eosinophilia, initials selection of treatments, and maintenance strategies. This variability likely reflects continued uncertainty regarding optimal management strategies and stresses the need for pediatric-specific ANZ guidelines to standardize EoE care. [ABSTRACT FROM AUTHOR]

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

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

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

Eosinophilic gastrointestinal diseases (EGIDs) are an emerging group of pathological entities characterized by an eosinophil-predominant infiltration of different tracts of the gut in the absence of secondary causes of eosinophilia. According to the specific tract of the gut involved, EGIDs can be classified into eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The epidemiology of EGIDs is evolving rapidly. EoE, once considered a rare disease, now has an incidence and prevalence of 7.7 new cases per 100,000 inhabitants per years and 34.4 cases per 100,000 inhabitants per year, respectively. Fewer data are available regarding non-EoE EGIDs, whose prevalence are estimated to range between 2.1 and 17.6 in 100,000 individuals, depending on age, sex, and ethnicity. Diagnosis requires the presence of suggestive symptoms, endoscopic biopsies showing abnormal values of eosinophils infiltrating the gut, and exclusion of secondary causes of eosinophilia. EoE typically presents with dysphagia and episodes of food bolus impactions, while EoG, EoN, and EoC may all present with abdominal pain and diarrhea, with or without other non-specific symptoms. In addition, although different EGIDs are currently classified as different entities, there may be overlap between different diseases in the same patient. Despite EGIDs being relatively novel pathological entities, the research on possible treatments is rapidly growing. In this regard, several randomized controlled trials are currently ongoing to investigate novel molecules, including ad-hoc steroid formulations, immunosuppressants, and mostly monoclonal antibodies that target the specific molecular mediators of EGIDs. This narrative review provides an up-to-date overview of available and investigational drugs for different EGIDs. [ABSTRACT FROM AUTHOR]

Introduction: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. Methods: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. Results: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94–5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). Discussion/Conclusion: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory condition with tissue eosinophilia resulting in esophageal dysfunction. The six-food elimination diet (SFED) is an EoE treatment approach that removes milk, wheat, soy, eggs, tree nuts/peanuts, and fish/shellfish. After histologic remission, food reintroduction occurs to identify a food trigger. Outcomes from large series of adults undergoing SFED and food reintroduction as clinical care are not known. METHODS: A retrospective review (2006–2021) of adult patients with EoE from an academic center was completed. Patients were classified as full responders (<15 eos/hpf) after SFED. If reintroduction was pursued, food triggers identified were recorded. RESULTS: Two hundred thirteen patients completed SFED. One hundred fifteen patients (54%) had response <15 eos/hpf after SFED. Seventy-seven percent of responders had symptom improvement. Thirty-two percent of initial nonresponders underwent repeat dietary elimination. Fifty-eight percent of patients (n = 123) achieved <15 eos/hpf after either initial or extended SFED. Seventy-eight percent of responders underwent food reintroduction. Sixty-nine percent had 1 food trigger identified, 24% had 2 allergens identified, and 4% had 3 allergens identified. The most common food triggers identified were milk, wheat, and soy. DISCUSSION: This study describes the largest cohort reported of adult patients with EoE completing SFED with food reintroduction. The overall SFED histologic response was 54%, which increased to 58% with 1 additional round of dietary therapy, suggesting that 31% may respond in a second attempt. Most patients who completed food reintroduction had a single food trigger identified. Dietary elimination with specific food trigger identification is a feasible alternative to medical therapy for adults with EoE. [ABSTRACT FROM AUTHOR]

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

Rationale: Eosinophilic esophagitis (EoE) has emerged from a case‐reportable illness in the early 1990s to a distinct clinicopathological entity. Increasing worldwide incidences have been observed, although due to various study designs estimates are inconsistent. Aim: To determine population‐based annual incidence rates over a time period of 25 years. Methods: A nationwide register‐based pathology (PALGA) search was performed to identify reports describing esophageal eosinophilia between 1995 and 2019. EoE was identified if the diagnosis was confirmed by the pathologist. Crude incidence rates were estimated by the number of new EoE cases per year and matched with population data. Results: Between 1995 and 2019, 7361 unique patients' reports mentioned esophageal eosinophilia, of these 4061 were classified as EoE (71% male, mean age 37.9 ± 18.4 years). In total, 639 (16%) children (<18 years) were diagnosed. The EoE incidence increased from 0.01 in 1995 (95% CI: 0.0 – 0.04) to 3.16 (95% CI: 2.90 – 3.44) per 100.000 inhabitants in 2019. EoE was significantly more prevalent in males (OR 2.48 | 95% CI: 2.32 – 2.65; vs. females p < 0.001) and adults (OR 1.42 | 95% CI: 1.31 – 1.55; vs. children p < 0.001). Highest incidences were observed in 2019, being 4.37 (95% CI: 3.94 – 4.84) vs. 1.97 (95% CI: 1.68 – 2.29) per 100.000 males and females, respectively (p < 0.001). No seasonal variation was observed. Conclusion: Over the past quarter century, the annual rates of newly diagnosed EoE patients raised dramatically and this increase has not reached a deceleration yet. [ABSTRACT FROM AUTHOR]