Search

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 10 healthy controls were compared using cytometry by time-of-flight. An antibody panel was designed that covers the major immunological cell populations with a 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. (A) Minimum spanning tree of eosinophil populations present in the blood of 10 patients with EoE before and after treatment with orodispersible budesonide as well as healthy subjects (HS) determined by X-shift clustering analysis. The sizes of the circles represent the sizes of the populations. The color of the circles indicates the levels of galectin-10, FOXP3, CD16, CD274 (PD-L1), IL-5R, and IL-2R expression as shown by the heat-map scale. Numbers indicate populations that are altered after treatment [1–3 ]. Phenotypes of populations 1–3 are shown below. (B) OPLS-DA was done to see which eosinophil markers could separate EoE patients before and after treatment (n  = 10). (C) Loading plots with jackknife confidence intervals for the eosinophil markers are shown as boxes with ticks. The markers closely positioned to the patient categories are positively associated with the patient category in question. The generated two-component model had an explanatory power of 53% (goodness of fit R2Y = 0.53) and stability of 37% (Q2Y = 0.37). Graphical Abstract [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disease. In Denmark, the budesonide orodispersible tablet (BOT) is recommended as a second-line treatment for proton pump inhibitor-refractory EoE patients. Aims: To evaluate the effectiveness of treatment with BOT in adult EoE patients in a population-based setting in Denmark. Methods: This was a retrospective, registry-based, DanEoE cohort study of all 76 adult EoE patients treated with BOT and diagnosed between 2007 and 2021 in the North Denmark Region. After medical record revision, the EoE diagnosis was defined according to the AGREE consensus. Symptomatic response was based on the information found in the patients' medical reports and histologic remission was defined as <15 eosinophils per high-power field (eos/hpf). Results: Histologic remission was achieved in 89% of the patients treated with BOT who underwent histologic evaluation. Clinicohistologic remission was achieved in 71% of the patients who underwent both symptomatic and histologic evaluation. Despite histologic remission, 18% of patients still experienced symptoms. Non-responders were found in 7% of the patients. Complications were rare, with dilation of strictures performed in 7% and food bolus obstruction (FBO) occurring in 3%. Discontinuation of the treatment due to unacceptable side effects was observed in 11% of the treated patients. Conclusions: Treatment with BOT effectively induced histologic remission in most of the EoE patients. Despite achieving histologic remission, approximately 1/5 of the patients were still symptomatic. Complications were rare. In non-responders and those with unacceptable side effects, alternative treatment options such as biologic agents might be needed. [ABSTRACT FROM AUTHOR]

Human sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed on subsets of immune cells. Siglec-8 is an immune inhibitory Siglec on eosinophils and mast cells, which are effectors in allergic disorders including eosinophilic esophagitis. Inhibition occurs when Siglec-8 is crosslinked by multivalent Siglec ligands in target tissues. Previously we discovered a high-affinity Siglec-8 sialoglycan ligand on human airways composed of terminally sialylated keratan sulfate chains carried on a single protein, DMBT1. Here we extend that approach to another allergic inflammatory target tissue, human esophagus. Lectin overlay histochemistry revealed that Siglec-8 ligands are expressed predominantly by esophageal submucosal glands, and are densely packed in submucosal ducts leading to the lumen. Expression is tissue-specific; esophageal glands express Siglec-8 ligand whereas nearby gastric glands do not. Extraction and resolution by gel electrophoresis revealed a single predominant human esophageal Siglec-8 ligand migrating at >2 MDa. Purification by size exclusion and affinity chromatography, followed by proteomic mass spectrometry, revealed the protein carrier to be MUC5B. Whereas all human esophageal submucosal cells express MUC5B, only a portion convert it to Siglec-8 ligand by adding terminally sialylated keratan sulfate chains. We refer to this as MUC5B S8L. Material from the esophageal lumen of live subjects revealed MUC5B S8L species ranging from ~1–4 MDa. We conclude that MUC5B in the human esophagus is a protein canvas on which Siglec-8 binding sialylated keratan sulfate chains are post-translationally added. These data expand understanding of Siglec-8 ligands and may help us understand their roles in allergic immune regulation. [ABSTRACT FROM AUTHOR]

Background 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. Objectives To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The document is a supplementary material for a study on eosinophilic esophagitis (EoE) conducted in Italy. It includes surveys conducted with clinicians and patients to gather information on various aspects of EoE, such as prevalence rates, diagnostic capacity, treatment options, impact on quality of life, and healthcare needs. The surveys cover topics such as the number of diagnosed patients, treatment efficacy, healthcare costs, and difficulties in diagnosis and management. The document provides valuable insights into the perspectives and experiences of clinicians and patients regarding EoE in Italy. [Extracted from the article]

Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12‐week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high‐fat/high‐calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open‐label, single‐center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.0 mg under fasting or fed conditions, with a 48‐h washout period before crossover to the alternative conditions. Serial plasma samples were collected before and up to 24 h after dosing. Pharmacokinetic (PK) parameters were calculated from plasma budesonide concentration–time profiles by noncompartmental analysis. The mean peak budesonide concentration (Cmax) was ∼13% lower under fed than under fasting conditions (604.1 vs 692.9 pg/mL). Areas under the concentration–time curves from dosing to the last measurable budesonide concentration and from dosing to infinity were ∼26% higher and ∼27% higher under fed than fasting conditions (3529 vs 2811 pg h/mL and 3892 vs 3075 pg h/mL, respectively). The median time to peak plasma budesonide concentration was significantly longer (∼1 h) under fed than fasting conditions (2.516 vs 1.286 h, P < .001). Safety and tolerability were also assessed throughout the study; all adverse events were mild or moderate in severity. Despite slight differences in budesonide PK parameters between fed and fasting conditions, the effect of food on systemic exposure to budesonide (BOS formulation) is not expected to be clinically meaningful. [ABSTRACT FROM AUTHOR]

A 9‐month‐old male presented with vomiting and dehydration with mild hypernatremia in the context of failure to thrive. He was later diagnosed with nephrogenic diabetes insipidus (NDI) during this hospitalisation and was also found to have eosinophilic esophagitis (EoE). He has since been growing well after EoE and NDI were properly managed. Molecular genetic testing revealed an unreported deletion in AQP2 which was deemed pathogenic and of autosomal dominant inheritance when correlated with his clinical findings and family history. This case report describes the clinical course of this patient in comparison to his family members and reviews current literature on autosomal dominant NDI caused by AQP2 mutations. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Post‐infectious disorders of gut‐brain interaction (PI‐DGBI) have significant impact on children and adolescents. The effect of COVID‐19 on PI‐DGBI‐associated symptoms in this population, however, is unknown.We performed electronic medical record searches to identify patients 8–17 years old with a SARS‐CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April–October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms—Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID‐19 test or the test result.One hundred and ninety‐six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self‐reported their child's COVID‐19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID‐19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID‐19 testing that was highest among patients with a positive COVID‐19 test. Abdominal pain and diarrhea prior to COVID‐19 testing predicted higher NP scores.Among symptomatic COVID‐19 tested children, we found increased severity of nausea‐associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID‐19 test. [ABSTRACT FROM AUTHOR]

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory condition. Associated pathologies for EoE are similar to those with metabolic-dysfunction-associated steatotic liver disease (MASLD). This study assesses whether an association exists between MASLD and EoE. Methods: We used National Inpatient Sample (NIS) 2020 data to identify adult patients. ICD-10 codes were used to identify patients with MASLD and EoE. The relationship between MASLD and EoE was assessed by multivariate analysis after adjusting for confounding factors, such as patient demographics, hospital characteristics, Charlson comorbidity index, obesity, obstructive sleep apnea (OSA), diabetes, hypertension (HTN), hyperlipidemia (HLD), inflammatory bowel disease (IBD), celiac disease (CD), gastroesophageal reflux disease (GERD), smoking, alcohol use, and irritable bowel syndrome (IBS). Results: Out of 26 million patients, 4,820 had a diagnosis of EoE. The majority of the patients were between 18 and 44 years of age (47.82%), male (54.05%), had private insurance (50.1%), and were in the highest income quartile (29.25%). A higher incidence of MASLD was noted in the EoE group than those without (6.1% vs.2.9%, p<0.001). After adjusting for confounding factors, MASLD had 2.38 times higher odds of having EoE (95% CI-1.82-3.11, p<0.001). Other factors noted to be associated with higher odds of EoE included younger age, Caucasian race, IBS, GERD, IBD, and CD. Conclusions: Our study reports a novel finding that MASLD and EoE are associated. Future prospective studies are needed to confirm and understand the clinical significance of this relationship and how one disease affects the other. [ABSTRACT FROM AUTHOR]

Background: Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco's Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state. Methods: We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids. To optimize the ADF-based medium, we evaluated the requirement of exogenous epidermal growth factor (EGF) and inhibition of transforming growth factor-(TGF)-β receptor-mediated signaling, both key regulators of the proliferation of human esophageal keratinocytes. We have modeled human esophageal epithelial pathology by stimulating esophageal 3D organoids with interleukin (IL)-13, an inflammatory cytokine, or UAB30, a novel pharmacological activator of retinoic acid signaling. Results: The formation of normal human esophageal 3D organoids was limited by excessive EGF and intrinsic TGFβ-receptor-mediated signaling. Optimized HOME0 improved normal human esophageal organoid formation. In the HOME0-grown organoids, IL-13 and UAB30 induced epithelial changes reminiscent of basal cell hyperplasia, a common histopathologic feature in broad esophageal disease conditions including eosinophilic esophagitis. Conclusions: HOME0 allows modeling of the homeostatic differentiation gradient and perturbation of the human esophageal epithelium while permitting a comparison of organoids from mice and other organs grown in ADF-based media. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the "atopic march" picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/objectives: An increase in the incidence of eosinophilic esophagitis (EoE) in children has been reported worldwide in the last decade. We conducted a study in a tertiary pediatric gastroenterology unit aimed at analyzing the clinical manifestations, biochemical markers, and endoscopic features of children with EoE in comparison to patients with non-eosinophilic esophagitis. Methods: This is a prospective analysis involving children with symptoms related to esophageal dysfunction, who had esophagogastroduodenoscopies with esophageal biopsies between January 2021 and April 2024 at "Dr. Victor Gomoiu" Clinical Children's Hospital, in Bucharest, Romania. For the analysis, patients were considered in either Group 1, classified as EoE, or in Group 2, classified as reflux esophagitis. Results: Among the total of 72 patients diagnosed with esophagitis, 17 patients (Group 1—study group) were classified as EoE and 55 were classified as reflux esophagitis (Group 2—control group). The sex ratio analysis showed a male predominance in the study group (71% vs. 32%, p = 0.002). The main symptoms were regurgitation, eructation, and nausea. Dysphagia was present in two (11.76%) patients from Group 1. Eosinophilia was more prevalent in the EoE group than in the individuals with gastroesophageal reflux disease (GERD) (10 (58.85%) vs. 10 (18.18%, p = 0.001)), as well as the total IgE (11 (64.70%) vs. 6 (10.9%, p = 0.001)). Conclusions: Pediatric gastroenterologists need to be aware of EoE atypical presentation and perform adequate biopsies, mainly in children with refractory GERD-like symptoms, dysphagia, and food bolus impaction. Further analyses in terms of prognosis and treatment response should be addressed in longitudinal studies. [ABSTRACT FROM AUTHOR]