Hypoxia-inducible microRNA-155 negatively regulates epithelial barrier in eosinophilic esophagitis by suppressing tight junction claudin-7.

MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. MiR-155 localization using in situ hybridization (ISH) in patient biopsies and intra-epithelial compartmentalization of miR-155 show expression predominantly within the basal epithelia. Epithelial miR-155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR-155 stable overexpression induced a functionally deficient epithelial barrier in 3D air-liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR-155 showed notable dilated intra-epithelial spaces. Unbiased RNA-sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin-7. Together, our data reveal a previously unappreciated role for miR-155 in mediating epithelial barrier dysfunction in esophageal inflammation.

Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia.

INTRODUCTION: Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories. METHODS: The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis. RESULTS: We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63). DISCUSSION: Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications.

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.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study.

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSIONS: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

One Year Into Dupilumab: Physician and Patient Experiences in Initiating Dupilumab for Pediatric Eosinophilic Esophagitis.

In 2022, the US Food and Drug Administration approved dupilumab for treatment of eosinophilic esophagitis (EoE). The aims of this study were to report physician and patient perspectives on initiating dupilumab. A 2-pronged approach was used: (1) data on physician prescribing practices was gathered via retrospective chart review of EoE patients prescribed dupilumab and (2) pediatric patients on dupilumab were approached to complete a questionnaire regarding reasons for initiation. During this time, 42 patients were prescribed dupilumab. From the physician's perspective, the primary reasons for dupilumab included nonresponse to topical corticosteroids (TCS) (52%), nonadherence (28%), adverse effects (10%), or to treat multiple atopic diseases (5%). The median dupilumab initiation time, from day prescribed to first injection, was 37 days [interquartile range (IQR) 37]. Almost all required prior authorization (PA) (98%), while 17% required letter of appeal and 2% required peer-to-peer. Fifteen patients (36%) completed the questionnaire portion of the study. From the patient's perspective, the primary reasons for dupilumab initiation included nonresponse to TCS (27%), nonadherence to TCS (27%), concern about adverse effects of TCS (7%), and treatment of multiple atopic diseases (33%). In conclusion, physicians are prescribing dupilumab primarily for nonresponse to TCS and almost all required PA with a long delay to starting dupilumab.

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.

Esophageal remodeling in eosinophilic esophagitis: Relationships to luminal captured biomarkers of inflammation and periostin.

BACKGROUND: Esophageal remodeling is a factor in disease progression and symptom severity for patients with eosinophilic esophagitis (EoE). Remodeling can begin early in children, resulting in stricture and food impaction. Detection of esophageal remodeling often depends on endoscopy and is appreciated only in its later stages. OBJECTIVE: We sought to determine whether luminal eosinophil-associated and remodeling proteins captured by the esophageal string test (EST) correlate with measures of esophageal remodeling and biomarkers of the epithelial-mesenchymal transition (EMT). METHODS: Patients with EoE (7-18 years old) were enrolled from 2 pediatric hospitals. Participants performed the EST and underwent endoscopy. Histology, distensibility measured by endoluminal functional lumen imaging probe, and symptoms were assessed. Protein quantitation by ELISA was performed on mucosal biopsy and EST samples. Tissue sections were evaluated for EMT. Outcome measures were summarized, and Spearman ρ was used to assess bivariate correlations. RESULTS: Forty patients (68% male) were enrolled (mean age, 12.5 years). Twenty-four (60%) had active disease (≥15 eosinophils per high-power field). EST-captured eotaxin-3, major basic protein 1, EDN, eosinophil peroxidase, and Charcot-Leyden crystal protein/galectin-10 showed significant correlations with peak eosinophils per high-power field (ρ 0.53-0.68, P < .001). Luminal proteins positively correlated with endoscopic features and markers of EMT, and negatively with esophageal distensibility. Periostin was captured by the EST and correlated with eosinophil density, basal zone hyperplasia, endoscopic appearance, and markers of EMT. CONCLUSION: Luminal markers of esophageal remodeling in addition to biomarkers of eosinophilic inflammation correlate with epithelial and functional remodeling in EoE.

Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field.

The US Food and Drug Administration hosted a workshop on July 21, 2021, to discuss the disease characteristics, natural history, and end points to assess treatment benefit in patients with eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE). Notably, EGIDs beyond EoE, such as eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis, herein referred to as non-EoE EGIDs, are understudied relative to EoE. This workshop provided a forum for open discussion among stakeholders-medical professionals (including their societies and research groups), Food and Drug Administration representatives, an industry representative, and a patient representative-to facilitate drug development. Experts in many disciplines related to EGIDs, including allergy, immunology, epidemiology, gastroenterology, and pathology, and both adult and pediatric clinicians contributed. Herein, we discuss some of the insights of the material presented at the meeting and present perspectives on moving the field forward toward drug approval.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Medication Adherence Aligns with Age and a Behavioral Checklist but Not Symptoms or Quality of Life for Patients with Eosinophilic Esophagitis.

OBJECTIVE: To measure adherence rates to swallowed topical steroids in children with eosinophilic esophagitis (EoE), describe factors related to adherence, and determine the association between adherence, symptoms, perceived disease severity, and quality of life in children with EoE. STUDY DESIGN: Subjects in this cross-sectional study of 117 children between 5 and 18 years old with EoE completed the Pediatric Eosinophilic Esophagitis Symptoms Score V2.0 (PEESS), Pediatric Quality of Life Inventory Eosinophilic Esophagitis Module (PedsQL EoE), a Medication-Taking Checklist (MTC), and a demographics questionnaire. Adherence rate was calculated based on reported number of missed doses/prescribed doses in the last week. Parent-reported measures were used for children aged 5-12 years and self-report was used for children aged 13-18 years. RESULTS: Adolescents had lower adherence rates than younger children (76.2 ± 24.5% vs 88.6 ± 16.7%, P = .002). Adherence rates were not associated with disease history, PEESS, or PedsQL EoE scores but instead correlated with MTC scores (Pearson r of 0.65, P < .001 for child-report and Pearson r of 0.74, P < .001 for parent-report). Symptomatology was associated with worse quality of life (PEESS Frequency: r = -0.7, P < .001; PEESS Severity: r = -0.71, P < .001 for children 5-12 years old; PEESS Frequency: r = -0.61, P < .001; PEESS Severity: r = -.5, P < .001 for adolescents). CONCLUSIONS: Unrelated to their clinical history, demographic factors, symptoms, and quality of life, adolescents with EoE have lower medication adherence rates. The MTC may serve as a clinical tool to discuss adherence and provide targeted educational counseling regarding adherence interventions.

Follow-up and symptom persistence after esophageal food impaction.

Esophageal food impactions (EFI) are associated with esophageal pathology, most commonly eosinophilic esophagitis (EoE). Obtaining biopsies provides opportunity for diagnosis, which is important since treatment of EoE decreases the risk for future EFI. Outpatient follow-up rates remain suboptimal and outcomes of patients without timely follow-up are unknown. We aimed to identify the factors associated with pediatric subspecialty follow-up post-EFI and to determine the symptom burden in patients without follow-up. We performed a retrospective review of patients presenting with EFI at a tertiary children's hospital between 2010 and 2018. Patients without subspecialty follow-up within 1 year of EFI were included in a prospective telephone survey investigating the barriers to care, outcomes, and symptoms. Clinical characteristics were compared between groups. Multivariate analysis was used to control for multiple variables. There were 127 EFI identified in 123 individuals (73% male, mean age: 12.2 years). Esophageal biopsies were collected in 76% of cases, and 49% of patients had follow-up. Individuals with follow-up were more likely (P ≤ 0.05) to have had biopsies. In a multivariate analysis, written recommendation for follow-up (Odds Ratio: 6.9 [2.4-19.5], P = 0.001) as well as atopic history and identified stricture were associated with a higher likelihood of follow-up. Those without follow-up had subsequent stricture (35%), dilation (44%), or EFI (39%), and 55% (12/22) described ongoing esophageal symptoms. Identification of treatable findings at time of EFI and ongoing symptom burden after EFI support an imperative for follow-up after EFI. Clear recommendations are a modifiable factor that may improve follow-up in this population.

Case Series: Role of Pill Esophagram to Identify Pediatric Patients With Eosinophilic Esophagitis Amenable to Therapeutic Dilation.

Eosinophilic esophagitis (EoE) is a chronic disease of the esophagus that leads to esophageal remodeling. Dysphagia is a common symptom that likely results from the inflammatory process or remodeling. Identifying patients that may benefit from dilation can be challenging because of difficulties in detecting subtle narrowing in patients with EoE. Here we report the benefits of a pill esophagram in the detection of esophageal narrowing in EoE. We identified a series of children with EoE and symptoms of dysphagia who underwent barium esophagram with a barium-coated pill to assess symptoms. Three subjects had a normal fluoroscopic esophagram but had pill retention for greater than 5 minutes. Subsequent esophagoscopy and esophageal dilation revealed mucosal rent after dilation. Subtle esophageal narrowing may not be captured with barium esophagram alone in children with EoE and dysphagia. Use of the barium pill in symptomatic patients can assist in identifying patients who may benefit from esophageal dilation.

Implementation of a Timed Barium Esophagram Protocol for Assessment of Esophageal Function in Children.

OBJECTIVES: Timed barium esophagram (TBE) is a fluoroscopic study that is widely employed as an adjunctive tool for diagnosing esophageal emptying disorders in adults (eg, achalasia, esophagogastric junction outflow obstruction [EGJOO]) and for following response to treatment. We aimed to describe the characteristics and feasibility of a pediatric TBE protocol and provide a first report of the potential value of TBE for assessment of esophageal emptying in the pediatric population. METHODS: Retrospective chart review of pediatric patients at a tertiary pediatric hospital who underwent TBE from October 2017 to October 2019. Patient and test characteristics were summarized using descriptive statistics. Results from patients who had both TBE and high-resolution esophageal manometry (HRM) were used to generate ROC curves for TBE to identify esophageal emptying disorders. RESULTS: Twenty-two patients underwent 25 TBE. Fourteen of 23 (61%) received 150 mL barium volume per protocol. Nearly half (42%) of subjects could tolerate ingesting barium within 20 seconds. Nine individuals underwent HRM. The sensitivity of standard adult TBE criteria (1 cm barium column height at 5 minutes) to detect emptying disorder was 100%, specificity 40%. A modified diagnostic cutoff (1.6 cm height at 5 minutes) offered 100% sensitivity, 80% specificity. CONCLUSIONS: TBE is feasible and should be considered an adjunctive noninvasive screen for impaired esophageal emptying in children. There was heterogeneous adherence to protocol for timing and volume of barium; however, studies remained interpretable. This population may benefit from different diagnostic cutoffs than adults, and clinical judgment should be used until specific diagnostic cutoffs are determined in children.

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders.

BACKGROUND: Little is known about the endoscopic and histologic findings of non-esophageal eosinophilic gastrointestinal diseases (EGID). AIM: To characterize the presenting endoscopic and histologic findings in patients with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) at diagnosis and 6 months after initiating the treatment. METHODS: We conducted a retrospective cohort study at 6 US centers associated with the Consortium of Eosinophilic Gastrointestinal Researchers. Data abstracted included demographics, endoscopic findings, tissue eosinophil counts, and associated histologic findings at diagnosis and, when available, after initial treatment. RESULTS: Of 373 subjects (317 children and 56 adults), 142 had EG, 123 EGE, and 108 EC. Normal endoscopic appearance was the most common finding across all EGIDs (62% of subjects). Baseline tissue eosinophil counts were quantified in 105 (74%) EG, 36 (29%) EGE, and 80 (74%) EC subjects. The mean peak gastric eosinophil count across all sites was 87 eos/hpf for EG and 78 eos/hpf for EGE. The mean peak colonic eosinophil count for EC subjects was 76 eos/hpf (range 10-500). Of the 29% of subjects with post-treatment follow-up, most had an improvement in clinical, endoscopic, and histologic findings regardless of treatment utilized. Reductions in tissue eosinophilia correlated with improvements in clinical symptoms as well as endoscopic and histologic findings. CONCLUSIONS: In this large cohort, normal appearance was the most common endoscopic finding, emphasizing the importance of biopsy, regardless of endoscopic appearance. Decreased tissue eosinophilia was associated with improvement in symptoms, endoscopic, and histologic findings, showing that disease activity is reversible.

Transnasal Endoscopy in Unsedated Children With Eosinophilic Esophagitis Using Virtual Reality Video Goggles.

BACKGROUND & AIMS: Evaluation and treatment of children with eosinophilic esophagitis (EoE) requires serial endoscopic, visual, and histologic assessment by sedated esophagogastroduodenoscopy (EGD). Unsedated transnasal endoscopy (TNE) was reported to be successful in a pilot study of children. We evaluated video goggle and virtual reality-based unsedated TNE in children with EoE, collecting data on rates of completion, adverse events, and adequacy of visual and histologic findings. METHODS: We performed a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE from January 2015 through February 2018. We analyzed data on patient demographics, procedure completion, endoscope type, adverse events, visual and histologic findings, estimated costs, and duration in the facility. Esophageal biopsies from the first 173 subjects who underwent TNE were compared with those from previous EGD evaluations. RESULTS: During 300 attempts, 294 TNEs were performed (98% rate of success). Fifty-four patients (age, 6-18 y) underwent multiple TNEs for dietary or medical management of EoE. There were no significant adverse events. Visual and histologic findings were adequate for assessment of EoE. TNE reduced costs by 53.4% compared with EGD (TNE $4393.00 vs EGD $9444.33). TNE was used increasingly from 2015 through 2017, comprising 31.8% of endoscopies performed for EoE. The total time spent in the clinic (front desk check-in to check-out) in 2018 was 71 minutes. CONCLUSIONS: In a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE, TNE was safe and effective and reduced costs of EoE monitoring. Advantages of TNE include reduced risk and cost associated with anesthesia as well as decreased in-office time, which is of particular relevance for patients with EoE, who require serial EGDs.

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference.

BACKGROUND & AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis. METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries used online communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences. RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents, and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement. CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2) on esophageal biopsy and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.

Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium.

OBJECTIVES: The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with EG, EGE, and EC. METHODS: In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses. RESULTS: Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements. CONCLUSIONS: In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.