Pediatric Eosinophilic Esophagitis Patients Research Articles

Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles. We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eos/HPF in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens. A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian. Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE.

Understanding of Eosinophilic Esophagitis in Children - A Comprehensive Study on Epidemiology, Clinical Manifestations, Diagnosis and Innovative Treatment Modalities

Introduction:&#x0D; In the late 1960s, probable cases of eosinophilic esophagitis (EoE) emerged, initially linked to esophageal rings and congenital causes or gastroesophageal reflux disease (GERD). Doubts about the GERD association arose due to poor responses to antisecretory therapy. EoE is now a significant pediatric health concern, impacting 1 to 7 cases per 10,000 children.&#x0D; Purpose of the Study:&#x0D; This study aims to comprehensively explore EoE's epidemiology, etiology, subtypes, clinical manifestations, diagnostic methods, and treatment modalities.&#x0D; Materials and Methods:&#x0D; The study employs a cross-sectional analysis of pediatric EoE patients, utilizing endoscopic evaluation and histological assessment. Three distinct EoE subtypes are identified based on pathogenic characteristics. Clinical manifestations, diagnostic methods, and treatments, including endoscopy, are examined.&#x0D; Results:&#x0D; Clinical manifestations span a broad spectrum in the pediatric population. Diagnostic methods include endoscopy, esophageal manometry, impedance-pH monitoring, capsule endoscopy, and string tests. Three distinct EoE subtypes are identified with unique characteristics. Treatment modalities involve dietary management, proton pump inhibitors, topical corticosteroids, biologic therapies, allergen immunotherapy, and endoscopic interventions.&#x0D; Conclusion:&#x0D; Formerly associated with GERD, EoE is now a significant pediatric health concern. The study underscores the importance of comprehensive diagnostic approaches and diverse treatment modalities, including promising biologic therapies and allergen immunotherapy. Understanding these aspects is crucial for effective management and improved outcomes in patients.

Monitoring pediatric eosinophilic esophagitis disease activity using an unsedated blind esophageal brushing model: A pilot study.

Recurrent upper endoscopies are essential for monitoring therapy response and disease activity in patients with eosinophilic esophagitis (EoE), leading to increased costs, procedural complications, and anesthesia exposure. The aim of this study was to examine an office-based model using serial sedation-free blind esophageal epithelial brushing (BEEB) to monitor therapy response through eosinophil-derived neurotoxin (EDN) levels and guide therapy plans in pediatric EoE patients. EoE patients (≤21 years of age) were enrolled in this prospective study. Subjects were placed on dietary, pharmacologic, or combination therapy with the goal of inducing or maintaining remission. To assess response to sequential interventions, subjects underwent sequential sedation-free BEEBs through nasogastric tubesto measure EDN levels. Based on serial brushings, an individual plan of diet, medications, or a combination of both was created for each subject, and a final endoscopy was then performed to validate the accuracy of the individual plans. Twenty-four subjects completed the study. The average peak eosinophil countin patients with active EoE was 58.1 ± 30.8 eosinophils per high-power field and mean EDN level was 165.2 ± 191.3 μg/mL. A total of 42 BEEBs were completed. Individual therapy plans based on sequential BEEB were accurate in 19 out of the 24 patients (79%) and specifically nine out of 10 patients (90%) treated with elimination diets. This study suggests that office-based sedation-free BEEBs can be used to monitor therapy response and disease activity in pediatric EoE patients.

Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients.

Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development. We used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity. Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE (CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7). In addition, we identified differential expression of several genes from the MUC and SPRR families, which have been limited in previous reports. Our findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, SPRR and MUC, that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.

Predictors of histologic response to mepolizumab in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus. Current treatment options are limited. One experimental therapy is antibodies against interleukin-5 (IL-5). However, it is unknown why some patients respond to anti-IL-5 treatment whereas others do not. We sought to delineate predictors of histologic response to anti-IL-5 therapy in pediatric EoE. This post hoc analysis of a multicenter, double-blind clinical trial (ClinicalTrial.gov identifier: NCT00358449) evaluated mepolizumab for the treatment of EoE in pediatric patients. Predictors were assessed for their association with a histologic response at week 12 of treatment. A histologic response was defined as either <15 eosinophils per hpf or a reduction in peak eosinophil counts by ≥50%. Predictors on univariate analysis with P < 0.10 were included in multivariate logistic regression models. Statistical significance for multivariate comparisons was set at P < 0.05. Patients with a higher BMI were more likely to attain histologic response at week 12, defined as <15 eosinophils per hpf [aOR, 1.31; 95% confidence interval (CI), 1.07-1.60; P = 0.008]. Higher BMI (aOR, 1.70; 95% CI, 1.06-2.74; P = 0.029) and signs of exudate plaques on endoscopy (aOR, 18.30; 95% CI, 2.11-158.53; P = 0.008) were significant predictors of histologic response at week 12 where a histologic response was defined as a reduction in peak eosinophil counts by ≥50. Higher BMI and signs of exudative plaques on endoscopy may be predictors of histologic response in pediatric EoE patients treated with antibodies against IL-5. Further studies are needed to validate our findings.

Novel Questionnaires for Assessing Signs and Symptoms of Eosinophilic Esophagitis in Children

Pediatric patients with eosinophilic esophagitis (EoE) experience heterogeneous symptoms and the patient's age may preclude reliable self-report of symptoms. The goal of this study was to develop a patient-reported outcome and an observer-reported outcome questionnaire to evaluate the signs and symptoms of EoE in pediatric patients (≥1 to <12 y of age) in a clinical trial setting. A concept-focused literature review, expert advice meetings, and concept elicitation interviews with pediatric EoE patients and their caregivers were conducted to identify disease-related signs and symptoms. Instructions, items, and response options were drafted. Cognitive debriefing interviews were conducted to evaluate children's and caregivers' ability to understand and respond to the questionnaires and to evaluate the comprehensiveness of the concepts measured. Results from the literature review, expert advice meetings (n= 6), and concept elicitation interviews (n= 24) informed the development of the Pediatric Eosinophilic Esophagitis Sign/Symptom Questionnaire intended for use by patients (PESQ-P) with EoE 8 years or older to younger than 12 years and an observer-reported outcome questionnaire planned for use by caregivers of patients (PESQ-C) 1 year old or older to younger than 12 years. Both questionnaires measure the same concepts; the PESQ-P assesses the frequency, duration, and/or severity of symptoms and the PESQ-C assesses the presence/absence of the signs/symptoms. The cognitive debriefing interviews (n= 17) demonstrated that participants were able to comprehend and complete the questionnaires as intended. This study provides evidence of the content validity of 2 novel questionnaires, PESQ-P and PESQ-C, designed to evaluate the symptom experience of pediatric EoE patients in a clinical trial setting.

Peripheral Blood Cell Counts Predict Distinct Endoscopic Phenotypes In Eosinophilic Esophagitis

Eosinophilic Esophagitis (EoE) can be divided into normal, inflammatory and fibrostenotic endoscopic phenotypes. There is currently no biomarker that predicts these endoscopic phenotypes. We hypothesized that peripheral blood cell counts are associated with distinct endoscopic phenotypes in pediatric and adult EoE patients.

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases

To characterize patient-reported symptoms and comorbidities by type of eosinophilic gastrointestinal disease (EGID) and compare the collected data among the evaluated patient population.A total of 715 pediatric and adult patients with a diagnosis of EGID were enrolled in the Consortium of Eosinophilic Gastrointestinal Disease Researchers Contact Registry and completed the study questionnaire between 2015 and 2018. EGIDs consisted of eosinophilic esophagitis (EoE) or non-EoE EGIDs, which consist of eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis.This study was a cross-sectional study. A 25-item questionnaire was curated to collect demographic data, types of EGID, symptoms, and management. Additionally, extraintestinal symptoms and various comorbidities were recorded, such as vitamin deficiencies and psychosocial comorbidities.Most patients who completed the questionnaire had EoE only (80%; n = 575), in comparison with those with non-EoE EGIDs with or without EoE (n = 210). The sex-distribution illustrated that boys (57%) and younger patients reported EoE only, in comparison with non-EoE EGIDs (16- vs 19-year-olds), which was statistically significant. Nausea (21%) and upper abdominal pain (23%) were the most prominent symptoms reported. Of note, the frequency of symptoms was higher among those with non-EoE EGIDs. Furthermore, patients with non-EoE EGIDs had a higher percentage of vitamin deficiencies (49.7%) and concomitant gastroparesis (27.3%). Every patient in the study reported extraintestinal symptoms, but those with non-EoE EGID reported an increased frequency (14 to 21% experienced weekly symptoms) and psychosocial concerns (16% to 26% experienced weekly symptoms). Adult EoE patients had a higher proportion of feeling isolated on a daily or weekly basis when treated with specific food-elimination diets. Similar outcomes were seen in both pediatric and adult EoE patients being treated with elemental diet therapy. After adjusting for food avoidance behaviors and diarrhea frequency, both specific food-elimination (odds ratio: 2.4) and elemental diet (odds ratio: 1.9) were still associated with at least weekly feelings of isolation for participants with EoE only.As a whole, patients with EGID have a high frequency of extragastrointestinal symptoms and a high reporting rate of comorbidities. When examining these disorders closely, patients with non-EoE EGIDs had more severe symptoms and a higher occurrence of nutritional, physical, and psychosocial comorbidities, in comparison with those with EoE only.From a diagnostic perspective, with this study, the authors illustrate poignant differences in the symptom presentation and laboratory findings (vitamin deficiencies) that may assist health care providers in determining the accurate diagnosis between EGIDs. Additionally, with this study, the authors are the first to highlight how impactful treatment plans are on patients psychosocially. EoE and other EGID disorders, when treated with restrictive dietary modifications, can have a negative impact on patients, particularly adolescents, and their social interactions. This outcome indicates the importance of a multidisciplinary approach in treatment and encourages more research to look for options that are not perceived as burdensome by the patient.

The role of endoscopy in eosinophilic esophagitis: from diagnosis to therapy

Endoscopy plays an important role in the management of eosinophilic esophagitis (EoE), since it is involved in the diagnosis, follow-up and treatment of this condition. In patients presenting with food impaction, dysphagia and other symptoms of suspected EoE, esophago-gastric-duodenoscopy (EGD) with multiple esophageal biopsies should be performed to confirm or rule out the diagnosis of EoE. The EREFS system, a validated instrument for assessment of the endoscopically-identified esophageal features in EoE (edema, rings, exudates, longitudinal furrows and strictures), is currently used in the clinical practice for the evaluation of the macroscopic aspects of esophageal mucosa during EGD. Multiple esophageal biopsies are mandatory to further confirm EoE diagnosis and subsequent response to treatment, since symptoms reported by patients do not always correlate with histological activity, and considering the low sensitivity of endoscopic assessment; a cut-off of ≥15 eosinophils in at least one high power field is the density threshold considered the standard for diagnosis (sensitivity 100%, specificity 96%). Other histological features, included in the EoE histologic scoring system (EoEHSS), are supportive for the diagnosis and for the assessment of inflammatory activity during follow-up. Esophageal dilation, performed either with Savary dilators/bougie or hydrostatic balloon, is an effective and safe treatment in both adult and pediatric EoE patients with fibrostenotic features, mainly in association with other therapeutic strategies which can control eosinophilic inflammation.

The role of endoscopy in eosinophilic esophagitis: from diagnosis to therapy

Endoscopy plays an important role in the management of eosinophilic esophagitis (EoE), since it is involved in the diagnosis, follow up and treatment of this condition. In patients presenting with food impaction, dysphagia and other symptoms of suspected EoE, esophago-gastric-duodenoscopy (EGD) with multiple esophageal biopsies should be performed to confirm or rule out the diagnosis of EoE. The EREFS system, a validated instrument for assessment of the endoscopically-identified esophageal features in EoE (edema, rings, exudates, longitudinal furrows and strictures), is currently used in the clinical practice for the evaluation of the macroscopic aspects of esophageal mucosa during EGD. Multiple esophageal biopsies are mandatory to further confirm EoE diagnosis and subsequent response to treatement, since symptoms reported by patients do not always correlate with histological activity, and considering the low sensitivity of endoscopic assessment; a cut-off of ≥ 15 eosinophils in at least one high power field is the density threshold considered the standard for diagnosis (sensitivity 100%, specificity 96%). Other histological features, included in the EoE histologic scoring system (EoEHSS), are supportive for the diagnosis and for the assessment of inflammatory activity during follow-up. Esophageal dilation, performed either with Savary dilators/bougie or hydrostatic baloon, is an effective and safe treatment in both adult and pediatric EoE patients with fibrostenotic features, mainly in association with other therapeutic strategies which can control eosinophilic inflammation.

STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy

Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P= .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P= .012. Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.

Motivations, Barriers, and Outcomes of Patient-Reported Shared Decision Making in Eosinophilic Esophagitis.

Little is known about patient choice in treatment of eosinophilic esophagitis (EoE). Determine motivators and barriers to using common EoE therapies and describe patient-reported shared decision making (SDM) and satisfaction with treatment. We developed and administered a Web-based survey on factors influencing EoE treatment choice, SDM, and satisfaction. Adults with EoE and adult caregivers of pediatric EoE patients were recruited via patient advocacy groups and at two centers. Descriptive statistics of multiple response questions and multivariable logistic regression were performed to identify predictors of SDM and satisfaction with treatment. A total of 243 adults (mean age 38.7years) and 270 adult caregivers of children (mean age 9.5years) completed the survey. Preventing worsening disease was the most common motivator to treat EoE. Barriers to topical steroids were potential side effects, cost, and preferring a medication-free approach. Inconvenience and quality of life were barriers to diet. Potential adverse events, discomfort, and cost were barriers to dilation. Nearly half (42%) of patients experienced low SDM, but those followed by gastroenterologists were more likely to experience greater SDM compared to non-specialists (OR 1.81; 95% CI 1.03-3.15). Patients receiving more SDM were more satisfied with treatment, regardless of provider or treatment type (OR 2.62, 95% CI 1.76-3.92). Patients with EoE pursue treatment mostly to prevent worsening disease. Common barriers to treatment are inconvenience and financial costs. SDM is practiced most by gastroenterologists, but nearly half of patients do not experience SDM, indicating a substantial area of need in EoE.

Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic TH2-assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of interleukin 9 (IL-9) expressing inflammatory cells. While IL-9 is known to affect barrier function in the intestine, the functional effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE. We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL-9 receptor, the adherens junction protein E-cadherin and the tight junction protein claudin-1. We treated primary human esophageal epithelial cells with IL-9 to understand its effects on E-cadherin expression and function. Active EoE subjects had increased epithelial expression of IL-9 receptor mRNA and protein (P < 0.05) and decreased membrane bound E-cadherin (P < 0.01) and claudin-1 (P < 0.05) expression. IL-9 receptor expression and mislocalized claudin-1 positively correlated and while membrane bound E-cadherin expression negatively correlated with the degree of histologic epithelial remodeling (P < 0.05). IL-9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (P < 0.01) and membrane bound E-cadherin in epithelial cell monolayers (P < 0.01). These data suggest that IL-9, its receptor, and its effects on E-cadherin may be important mechanisms for epithelial barrier disruption in EoE.

A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions.

Eosinophilic esophagitis (EoE), a Th2-type allergic immune disorder characterized by an eosinophil-rich esophageal immune infiltrate, is often associated with food impaction (FI) in pediatric patients but the molecular mechanisms underlying the development of this complication are not well understood. We aim to identify molecular pathways involved in the development of FI. Due to large variations in disease presentation, our analysis was further geared to find markers capable of distinguishing EoE patients that are prone to develop food impactions and thus expand an established medical algorithm for EoE by developing a secondary analysis that allows for the identification of patients with food impactions as a distinct patient population. To this end, mRNA patterns from esophageal biopsies of pediatric EoE patients presenting with and without food impactions were compared and machine learning techniques were employed to establish a diagnostic probability score to identify patients with food impactions (EoE+FI). Our analysis showed that EoE patients with food impaction were indistinguishable from other EoE patients based on their tissue eosinophil count, serum IgE levels, or the mRNA transcriptome-based p(EoE). Irrespectively, an additional analysis loop of the medical algorithm was able to separate EoE+FI patients and a composite FI-score was established that identified such patients with a sensitivity of 93% and a specificity of 100%. The esophageal mRNA pattern of EoE+FI patients was typified by lower expression levels of mast cell markers and Th2 associated transcripts, such as FCERIB, CPA3, CCL2, IL4, and IL5. Furthermore, lower expression levels of regulators of esophageal motility (NOS2 and HIF1A) were detected in EoE+FI. The EoE+FI -specific mRNA pattern indicates that impaired motility may be one underlying factor for the development of food impactions in pediatric patients. The availability of improved diagnostic tools such as a medical algorithm for EoE subpopulations will have a direct impact on clinical practice because such strategies can identify molecular inflammatory characteristics of individual EoE patients, which, in turn, will facilitate the development of individualized therapeutic approaches that target the relevant pathways affected in each patient.

ATOPY PATCH TESTING IN PEDIATRIC PATIENTS WITH PROTON PUMP NON-RESPONSIVE EOSINOPHILIC ESOPHAGITIS

Introduction The role of atopy patch testing (APT) in Eosinophilic Esophagitis (EoE) remains controversial with no clear guidance for utility in the Food Allergy Practice Parameters. This exploratory study examines the use of APT in pediatric patients with EoE. Methods A retrospective chart review from 08/2017 to 06/2018 was conducted at a large academic Allergy/Immunology Division. Pediatric patients with a diagnosis of EoE who underwent APT in conjunction with skin prick testing to guide food elimination were identified. Results of APT and response to dietary elimination were evaluated using descriptive statistics. Results 45 patients, ages 2 to 18 years, were identified with initial screening. 5 patients had APT prior to second biopsy showing PPI responsiveness and were excluded. Three patients were lost to follow-up. 1 patient was diagnosed with an eating disorder and did not undergo food elimination. 5 additional patients have follow-up endoscopy pending. A total of 31 patients were included in final assessment: 23 males and 8 females, average age 9 years. Of the 31 patients, 1 had improvement on biopsy that could be uniquely attributed to APT. The remaining 30 patients (97%) had APT that was not useful in identification of triggering foods. Conclusions In our sample of pediatric EoE patients, APT was not useful in identifying foods for removal. Given the productivity loss for both patients and parents as well as the increased financial costs of patch tests and three additional visits, guidelines on EoE management should be adapted to more strongly discourage APT for identification of triggering foods.

Comparison of comorbid diagnoses in children with and without eosinophilic esophagitis in a large population

BackgroundPrevious reports suggest a higher prevalence of comorbid diseases in patients with eosinophilic esophagitis (EoE), although few have systematically quantified comorbidities in pediatric patients. ObjectiveTo define the rate of comorbid diagnoses in pediatric EoE patients compared with rates in those without EoE. MethodsRetrospective cross-sectional review of electronic medical records for patients seen in a single large pediatric primary care network between January 2007 and December 2016 (n = 456,148). International Classification of Diseases, Ninth and Tenth Revision codes were used to determine prevalence rates for coexisting diagnoses. ResultsA total of 428 patients held a diagnosis for EoE. Significant differences in rate of comorbid diseases included allergic rhinoconjunctivitis (60.0% of EoE cohort vs 17.4% of non-EoE cohort, P < .0001); asthma (59.8% of EoE, 21.4% of non-EoE, P < .0001); atopic dermatitis (17.8% of EoE, 6.6% of non-EoE, P < .0001); adrenal insufficiency (2.6% of EoE, 0.4% of non-EoE, P < .0001); autism spectrum disorder (7.5% of EoE, 1.9% of non-EoE, P < .0001); celiac disease (5.6% of EoE, 0.9% of non-EoE, P < .0001); connective tissue diseases (1.4% of EoE, 0.1% of non-EoE, P < .0001); cystic fibrosis (0.9% of EoE, 0.05% of non-EoE, P < .0001); inflammatory bowel disease (0.7% of EoE, 0.2% of non-EoE, P = .03); type 1 diabetes mellitus (1.2% of EoE, 0.3% of non-EoE, P = .0069). ConclusionChildren with EoE have markedly higher rates of both atopic and non-atopic diseases compared with children without EoE. These associations have important implications for comprehensive EoE care and future research regarding associated disease mechanisms.

Pediatric Eosinophilic Esophagitis Is Associated With Increased Lamina Propria Immunoglobulin G4-Positive Plasma Cells.

Eosinophilic esophagitis (EoE) is considered a TH2-mediated food allergy disease that leads to submucosal esophageal fibrosis and strictures. Recent studies focused on adults with EoE identified a strong association with elevated esophageal IgG4 immunostaining. Our study aimed to determine the association of IgG4 with EoE in pediatric patients. Using our local EoE research registry, we identified 41 adequate biopsies from EoE patients. We used 10 age- and sex-matched patients with no diagnostic abnormalities at endoscopy or on biopsy. Using a monoclonal antibody to Immunoglobulin G4 (IgG4), we determined the maximum density of IgG4-positive plasma cells (IgG4-PC) per high-power field (hpf). Using a semi-quantitative assessment, we also graded the noncellular staining of the lamina propria and epithelium. Our EoE cohort consisted predominantly of boys with an average age of 5.9 years and 63% had a documented IgE-based food allergy. Median peak eosinophilia was 40 eosinophils/hpf and the median IgG4-PC density was 39/hpf in the active esophagitis patients, compared with a median of 0 IgG4-PC/hpf in the non-EoE patients (P = 0.0001). EoE patients with a food allergy showed a significantly higher IgG4-PC density (44.5/hpf) than those without a food allergy (8/hpf; P = 0.0385). There was no significant association between IgG4-PC density and peak eosinophilia (r = 0.0011). We demonstrate that active esophagitis in pediatric EoE patients is associated with elevated levels of IgG4-positive plasma cells, which was more significant in EoE patients with a documented food allergy. Our study also adds to the growing literature that EoE may involve more than just an exaggerated TH2 immune response.

Practice Pattern Variation in Pediatric Eosinophilic Esophagitis in the Carolinas EoE Collaborative: A Research Model in Community and Academic Practices.

Differences in the initial management of pediatric eosinophilic esophagitis (EoE) by practice setting have not been well characterized. We aimed to characterize these differences for sites in the Carolinas EoE Collaborative (CEoEC), a multicenter network of academic and community practices. We performed a retrospective cohort study of pediatric EoE patients at five CEoEC sites: University of North Carolina (UNC) Hospital, Charlotte Asthma and Allergy Specialists, Greenville Health Systems, Wake Forest Baptist Medical Center, and the Medical University of South Carolina Hospital. Cases of EoE were defined by consensus guidelines. Data were extracted from electronic medical records. We tested for differences among sites and used a multinomial model (polytomous regression) to assess associations between treatment and site, adjusting on patient factors. We identified 464 children with EoE across the CEoEC sites. The median age was highest at Wake Forest (11.4 years), the median eosinophil count was highest at UNC (69 eos/hpf), and UNC had the most male patients (82%). UNC used topical steroids for initial treatment in 86% of cases, compared with <1% in Greenville (P < 0.01). Greenville used dietary elimination more frequently than UNC (81% vs 2%, P < 0.01). Differences in treatment approach held after adjusting for potential baseline confounders. There was no significant association between patient factors and initial treatment approach. Significant differences in EoE patient factors and treatment approaches were identified across CEoEC sites and were not explained by patient or practice factors. This suggests that institutional or provider preferences drive initial treatment approaches, and that more data are needed to drive best practice decisions.

IgG4 is closely associated with eosinophilic esophagitis

Rosenberg et al .’s study (1) confirms the presence of abundant IgG4 in eosinophilic esophagitis (EoE) and has added important novel findings: that the abundant IgG4 is also present in pediatric EoE patients, that IgG4 content correlates with the degree of disease activity as measured by both eosinophil counts and by other histologic findings, and that IgG4 content also correlates with many, but not all, of the EoE mRNA markers. Of particular note is the correlation with IL-10, which induces expression of IgG4 rather than IgE (2). Together, these findings show that IgG4 is closely associated with EoE. This is an important confirmation and extension of the prior work. In contrast, relatively modest and variable IgG4 associations are seen in many other allergic and inflammatory diseases.

Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.

Swallowed topical steroids (STS) are the only effective pharmacological therapy for eosinophilic esophagitis (EoE). Thus far, studies of small populations of EoE patients have reported conflicting results in relation to adrenal insufficiency (AI). We sought to measure AI in a clinical setting in children taking STS for EoE. We performed a quality improvement study of pediatric EoE patients seen in a multidisciplinary clinic, who were treated with STS for at least 3 months. Two hundred twenty-five patients completed questionnaires to assess for signs of AI. All patients were requested to have fasting morning cortisol levels completed and if abnormal (<5 μg/dL or 139 nmol/L) twice, endocrinology consultation, and low-dose adrenocorticotropic hormone stimulation test were performed. A peak stimulated cortisol level of <18 μg/dL or 500 nmol/L was diagnostic of AI. Five of 106 STS-treated EoE patients who had morning cortisol levels drawn had AI. All 5 of these patients had asthma and were on additional topical steroid treatments. The number of steroid modalities and dose of steroid were not significant risk factors. Despite this low percentage, the life-threatening potential of AI warrants patient screening, as patients with iatrogenic AI are typically asymptomatic until an emergency triggers adrenal crisis. Further multicenter studies are needed to better define the risk attributable to STS alone, particularly in patients receiving combined steroid modalities.