Endoscopic Features of Eosinophilic Esophagitis.

Edema, rings, exudates, furrows, and strictures (EREFS) represent the major endoscopic features of eosinophilic esophagitis (EoE). The Endoscopic Reference System (EREFS) grading system is easy to learn and apply during daily clinical practice in the diagnosis and follow-up of EoE patients. When endoscopy is performed by an EoE-experienced physician, the EREFS criteria will identify the majority of EoE patients. The EREFS score from the area of greatest involvement of the esophagus should be reported. The EREFS grading system was formally validated as an endoscopy score and several randomized placebo-controlled trials have shown responsiveness of the EREFS score to therapeutic interventions.

Histopathology of Eosinophilic Esophagitis.

Microscopic examination of esophageal biopsies is essential to diagnose eosinophilic esophagitis (EoE). Eosinophil inflammation is the basis for the diagnosis, but additional abnormalities may contribute to persistent symptoms and epithelial barrier dysfunction. Both peak eosinophil count and assessments of additional features should be included in pre-therapy and post-therapy pathology reports. Pathologic abnormalities identified in esophageal biopsies of EoE are reversible in contrast to esophageal strictures.

Eosinophilic oesophagitis in a Nigerian adolescent: a case report.

Eosinophilic oesophagitis (EoE) is a chronic immune and antigen-mediated disease characterized by symptoms related to oesophageal dysfunction, and histologically, is marked by eosinophilic infiltrate in the oesophageal mucosa. It is prevalent in developed countries and considered rare in developing countries. There is an interplay of allergic and genetic factors in the aetiology of EoE. This is a report of EoE in a 15-year-old female adolescent in Nigeria who presented to the University of Calabar Teaching Hospital with recurrent vomiting, abdominal pain, weight loss, and dysphagia. She had received treatment for Gastro-oesophageal disease three years earlier and was lost to follow-up. Weight on admission was 39 kg and height 170 cm with a BMI below the 3rd centile. Peripheral blood showed an eosinophil count of four percent. The abdominal computed tomography (CT) scan and upper gastrointestinal (GI) series were normal. Faecal antigen for H. pylori and ova for stool parasites were negative. Histologic findings of proximal and distal oesophageal mucosal biopsies showed greater than 20 eosinophils per high power field. The histology of the stomach and duodenum were normal. She was initially treated with a protein pump inhibitor, with no improvement. Swallowed fluticasone propionate and eliminating peanuts, wheat, egg, and milk from her diet were introduced. Symptoms improved with the patient no longer vomiting and had an increase in weight gain. She was discharged to follow up. This case shows that EoE occurs in developing countries, but diagnosis may be missed. There is a need for a high index of suspicion among gastroenterologists in patients with symptoms suggestive of GERD not responding to therapy.

Eosinophilic Esophagitis: What the Otolaryngologist Needs to Know.

Eosinophilic esophagitis is a male-predominant disease with presentations ranging from nonspecific feeding issues to dysphagia and food impaction. The currently proposed pathophysiology is a combination of genetics, allergens, and epithelial barrier impairment. Diagnosis is reliant on history, endoscopic examination, and biopsy. Recent guidelines recognize the role of concurrent gastroesophageal reflux disease. Treatment is based on 3 paradigms: diet, drugs, and dilation. Drug therapy has historically focused on topical corticosteroids; as of 2022, dupilumab was approved for targeted biologic therapy. Dilation is reserved for symptomatic and anatomic management. As this clinical entity is better understood, additional therapies will hopefully be developed.

Sublingual immunotherapy for cedar pollinosis possibly triggers eosinophilic esophagitis.

Sublingual immunotherapy (SLIT) is an effective and popular treatment for cedar pollinosis. Although SLIT can cause allergic side effects, eosinophilic esophagitis (EoE) is a lesser-known side effect of SLIT. A 26-year-old male with cedar pollinosis, wheat-dependent exercise-induced anaphylaxis, and food allergies to bananas and avocados presented with persistent throat itching, difficulty swallowing, heartburn, and anterior chest pain 8 days after starting SLIT for cedar pollinosis. Laboratory examination showed remarkably elevated eosinophils, and esophagogastroduodenoscopy revealed linear furrows in the entire esophagus. Histological examination of an esophageal biopsy specimen revealed high eosinophil levels. The patient was strongly suspected with EoE triggered by SLIT. The patient was advised to switch from the swallow to the spit method for SLIT, and the symptoms associated with SLIT-triggered EoE were reduced after switching to the spit method. This case highlights the importance of recognizing SLIT-triggered EoE as a potential side effect of SLIT for cedar pollinosis, especially with the increasing use of SLIT in clinical practice. EoE can occur within a month after initiating SLIT in patients with multiple allergic conditions, as observed in our case. Furthermore, the spit method should be recommended for patients who experience SLIT-triggered EoE before discontinuing SLIT.

[Eosinophilic oesophagitis and eosinophilic gastrointestinal diseases].

INTRODUCTION: Eosinophilic oesophagitis (EoE) was first described as an orphan disease in the 1990s, but its incidence and prevalence has increased dramatically in the last 20 years. EoE is now the most common cause of dysphagia in young adulthood. EoE is diagnosed endoscopically (with biopsies taken from the oesophagus). Treatment options consist of dietary measures and medications. The latter include PPI (as an off-label medication) and the approved drugs Jorveza (budesonide, topical cortisone preparation) and the monoclonal antibody Dupixent (dupilumab, subcutaneous). The response to therapy is high and the long-term outcome, if treated early, is excellent. However, the disease often remains undetected, mostly due to compensation mechanisms on the part of the patients. Much rarer than EoE are the non-EoE eosinophilic gastrointestinal diseases (EGIDs), in which the eosinophilic tissue infiltration is found in gastrointestinal segments distal to the oesophagus. Their clinical presentation is often non-specific. Pathophysiologically, overlaps with EoE are present. Therapies are also analogous to EoE. An increasing prevalence and incidence is to be expected.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an atopic disease in which eosinophils infiltrate the esophageal mucosa and may result in a variety of upper gastrointestinal symptoms. Chief among these are dysphagia, heartburn, and food bolus obstruction in adults whereas children often present with abdominal pain or vomiting. Eosinophilic esophagitis is a chronic condition that if not detected and left untreated could lead to the development of subepithelial fibrosis and esophageal stenosis. The diagnosis of EoE is confirmed in a patient presenting with characteristic EoE symptoms, classic signs on endoscopy, and biopsy results showing >15 eosinophils/hpf. A number of useful treatments against EoE are currently available with new therapeutics on the horizon. The former include PPIs, topical steroids, and elimination diet; the latter comprise novel biologics including the monoclonal antibody dupilumab. All these treatments can improve symptoms and reduce esophageal eosinophil count. This brief introductory review describes the detection, diagnosis, and management of EoE.

A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation, but also heterogeneous presentations involving fibrostenotic esophageal remodeling and esophageal dysmotility. We aimed to define and evaluate phenotypes of EoE using functional lumen imaging probe (FLIP) panometry (ie, a PhysioMechanical classification of EoE). METHODS: Patients with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP studies were analyzed for distensibility plateau and compliance of the esophageal body, maximum esophagogastric junction diameter, and contractile response pattern. These FLIP features were then applied to define PhysioMechanical classifications. RESULTS: A total of 215 patients with EoE (mean [standard deviation] age 38 [12] years; 31% female) were included. Seven PhysioMechanical classifications were identified that differed by various clinical characteristics, including symptom duration (P < .001) and Endoscopic EoE Reference Scores (EREFS) (P < .001). In particular, patients with "nonreactive fibrostenosis" (n = 14), had greater symptom duration (median [interquartile range] 20 [10-30] years) and more frequently had EREFS grade 2 or 3 ring scores (14 of 14 patients) than patients with a "normal" PhysioMechanical classification (symptom duration: 3 [1-8] years; 4 of 50 [8%] had EREFS grade 2 or 3 rings). In addition, among patients off treatment at cross-sectional evaluation (n = 46), there was a difference between PhysioMechanical classifications in future proton pump inhibitor (PPI) response rates (ie, achieving peak mucosal eosinophil count <15 per high-powered field after PPI treatment); P = .009. PPI response ranged from 87% (13 of 15 patients) with "isolated esophagogastric junction outflow obstruction" to 11% (1 of 9 patients) with "spastic-reactive fibrostenosis." CONCLUSIONS: Classifying PhysioMechanical esophageal function in EoE based on FLIP panometry features may facilitate defining disease severity and directing management in EoE.

MicroRNA dysregulation and therapeutic opportunities in esophageal diseases.

MicroRNAs (miRNAs) are a class of small endogenous RNA molecules between 18 and 25 nucleotides long. The primary function of miRNAs is in the posttranscriptional regulation of mRNA targets through RNA interference culminating in mRNA degradation or translational repression. MiRNAs are fundamental in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and inflammation. Among this includes the uncovered potential of miRNAs in overall esophageal disease with a focus on the clinicopathologic allergic disease eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and the tumorigenic continuum from Barrett's esophagus (BE) toward esophageal adenocarcinoma (EAC). Although these pathologies are distinct from one another, they share pathophysiological elements such as an intense inflammatory milieu, esophageal dysfunction, and as presented in this review, an overlap in miRNA expression which contributes to overall esophageal disease. The overlap in the dysregulated miRNA transcriptome of these pathologies highlights the key role miRNAs play in contributing to esophageal disease progression. Owing to this notable dysregulation, there is an attractive utility for miRNAs as diagnostic and prognostic biomarkers in esophageal diseases that already require invasive endoscopies and biopsy retrieval. In this review miRNAs within EoE, GERD, BE, EAC, and esophageal achalasia are discussed, as well as reviewing a core set of miRNAs shared in the disease progression among some of these pathologies, along with the potential utility of targeting miRNAs as therapeutic options in overall esophageal disease.

Characterization of Eosinophilic Esophagitis in Infants and Toddlers.

OBJECTIVES: The objective of this study is to determine demographic and clinical characteristics of infants and toddlers <2 years with eosinophilic esophagitis (EoE) and to assess treatment response in this rarely studied pediatric age group. METHODS: Retrospective study of children <2 years diagnosed with EoE at a single center from 2016 to 2018. EoE was defined by ≥15 eosinophils per high power field (eos/hpf) on at least 1 esophageal biopsy. Demographics, symptoms, and endoscopic findings were collected via chart review. EoE treatment [proton pump inhibitor (PPI), swallowed steroids, dietary restriction, or a combination] and treatment responses on all follow-up endoscopies were reviewed, with remission defined as <15 eos/hpf. RESULTS: Forty-two children ages 1.3 ± 0.4 years underwent 3.8 ± 2.3 endoscopies over 3.6 ± 1.7 years of follow-up. Thirty-six children (86%) were male, and comorbidities included atopy (86%), reflux (74%), and a history of cow's milk protein allergy (40%). Common symptoms were feeding difficulties in 67% of patients (with gagging or coughing with feeding in 60% and difficulty with progression to pureed or solid foods in 43%), vomiting (57%), and coughing/wheezing (52%). Of the 37 patients with follow-up endoscopies, 25 (68%) had histologic remission. There was an effect of therapy type on histologic response ( P = 0.004) with the best responses seen on combinations of diet/steroids or diet/PPI and the worst response seen on PPIs alone. All patients showed improvement in ≥1 symptom at the time of first follow-up endoscopy. CONCLUSIONS: EoE should be considered in young children with feeding difficulties, vomiting, or respiratory symptoms. All patients improved clinically with standard medical or dietary interventions, however there is dissociation between clinical and histologic response with only 2 of 3 patients achieving histologic remission.

Endoscopy in Pediatric Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergen-mediated clinicopathologic condition that currently requires esophagogastroduodenoscopy with biopsies and histologic evaluation to diagnose and monitor its progress. This state-of-the art review outlines the pathophysiology of EoE, reviews the application of endoscopy as a diagnostic and therapeutic tool, and discusses potential complications related to therapeutic endoscopic interventions. It also introduces recent innovations that can enhance the endoscopist's ability to diagnose and monitor EoE with minimally invasive procedures and perform therapeutic maneuvers more safely and effectively.

Two cases of eosinophilic gastrointestinal disorder due to newly appearing food allergies after cord blood transplantation.

Eosinophilic gastrointestinal disorders (EGIDs) are infrequent complications after allogeneic hematopoietic cell transplantation (allo-HCT). Furthermore, it is well-known that allergic diseases are transferable after allo-HCT from allergic donors to non-allergic recipients. However, the type of graft-versus host disease (GVHD) prophylaxis that leads to allergic disease transfer is unclear. Furthermore, no study has reported a case of acquired food allergy resulting in EGID that was detected based on the clinical course and the detection of antigen-specific immunoglobulin E after allo-HCT. We encountered two patients with acute leukemia accompanied by eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) due to newly appearing food allergy after cord blood transplantation (CBT) with T-cell non-depletion GVHD prophylaxis. Despite having no history of allergic disease, the patients experienced allergic symptoms due to dairy products (Case 1) and eggs (Case 2) after CBT. They subsequently experienced severe nausea, heartburn, and anorexia (Case 1) and diarrhea (Case 2). Cases 1 and 2 were diagnosed with EoE and EGE, respectively, based on endoscopic and histological examinations. Dietary treatment without steroids improved the symptoms in both cases. These cases highlight that the unexpected transfer of food allergy after CBT can lead to EGIDs, especially in patients receiving T-cell non-depletion GVHD prophylaxis.

Quality Indicators for the Diagnosis and Management of Eosinophilic Esophagitis.

INTRODUCTION: Despite best practice recommendations for managing eosinophilic esophagitis (EoE), variation in care exists. METHODS: We used established methodology for quality indicator development to identify metrics to define quality for the treatment of EoE. RESULTS: Among 29 proposed quality indicator statements, 9 (31%) were adopted as highly valid across all categories. Two (22%) of these statements were identified as having existing or suspected quality gaps. DISCUSSION: We identified highly valid EoE quality indicators for adult gastroenterologists, which can be used for quality improvement with resulting benefits for patient outcomes.

Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice - International Expert Recommendations.

BACKGROUND & AIMS: There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor patients with EoE in routine clinical practice, on the basis of available clinical evidence and expert opinion. METHODS: A multidisciplinary, international group of EoE experts identified the following important 3 questions during several consensus meetings: why, by what means, and when to monitor patients with EoE. A steering committee was named, and 3 teams were formed to review literature and to formulate statements for each topic. In a Delphi survey, a level of agreement of ≥75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed, and statements were rephrased/rewritten if necessary. RESULTS: Eighteen EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university-based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring patients with EoE. Each statement attained ≥75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. CONCLUSIONS: It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured, and, under certain conditions, individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side effects, adjusting therapy, and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.

Mean nocturnal baseline impedance and endoscopic mucosal impedance measurements in patients with eosinophilic esophagitis: a new tool for follow up and management?

Eosinophilic esophagitis (EoE) is the second most common cause of chronic esophageal inflammation after GERD, with increasing incidence and prevalence across all age groups. Since current diagnosis and follow up of EoE require endoscopy with biopsies, there is an increased interest in non or less invasive tests for its diagnosis and follow up. Baseline mucosal impedance measurement allows evaluation of mucosal barrier properties and is widely accepted as an adjunct method in GERD diagnosis. As EoE is associated with increased mucosal permeability, the use of baseline impedance to evaluate mucosal integrity has been investigated in several studies. It was found that baseline mucosal impedance, measured either during 24 h reflux monitoring or during endoscopy, was significantly lower in all parts of the esophagus in EoE patients. Impedance measurement correlated with eosinophil counts on biopsies, offering a tool to monitor treatment response. Additionally, baseline impedance patterns differed between those responding to proton pump inhibitor (PPI) treatment and those resistant to PPI, potentially allowing to tailor future treatment to the individual patient. In summary, baseline impedance measurement offers a potential tool for diagnosis and follow up in EoE. Its exact place in EoE treatment is yet to be determined and requires further future studies.

Eosinophilic Gastrointestinal Diseases: The Pathogenesis, Diagnosis, and Treatment.

Eosinophilic gastrointestinal diseases are delayed-type chronic allergic disorders that show gastrointestinal eosinophil dense infiltration, with an exaggerated Th2-type immune reaction considered to be an important mechanism. These diseases can be roughly divided into two types: eosinophilic esophagitis, mainly found in young and middle-aged men, and eosinophilic gastroenteritis, which is found in both genders equally. A diagnosis of eosinophilic esophagitis is suspected when characteristic endoscopic findings, including longitudinal furrows and rings, are noted. However, characteristic endoscopic abnormalities are rarely found in cases with eosinophilic gastroenteritis, so multiple biopsy sampling from the apparently normal gastrointestinal mucosal surface is important for making an accurate diagnosis. The administration of systemic glucocorticoid is the standard treatment for eosinophilic gastroenteritis, while acid inhibitors and topical glucocorticoid swallowing therapy are effective for eosinophilic esophagitis. Anti-cytokine therapies for eosinophilic gastrointestinal diseases are currently under development.

Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry.

Rationale: Eosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals. Methods: We queried the U.S. Immunodeficiency Network (USIDNET) for patient records including the terms eosinophilic esophagitis, gastritis, enteritis, or colitis. We analyzed 74 patient records from the database, including diagnoses, demographics, infectious history, laboratory findings, genetic studies, therapeutic interventions, and clinical outcomes. Results: We examined 74 patient records. A total of 61 patients had isolated EoE, and 13 had distal gastrointestinal involvement consistent with EGID. The most common IEI were common variable immunodeficiency (43.2%), some form of combined immunodeficiency (21.6%), chronic granulomatous disease (8.1%), hyper-IgE syndrome (6.8%), and autoimmune lymphoproliferative syndrome (6.8%). The median age at presentation with IEI was 0.5 years (IQR 1.725, max 39 years) and 56.76% were male. Approximately 20% of the patients in the cohort received a hematopoietic stem cell transplantation for treatment of IEI, but the timing of the HSCT in relationship to the EGID diagnosis was unknown. Conclusions: Here, we report EGID in a diverse cohort of IEI patients, suggesting that both non-EoE EGID and EoE can be seen as comorbid conditions with a variety of IEI. Our data suggests that EGID may be more common in patients with IEI than would be expected based on estimates of EGID in the general population.