Explore the vast range of titles available.

The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase β2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model.

A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on a systematic search of non-EoE EGID for which tolerance to causative foods and histological and symptomatic improvements were achieved following dupilumab administration, after elimination diets and omalizumab and mepolizumab treatments. Driven by this case, we investigated the efficacies of biological treatments in non-EoE EGID cases based on the patient studied herein, and other patients identified in the conducted systematic review. Seven articles, including five different biologics, were reviewed. Both clinical efficacies and impact differences among the targeted molecules are demonstrated in this study. Our findings show that dupilumab may affect mechanisms that can suppress symptoms induced by offending foods that are different from those induced by other biologics as identified in the conducted systematic review. Additional studies are required to address the unmet needs of non-EoE EGID treatments.

Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases (non-EoE EGIDs) are poorly understood. Evaluate clinical manifestations, diagnostics and treatment of non-EoE EGIDs at four hospitals in the Netherlands from 1991 to 2019. For this retrospective cohort study, centralized nationwide network and registry for cyto- and histopathology in the Netherlands (PALGA) was used. Seventy patients consented to participate. Median duration of follow up was 26 months, and median age was 36 years. About 44% had eosinophilic colitis (EoC) and 30% had > 1 GI location (multisite EGID). Most patients (91%) had mucosal type, 6% muscular and 3% serosal EGID. Three patients (4%) did not have follow up. Relapsing remitting in 21% (14/67) patients, with most being multisite (43%; 9/21). Single flares in 57% and chronically symptomatic in 22% of population. Concomitant atopy was seen in 29%. Normal endoscopy results in 61%; ileum was commonly identified normal area. Partial or complete symptom improvement to treatment seen in 71%. Results of the longitudinal retrospective Dutch study do not show progression from single site to multisite EGID or change in EGID type. We conclude that identifying patients requires further research as majority of patients had normal endoscopy and vague abdominal symptoms.

Asthma is among the most common chronic respiratory diseases, affecting approximately 3340 individuals per 100,000 worldwide. It is a heterogeneous condition associated with airway hyperresponsiveness and chronic inflammation. Severe asthma (SA) affects 3–10% of patients, most of whom exhibit Type 2 (T2) inflammation with elevated eosinophil counts or increased fractional exhaled nitric oxide. Although the Global Initiative for Asthma provides detailed guidelines for SA, patients with marked hypereosinophilia (HE; >1500 cells/µL) who do not meet diagnostic criteria for hypereosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA) remain insufficiently addressed. In such cases, oral corticosteroids, and T2-targeted monoclonal antibodies (MAbs) inhibiting interleukin-5 or its receptor are the main therapeutic options. For instance, mepolizumab is approved for EGPA, HES, and chronic rhinosinusitis with nasal polyps, but its use in hypereosinophilic SA is limited by eligibility, tolerance, or effectiveness. SA with HE not classified as HES or EGPA is exceptionally rare and may be diagnosed by the exclusion of other potential causes of HE. This review analyzes recent studies and case reports, aiming to expand the understanding of this underrecognized clinical entity, its relation to T2 inflammation and eosinophilic disorders, and to highlight the need for improved diagnostic and therapeutic strategies.

Rare eosinophilic disorders are challenging to manage due to their heterogeneity and lack of targeted therapies. Benralizumab, an anti-IL-5 receptor monoclonal antibody approved for the treatment of severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA), has not been systematically studied in other eosinophilic conditions. To assess the efficacy and safety of benralizumab in adults with rare, non-asthmatic eosinophilic disorders over 52 weeks. In this single-center, prospective, open-label study, 17 adults with diverse eosinophilic diseases received benralizumab 30 mg every 4 weeks for 24 weeks; responders continued up to 52 weeks. The primary endpoint was ≥50% reduction in peripheral eosinophil counts or tissue infiltration. Secondary outcomes included symptom improvement, reduced exacerbations, corticosteroid withdrawal, and safety. Of the 19 enrolled patients, 17 initiated treatment. Sixteen achieved clinical resolution, and all showed complete peripheral eosinophil depletion. Corticosteroids were discontinued in all completers. One patient had a partial response, and one discontinued due to mild, unrelated liver enzyme elevation. No serious adverse events occurred. Relapses were observed after treatment cessation. Efficacy was demonstrated across heterogeneous conditions, including eosinophilic leukemia, folliculitis, vaginitis, and IgG4-related disease. Benralizumab is safe, well-tolerated, and effective in diverse rare eosinophilic disorders, enabling corticosteroid discontinuation and symptom control. These findings support its broader therapeutic potential and warrant further investigation.

Eosinophilic disorders represent a group of pathologic conditions with highly heterogeneous pathophysiology and clinical presentation and variable prognosis, ranging from asymptomatic or mild, to severe and complex cases, with fatal outcome. Interest in this group of disorders has increased during the last two decades, with consistent progress made regarding understanding of molecular mechanisms, refining of diagnostic criteria, classification and evaluation of therapeutic options. There are still many gaps and difficulties in evaluating eosinophilic syndromes and diseases in medical practice. The disease prognosis depends mainly on the cause and mechanism of eosinophilia, on severity of organ dysfunction and on accurate diagnosis and response to treatment. Besides primary hypereosinophilic syndromes and secondary (reactive) eosinophilias, many associated or idiopathic forms have been described, making this topic a complex and difficult medical entity. An important aim of the experts in the field is to agree upon a more clear and practically useful classification, a better characterization of various phenotypes and endotypes of eosinophilic diseases and to identify novel biomarkers and more effective therapies. The aim of this paper is to review recent data from the literature regarding definition, classification and diagnosis criteria of eosinophilic diseases and to propose a revised and updated diagnostic algorithm useful in clinical practice.

Hypereosinophilia (HE) is a heterogeneous condition that can be reported in various (namely inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. In 1975, Chusid et al. published the first diagnostic criteria of hypereosinophilic syndromes (HES). Over the years, as both basic and clinical knowledge improved, several updates have been suggested, with a focus on better distinguishing isolated or asymptomatic eosinophilia from diseases with specific eosinophil-related organ damage. Moreover, underlying molecular and cellular mechanisms of eosinophilia gradually became the cornerstone of successive attempts to classify HE-related diseases. In 2011, the International Cooperative Working Group on Eosinophil Disorders criteria emerged from a multidisciplinary Working Conference on Eosinophil Disorders and Syndromes, and provided substantial contribution to the clarification of general concepts and definitions in the field of HE. Yet, owing to the low prevalence of HE/HES, to the numerous diseases encompassed in the spectrum of HE-related disorders (with sometimes overlapping phenotypes), many questions are left unanswered (e.g., the need to better standardize the use of modern molecular tools, or the clinical relevance of distinguishing different subtypes of idiopathic HES). Here, we review the current state of knowledge in the fields of classification and diagnosis criteria of HE-related diseases, with emphasis on the analysis of both strengths and weaknesses of present concepts and their usefulness in daily practice.

Background: Eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), part of the spectrum of eosinophilic gastrointestinal disorders (EGID), share pathogenic similarities. We examined differences regarding clinical characteristics and treatment outcomes between EoE and EGE cases. Methods: Two-hundred fifteen EGID patients, including 181 with EoE and 34 with EGE, diagnosed at Shimane University Hospital between February 2011 and March 2019 were enrolled. Information regarding clinical parameters and treatment outcomes was reviewed. Results: EoE showed significant male predominance (82.3%) as compared with EGE (50.0%) (p < 0.001). Furthermore, patients with EoE were significantly older and had a higher body mass index (24.8 ± 4.0 vs. 22.2 ± 4.3, p < 0.05). Over 90% of the EoE patients were initially given proton pump inhibitor (PPI) treatment, of whom 73.2% showed clinical and histological remission. Vonoprazan, a more potent acid inhibitor than PPI, was effective in two-thirds of the nonresponsive EoE patients initially treated with a PPI. In contrast, oral glucocorticoid administration was mainly given to patients with EGE (58.8%). Of 13 EGE patients treated with a food-elimination diet, responsible foods were successfully identified in 9, with 7 controlled in a state of remission without glucocorticoid therapy. Conclusions: We found different clinical characteristics and treatment strategies in the present EoE and EGE cases. Most of the EoE patients responded to and were maintained by acid suppressive therapy, using PPI or vonoprazan. For EGE patients, glucocorticoid administration was mainly used though food-elimination diet therapy also showed beneficial effects.

Eosinophils are key components of our host defense and potent effectors in allergic and inflammatory diseases. Once recruited to the inflammatory site, eosinophils release their cytotoxic granule proteins as well as cytokines and lipid mediators, contributing to parasite clearance but also to exacerbation of inflammation and tissue damage. However, eosinophils have recently been shown to play an important homeostatic role in different tissues under steady state. Despite the tremendous progress in the treatment of eosinophilic disorders with the implementation of biologics, there is an unmet need for novel therapies that specifically target the cytotoxic effector functions of eosinophils without completely depleting this multifunctional immune cell type. Recent studies have uncovered several endogenous molecules that decrease eosinophil migration and activation. These include short chain fatty acids (SCFAs) such as butyrate, which are produced in large quantities in the gastrointestinal tract by commensal bacteria and enter the systemic circulation. In addition, high-density lipoprotein-associated anti-inflammatory apolipoproteins have recently been shown to attenuate eosinophil migration and activation. Here, we focus on the anti-pathogenic properties of SCFAs and apolipoproteins on eosinophil effector function and provide insights into the potential use of SCFAs and apolipoproteins (and their mimetics) as effective agents to combat eosinophilic inflammation.

Eosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals. We queried the U.S. Immunodeficiency Network (USIDNET) for patient records including the terms eosinophilic esophagitis, gastritis, enteritis, or colitis. We analyzed 74 patient records from the database, including diagnoses, demographics, infectious history, laboratory findings, genetic studies, therapeutic interventions, and clinical outcomes. We examined 74 patient records. A total of 61 patients had isolated EoE, and 13 had distal gastrointestinal involvement consistent with EGID. The most common IEI were common variable immunodeficiency (43.2%), some form of combined immunodeficiency (21.6%), chronic granulomatous disease (8.1%), hyper-IgE syndrome (6.8%), and autoimmune lymphoproliferative syndrome (6.8%). The median age at presentation with IEI was 0.5 years (IQR 1.725, max 39 years) and 56.76% were male. Approximately 20% of the patients in the cohort received a hematopoietic stem cell transplantation for treatment of IEI, but the timing of the HSCT in relationship to the EGID diagnosis was unknown. Here, we report EGID in a diverse cohort of IEI patients, suggesting that both non-EoE EGID and EoE can be seen as comorbid conditions with a variety of IEI. Our data suggests that EGID may be more common in patients with IEI than would be expected based on estimates of EGID in the general population.