Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis.

BACKGROUND: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24. RESULTS: A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events. CONCLUSIONS: In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age.

BACKGROUND: Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents. METHODS: In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically. RESULTS: In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B. CONCLUSIONS: Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.).

Persistent esophageal changes after histologic remission in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood, and chronic EoE-directed therapy is therefore required to prevent long-term sequelae. OBJECTIVE: We investigated whether EoE patients in histologic remission have persistent dysregulation of esophageal gene expression. METHODS: Esophageal biopsy samples from 51 pediatric and 52 adult subjects with EoE in histopathologic remission (<15 eosinophils per high-power field [eos/hpf]) and control (48 pediatric and 167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE diagnostic panel, which comprises a set of 94 esophageal transcripts differentially expressed in active EoE. RESULTS: Defining remission as <15 eos/hpf, we identified 51 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (false discovery rate < 0.05). Using the stringent definition of remission (0 eos/hpf), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (false discovery rate < 0.05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the endoscopic reference system score (Spearman r = 0.35, P = .011), specifically correlating with the rings' endoscopic reference system subscore (r = 0.53, P = .004). CONCLUSION: We have identified persistent EoE-associated esophageal gene expression in patients with disease in deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE.

Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis.

BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains. CONCLUSIONS: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

Advances and Ongoing Challenges in Eosinophilic Gastrointestinal Disorders presented at the CEGIR/TIGERS Symposium at the 2024 American Academy of Allergy, Asthma, & Immunology Meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Prevalence and Costs of Esophageal Strictures in the United States.

BACKGROUND & AIMS: Esophageal strictures are a leading cause of dysphagia, but data regarding the epidemiology of esophageal strictures are limited. This study aimed to investigate the prevalence, health care utilization, and financial burden of esophageal strictures in the United States. METHODS: We performed a retrospective cohort study using 2 large national insurance claims databases (MarketScan and Medicare). Using International Classification of Diseases-9 and -10 diagnostic codes, annual prevalence was calculated for both cohorts overall, and stratified by age and sex strata. Most common diagnostic and procedural codes associated with esophageal strictures were extracted and analyzed to estimate health care utilization. Direct annual medical costs of esophageal strictures were calculated. RESULTS: The annual prevalence of esophageal strictures in MarketScan in 2021 was 203.14 cases/100,000 people, whereas the annual prevalence in Medicare cohort in 2017 was 1123.47 cases/100,000. Although rates were relatively stable over time, esophageal stricture prevalence increased with advancing age. No prevalence differences were noticed between males and females. Gastroesophageal reflux disease/erosive esophagitis was the top diagnostic code associated with esophageal strictures, although an increase in the proportion of eosinophilic esophagitis codes was noted over time. Esophageal dilation codes were present in ∼50% of stricture cases. The total health care costs associated with esophageal strictures were estimated at $1.39 billion in 2017. CONCLUSIONS: Esophageal strictures are common, affecting between 1/100 and 1/1000 patients in the United States, with the highest rates seen in patients aged 75 years and older. Accordingly, strictures have a significant financial burden on the health care system, with costs greater than $1 billion annually.

The Natural History of Eosinophilic Gastrointestinal Diseases Is Influenced by Age of Onset and Location of Involvement.

INTRODUCTION: It is unknown whether concomitant esophageal involvement or anatomic location of eosinophilic infiltration affects the natural history of eosinophilic gastrointestinal disease (EGID). METHODS: A retrospective cohort study was performed using the University of North Carolina EGID Clinicopathologic Database. Patients were adults and children with a prior EGID diagnosis based on clinicopathologic features. Demographics, clinical characteristics, treatment information, and procedural data were extracted from medical records. Clinical course and flare history were characterized. RESULTS: Among 97 patients, 43% had EGID + esophageal involvement and 57% had EGID only. Patients with esophageal involvement had a longer diagnostic delay preceding diagnosis (36.6 vs 11.6 months, P = 0.001), more dysphagia (50% vs 18%; P = 0.001), required more chronic therapy (77% vs 52%, P = 0.016), and exhibited more progressive disease (25% vs 6%, P = 0.027). A continuous disease course was most common in eosinophilic gastritis (78%) while patients with eosinophilic gastritis + eosinophilic enteritis (29%) and eosinophilic enteritis + eosinophilic colitis (50%) had the highest proportion of progressive and relapsing disease, respectively ( P = 0.045). A continuous disease course occurred more frequently in children (71%, P = 0.03) and those with single organ involvement (65%), whereas adults had more relapsing (39%) or progressive disease (18%). DISCUSSION: EGIDs with and without esophageal involvement display many similarities, although patients with esophageal involvement more frequently had dysphagia, had progressive disease courses, and required more chronic therapy. Location of involvement and age of onset affected the natural history with higher proportions of relapsing or progressive disease seen in adults and patients with small bowel or multiorgan involvement while a continuous disease course was more common in children and patients with gastric-only involvement.

Healthcare Resource Utilization and Costs Associated With Eosinophilic Esophagitis Among Commercially Insured Patients in the United States.

INTRODUCTION: To evaluate real-world healthcare resource utilization (HCRU) and costs associated with eosinophilic esophagitis (EoE) in the United States. METHODS: Retrospective case-control cohort analysis of Optum Clinformatics claims data (January 2008-September 2020) comparing unadjusted and adjusted HCRU (visits per 1,000 patients per month) and all-cause costs (per patient per month). RESULTS: Patients with EoE incurred significantly higher monthly HCRU (adjusted Δ [95% confidence interval]: inpatient visits, 2.8 [0.1-4.0]; emergency department visits, 14.7 [4.3-32.1]; outpatient visits, 388.8 [362.1-418.0]); and costs ($581 [$421-$600]) vs matched controls (all P < 0.001). DISCUSSION: EoE imposes substantial economic burden. More effective and targeted treatments that improve outcomes for patients are needed.

Dupilumab Improves Health-Related Quality of Life and a Range of Symptoms in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study. METHODS: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo. RESULTS: At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24. DISCUSSION: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Adherence to prescription proton pump inhibitor therapy amongst individuals diagnosed with Barrett's esophagus.

INTRODUCTION: In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described. METHODS: We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups. RESULTS: 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year. DISCUSSION: Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.

Vitamin D Levels as a Potential Modifier of Eosinophilic Esophagitis Severity in Adults.

BACKGROUND: Vitamin D deficiency is associated with atopic and immune-mediated diseases but has not been extensively assessed in eosinophilic esophagitis (EoE). We aimed to assess if vitamin D levels in newly diagnosed EoE patients were lower than in non-EoE controls and examine levels in relation to EoE clinical features. METHODS: This secondary analysis of a prospective cohort study used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained and stored at -80oC. Serum 25-hydroxy-vitamin D3 (25(OH)D3) was measured by ELISA. Levels for cases and controls were compared at baseline. Within cases, 25(OH)D3 levels were compared for clinical, endoscopic, and histologic measures. RESULTS: We analyzed 40 EoE and 40 non-EoE controls. Mean serum 25(OH)D3 level was slightly lower in EoE patients than controls (30.9 ± 15.3 ng/mL vs. 35.9 ± 15.4; p = 0.15). After controlling for age, sex, and race, adjusted levels were 10.8 ng/mL lower in EoE patients (95% CI: -19.0, -2.5), but 25(OH)D3 deficiency (< 20ng/mL) was similar in cases and controls (20% vs. 15%; p = 0.56). Levels of 25(OH)D3 were not associated with differences in clinical or endoscopic features of EoE, and EREFS and eosinophil counts did not significantly correlate with 25(OH)D3 levels (R of -0.28 [p = 0.08] and - 0.01 [p = 0.93], respectively). 25(OH)D3 levels were lower in EoE cases with lamina propria fibrosis (23.2 ± 9.6 vs. 45.0 ± 17.7; p = 0.03). CONCLUSIONS: After adjusting for age, sex, and race, 25(OH)D3 levels were lower in EoE cases than controls, but deficiency was not common. 25(OH)D3 levels were generally similar across most EoE disease features.

Epidemiology and Racial Differences of EoE Patients in a U.S. Veterans Population.

BACKGROUND: Eosinophilic esophagitis (EoE) is increasing in prevalence but there is a lack of population-based studies. We sought to determine the prevalence, demographics, and associated atopic diseases in the Veterans Affairs (VA) population. METHODS: A nationwide analysis of data from the VA patient population was done using a Veterans Health Administration database. EoE was identified using ICD9 (530.13) and ICD10 (K20.0) codes from October 2008 to June 2020. Demographic data, smoking status, BMI, treatment, and ICD codes for atopic diagnoses were collected. Two sample proportion z-tests, Chi-square tests, two-sample t tests, and one-way ANOVA were used to assess associations across demographic categories. RESULTS: We identified a total of 11,775 patients with an EoE diagnosis: 91% male, 83% White, 8.6% Black, and 5% were of Hispanic ethnicity. The prevalence of EoE increased over time. At diagnosis, the mean age was 48.5 years overall, 51.6 years for Black patients, 45.3 years for Hispanic patients, and 48.2 years for Whites. Dysphagia was the most common symptom overall, but a higher percentage of Blacks and females were found to report chest pain (p < 0.0001, h = 0.32). With the exception of urticaria and atopic dermatitis, both Blacks and Hispanics had a higher incidence of atopic conditions compared to other races and ethnicities (p < 0.0001). CONCLUSION: While EoE is seen primarily in White males, our study shows that a notable percentage of patients were Black or Hispanic, suggesting that EoE should be considered in non-white patients. The later age of diagnosis in this group could represent a lack of awareness about EoE among non-white patients. More research is needed to study these associations.

Performing Esophageal Biopsies Is Safe During Upper Endoscopy for Food Impaction but Are Underperformed in Certain Populations.

BACKGROUND: Despite recommendations to perform esophageal biopsies during esophagogastroduodenoscopy (EGD) for esophageal food impaction to evaluate for eosinophilic esophagitis (EoE), endoscopists often forgo biopsies. There are minimal data on the risks of biopsies in this setting. AIMS: To determine the safety of performing biopsies during EGD for food impaction. METHODS: We conducted a retrospective cohort study of patients who presented to University of North Carolina Hospitals from 2014 to 2021 with endoscopically confirmed food impaction. Data were abstracted from the medical records. Baseline clinical characteristics, procedural details, and adverse events were compared between patients who did and did not undergo biopsy. Adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extra-esophageal (aspiration, respiratory compromise, hypotension, arrhythmia). RESULTS: Of 188 patients who underwent EGD for food impaction, 73 (39%) had biopsies taken. Older and non-White patients were less likely to be biopsied. None of the Black patients had biopsies taken. Only 2 (2.7%) of the 73 biopsied patients had an adverse event, and neither was related to the biopsies. Patients who were biopsied were less likely to experience adverse events. There were no differences in re-admission, ICU admission, or 30-day mortality between patients who were and were not biopsied. CONCLUSIONS: Esophageal biopsies remain underperformed during EGD for food impaction, especially in certain patient populations. Esophageal biopsies at the time of food impaction are unlikely to cause adverse events. Safety concerns should not preclude biopsies, and biopsies should be performed in the absence of extenuating circumstances.

Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases.

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets.

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

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.

A clinical predictive model identifies pediatric patients at risk for eosinophilic esophagitis.

BACKGROUND: Identifying children needing endoscopic evaluation for suspected eosinophilic esophagitis (EoE) is crucial for prompt diagnosis and management. AIMS: We aimed to develop a clinical prediction tool to distinguish children with EoE from children without the disease before endoscopy. METHODS: We conducted a retrospective case-control study of children undergoing upper endoscopy at a tertiary care center. Clinical characteristics before endoscopy were extracted from 380 EoE cases and 380 controls without EoE. We built a predictive model for case-control status and performed age-stratified analyses. RESULTS: After multivariable analysis, history of adaptive eating behaviors, food allergy, food impaction, male sex, and regurgitation were independently associated with EoE, and abdominal pain and failure to thrive with control status (AUC 0.81). Food allergy and male sex were predictors of EoE across all ages. Regurgitation and adaptive eating behaviors were specific to EoE in early (0-5 years) (AUC 0.74) and middle childhood (6-11 years) (AUC 0.82), while dysphagia and food impaction were specific to EoE in the adolescence (12-17 years) (AUC 0.87). CONCLUSION: We determined age-specific clinical features that predict EoE with good discrimination in a pediatric population before endoscopy. Validation of this model in an independent population can confirm the utility of this tool.