Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

Loneliness and Depressive Symptoms Are High Among Older Adults With Digestive Disease and Associated With Lower Perceived Health.

BACKGROUND & AIMS: Current approaches to managing digestive disease in older adults fail to consider the psychosocial factors contributing to a person's health. We aimed to compare the frequency of loneliness, depression, and social isolation in older adults with and without a digestive disease and to quantify their association with poor health. METHODS: We conducted an analysis of Health and Retirement Study data from 2008 to 2016, a nationally representative panel study of participants 50 years and older and their spouses. Bivariate analyses examined differences in loneliness, depression, and social isolation among patients with and without a digestive disease. We also examined the relationship between these factors and health. RESULTS: We identified 3979 (56.0%) respondents with and 3131 (44.0%) without a digestive disease. Overall, 60.4% and 55.6% of respondents with and without a digestive disease reported loneliness (P < .001), 12.7% and 7.5% reported severe depression (P < .001), and 8.9% and 8.7% reported social isolation (P = NS), respectively. After adjusting for covariates, those with a digestive disease were more likely to report poor or fair health than those without a digestive disease (odds ratio [OR], 1.25; 95% CI, 1.11-1.41). Among patients with a digestive disease, loneliness (OR, 1.43; 95% CI, 1.22-1.69) and moderate and severe depression (OR, 2.93; 95% CI, 2.48-3.47; and OR, 8.96; 95% CI, 6.91-11.63, respectively) were associated with greater odds of poor or fair health. CONCLUSIONS: Older adults with a digestive disease were more likely than those without a digestive disease to endorse loneliness and moderate to severe depression and these conditions are associated with poor or fair health. Gastroenterologists should feel empowered to screen patients for depression and loneliness symptoms and establish care pathways for mental health treatment.

Predicting Incident Adenocarcinoma of the Esophagus or Gastric Cardia Using Machine Learning of Electronic Health Records.

BACKGROUND & AIMS: Tools that can automatically predict incident esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using electronic health records to guide screening decisions are needed. METHODS: The Veterans Health Administration (VHA) Corporate Data Warehouse was accessed to identify Veterans with 1 or more encounters between 2005 and 2018. Patients diagnosed with EAC (n = 8430) or GCA (n = 2965) were identified in the VHA Central Cancer Registry and compared with 10,256,887 controls. Predictors included demographic characteristics, prescriptions, laboratory results, and diagnoses between 1 and 5 years before the index date. The Kettles Esophageal and Cardia Adenocarcinoma predictioN (K-ECAN) tool was developed and internally validated using simple random sampling imputation and extreme gradient boosting, a machine learning method. Training was performed in 50% of the data, preliminary validation in 25% of the data, and final testing in 25% of the data. RESULTS: K-ECAN was well-calibrated and had better discrimination (area under the receiver operating characteristic curve [AuROC], 0.77) than previously validated models, such as the Nord-Trøndelag Health Study (AuROC, 0.68) and Kunzmann model (AuROC, 0.64), or published guidelines. Using only data from between 3 and 5 years before index diminished its accuracy slightly (AuROC, 0.75). Undersampling men to simulate a non-VHA population, AUCs of the Nord-Trøndelag Health Study and Kunzmann model improved, but K-ECAN was still the most accurate (AuROC, 0.85). Although gastroesophageal reflux disease was strongly associated with EAC, it contributed only a small proportion of gain in information for prediction. CONCLUSIONS: K-ECAN is a novel, internally validated tool predicting incident EAC and GCA using electronic health records data. Further work is needed to validate K-ECAN outside VHA and to assess how best to implement it within electronic health records.

Real-World Effectiveness and Use of Dupilumab in Eosinophilic Esophagitis.

INTRODUCTION: Dupilumab, the first US Food and Drug Administration-approved treatment for eosinophilic esophagitis (EoE), lacks real-world data on use and effectiveness. METHODS: We conducted a retrospective cohort study of 70 patients with EoE prescribed dupilumab, comparing prescriber type, indication, follow-up, and response. RESULTS: Indications varied with gastroenterologists commonly prescribing for treatment-refractory cases and allergists as first-line therapy. Endoscopic assessment was lacking in 25.9%, but those with follow-up showed high histologic remission (92.3% first-line and 85% previous treatment failure). DISCUSSION: Dupilumab demonstrates effectiveness across EoE severity, including milder disease without previous treatment failure. Improving follow-up and assessing cost-effectiveness will help clarify its role in the treatment algorithm.

Treatment preference archetypes in eosinophilic esophagitis and their implications for therapy.

BACKGROUND: Little is known about how patients make decisions about and prioritize, therapies and disease management in eosinophilic esophagitis (EoE). We aimed to systematically identify and characterize patient perspectives and attitudes that influence decision making for EoE management. METHODS: To understand the diverse attitudes and values of EoE patients, we designed a study using the Q-method. We iteratively developed 31 statements related to EoE disease management. Participants sorted statements by ranking from +4 (most agree) to -4 (most disagree). By-person factor analysis, using 2- and 3- factor rotation, revealed distinct preference archetypes. RESULTS: Thirty-four adults with EoE (mean age 40.9, 51.4% male, 82.9% White) were recruited from gastroenterology and allergy clinics from a single center. We identified two treatment-centered archetypes: Medication preference, driven by symptoms and the desire to minimize risk of complications, and Natural treatment preference, focusing on identifying trigger foods and diet adherence. Three-factor analysis revealed an additional archetype: Treatment ambivalent, a view of EoE as a mild and episodic (not chronic) disease with low priority to treat. Comparison by factor revealed 54% of those in the natural preference archetype were recategorized as treatment ambivalent, suggesting that they see natural treatment as a less complicated or milder strategy and may be at risk of nonadherence and reduced treatment uptake. CONCLUSIONS: We identified three distinct treatment preference archetypes among individuals with EoE, underscoring the need for personalized treatment strategies, especially for those favoring natural approaches but masking ambivalence, and may be at risk for nonadherence or loss to follow-up.

Effect of benralizumab on histopathology and inflammatory signatures in a clinical cohort of eosinophilic esophagitis.

A preliminary report from the recent phase 3 trial of benralizumab, a monoclonal antibody that binds to interleukin-5 receptor alpha (IL5Rα), in patients with EoE revealed that medication use led to tissue eosinophil eradication but did not meet the clinical endpoint of symptom resolution. Here, we characterized the clinical, endoscopic, histologic, and transcriptional changes in patients with active EoE following benralizumab treatment. We retrospectively examined patients with EoE treated with benralizumab at the University of Utah (n = 11) and reviewed reported clinical symptoms, circulating and tissue eosinophilia, and endoscopic and histologic scores. Gene expression profiles from available esophageal tissue from benralizumab-treated patients were compared to those from patients with remission EoE (n = 5), active EoE (n = 10), and controls (n = 22). Benralizumab treatment resulted in partial symptom improvement and significant reduction in tissue eosinophilia, and endoscopic and histologic disease scoring (P < 0.01). Histologic score reductions were driven by eosinophil feature scores, while scores for epithelial features (basal cell hyperplasia and dilated intercellular spaces) were similar to those in active EoE. The gene signatures in benralizumab-treated patients mimicked those of active EoE (e.g. upregulation of POSTN, CDH26, CCL26, and downregulation of DSG1). RNA profiles and pathways support histologic findings of impaired epithelial function that persists despite benralizumab treatment. In conclusion, despite eosinophil eradication, patients treated with benralizumab had persistent epithelial injury at the histologic and transcriptional level. In this cohort, benralizumab therapy failed to eradicate inflammation and epithelial dysfunction showing that interleukin-5 receptor alpha blockade monotherapy is insufficient to control EoE.

Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis.

Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers.

Yield of Repeat Endoscopy for Barrett's Esophagus After Normal Index Endoscopy.

INTRODUCTION: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD. METHODS: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC. RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40). DISCUSSION: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.

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.

Provider Beliefs, Practices, and Perceived Barriers to Dietary Elimination Therapy in Eosinophilic Esophagitis.

INTRODUCTION: Despite effective dietary treatments, physicians prefer medications for eosinophilic esophagitis (EoE). METHODS: We conducted a web-based survey of providers to assess the perceived effectiveness, practice patterns, and barriers to EoE dietary therapy. RESULTS: Providers view diet as the least effective treatment. The greatest barrier was the belief that patients are disinterested and unlikely to adhere (58%). With less access to dietitians (56%), nonacademic providers often manage diets without dietitian guidance (41%). DISCUSSION: Given high patient acceptance for diets and multiple treatment options for EoE, clinicians need evidence-based knowledge on EoE diets, access to dietitians, and awareness of patient preferences.

Eosinophilic esophagitis: Immune mechanisms and therapeutic targets.

Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and is clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia and esophageal food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation and alterations of the esophageal squamous epithelium, such as basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), are thought to contribute to esophageal dysfunction and disease symptoms. Corroborative clinical and discovery science-based studies have established that EoE is characterized by an underlying allergic inflammatory response, in part, related to the IL-13/CCL26/eosinophil axis driving dysregulation of several key epithelial barrier and proliferative regulatory genes including kallikrein (KLK) serine proteases, calpain 14 (CAPN14) and anoctamin 1 (ANO1). The contribution of these inflammatory and proliferative processes to the clinical and histological manifestations of disease are not fully elucidated. Herein, we discuss the immune molecules and cells that are thought to underlie the clinical and pathologic manifestations of EoE and the emerging therapeutics targeting these processes for the treatment of EoE.

Nature with Nurture: the Role of Intrinsic Genetic and Extrinsic Environmental Factors on Eosinophilic Esophagitis.

PURPOSE OF REVIEW: As the rising prevalence and incidence of eosinophilic esophagitis (EoE) has quickly outpaced the rate of esophageal biopsies, particularly in Westernized countries, several studies have suggested a link between intrinsic genetic and extrinsic environmental risk factors and the development, presentation, and diagnosis of EoE. This review aims to critically assess existing studies describing the role of the environment on the development, symptomatic presentation, and diagnosis of this recently recognized chronic immune-mediated disease. RECENT FINDINGS: We present and critically evaluate the working hypotheses and supportive studies thus far on environmental factors on EoE, describe sources of potential bias in diagnosis due to socioeconomic factors and thus undermining studies of EoE etiology, and highlight opportunities for future research. As genetics alone do not explain the rapid rise of EoE, we must look to environmental, or extrinsic, factors both in the early-life period which shape the development of the gut microbiome, as well as later life contributing to diagnosis of this new disease. Future etiologic studies linking risk factors to EoE development in individual patients are needed.

What patients with eosinophilic esophagitis may not share with their providers: a qualitative assessment of online health communities.

BACKGROUND: Little is known about how patients with eosinophilic esophagitis (EoE) experience their symptoms, receive care, and cope with their disease. Patients commonly seek peer support from online communities, which provide insights on unmet needs and barriers to care. We performed a qualitative analysis of electronic health forums to characterize patient-to-patient conversations about EoE symptoms and the experience of disease. METHODS: We identified three publicly accessible electronic health forums hosting EoE communities. Conversation threads posted between July 2018 and June 2020 were coded using emergent and a priori codes based on the THRIVE conceptual framework of coping with chronic illness. RESULTS: Of 659 threads (4,933 posts) collected over two years, a random sample of 240 threads (30 per 3-month quarter) were selected for analysis. Thematic saturation was reached after 172 threads. Patient experience of EoE was driven by their perspectives in four key domains: (i) perception of EoE as episodic rather than chronic, (ii) treatment choices, (iii) personal definitions of success in the disease, and (iv) views of providers. CONCLUSION: Online health communities are a valuable and unfiltered source of patient perspectives that can be used to understand patient needs and goals. EoE patients interpret their disease as sporadic events and lack reliable sources of knowledge, which may influence how patients prioritize treatment. If providers are to succeed in providing high-quality EoE care, they need to equip themselves with evidence-based knowledge, engage in shared decision making, and look outside of clinical settings to recognize barriers to disease management.

Management of eosinophilic esophagitis associated food impaction in Europe and the United States.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge-The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings-Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

Variability in Practices of Compounding Budesonide for Eosinophilic Esophagitis.

INTRODUCTION: Little is known about the use of compounded steroids for eosinophilic esophagitis (EoE). METHODS: We conducted a telephone survey of all compounding pharmacies in Michigan and queried about practices and costs of compounded budesonide for EoE. RESULTS: Of 68 Michigan pharmacies, 93% responded, and 20 (29%) offer compounded budesonide suspension for EoE. Formulations, dose, and instructions for use varied across pharmacies. The mean cost for a 30-day supply was $74.50. DISCUSSION: Although few compounding pharmacies offer budesonide suspension and there are substantial variations in formulations, this may be a significantly more affordable treatment option for many.

Challenges and Opportunities in Social Media Research in Gastroenterology.

In recent years, social media has transformed how we as gastroenterologists communicate with each other and has grown into an arena of knowledge and peer support for patients. Gastroenterologists commonly use social media for education networking, patient populations use social media for peer support and advocacy, but little is known about how gastroenterologists can use social media to conduct thoughtful and rigorous patient-centered research. Therefore, we aim to introduce the scope of social media research, highlight prominent examples in gastroenterology, and review innovative opportunities and unique challenges to using and studying social media for research.

Making Social Media Work for You.

Social media (SoMe) can be an effective professional tool for the gastroenterologist or trainee. SoMe can support a gastroenterologist's efforts to brand themselves, network, learn, educate, and advocate for patients. SoMe for professional use should be approached with specific aims in mind, in order to optimize impact and productivity.

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

BACKGROUND: Little is known about patient choice in treatment of eosinophilic esophagitis (EoE). AIM: Determine motivators and barriers to using common EoE therapies and describe patient-reported shared decision making (SDM) and satisfaction with treatment. METHODS: 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. RESULTS: A total of 243 adults (mean age 38.7 years) and 270 adult caregivers of children (mean age 9.5 years) 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). CONCLUSIONS: 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.

Management of eosinophilic esophagitis is often discordant with guidelines and not patient-centered: results of a survey of gastroenterologists.

Published guidelines for the management of eosinophilic esophagitis (EoE) recommend an initial trial of proton pump inhibitors (PPI), histologic assessment for response to therapy, and tailoring treatments to patient needs and provider resources. Effectiveness studies directly comparing therapies are lacking, leaving a situation ripe for shared decision making. We aimed to assess gastroenterologists' adherence to guidelines and how they respond to EoE patients' preferences regarding management. We administered a web-based survey to practicing US gastroenterologists, assessing knowledge, and practice patterns in the management of EoE, including comfort with alternative treatments to steroids. Ninety-two providers responded, including 55% in private practice. Nearly half (47%) reported spending ≤10 minutes on initial education and counseling and 48% recommended PPI monotherapy prior to other strategies. Of those who did not start with PPI monotherapy, 55% chose topical steroids ± PPI and 26% dietary elimination ± PPI. Despite this, 90% felt comfortable allowing a patient to start dietary elimination instead of steroids, but less comfortable with dilation alone (39%) or no treatment (30%). Upon symptomatic resolution, 72% of academic providers recommended endoscopy with biopsies to demonstrate histologic response to treatment, compared to 27% in private practice. There are substantial variations in adherence to guidelines regarding PPI use and assessing response to therapy. Gastroenterologists prefer topical steroids over other treatment modalities and most spend little time educating and counseling, which may limit informed decision making. Strategies aimed at decreasing these variations in management and promoting shared decision making in EoE are needed.