Eosinophilic Esophagitis Disease Research Articles

Symptoms and treatment of eosinophilic esophagitis prior to, during, and after pregnancy

Eosinophilic esophagitis disease course varies during pregnancy. Many patients' symptoms improve during pregnancy and worsen after. Pregnant patients often opt to decrease pharmacotherapy, highlighting the importance of discussing medication safety data, adverse outcomes associated with diet restriction, and close follow-up.

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

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. 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. 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). 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.

Elimination Diet or Swallowed Topical Steroid Treatment of Pediatric Eosinophilic Esophagitis: Five-Year Outcomes.

Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease of the esophagus commonly treated with swallowed topical steroids (STS) or elimination diets (EDs). Evidence of a long-term response to EDs in pediatric patients is sparse. Our study sought to understand the natural history of pediatric EoE treated exclusively with EDs and to examine a similar population of STS-treated EoE subjects. We hypothesized that long-term adherence to an effective ED would result in ongoing EoE disease remission. We conducted a retrospective study of pediatric EoE subjects who had at least 2 visits to a multidisciplinary clinic. Subjects were identified who had (1) a new referral with a suspected diagnosis of EoE; (2) received either EDs or STS alone, and (3) completed both a diagnostic and a posttreatment endoscopy. Concomitant proton-pump inhibitor use was allowed. We collected demographics, clinical features, treatment plans, and associated side effects on each subject. Remission was defined as fewer than 15 eosinophils/high-powered field. We screened the electronic medical record from 2015 to 2016 for subjects cared for in the Gastrointestinal Eosinophilic Diseases Program who fit criteria for inclusion in this analysis. One hundred ninety-nine subjects were identified, 16 who received exclusive EDs and 15 who were treated with STS. Treatment of these subjects was documented for 4.8 and 5.2 years, respectively (P= .51). Significant differences between the groups were observed in average age at EoE diagnosis (3.5 y ED vs 7.8 y STS; P= .002) and in number of endoscopies (6.6 in ED vs 4.5 in STS; P= .03). Fifteen of 16 subjects treated with ED attained histological remission. The initial effective ED removed a mean of 7.7 foods and the final ED removed a mean of 4 foods. No food impactions or esophageal dilations occurred in the ED group. The STS group required an average of 3.7 dose/formulation changes, 4 subjects required 1 or more dilations, 1 subject had 2 food impactions, and 2 were diagnosed with adrenal insufficiency. Treatment with either ED or STS can lead to long-term remission of EoE. In this study, fewer side effects developed in the ED group than the STS group, but the validity of this conclusion is limited by the small sample size and reinforces the need for prospective study to explore these initial findings.

Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity.

Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co-localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits. This study included adult subjects with EoE (n = 13) and non-EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co-localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4-food protein interactions were confirmed with co-immunoprecipitation and mass spectrometry. IgG4-CMP co-localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co-localization was also significantly higher in the active EoE group compared to non-EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil-derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain-14 in IgG4-enriched areas. Co-immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens. These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression.

The Severity of Reduced Esophageal Distensibility Parallels Eosinophilic Esophagitis Disease Duration

Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP). Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay). A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho= -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P= .004), while there was not a significant difference among patients with <15 eos/hpf (P= .060). Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE.

SUCCESSFUL TREATMENT OF REFRACTORY PEDIATRIC EOSINOPHILIC ESOPHAGITIS WITH DUPILUMAB

<h3>Introduction</h3> Eosinophilic esophagitis (EoE) is a chronic T-helper 2 (Th2) antigen driven disease characterized by eosinophilic infiltrates in the esophageal mucosa. Currently, there are no therapies approved by the United States Food and Drug Administration (FDA) for EoE in patients under twelve years of age. Expert guidance recommends the use of proton pump inhibitors (PPI), swallowed corticosteroids, elimination diets, and esophageal dilation<i>.</i> However, these interventions do not ameliorate symptoms and eosinophilic inflammation in all cases. Herein, we describe the successful treatment of a ten-year-old patient with EoE refractory to guideline-directed therapy with dupilumab. <h3>Case Description</h3> Our patient is a ten-year-old male with failure to thrive and EoE refractory to dietary change, swallowed corticosteroids, and PPI therapy. Due to the severity of his disease, the patient was initiated on monthly dupilumab injections. Following 6 months of dupilumab therapy (300mg subcutaneously Q4 weeks) he experienced endoscopic and histologic remission (0 eos/hpf). He remained in clinical and histologic remission more than 3 months after milk was reintroduced into the diet. <h3>Discussion</h3> We report the histologic, endoscopic, and symptomatic improvement in refractory pediatric EoE following treatment with monthly dupilumab in a ten-year-old male. Our findings suggest that the use of dupilumab can be extended to the pediatric population. Additionally, our case suggests that monthly injections, rather than the weekly injections utilized for adult EoE treatment, may be sufficient. Lastly, dupilumab also allowed for the liberalization of our patient's diet with sustained histologic and endoscopic resolution. In summary, dupilumab successfully treated refractory EoE and sustained disease remission despite allergen reintroduction.

PATIENT-REPORTED SYMPTOMS OF EOSINOPHILIC ESOPHAGITIS IN THE UNITED STATES: EVIDENCE FROM REAL-WORLD CLINICAL PRACTICE

<h3>Introduction</h3> Eosinophilic esophagitis (EoE) is a chronic, allergen-induced, inflammatory disease of the esophagus, with common symptoms of dysphagia, food impaction, abdominal pain, and nausea. This real-world study describes US patient self-reported EoE symptoms and impacts on well-being and activities of daily living (ADL). <h3>Methods</h3> We analyzed data from the Adelphi Real World EoE Disease Specific Programme collected in 2020 in the US. Included patients were ≥12 years old with biopsy-confirmed EoE (esophageal count of ≥15 eosinophils/high power field) who were currently receiving prescribed EoE treatment. <h3>Results</h3> Overall, 177 US patients with EoE completed surveys, and mean age at symptom onset was 33.1 years. The most common presenting symptoms were difficulty swallowing (61%) and heartburn/acid reflux (60%). During the previous 7 days, patients experienced a mean 0.4 day of chest pain, 0.6 day of stomach pain, 1.3 days of a burning feeling in their chest, 0.8 day of food/liquid coming back up into their throat, and 0.3 day of throwing up. Patients reported impacts of EoE symptoms on mental well-being and ADL; notably, 55% of patients reported that they were worried about choking (<b>Figure</b>). One-fifth of patients reported feeling moderately anxious or depressed. Patients reported a mean score of 86.5 when asked to rank their health on a visual analogue scale ranging from 0 (worst possible) to 100 (perfect health). <h3>Conclusion</h3> Our results show that many patients with EoE reported effects on social, emotional, mental, and overall health. With limited FDA-approved medications in the US, new targeted treatment options are needed.

CHARACTERIZATION OF PATIENTS WITH EOSINOPHILIC ESOPHAGITIS MANAGED BY GASTROENTEROLOGISTS AND ALLERGISTS: REAL-WORLD CLINICAL PRACTICE EVIDENCE

<h3>Introduction</h3> Eosinophilic esophagitis (EoE) is a chronic, allergen-induced inflammatory disease of the esophagus. Although most patients are managed by gastroenterologists, some are managed by allergists. This real-world study seeks to understand any differences among patients with EoE managed by gastroenterologist versus allergists. <h3>Methods</h3> This study was an analysis of the Adelphi EoE Disease Specific Programme collected in 2020 in the United Stated and five European countries. Included patients were ≥12 years old, with biopsy-confirmed EoE and receiving prescribed EoE treatment. All patients were treated and managed by either gastroenterologists or allergists. <h3>Results</h3> Among 1001 patients with EoE, 9% were allergist-treated patients (ATP), and 91% were gastroenterologist-treated patients (GTP) (<b>Figure</b>). Prior to diagnosis, a greater percentage of ATP experienced food impaction and choking on food while a greater percentage of GTP experienced dysphagia. A greater percentage of ATP had comorbidities, particularly in atopic conditions. ATP had been treated on average 1 year longer since diagnosis than GTP, and a greater percentage of ATP changed treatments. A substantially greater percentage of GTP had tissue eosinophil counts >15 eosinophils/high power field vs ATP (60% vs 36%). GTP had undergone dilation more often than ATP, and dilation was more often performed after admittance to emergency room/hospital for GTP than ATP (36% versus 9%). <h3>Conclusion</h3> A greater percentage of GTP had dysphagia, and they had higher tissue eosinophilia and more frequent dilations, while a greater percentage of ATP reported food impaction/choking on food, had comorbidities, and had been on treatment longer.

Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE is one of the leading causes of chronic refractory dysphagia in adults and children. EoE is a clinicopathologic disorder and the histological portion of the diagnosis requires enumerating the density of esophageal eosinophils in esophageal biopsies, and evaluating additional features such as basal zone hyperplasia is helpful. However, this task requires time-consuming, somewhat subjective manual analysis, thus reducing the ability to process the complex tissue structure and infer its relationship with the patient's clinical status. Previous artificial intelligence (AI) approaches that aimed to improve histology-based diagnosis focused on recapitulating identification and quantification of the area of maximal eosinophil density, the gold standard manual metric for determining EoE disease activity. However, this metric does not account for the distribution of eosinophils or other histological features, over the whole slide image. Here, we developed an artificial intelligence platform that infers local and spatial biomarkers based on semantic segmentation of intact eosinophils and basal zone distributions. Besides the maximal density of eosinophils [referred to as Peak Eosinophil Count (PEC)] and a maximal basal zone fraction, we identify the value of two additional metrics that reflect the distribution of eosinophils and basal zone fractions. This approach enables a decision support system that predicts EoE activity and potentially classifies the histological severity of EoE patients. We utilized a cohort that includes 1,066 biopsy slides from 400 subjects to validate the system's performance and achieved a histological severity classification accuracy of 86.70%, sensitivity of 84.50%, and specificity of 90.09%. Our approach highlights the importance of systematically analyzing the distribution of biopsy features over the entire slide and paves the way toward a personalized decision support system that will assist not only in counting cells but can also potentially improve diagnosis and provide treatment prediction.

S1553 Association of EoE and Celiac Disease in a National VA Database

Introduction: Conflicting evidence exists regarding the association between Eosinophilic Esophagitis (EoE) and Celiac Disease, leaving clinicians questioning whether it is necessary to perform small bowel biopsies during endoscopy for patients with EoE. We sought to assess the relationship between EoE and Celiac Disease in a large population-based study to better assess the utility of this procedure in this setting. Methods: We performed a nationwide, retrospective case control study using patient data from the Department of Veterans Affairs electronic health records (EHR). Using ICD9 and ICD10 codes, patients with EoE (530.13, K20.0) and Celiac Disease (579.0, K90.0) were identified. The prevalence of EoE in Celiac Disease and the prevalence of Celiac Disease in EoE, as well as odds ratios of the respective conditions, were determined. Results: Using a random sample of 1,110,189 VA patients, we identified 1,022 cases of EoE (0.092%) and 1,285 cases of Celiac Disease (0.116%), where the prevalence of Celiac Disease within the EoE cohort was found to be 1.08% (n=11), reflecting an elevated odds of Celiac in EoE (OR= 9.46, 95% CI: 4.89,16.32) (Table). Additionally, the prevalence of EoE within the Celiac cohort was 0.86%, which also indicated an elevated odds of EoE in Celiac Disease (OR= 9.46, 95% CI: 4.89,16.32) (Table). Adjusting for race, ethnicity, and gender resulted in a similar OR (OR=8.66, CI: 4.47, 14.95). When stratified by race and ethnicity, we found that all patients with both EoE and Celiac Disease were White and non-Hispanic. When stratified by gender, 10 of the 11 patients with both EoE and Celiac Disease were found to be male. Conclusion: The results of our study show that there is an increased odds of Celiac Disease within EoE and vice versa in VA patients when compared to the general population. These results suggest that in EoE and Celiac patients, Celiac Disease and EoE should be actively looked for and that there should be a low threshold to biopsy, especially if there are any symptoms or mucosal changes that are suggestive of disease. However, further research into the association of Celiac Disease and EoE with prospective studies are needed. Table 1. - Prevalence of EoE and Celiac Disease among patients in the VA EHR Patients with EoE Patients without EoE Patients with Celiac Disease 11 1,274 Patients without Celiac Disease 1,011 1,107,893

Eosinophilic Esophagitis: Cytokines Expression and Fibrotic Markers in Comparison to Celiac Disease.

Introduction: Eosinophilic esophagitis (EoE) is now recognized as the main inflammatory condition that leads to fibrosis, unlike other chronic inflammatory gastrointestinal diseases, such as celiac disease. The aim of our study is to characterize the collagen deposition and cytokine expression involved in the fibrogenic response in patients affected by EoE in comparison to celiac disease. Materials and Methods: Consecutive patients with a clinical suspicion of untreated EoE or active celiac disease were enrolled. In the control group, patients with negative upper endoscopy were included. Total RNA was isolated from biopsy specimens using a commercial kit (SV Total RNA Isolation System, Promega Italia Srl). Quantitative real-time PCR (qRT-PCR) was performed in triplicate using a StepOne™ Real-Time PCR instrument (Thermo Fisher Scientific, Monza, Italy). mRNA encoding for inflammatory molecules: interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and fibrotic markers: transforming growth factor beta 1 (TGF-β), mitogen-activated protein kinase kinase kinase 7 (MAP3K7), serpin family E member 1 (SERPINE1), were quantified using TaqMan Gene Expression Assays (Applied Biosystems). RESULTS. In EoE, the qPCR analysis showed an increase in all the inflammatory cytokines. Both IL-5 and Il-3 mRNA expression resulted in a statistically significant increase in oesophageal mucosa with respect to the celiac duodenum, while no differences were present in IL-4 expression. TGF-β expression was similar to the controls in the mid esophagus but reduced in the distal EoE esophagus (RQ: 0.46 ± 0.1). MAP3K7 expression was reduced in the mid esophagus (RQ: 0.59 ± 0.3) and increased in the distal esophagus (RQ: 1.75 ± 0.6). In turn, the expression of SERPINE1 was increased in both segments and was higher in the mid than in the distal esophagus (RQ: 5.25 ± 3.9, 1.92 ± 0.9, respectively). Collagen deposition was greater in the distal esophagus compared to the mid esophagus [18.1% ± 8 vs. 1.3% ± 1; p = 0.008]. Conclusions: The present study confirms the esophageal fibrotic involution involving the distal esophagus and shows that the inflammatory pathway in EoE is peculiar to this disease and different from other chronic inflammatory gastrointestinal disorders such as celiac disease.

Eosinophilic esophagitis auxiliary diagnosis based on a peptide ligand to eosinophil cationic protein in esophageal mucus of pediatric patients

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils’ counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.

A Deep Multi-Label Segmentation Network For Eosinophilic Esophagitis Whole Slide Biopsy Diagnostics.

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus associated with elevated numbers of eosinophils. Disease diagnosis and monitoring require determining the concentration of eosinophils in esophageal biopsies, a time-consuming, tedious and somewhat subjective task currently performed by pathologists. Here, we developed a machine learning pipeline to identify, quantitate and diagnose EoE patients' at the whole slide image level. We propose a platform that combines multi-label segmentation deep network decision support system with dynamics convolution that is able to process whole biopsy slide. Our network is able to segment both intact and not-intact eosinophils with a mean intersection over union (mIoU) of 0.93. This segmentation enables the local quantification of intact eosinophils with a mean absolute error of 0.611 eosinophils. We examined a cohort of 1066 whole slide images from 400 patients derived from multiple institutions. Using this set, our model achieved a global accuracy of 94.75%, sensitivity of 94.13%, and specificity of 95.25% in reporting EoE disease activity. Our work provides state-of-the-art performances on the largest EoE cohort to date, and successfully addresses two of the main challenges in EoE diagnostics and digital pathology, the need to detect several types of small features simultaneously, and the ability to analyze whole slides efficiently. Our results pave the way for an automated diagnosis of EoE and can be utilized for other conditions with similar challenges.

Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission

Mast cells (MCs) are pleiotropic cells that accumulate in the esophagus of patients with eosinophilic esophagitis (EoE) and are thought to contribute to disease pathogenesis, yet their properties and functions in this organ are largely unknown. This study aimed to perform a comprehensive molecular and spatial characterization of esophageal MCs in EoE. Esophageal biopsies obtained from patients with active EoE, patients with EoE in histologic remission, and individuals with histologically normal esophageal biopsies and no history of esophageal disease (ie, control individuals) were subject to single-cell RNA sequencing, flow cytometry, and immunofluorescence analyses. This study probed 39,562 single esophageal cells by single-cell RNA sequencing; approximately 5% of these cells were MCs. Dynamic MC expansion was identified across disease states. During homeostasis, TPSAB1highAREGhigh resident MCs were mainly detected in the lamina propria and exhibited a quiescent phenotype. In patients with active EoE, resident MCs assumed an activated phenotype, and 2 additional proinflammatory MC populations emerged in the intraepithelial compartment, each linked to a proliferating MKI67high cluster. One proinflammatory activated MC population, marked as KIThighIL1RL1highFCER1Alow, was not detected in disease remission (termed "transient MC"), whereas the other population, marked as CMA1highCTSGhigh, was detected in disease remission where it maintained an activated state (termed "persistent MC"). MCs were prominent producers of esophageal IL-13 mRNA and protein, a key therapeutic target in EoE. Esophageal MCs comprise heterogeneous populations with transcriptional signatures associated with distinct spatial compartmentalization and EoE disease status. In active EoE, they assume a proinflammatory state and locally proliferate, and they remain activated and poised to reinitiate inflammation even during disease remission.

Prevalence and Predictors of Compromised Bone Mineral Density in Pediatric Eosinophilic Esophagitis

To determine if patients with eosinophilic esophagitis (EoE) have decreased bone mineral density (BMD) more than what would be expected for their age and determine if the decreased bone density is more associated with certain comorbidities or treatments.A total of 269 patients with EoE were evaluated at the Cincinnati Children’s Hospital Medical Center Gastroenterology Outpatient Clinic. The inclusion criteria were patients 3 to 21 years who have a diagnosis of EoE on the basis of clinical history and pathology and have undergone a lumbar spine dual-energy radiograph absorptiometry (DXA) scan between January 1, 2014, to December 31, 2017.This study was a retrospective chart review. Specifically, charts were evaluated to find the patient’s first DXA scan within the study period. Demographic data included age at the time of the scan and EoE disease burden. Investigators also documented any comorbidities such as history of atopic disease, connective tissue diseases, eosinophilic gastrointestinal diseases, and immunoglobulin E (IgE)-mediated food allergies. Treatment information collected included corticosteroids, proton pump inhibitors (PPIs), 5-food and 6-food elimination diet, and elemental diet. From each chart, they noted if patients had ever been on these treatments in their lifetime, within the year preceding the DXA scan, or at the time of the DXA scan.The mean lumbar spine BMD z score of −0.5 was lower than the expected value of 0, and the prevalence of low BMD was 8.6% in comparison with the predicted value of 2.5%, both statistically significant. By using predictive multivariate models, PPI use at any point in the patient’s lifetime, the 5-food or 6-food elimination diet, and a history of IgE-mediated food allergies had negative correlations with BMD scores (−0.65, −0.27, and −0.28, respectively). Boys were at an increased risk of low BMD scores (odds ratio (OR): 4.84). Of note, corticosteroid use was not associated with lower BMD scores. Patients with a higher BMI, with a higher height-for-age, and who had active EoE were less likely to have a low BMD (OR: 0.43, OR: 0.33, and OR: 0.34, respectively).Pediatric patients with EoE have a lower BMD than their peers and a higher prevalence of low BMD. Risk factors to consider for these patients to develop low BMD include a history of IgE-mediated food allergies. Treatments such as restrictive food-elimination diets and PPI use also increase the risk of these patients developing lower BMD.There is prominent use of PPIs in pediatric patients with EoE, both to treat esophageal inflammation and protect the gastric mucosa with steroids treatment. Additionally, the use of dietary modifications to eliminate potential triggers is commonly used to treat EoE. Although both forms of treatments are effective in managing EoE, in this study, it is indicated that there may be negative impacts on bone health that should be considered in their management plan. Because this study is a retrospective analysis, it supports the need for a prospective study to evaluate factors that contribute to low BMD in pediatric patients with EoE and potential screening tools to identify those at greater risk of low BMD in this population.

Esophageal Dysmotility Is Associated With Disease Severity in Eosinophilic Esophagitis

An association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE. A total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP. FLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau <17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range [IQR], 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field [hpf]; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf). Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.

Esophageal Hypervigilance and Symptom-Specific Anxiety in Patients with Eosinophilic Esophagitis

Patient symptom reporting often does not correlate with the pathophysiological markers of esophageal disease, including eosinophilic esophagitis (EoE). Esophageal hypervigilance and symptom-specific anxiety are emerging as important considerations in understanding symptom reporting. As such, we aimed to conduct the first study of these constructs in EoE. A retrospective review of an EoE patient registry was conducted and included eosinophils per high power field (from esophagogastroduodenoscopy biopsy: proximal, distal), endoscopic reference score, distal distensibility plateau (functional luminal imaging probe), Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, Northwestern Esophageal Quality of Life scale, and the Esophageal Hypervigilance and Anxiety Scale. Correlational and regression analyses evaluated relationships of hypervigilance and anxiety with Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, and Northwestern Esophageal Quality of Life scale when controlling for histology and endoscopic severity. One hundred and three patients had complete data, 69.9% were male, and the mean (SD) age was 40.66 (13.85) years. Forty-one percent had elevated dysphagia and 46% had elevated hypervigilance and anxiety. Esophageal symptom-specific anxiety emerged as the most important predictor of Brief Esophageal Dysphagia Questionnaire severity (44.8% of the variance), Visual Dysphagia Question of EoE Activity Index severity (26%), and poor health-related quality of life (HRQoL) (55.3%). Hypervigilance was also important, but to a lesser extent. Pathophysiological variables did not significantly predict symptoms or HRQoL. Recent food impaction can predict symptom-specific anxiety and proton pump inhibitor use can reduce hypervigilance. Hypervigilance and symptom-specific anxiety are important for our understanding of self-reported patient outcomes in EoE. These processes outweigh endoscopic and histologic markers of EoE disease activity across dysphagia, difficulty eating, and HRQoL. Clinicians should assess hypervigilance and anxiety, especially in patients with refractory symptoms and poor HRQoL.

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS): An International Multidisciplinary Consensus

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS): An International Multidisciplinary Consensus

Platelet association with leukocytes in active eosinophilic esophagitis

We previously demonstrated that the percentage of blood eosinophils that are associated with platelets and thus positive for CD41 (integrin αIIb-subunit) correlates with and predicts peak eosinophil count (PEC) in biopsies of eosinophilic esophagitis (EoE) patients after treatment. Thus, flow cytometric determination of CD41+ eosinophils is a potential measure of EoE disease activity. Determinants of association of platelets with eosinophils and other leukocytes in EoE are largely unknown. The objectives of this study were to test the hypotheses that platelets associate with blood leukocytes other than eosinophils in EoE and that such associations also predict EoE activity. Whole blood flow cytometry was performed on samples from 25 subjects before and after two months of standard of care EoE treatment. CD41 positivity of cells within gates for eosinophils, neutrophils, monocytes, lymphocytes, and natural killer cells was compared. We found that percent CD41+ neutrophils, monocytes, and eosinophils correlated with one another such that principal component analysis of the five cell types identified “myeloid” and “lymphoid” factors. Percent CD41+ neutrophils or monocytes, or the myeloid factor, like CD41+ eosinophils, correlated with PEC after treatment, and CD41+ neutrophils or the myeloid factor predicted PEC < 6/high power field after treatment, albeit with lower area under the curve than for CD41+ eosinophils. We conclude that the processes driving platelets to associate with eosinophils in EoE also drive association of platelets with neutrophils and monocytes and that association of platelets with all three cell types is related to disease activity. Clinicaltrials.gov identifier: NCT02775045.

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions.

Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis.