Role of endoscopy in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease involving inflammation of the esophagus. Endoscopy is essential in the diagnosis and treatment of EoE and shows typical findings, including esophageal edema, rings, exudates, furrows, and stenosis. However, studies involving pediatric and adult patients with EoE suggest that even a normally appearing esophagus can be diagnosed as EoE by endoscopic biopsy. Therefore, in patients with suspected EoE, biopsy samples should be obtained from the esophagus regardless of endoscopic appearance. Moreover, follow-up endoscopies with biopsy after therapy initiation are usually recommended to assess response. Although previous reports of endoscopic ultrasonography findings in patients with EoE have shown diffuse thickening of the esophageal wall, including lamina propria, submucosa, and muscularis propria, its role in EoE remains uncertain and requires further investigation. Endoscopic dilation or bougienage is a safe and effective procedure that can be used in combination with medical and/or dietary elimination therapy in patients with esophageal stricture for the management of dysphagia and to prevent its recurrence.

Children with eosinophilic esophagitis non-responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile.

BACKGROUND: A combination of proton-pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non-responders (EoE-PPI-TSnr; n = 7) and responders (EoE-PPI-TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. METHODS: Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. RESULTS: In all, 3164 upregulated and 3154 downregulated genes distinguished EoE-PPI-TSnr from EoE-PPI-TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE-PPI-TSnr. There was a 56% overlap in dysregulated genes between EoE-PPI-TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic-erythroid progenitors, and T helper type 1 cells were significantly higher in EoE-PPI-TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE-PPI-TSnr and correlated with the key pathways. CONCLUSION: Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

Identification of gaps in the delivery of high-quality care of patients with eosinophilic esophagitis.

Quality indicators (QIs) are standardized metrics that can be used to quantify health care delivery and identify important areas for practice improvement. Nine QIs pertaining to the diagnosis and management of eosinophilic esophagitis (EoE) were recently established. We therefore aimed to identify existing gaps in care using these QIs. This is a retrospective, multicenter study utilizing recently established EoE QIs to evaluate practice patterns among adult gastroenterologists in the diagnosis and management of EoE. Three patient cohorts of 30 patients each presenting with dysphagia, food impaction, and new diagnosis of EoE, respectively, were obtained, yielding 120 patients per site to assess for every QI. Summary statistics were reported across two main themes: diagnosis and management. Subsequent analysis of gaps in care was then performed. The domain of diagnosis of EoE (QI 1 and 2) had the most notable gap in care with only 55% of the presenting patients undergoing appropriate evaluation for EoE. The domain of management of EoE had overall higher QI fulfillment-however it also contained significant intra-category variation in care. Notably, while 79% of patients had clinical follow-up within 1 year from remission, only 54% underwent surveillance endoscopy within 2 years of remission. In contrast, 100% of patients with symptomatic strictures independent of histologic response underwent endoscopic dilation (QI 4). Management approaches for EoE are evolving and variation in care delivery exists. We identified significant gaps in both diagnosis of EoE especially amongst patients presenting with index food impaction and long term management of EoE, when retrospectively evaluating care patterns using newly established QIs. This is the first study of its kind to utilize these previously established QIs to objectively identify care gaps that exist in EoE amongst several institutions. These findings also highlight the importance of QIs and standardization of management of complex chronic diseases like EoE to help bridge these gaps and provide a framework to measure adherence to these best practices.

Sustained clinical and histopathological remission in a patient with eosinophilic esophagitis and type-2 comorbidities at 18 months after discontinuation of dupilumab.

Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, type-2 inflammatory disease with the potential to significantly impact an individual's quality of life. Conventional treatments often result in varied responses, prompting the need for novel therapeutic approaches. We present the case of a 19-year-old male with a medical history marked by eosinophilic esophagitis, severe atopic dermatitis (AD), asthma, and allergic rhinitis. Despite undergoing diverse topical and systemic interventions to address his AD and EoE, the patient's symptoms persisted. However, following the initiation of dupilumab therapy-a dual IL-4 and IL-13 receptor antagonist-the patient experienced a substantial reduction in his Eczema Area and Severity Index score. Notably, a marked improvement was also seen regarding his symptoms of eosinophilic esophagitis. A subsequent esophageal biopsy revealed a significant decrease in eosinophilic inflammation, consistent with established clinical and histologic remission criteria. These findings corroborate the patient's reported relief from symptoms. This case underscores the potential efficacy of dupilumab as a promising therapeutic agent in managing eosinophilic esophagitis. Dupilumab offers a dual benefit of alleviating symptoms and achieving histologic and clinical remission. This novel approach presents a noteworthy advancement in the treatment of EoE.

Investigating immune profile by CyTOF in patients with Eosinophilic Esophagitis after treatment with orodispersible budesonide.

Eosinophilic esophagitis (EoE) is a chronic Th2 mediated inflammatory disease of the esophagus driven by dietary or inhalant allergens which if left untreated, leads to fibrosis and poor esophageal function. Although the inflammation in the esophagus is dominated by eosinophils, there are also elevated levels of T and B cells. Blood samples from ten patients with EoE before and after treatment with orodispersible budesonide and ten healthy controls were compared using cytometry by time-of-flight (CyTOF). An antibody panel was designed that covers the major immunological cell populations with particular focus on eosinophils. The data was analyzed with multivariate methods and cluster analysis. Correlation analysis was done between immune markers and endoscopic, histological and symptomatologic assessments. Our analysis revealed that patients with EoE had lower levels of effector memory T cells after treatment with orodispersible budesonide to the same level as healthy subjects. In addition, more suppressive eosinophils were present in the circulation of EoE patients before treatment and more immature eosinophils were present after treatment. Furthermore, levels of galectin-10+ eosinophils correlated with histological findings in esophageal tissue from EoE patients. In all patients, the peak eosinophils were decreased after treatment with orodispersible budesonide. Intriguingly, 90% of the patients had remission in the histological assessment and 50% improved in the endoscopic assessment. This study reports a detailed immune profile in patients with EoE before and after treatment with orodispersible budesonide and it is a step toward finding blood-based immune parameters that could be useful to monitor response to treatment.

Insights into the clinical, immunologic, and genetic underpinnings of food allergy.

The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020-a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy-based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease.

Analyzing Racial Disparities in Pediatric Atopic Comorbidity Emergency Department Visitation using Electronic Health Records.

BACKGROUND: Although atopic diseases and associated co-morbidities are prevalent in children, little is known about racial differences in emergency department (ED) visitation. OBJECTIVE: We sought to examine racial differences in ED visitation among children with allergic comorbidities. METHODS: We conducted a retrospective study of patients (<21 years) who visited the ED at a large pediatric hospital for atopic dermatitis (AD), food allergy (FA), asthma, allergic rhinitis (AR), and eosinophilic esophagitis (EoE) from 2015 to 2019. We determined the probability of ED encounter-free using hazard ratios (HR) and time to recurrence (TTR) of ED encounter for patients identified as Black/African American (AA) and White/European American (EA). We assessed potentially underlying allergic, demographic, and place-based factors, and potential interactions between factors. RESULTS: A total of 30,894 patients (38% AA, 62% EA) had 83,078 ED encounters (38,378 first ED encounters, and 44,700 recurrent ED encounters) during the study period. Asthma and AR showed the highest rate of comorbidity in ED encounters in both AA and EA children. AA children exhibited higher HR for encounter following index AD and asthma encounters. We found an interaction between the type of insurance and race in ED encounters for AD, FA, AR, and EoE. In AA children, those insured by Medicaid demonstrated a higher HR for any encounter compared to those with commercial insurance. Conversely, in EA children, those with Medicaid insurance showed a lower HR compared to their commercially insured peers. Regardless of race, allergic comorbidity increased the HR of ED encounter (1.12-1.62) for all allergic diseases. At 5-years follow up, mean differences in TTR were shorter in AA children compared to EA children in AD, FA, and asthma. CONCLUSION: Identification of disease-specific racial disparities in ED visitation related to atopic diseases is a necessary first step toward the design and implementation of interventions capable of equitably reducing emergency care in atopic comorbid children.

The Spectrum of Sarcina Colonization in the Gastrointestinal Tract of Pediatric and Adolescent Patients.

Introduction. Sarcina organisms are rare, gram-positive, sugar-fermenting cocci, identifiable in tissues only by histologic examination or molecular testing. Since its discovery, the pathogenicity and relevance of Sarcina in the human gastrointestinal tract has remained ill-defined. A recent literature review of 66 reported examples demonstrated the potential for severe complications such as emphysematous gastritis and gastric perforation. In pediatrics, colonization is associated with mucosal alterations and/or gastrointestinal dysmotility/obstruction with variable outcomes, including death secondary to gastric perforation. Yet, the features of Sarcina colonization within the gastrointestinal tract of adolescents are poorly understood and rarely reported. Methods. We present the gastrointestinal histopathological findings and the complete history of 4 pediatric patients with Sarcina colonization at our institution. Additionally a literature review with focus in the keywords "Sarcina" and "gastrointestinal' was performed, and the clinical and histopathological features of all previously reported examples of Sarcina in the gastrointestinal tract of pediatric patients were summarized. Results. All 4 patients had delayed gastric emptying, 3 of them due to neurologic disease, and one with pyloric obstruction due to duodenal ulceration with Helicobacter gastritis. In the 3 patients with available esophageal biopsies, it was associated to esophagitis with increased intraepithelial eosinophils. Conclusion. The potential pathogenicity of Sarcina colonization in the gastrointestinal tract of pediatric patients needs to be reevaluated. Due to potential serious complications, the identification of these organisms in the gastrointestinal tract sample should be reported and warrants further evaluation for possible gastrointestinal dysmotility or other mucosal alterations.

Amphiregulin-producing TH2 cells facilitate esophageal fibrosis of eosinophilic esophagitis.

Background: Massive eosinophil infiltration into the esophagus is associated with subepithelial fibrosis and esophageal stricture in patients with eosinophilic esophagitis (EoE). However, the pathogenesis of esophageal fibrosis remains unclear. Objective: We sought to elucidate the cellular and molecular mechanisms underlying the induction of esophageal fibrosis. Methods: We established a murine model of EoE accompanied by fibrotic responses following long-term intranasal administration of house dust mite antigen. Using this murine model, we investigated the characteristics of immune cells infiltrating the fibrotic region of the inflamed esophagus using flow cytometry and histological analyses. We also analyzed the local inflammatory sites in the esophagus of patients with EoE using single-cell RNA sequencing, flow cytometry, and immunohistochemistry. Results: Enhanced infiltration of both amphiregulin-producing and IL-5-producing TH2 cells was detected in the fibrotic area of the esophagus in mice subjected to repeated house dust mite exposure. Deletion of amphiregulin in CD4+ T cells ameliorates esophageal fibrosis. An analysis of human esophageal biopsy samples showed that the infiltration of amphiregulin-producing CD4+ T cells was higher in patients with EoE than in control patients. Furthermore, the number of infiltrated amphiregulin-producing CD4+ T cells was associated with the degree of esophageal fibrosis in patients with EoE. Conclusions: Amphiregulin, produced by TH2 cells, contributes to esophageal fibrosis in EoE and may be a therapeutic target.

Wheat-Related Disorders in Children: A 360-Degree View.

Immunological illnesses related to wheat represent an epidemiologically relevant phenomenon at a pediatric age. The term "Wheat-related disorders" involves a spectrum of diseases: celiac disease, IgE-mediated wheat allergy, non-IgE mediated wheat allergy, wheat-related eosinophilic esophagitis, and non-celiac gluten sensitivity. Their pathogenesis is different. At the same time, wheat represents their common point. This article aims to the state-of-the-art and new clinical evidence in pediatric age.

Decisions With Patients, Not for Patients: Shared Decision-Making in Allergy and Immunology.

Shared decision-making (SDM) is an increasingly implemented patient-centered approach to navigating patient preferences regarding diagnostic and treatment options and supported decision-making. This therapeutic approach prioritizes the patient's perspectives, considering current medical evidence to provide a balanced approach to clinical scenarios. In light of numerous recent guideline recommendations that are conditional in nature and are clinical scenarios defined by preference-sensitive care options, there is a tremendous opportunity for SDM and validated decision aids. Despite the expansion of the literature on SDM, formal acceptance among clinicians remains inconsistent. Surprisingly, a significant disparity exists between clinicians' self-reported adherence to SDM principles and patients' perceptions of its implementation during clinical encounters. This discrepancy underscores a fundamental issue in the delivery of health care, where clinicians may overestimate their integration of SDM, while patients' experiences suggest otherwise. This review critically examines the factors contributing to this inconsistency, including barriers within the health care system, clinician attitudes and behaviors, and patient expectations and preferences. By elucidating these factors in the fields of food allergy, asthma, eosinophilic esophagitis, and other allergic diseases, this review aims to provide insights into bridging the gap between clinician perception and patient experience in SDM. Addressing this discordance is crucial for advancing patient-centered care and ensuring that SDM is not merely a theoretical concept but a tangible reality in the.

Development and dysfunction of structural cells in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a disorder characterized by dysfunction and chronic local inflammation of the esophagus. The incidence and prevalence of EoE are increasing worldwide. The mechanisms responsible are poorly understood, and effective treatment options are limited. From the lumen outward, the esophagus comprises stratified squamous epithelium, lamina propria, and muscle. The tissue-specific nature of EoE strongly suggests that structural cells in the esophagus are involved in the EoE diathesis. Epithelial basal cell hyperplasia and dilated intercellular spaces are cardinal features of EoE. Some patients with EoE develop lamina propria fibrosis, strictures, or esophageal muscle dysmotility. Clinical symptoms of EoE are only weakly correlated with peak eosinophil count, implying that other cell types contribute to EoE pathogenesis. Epithelial, endothelial, muscle, and fibroblast cells can each initiate inflammation and repair, regulate tissue resident immune cells, recruit peripheral leukocytes, and tailor adaptive immune cell responses. A better understanding of how structural cells maintain tissue homeostasis, respond to cell-intrinsic and cell-extrinsic stressors, and exacerbate and/or resolve inflammatory responses in the esophagus is needed. This knowledge will facilitate the development of more efficacious treatment strategies for EoE that can restore homeostasis of both hematopoietic and structural elements in the esophagus.

Triggers for eosinophilic esophagitis (EoE): The intersection of food allergy and EoE.

Eosinophilic esophagitis and IgE-mediated food allergy are both food-triggered diseases that are increasing in prevalence. They share many clinical links, including significant comorbidity and similar food triggers, and as atopic diseases, they likely share upstream mechanisms related to barrier function and signals leading to TH2 skewing. In this review, we focus on links between eosinophilic esophagitis and IgE-mediated food allergy with an emphasis on what insights may be derived from overlapping food triggers and immune phenotypes. Through further investigation of these connections, we may be able to better understand not only IgE-mediated food allergy and eosinophilic esophagitis but also general atopic response to food proteins and evolution of allergic response to food.

Histological Remission of Eosinophilic Esophagitis Following Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia.

Eosinophilic esophagitis (EoE) is an immune/antigen-mediated disease with an increasing incidence over the last decade. Clinicopathological remission can be achieved through different treatment options but often requires chronic therapy. To our knowledge, this is the first report of EoE wherein the patient (a 54-year-old man) achieved histological remission after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia. Overall, despite the success of EoE treatment in this case, further studies are needed to establish allogeneic HSCT as a curative option for EoE.

Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS: A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS: A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION: Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

Adherence to therapeutic gastroscopy guidelines for acute esophageal food bolus impaction: Impact on adverse outcomes and length of stay.

Background and Aim: According to the European Society of Gastrointestinal Endoscopy (ESGE), gastroscopy should be conducted within 6 h for complete obstruction and 24 h for incomplete obstruction due to food bolus impaction. This study explores whether adults with acute esophageal food bolus (FB) impaction experience adverse outcomes when their time to esophagogastroduodenoscopy (EGD) deviates from the recommended guidelines. Methods: A retrospective review was performed on the records of 248 patients who presented at the study site between 2015 and 2022 with symptoms of FB impaction. Results: Two hundred and forty-eight patients underwent EGD for FB impaction. Grade 1 (erosion, ulceration), Grade 2 (tear), and Grade 3 (perforation) complications were present in 31.6%, 6.9%, and 0.8% of cases, respectively. Of the 134 (54.0%) patients with complete obstruction, 51 (38.1%) received EGD within the recommended 6 h. Of the 114 (46%) patients with incomplete obstructions, 93 (81.6%) received EGD within the recommended 24 h. There was no statistically significant correlation between length of stay (LOS) post-EGD and any of ingestion to presentation time, presentation to EGD time, or ingestion to EGD time. Age and complication level were greater predictors of longer LOS than presentation to EGD time. Patients who presented in hours were significantly more likely to receive EGD within the 6- and 24-h guidelines than those who presented out of hours (50.7% vs 22.0%). Conclusion: Neither time to EGD from ingestion of food bolus nor time to EGD from hospital presentation correlated with complication rate, complication severity, or length of stay post-EGD.