Eosinophilic Esophagitis Research Articles

Budesonide oral suspension (Eohilia) for eosinophilic esophagitis.

Eohilia (Takeda), an oral suspension formulation of the corticosteroid budesonide, has been approved by the FDA for treatment of eosinophilic esophagitis (EoE) in patients ≥11 years old. It is the first oral drug to be approved in the US for this indication. The subcutaneously injected interleukin (IL)-4 receptor antagonist dupilumab (Dupixent) is approved for treatment of EoE in patients ≥1 year old who weigh ≥15 kg.

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.

Novel transcriptomic panel identifies histologically active eosinophilic oesophagitis

Background and aimsEosinophilic oesophagitis (EoE) is characterised by symptoms of esophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a...

A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology

BackgroundDupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. ObjectiveTo perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. MethodsA systematic review of the literature was performed, and an expert Delphi Panel was assembled. ResultsThe available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. ConclusionVaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Eosinophil-derived extracellular vesicles: isolation and classification techniques and implications for disease pathophysiology.

Eosinophils are leukocytes characterized by their ability to release granule content that is highly rich in enzymes and proteins. Besides the antihelminthic, bactericidal, and antiviral properties of eosinophils and their secretory granules, these also play a prominent role in the pathophysiology of diseases such as asthma, eosinophilic esophagitis, and other hypereosinophilic conditions by causing tissue damage and airway hyperresponsiveness. Although this cell was first recognized mainly for its capacity to release granule content, nowadays other capabilities such as cytokine secretion have been linked to its physiology, and research has found that eosinophils are not only involved in innate immunity, but also as orchestrators of immune responses. Nearly 10 yr ago, eosinophil-derived extracellular vesicles (EVs) were first described; since then, the EV field has grown exponentially, revealing their vital roles in intracellular communication. In this review, we synthesize current knowledge on eosinophil-derived EVs, beginning with a description of what they are and what makes them important regulators of disease, followed by an account of the methodologies used to isolate and characterize EVs. We also summarize current understanding of eosinophil-derived vesicles functionality, especially in asthma, the disease in which eosinophil-derived EVs have been most widely studied, describing how they modulate the role of eosinophils themselves (through autocrine signaling) and the way they affect airway structural cells and airway remodeling. Deeper understanding of this cell type could lead to novel research in eosinophil biology, its role in other diseases, and possible use of eosinophil-derived EVs as therapeutic targets.

Prevalence, incidence and treatment patterns of prurigo nodularis in England: a retrospective database analysis.

Prurigo nodularis (PN) is a pruritic skin disease characterized by multiple intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are limited studies on the epidemiology and treatment pathways of PN, especially moderate-to-severe PN, from England. To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Adult patients (aged ≥ 18 years) with a PN-specific diagnosis code allocated any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date; IDD) was recorded during the identification period, with data available 6 months before and ≥ 12 months after the IDD. Patients were classified as having moderate-to-severe PN (MSPN) or mild PN (MiPN), based on the presence or absence of a prescription record, post-IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1 : 1 according to age, sex and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post-IDD were analysed. A total of 8933 patients (MSPN, n = 2498; MiPN, n = 6435) were included in the study; 2462 patients with MiPN and 2462 with MSPN were included for the comparative analysis. The presence of atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The overall prevalence of cases of PN increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super-potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second-generation antihistamines, oral and injectable systemic corticosteroids, methotrexate, antidepressants and tacrolimus were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The epidemiology of PN was consistent with that found in other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs compared with patients with MiPN.

Corrigendum to ‘‘Sex Differences in Clinical Presentation and Management in Eosinophilic Esophagitis”

Corrigendum to ‘‘Sex Differences in Clinical Presentation and Management in Eosinophilic Esophagitis”

Single-cell RNA-sequencing of human eosinophils in allergic inflammation in the esophagus

Eosinophils are elusive cells involved in allergic inflammation. Single-cell RNA-sequencing (scRNA-seq) is an emerging approach to deeply characterize cellular properties, heterogeneity, and functionality. We sought to comprehensively characterize the transcriptome and biological functions of human eosinophils at a site of severe allergic inflammation in the esophagus (ie, eosinophilic esophagitis [EoE]). We employed a gravity-based scRNA-seq methodology to sequence blood eosinophils from patients with EoE and control individuals compared to a reanalyzed public scRNA-seq dataset of human esophageal eosinophils of EoE patients. We used flow cytometry, immunostaining, and a stimulation assay to verify mRNA findings. In total, scRNA-seq was obtained from 586 eosinophils (188 from blood [n= 6 individuals] and 398 from esophagus [n= 6 individuals]). The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably IFN-γ, IL-10, histamine and leukotrienes, and succinate. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and the hallmark eosinophil gene CLC. Aweb of bidirectional eosinophil interactions with other esophageal populations was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DNAX-activation protein-12 (also known as TYROBP) interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling. In EoE, esophageal eosinophils exist as 2 populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to potentially intersect with diverse cell types.

Quality of Life in Children With Eosinophilic Esophagitis in Saudi Arabia

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that can adversely affect the quality of life (QOL) in children. We aim to investigate the burden of EoE on the QOL in children aged 2-18 years and identify factors that influence their QOL. A multicenter cross-sectional study was conducted in six Saudi pediatric hospitals. Pediatric Quality of Life 3.0 EoE Module was used to measure the QOL of children with EoE. Thirty-six families (36 parents and 33 children) were enrolled. The most reported symptoms were vomiting (50%), dysphagia (44.4%), and food impaction (36.1%). The mean total score of the parent-proxy report of the Pediatric Quality of Life EoE was 82.9 ± 10.3 versus the children's self-reported score of 77.28 ± 13.6 (p = .043). Recurrent emergency department visits were associated with a lower QOL, and a positive family history of EoE was associated with a better QOL.

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

Shared Decision-Making (SDM) is an increasingly implemented patient-centred 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 healthcare, 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 healthcare system, clinician attitudes and behaviours, 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-centred care and ensuring that SDM is not merely a theoretical concept but a tangible reality in the practice of Allergy and Immunology.

Les phénotypes patients : regards du dermatologue et allergologue sur le traitement des patients atteints de DA selon leur profil atopique

Atopic diseases are heterogeneous. Alongside atopic dermatitis (AD), they include allergic asthma, allergic rhinitis and nasal polyposis, atopic ocular surface diseases (keratoconjunctivitis), IgE-mediated food allergies, and eosinophilic esophagitis. With the development of targeted treatments, the current management of AD, based on a single algorithm common to all patients, is less suited for managing patients with varied atopic profiles. This article discusses systemic therapeutic options based on the atopic comorbidities associated with AD. For instance, in comorbid asthma, dupilumab is currently the only biologic indicated for patients with moderate to severe AD and severe asthma. It is the preferred biotherapy for patients with a dual severe phenotype, both cutaneous and respiratory. However, the asthma phenotypes classically associated in our patients with moderate to severe AD are most often mild to moderate and controllable with inhaled treatments. Therefore, the use of biotherapy targeting IL-13 or JAK inhibitors remain recommended for the treatment of AD in this context, similarly to dupilumab.

CO136 Unmet Treatment Needs in the Management of Patients With Eosinophilic Esophagitis: Insights From a Real-world Survey

CO136 Unmet Treatment Needs in the Management of Patients With Eosinophilic Esophagitis: Insights From a Real-world Survey

Potential missed opportunities for the diagnosis, treatment, and follow-up of eosinophilic esophagitis: analysis of endoscopic food impaction management

Potential missed opportunities for the diagnosis, treatment, and follow-up of eosinophilic esophagitis: analysis of endoscopic food impaction management

Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan.

Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration(FDA) and the European Medicines Agency (EMA)also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.

French recommendations for the diagnosis and management of eosinophilic esophagitis in adults (SNFGE) – Short text

French recommendations for the diagnosis and management of eosinophilic esophagitis in adults (SNFGE) – Short text

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70–145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient’s age, and patients’ origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.What is Known:• Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness.What is New:• Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy.• PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study

BackgroundInflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking.MethodsThis study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990–2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed.ResultsDuring a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86–1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison.ConclusionsIn this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Comparative Assessment of Esophageal Proteomics in Eosinophilic Esophagitis Using SOMAscan

Comparative Assessment of Esophageal Proteomics in Eosinophilic Esophagitis Using SOMAscan

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

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

Transnasal Endoscopy Acquires Esophageal Biopsies Adequate for Comprehensive Pathology Evaluation in Patients With Eosinophilic Esophagitis.

Transnasal endoscopy (TNE) does not require general anesthesia, an attractive characteristic for monitoring eosinophilic esophagitis (EoE). We evaluated the adequacy of TNE-obtained esophageal biopsies using the EoE Histology Scoring System (EoEHSS). The Cincinnati Center for Eosinophilic Disorders database was searched for esophageal biopsies obtained by the same endoscopist, using either TNE or conventional endoscopy (CE). Whole-slide biopsy images were evaluated. The Mann-Whitney test was used for median (interquartile range) values and Fisher exact test for categorical variables. P ≤ .05 was considered significant. Median age (P = .82) or height (P = .83) did not differ between TNE (n = 17) and CE (n = 17) groups. Although median largest piece size (mm2) differed between the groups (TNE: 0.59 (0.45, 0.86), CE: 2.24 (1.09, 2.82), P < .001), all 8 EoEHSS features were evaluated in each group; only 1 feature (lamina propria fibrosis) was missing in both groups (TNE: 19/34, CE: 11/34, P = .09). The median peak eosinophil count/high-power field differed (TNE: 3 (0, 29), CE: 16 (1, 66), P = .03), but overall grade (TNE: 0.17 (0.10, 0.29), CE: 0.22 (0.14, 0.46), P = .12), stage (TNE: 0.14 (0.10, 0.24), CE: 0.20 (0.10, 0.43), P = .15), and non-eosinophil-related individual EoEHSS scores did not differ. TNE- and CE-obtained esophageal biopsies are similarly sufficient for evaluation of key pathological features in EoE.