Recurrent croup (RC) is characterized by recurrent episodes of stridor, barking cough, and hoarseness. While viral infections are the primary cause in croup, RC is thought to be caused by non-infectious etiologies such as structural airway abnormalities, allergic disorders, airway hyperresponsiveness and gastroesophageal reflux (GERD). Recent studies have suggested a potential link between esophageal diseases, particularly GERD/reflux esophagitis and eosinophilic esophagitis (EoE), and RC. This retrospective study aims to explore the association between esophageal disorders and RC through a multidisciplinary approach. A total of 68 patients with RC were identified in our aerodigestive center, 47 of whom underwent dual or triple endoscopy. Of these, 17 patients (36 %) were found to have esophageal disease, including EoE (15 %) and reflux esophagitis (19 %). Notably, food allergies were significantly more prevalent in the EoE group, and all patients with EoE had reported GI symptoms previously. While airway abnormalities were common across all groups, there were no significant differences between patients with and without esophageal disease. The study highlights the prevalence of esophageal diseases in patients with RC, particularly EoE, and a multidisciplinary aerodigestive evaluation may be beneficial for diagnosing concomitant esophageal conditions. Further studies are needed to determine the causal relationship between esophageal disorders and RC.

Eosinophilic Esophagitis (EoE) is a chronic food allergy that causes esophageal inflammation and fibrosis and manifests with symptoms of reflux, chest pain, swallowing difficulty, and food impactions. Though the prevalence of EoE is increasing by ~15% each year, our understanding of EoE immunopathology is limited. A noted feature of EoE is the presence of food-specific IgG4 antibodies in the circulation and esophageal tissue. Production of IgG4 is confined to IL-10+ B cells (Bregs) in other allergic diseases, suggesting Bregs may be present in EoE.

We examined circulating Bregs in patients with EoE milk allergy. In parallel, we performed mechanistic investigations of the role of Bregs in a murine model of food-antigen-dependent EoE. Flow cytometry and histologic analyses were used to assess esophageal and draining lymph node immune cells, and in vitro assays were used to evaluate Breg functional capacity.

Breg frequency was reduced in both EoE milk allergic subjects and an EoE disease model. Murine Breg suppressive capacity was impaired during EoE-like inflammation. Inducible deletion of Breg-derived IL-10 worsened EoE-like inflammation, while adoptive transfer of IL-10 sufficient Bregs suppressed DC activation and improved esophageal eosinophilia. IFNγ was sufficient to suppress Breg expansion and IL-10 production in vitro and contributed to Breg dysfunction and esophageal inflammation in vivo.

Bregs play an immunoregulatory role during EoE by controlling esophageal eosinophilia but are functionally impaired due to IFNγ-mediated signaling. These findings have important implications for understanding EoE's etiology and implementing future therapies that target IFNγ.

Eosinophilic gastrointestinal disorders, including eosinophilic esophagitis, are chronic Th2 mediated diseases. Establishing a diagnosis and initiating treatment is crucial to limit disease progression that may lead to tissue remodeling and the development of strictures that significantly impact patient quality of life. Expert consensus guidelines provide a framework for treating eosinophilic esophagitis with diet elimination, proton pump inhibitors, swallowed topical steroids, or dupilumab and for monitoring with sedated endoscopy for gross and histologic evaluation. While this provides an established algorithm for treating and monitoring eosinophilic esophagitis, there is less established for the rarer eosinophilic gastrointestinal disorders (eosinophilic gastritis, enteritis, and colitis). Research advancements continue to emerge at a rapid pace, identifying potential biomarkers, therapeutic targets, and monitoring strategies. In this article, we review the current accepted methods for treating and monitoring eosinophilic gastrointestinal disorders with a focus on eosinophilic esophagitis, assess what is currently under investigation, and provide an aspirational vision for future disease management with a streamlined algorithm of personalized medicine and less invasive monitoring.

Budesonide orodispersible tablets (BOT) have been shown to be efficacious for eosinophilic oesophagitis (EoE) in clinical trials. This study evaluated the real-world effectiveness of BOT in a retrospective cohort of 94 patients across six tertiary centres. 61% of patients achieved histological remission and 39% clinicohistological remission following induction therapy. Adverse events were reported by 16% of patients and 17% were noted to have incorrect technique of administration. BOT was demonstrated to have lower rates of clinicohistological remission in real-world practice than reported in clinical trials, largely due to incorrect technique and cessation due to adverse events.

Eosinophilic esophagitis (EoE) is a type 2 inflammatory esophageal disease that presents in adults as dysphagia and food impaction. EoE is characterized by a predominance of T helper 2 cells among the T cell population. Environmental agents, including food antigens and aeroallergens, trigger EoE. EoE exhibits immunoglobulin E- (IgE-) and non-IgE-mediated allergic responses to these environmental allergens. Local antigen-specific IgE can also trigger mast cell degranulation, thereby worsening EoE. Individuals with atopic dermatitis, asthma, IgE-mediated food allergy, or allergic rhinitis are at a higher risk of developing EoE. EoE treatment aims to achieve clinical improvement, endoscopic mucosal healing, and reduction in or resolution of histological inflammation. However, attaining and maintaining "deep remission" with conventional treatments can be challenging, underscoring the need for targeted therapies. This expert opinion focuses on the latest global recommendations for using novel therapies to improve outcomes in patients with EoE. It also highlights current practices in the Greater Gulf region to manage EoE, identify challenges, and address future educational gaps.

Eosinophilic esophagitis (EoE) is a chronic, progressive type 2 inflammatory disorder of the esophagus, characterized by abnormal eosinophil accumulation in esophageal epithelium. Undiagnosed or undertreated EoE leads to increased risk of fibrostenosis, strictures, and food impaction due to persistent inflammation, deeply impacting patients' health-related quality of life (HRQoL).

To gather insights on comprehensive assessment of EoE, comprising clinical, endoscopic, histological outcomes, adaptive behaviors and HRQoL; to define proper evaluation of disease control and impact of continuous versus noncontinuous treatment to reach full disease control. Finally, to validate an algorithm for disease control, switching criteria, and follow-up.

Literature review, survey, and panel expert opinion building by a multidisciplinary Italian EoExpert Panel (EoExpert) of nine specialists from various Italian institutions.

Non-systematic literature review, followed by a survey including 21 questions on the different topics. Results were then discussed and validated by EoExpert.

The current diagnostic pathway often does not allow early detection of EoE patients, especially in the presence of adaptive behaviors and unawareness of EoE best practices. In addition, there is a lack of a shared "control" definition. EoExpert reviewed, shared, and recommended two novel management tools for EoE, represented by I.M.P.A.C.T. Questionnaire to uncover adaptive behaviors and S.C.O.P.E. (Symptoms Control, Observation, Pathological Evaluation) scheme for comprehensive treatment efficacy evaluation. EoExpert's recommendations were gathered and turned into a therapeutic management algorithm for the definition of disease control and switching criteria.

This document provides a standardized approach to EoE management in pediatric and adult settings, highlighting the importance of timely diagnosis in a multidisciplinary setting, of using unified criteria for assessment of disease control through the adoption of a comprehensive approach and of following up patients. These recommendations highlight the critical role of increased awareness and standardized care in EoE clinical setting for lifelong management.

Gastrointestinal disorders originate in the gastrointestinal tract (GIT), and the therapies can benefit from direct access to the GIT achievable through the oral route. RNA molecules show great promise therapeutically but are highly susceptible to degradation and often require a carrier for cytoplasmic access. Lipid nanoparticles (LNPs) are clinically proven drug-delivery agents, primarily administered parenterally. An ideal Orally Delivered (OrD) LNP formulation should overcome the diverse GI environment, successfully delivering the drug to the site of action. A versatile OrD LNP formulation has been developed to encapsulate and deliver siRNA and mRNA in this paper. The formulations were prepared by the systematic addition of cationic lipid to the base LNP formulation, keeping the total of cationic lipid and ionizable lipid to 50 mol%. Biorelevant media stability depicted increased resistance to bile salt mediated destabilization upon the addition of the cationic lipid, however the in vitro efficacy data underscored the importance of the ionizable lipid. Based on this, OrD LNP was selected comprising of 20% cationic lipid and 30% ionizable lipid. Further investigation revealed the enhanced efficacy of OrD LNP in vitro after incubation in different dilutions of fasted gastric, fasted intestinal media, and mucin. Confocal imaging and flow cytometry confirmed uptake while in vivo studies demonstrated efficacy with siRNA and mRNA as payloads. Taken together, this research introduces OrD LNP to deliver nucleic acid locally to the GIT.

Few data compare topical corticosteroid (tCS) dosing regimens and outcomes. We aimed to compare treatment outcomes in patients with eosinophilic esophagitis (EoE) by once or twice daily dosing regimens.

We conducted a retrospective cohort study using the UNC EoE Clinicopathologic Database of newly diagnosed patients with EoE treated with a tCS who had a follow-up endoscopy with biopsy. Baseline data and outcomes were extracted. Bivariate and multivariate analyses compared patients at baseline and following initial tCS given as a once or twice daily dose.

A total of 522 patients met inclusion criteria, 122 patients on once daily dosing (72% male; 91% white) and 400 patients on twice daily dosing (66% male; 89% white). Patients on twice daily dosing were older (28.8 ± 18.2 vs 24.3 ± 18.0; P = .01) and reported more heartburn (40% vs 25%; P = .004). On bivariate analysis, global symptomatic response (78% vs 76%; P = .82), posttreatment eosinophil count (20.8 ± 27.2 vs 25.6 ± 39.4; P = .21), posttreatment EoE Endoscopic Reference Score (2.2 ± 1.8 vs 2.2 ± 2.0; P = .92), and histologic response (<15 eos/hpf; 56% vs 58%; P = .66) did not differ by dosing frequency. Candida was less frequent with daily dosing (2% vs 8%; P = .04). In multivariate analysis, the odds of histologic response did not differ by dose groups (adjusted odds ratio, 1.03; 95% confidence interval, 0.67-1.60).

EoE outcomes did not differ by daily or twice daily dosing regimens. These results inform tCS dosing regimens and reassure that both are effective.

Eosinophilic esophagitis (EoE) is a type 2 helper T (Th2) cell immune-mediated gastrointestinal disease. Accumulating evidence has supported allergic etiology as an underlying mechanism for EoE, but the magnitude of the correlation between EoE and atopy remains ambiguous. Hence, we performed a meta-analysis to evaluate and compare the rate of co-existing common atopic diseases between EoE and non-EoE patients.

We searched through electronic databases and reference lists of review articles for studies describing co-existing rates of atopic diseases in EoE and non-EoE patients. EoE was diagnosed based on clinical and pathological evaluations. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. Random-effects models were used for analyses. Quantitative results were presented as odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were performed to explore and to identify heterogeneity across studies. Publication bias was examined by Egger's test and visualized by funnel plots.

Altogether, 27 studies containing 1831 cases and 2982 controls were enrolled. 57.2% of EoE patients had co-existing atopic disease. Patients with EoE were more likely to comorbid with atopic diseases (OR = 3.56, 95% CI: 2.27 to 5.59, I 2  = 78%), including asthma (OR = 2.43, 95% CI: 1.94 to 3.06, I 2  = 29%), allergic rhinitis (OR = 5.39, 95% CI: 3.29 to 8.84, I 2  = 78%), atopic dermatitis (OR = 2.46, 95% CI: 1.89 to 2.30, I 2  = 12%) and food allergy (OR = 4.93, 95% CI: 3.96 to 6.14, I 2  = 0%) than non-EoE controls. Heterogeneity sources were explored and identified via subgroup and sensitivity analyses, with the majority of subgroup estimates aligning with the primary findings. No significant publication bias was detected.

Our findings suggest that EoE patients are more likely to comorbid atopic diseases, favoring the allergic diathesis of EoE. Clinicians should be alert for EoE in allergic patients having upper gastrointestinal symptoms. However, the causality between EoE and atopic diseases was not revealed and remains to be explored.

Eosinophilic esophagitis (EoE) is a chronic disease which clinically presents with symptoms related to esophageal dysfunction, while pathologically it is characterized by eosinophilic infiltration of esophageal epithelium. Most patients with EoE present with food and/or inhalant allergy symptoms. The results of animal model studies and genetic studies, as well as the efficacy of elimination diets in managing the symptoms, suggest an atopic background of the disease. The aim of this study was to evaluate the prevalence of EoE in a group of patients with upper gastrointestinal symptoms and food and/or inhalant allergies and to assess the influence of drugs used in type I allergies on the results of endoscopic, histopathological, and immunohistochemical tests. Methods: This was a prospective observational study. Patients with inhalant/food allergies and upper esophageal symptoms constituted the study group while patients without allergies who were diagnosed with dyspepsia or irritable bowel syndrome constituted the control group. All study group subjects underwent allergy testing, including prick testing and blood tests. All participants underwent a gastroscopy with specimen collection. Esophageal specimens were stained for eotaxin-1 and desmoglein-1. Results: Based on histopathology results, eosinophilic esophagitis was found in 9 of the 73 patients from the study group. All patients with EoE presented with multimorbidity and were diagnosed with at least one allergic disease in addition to EoE. Positive staining for CCL-11 was found in 56 (78%) patients in the study group, including all patients with EoE while only 3 (17%) individuals from the control group showed positive staining. The presence of DSG-1 in esophageal specimens was detected in 6 (7%) subjects from the study group in contrast to 14 (78%) subjects from the control group. DSG-1 was not found in any of the specimens of patients diagnosed with EoE. Conclusions: EoE is a rare disease, usually accompanied by allergic multimorbidity. Positive staining for eotaxin-1 and negative staining for desmoglein-1 in patients with esophageal symptoms and allergies but who did not meet EoE diagnostic criteria could be indicative of subclinical course of the disease or a masking effect of corticosteroids. It is now vitally important for both researchers and practicing clinicians to recognize that eosinophilic esophagitis (EoE) is not a homogeneous disease but rather consists of multiple subtypes (phenotypes). The so-called "classic" form of EoE-defined by current diagnostic criteria as the presence of more than 15 eosinophils per high power field on histopathological examination-appears to represent only the tip of the iceberg. There is an urgent need for further research in order to refine endoscopic techniques, expand the scope of histopathological assessments, and identify novel biomarkers to better define the distinct phenotypes of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition with an incompletely understood immuno-pathogenesis involving a T2 response. EoE is triggered by food allergens although, unlike IgE-mediated allergies, it exhibits high IgG4 levels in oesophageal biopsies and in circulation. We investigated whether other antibody isotypes specific for food allergens are elevated in EoE and vary with disease activity.

Plasma samples from patients with active EoE (n = 51), inactive EoE (n = 82) and non-EoE controls (n = 14) were analysed for food-specific IgG and IgA subclasses against casein, whey, wheat, egg and individual cow's milk allergens by ELISA. α-lactalbumin (Bos d 4)- and β-lactoglobulin (Bos d 5)-specific B cells were measured by flow cytometry in a subset of patients.

Food allergen-specific antibodies in the plasma varied across EoE subgroups and non-EoE controls. Elevated IgG4 in EoE patients confirmed a strong antibody response to food allergens, including casein, wheat and egg. αS1-casein (Bos d 9)-specific IgG, IgG2, IgG4, IgA1 and IgA2 differed between EoE and non-EoE controls and between active and inactive EoE. β-casein (Bos d 11, A1 variant) measurements showed higher levels of specific IgG2 and IgG4 in both EoE groups, whereas whey-derived allergens showed opposing responses: Bos d 4 responses favoured IgG4, and Bos d 5 responses were elevated across multiple IgG and IgA subclasses in EoE. Allergen-specific B cells could not be isolated from the circulation.

Our findings reveal distinct antibody profiles in EoE plasma, with elevated IgG and IgA subclasses beyond IgG4, highlighting a complex immune response to food allergens. Differential antibody responses support their clinical relevance in dietary management strategies, while the absence of allergen-specific B cells in circulation likely restricts antibody production to the inflamed oesophagus. Future research should explore whether these antibody profiles can guide personalised treatment and novel therapeutic targets in EoE.

The synthetic cortisol analog budesonide (BUD) is an essential drug employed to manage chronic inflammatory diseases in humans, mainly those involving gastroenteric and airway mucosa, such as rhinitis, laryngitis, bronchitis, esophagitis, gastritis, and colitis, with high levels of success. As a glucocorticoid, BUD prevents the expression of pro-inflammatory cytokines/chemokines and the recruitment of immune cells into the inflamed mucosa. However, emerging evidence indicates that BUD, unlike classical glucocorticoids, is also a potent modulator of stem and cancer cell behavior/plasticity. Certainly, BUD stabilizes cell-cell adhesions, preventing embryonic stem cell differentiation and inhibiting the development of 3D gastruloids. In addition, BUD inhibits the motile/invasive propensity of different cancer cells, including breast, lung, and pancreatic cancer. Finally, it prevents the infection of positive single-stranded human-infecting RNA viruses such as SARS-CoV-2. At a molecular level, BUD induces epigenetic changes and modifies the transcriptome of epithelial, stem, and cancer cells, providing molecular support to the immune cell-independent activity of BUD. Here, we performed an in-depth review of these unexpected activities of BUD, identified by unbiased drug screening programs, and we emphasize the molecular mechanisms modulated by this efficacious drug that deserve further research.

Introduction: The atopic march refers to the progression of allergic disorders from atopic dermatitis (AD) in early childhood to food allergies, eosinophilic esophagitis (EOE), and later respiratory allergies such as asthma and allergic rhinitis. Mutations in the filaggrin gene, which compromise skin barrier function, are strongly associated with this progression and contribute to allergic sensitization. Case Presentation: We introduce a 7-year-old boy with severe AD, food anaphylaxis, EOE, allergic rhinitis, and asthma associated with a filaggrin mutation (c.5152C>T). His clinical course illustrates the atopic march, with initial skin involvement progressing to gastrointestinal and respiratory allergic manifestations. Conclusion: Understanding the genetic factors that drive this progression may help identify targets for early intervention to prevent the further development of allergic disease.

Eosinophilic oesophagitis (EoE) is a chronic and progressive immune-mediated condition, typically affecting young atopic male adults and potentially leads to organ dysfunction and fibrosis. The clinical spectrum widely varies -from non-troublesome dysphagia to food impaction- and hence the rate of misdiagnosis and diagnostic delay are high, especially when presenting with minor symptoms, such as heartburn and acid regurgitation. There have been several major therapeutic breakthroughs for the management of EoE in recent years. Highly effective conventional agents with oesophagus-specific formulations (i.e. orodispersible budesonide) and a biological agent (i.e. dupilumab) now have a formal indication. Oesophageal dilation may be indicated in case of strictures, which are more common in longstanding and untreated disease. Therefore, the early diagnosis of this disorder and specialist referral is if of great importance. The evaluation of alarm signs and typical presentation patterns should allow a more straightforward recognition. The emergency and internal medicine doctors should actively be involved in this process and take part to the multidisciplinary care of patients with EoE, to allow better patient care and clinical outcomes.

Untreated eosinophilic esophagitis (EoE) can result in the development of fibrostenosis over time, but there are few data on whether successful treatment in childhood decreases this risk as children with EoE transition to adulthood.

To determine whether histologic response or endoscopic normalization after EoE treatment is associated with decreased development of fibrostenosis.

Pediatric subjects were identified from a large EoE database at an academic referral center. Medical records were reviewed for the primary outcome of fibrostenosis, defined as esophageal stricture, narrowing, or dilation. We assessed the proportion of histologic responders and normal endoscopies at the first, second, and last esophagogastroduodenoscopy (EGD) on record following diagnosis. We created Kaplan-Meier curves to assess time to fibrostenosis and estimated hazard ratios using Cox proportional analysis.

Among 166 patients, the mean age at diagnosis was 10.2 years. Over a mean follow-up time of 4.7 ± 4.5 years, patients had an average of 4.3 ± 4.2 EGDs. The percent of patients with fibrostenosis was 9%, 15%, and 16% at first, second, and last EGD. Patients with histologic response at second follow-up developed fibrostenosis at a lower rate than non-responders (HR = 0.37, 95% CI 0.14-0.99), as did those with normal endoscopic findings at first follow-up (HR = 0.27, 95% CI 0.08-0.90).

Histologic response and endoscopic normalization lead to lower rates of fibrostenosis in children with EoE. Though the development of fibrostenosis was relatively uncommon, occurring in < 20% of children with EoE who were followed long term, it is reasonable to target treatment goals of histologic response and endoscopic normalization.

Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.

We hypothesized that chronic EoE inflammation induces pathogenic fibroblasts with dysfunctional tissue regeneration and motility.

We used single-cell RNA sequencing, fluorescence-activated cell sorting analysis, and fibroblast differentiation and migration assays to decipher the induced and retained pathogenic dysfunctions in EoE versus healthy esophageal fibroblasts.

Differentiation assays demonstrated that active EoE fibroblasts retain regenerative programs for rigid cells such as chondrocytes (P < .05) but lose healthy fibroblast capacity for soft cells such as adipocytes (P < .01), which was reflected in biopsy sample immunostaining (P < .01). EoE, but not healthy, fibroblasts show proinflammatory and prorigidity transcriptional programs on single-cell RNA sequencing. In vivo, regenerative fibroblasts reside in perivascular regions and near the epithelial junction, and during EoE, they have significantly increased migration (P < .01). Flow analysis and functional assays demonstrated that regenerative EoE fibroblasts have decreased surface CD73 expression and activity (both P < .05) compared to healthy controls, indicating aberrant adenosine triphosphate handling. EoE fibroblast dysfunctions were induced in healthy fibroblasts by reducing CD73 activity and rescued in EoE using adenosine repletion.

A normalization of perturbed extracellular adenosine triphosphate handling and CD73 could improve pathogenic fibroblast dysfunction and tissue regeneration in type 2 inflammatory diseases.

Exposure to Helicobacter pylori (H. pylori) has been associated with a decreased risk of eosinophilic oesophagitis (EoE).

The aim of this study is to determine the association between H. pylori infection and EoE in this updated meta-analysis.

We searched MEDLINE, Scopus and ISI Web of Science, through to November 2024. We included studies reporting the status of H. pylori infection in patients with and without EoE or oesophageal eosinophilia (EE). We used a random-effects model to pool estimates.

We analysed 19 studies including 1.704.821 subjects. H. pylori infection was associated with a 46% lower risk of EoE/EE (OR: 0.54, 95% CI 0.43 to 0.67). Comparable findings were observed when subgrouping studies by location or design. There was a nonsignificant decrease in odds for EoE in paediatric patients exposed to H. pylori (OR 0.57, 95% CI 0.26 to 1.24), and in studies using serology to diagnose H. pylori (OR: 0.41, 95% CI 0.16 to 1.04). We found lower odds of EoE compared with the overall findings in studies that diagnosed H. pylori only by gastric biopsy (OR 0.43, 95% CI 0.25 to 0.74) and in those published after 2019 (OR 0.44, 95% CI 0.28 to 0.68).

Exposure to H. pylori was significantly associated with decreased odds of EoE/EE. As a stronger protective effect was found in more recent studies, the epidemiology of this association may evolve and deserve to be further monitored.

The term "feeding difficulties" (FD) encompasses a range of phenotypes characterized by inadequate food intake and/or inappropriate eating habits for a given age. Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition often affecting children. It leads to esophageal dysmotility, potentially impacting feeding/eating. However, little is known regarding the true prevalence of feeding/eating difficulties in children with EoE. The main objective of this systematic review was to address this knowledge gap and determine the impact of FD in children with EoE. We searched eight international databases for all published studies from inception until March 2024. All publications were screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses, so a narrative synthesis of quantitative data was performed. A total of 3442 abstracts were assessed, 29 underwent full-text screening. Ten studies met eligibility criteria and were analyzed. Across these, 18 different terms to define FD and 6 diagnostic tools were used. All included papers reported quantitative data on the FD prevalence in children with EoE, ranging from 13% to 75.3%. Concomitant IgE food sensitization/allergy was common (26.2%-88%) but its impact on FD occurrence was unclear. The current literature suggests that FD is prevalent among children with EoE, particularly those with associated IgE-mediated food allergies. However, the heterogeneity of terminologies and diagnostic tools makes drawing conclusions challenging, as it might have impacted outcomes. Further research and guidance on the diagnosis and management of FD in children with EoE are needed to appropriately identify and manage such patients.

Non-esophageal eosinophilic gastrointestinal diseases (non-EoE EGIDs) are allergic conditions where Th-2-predominant inflammation causes symptoms related to gastrointestinal tract dysfunction. No studies have reported the incidence of non-EoE EGIDs. In addition, little is known about the influence of lifestyle factors on the condition.

We used a large health claim database from January 2005 to September 2022. Non-EoE EGIDs cases were identified on the basis of the International Classification of Diseases-tenth Revision code, K52.8. The incidence and prevalence of non-EoE EGIDs were estimated by Poisson and binomial distribution, respectively. For each case, 10 controls were randomly selected for a nested case-control study to identify potential risk factors of non-EoE EGIDs.

Of 15,200,895 individuals, 1,368 new cases of non-EoE EGIDs were identified. The incidence and prevalence of non-EoE EGIDs in 2022 were 3.07 (95% CI 2.67-3.52) per 100,000 person-years and 17.23 (95% CI 16.38-18.11) per 100,000 individuals, respectively, which were approximately 6 and 9 times higher than those in 2010. Allergic rhinitis (OR 1.63 (95% CI 1.16-2.29), p = 0.005), chronic sinusitis (OR 2.41 (95% CI 1.58-3.66), p < 0.001), and urticaria (OR 2.32 (95% CI 1.45-3.70), p < 0.001) were related to an increased risk of adult non-EoE EGIDs. Whilst atopic dermatitis (OR 2.28 (95% CI 1.35-3.86), p = 0.006) and the perinatal factors (OR 3.68 (95% CI 1.13-12.02), p = 0.031) were associated with an increased risk of pediatric non-EoE EGIDs. No association was seen with lifestyle factors such as obesity, smoking and alcohol consumption.

The incidence and prevalence of non-EoE EGIDs have increased over the past two decades.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease marked by eosinophilic inflammation and esophageal dysfunction, with a significant impact on morbidity, quality of life, and health care utilization. Once considered rare, EoE has become increasingly prevalent, with global estimates exceeding 140 cases per 100,000 individuals. This rise highlights the need to better understand the natural history and disease course to inform diagnosis and management strategies. Evidence suggests that EoE is a progressive condition, such that untreated inflammation contributes to esophageal remodeling and fibrotic complications over years to decades. Patients can develop esophageal food impactions, leading to emergency department utilization and the need for emergent endoscopy. In addition, patients with fibrostenotic disease can require serial dilations. Long-term management, including dietary therapy, proton pump inhibitors, topical corticosteroids, and newer therapies such as dupilumab, demonstrate promise in altering the disease course. However, variability exists in the strength of evidence regarding each therapy's ability to halt or reverse fibrosis. Knowledge gaps persist, particularly in defining fibrosis, identifying phenotypes prone to progression, and tailoring therapies to individual patients. Addressing these gaps will require continued research into understanding fibrosis progression and how therapies alter this trajectory. These efforts are poised to significantly improve clinical care and enhance outcomes for patients with EoE.

The diagnosis and monitoring of eosinophilic esophagitis (EoE), a common pediatric pathology, typically involves invasive procedures such as an upper endoscopy with biopsies, imposing a significant burden on patients and healthcare systems. We aimed to assess miR-21-5p and miR-223-3p levels in pediatric EoE patients and evaluate their as potential non-invasive biomarkers of disease activity and response to treatments. We enrolled 13 children with EoE and 8 controls. Plasma and esophageal mucosa samples from patients were collected at diagnosis and after 8-10 weeks of therapy and compared with control samples. After microRNA(miRNA) extraction, the levels of miR-21-5p and miR-223-3p and their relevant target genes were analyzed. Bioinformatic analysis was used to identify the predicted target genes and pathways that are potentially relevant for disease pathophysiology. Plasma levels of miR-21-5p and miR-223-3p were significantly higher in EoE patients than in the controls, reflecting their levels in esophageal mucosa. The target genes of these miRNAs are involved in key signaling pathways (MAPK, Ras, and FoxO), relevant for EoE pathophysiology. Among these, STAT3 (Signal Transducer and Activator of Transcription 3) and PTEN (Phosphatase and Tensin Homolog), which are significantly downregulated in patient esophageal mucosa, are implicated in eosinophilic gastroenteropathies and autoimmune diseases. Following therapy (proton pump inhibitors and/or fluticasone propionate), plasma and tissue expression of both miRNAs significantly decreased and were no longer different from the controls. These microRNAs may serve as complementary non-invasive EoE markers and reduce the need for endoscopy/biopsies.

Esophageal stricture is a prevalent condition affecting the digestive system, primarily marked by dysphagia and the obstruction of food passage through the esophagus. This narrowing of the esophageal lumen can significantly impact a person's ability to eat and drink comfortably, often leading to a decrease in nutritional intake and quality of life.

To explore the current research status and future trends of esophageal stricture through bibliometric analysis.

Literature on esophageal stricture from 2004 to 2023 was retrieved from the Web of Science Core Collection. Statistical analysis was performed using Excel, VOSviewer, CiteSpace, and RStudio. This study provides data on annual production trends, countries/regions, influential authors, institutions, journals, references, and keywords.

The study included 1485 publications written by 7469 authors from 1692 institutions across 66 countries/regions, published in 417 journals. The United States, China, and Japan are the major contributors to this field, with many quality papers. Song Ho-young, Diseases of the Esophagus, Gastrointestinal Endoscopy, and Mayo Clinic are the top authors, journals, co-cited journals, and institutions, respectively. The most frequent keywords are stent, endoscopy, management, etiology, and prevention; regenerative medicine, endoscopic injection, and autologous tissue transplantation are the latest research frontiers. These keywords reflect continuous advancements in technical innovation, treatment strategies, preventive measures in the esophageal stricture research field, and a sustained focus on improving patient prognosis. In contrast, the basic sciences were underrepresented.

This study provides an insightful analysis of the developments in the field of esophageal stricture over the past twenty years, with stent placement is currently a hot research topic.

Accurate identification of eosinophils in tissue sections is required for diagnosis of eosinophilic esophagitis in humans and the assessment of severity of disease in allergy models. The pig may be a good model for sensitization and allergy models due to anatomical, physiological, and immunological similarities to humans. However, comparative studies on histochemical detection of eosinophils in fixed porcine tissue are lacking.

Qualitative and quantitative comparisons were performed for six histochemical methods previously reported for eosinophil and mast cell detection in other species. Astra Blue/Vital New Red, Congo Red, Luna, Sirius Red, Toluidine Blue, and modified regressive Hematoxylin & Eosin were applied to formalin-fixed paraffin embedded full-thickness sections of porcine esophagus. Specimens were collected from young, crossbred pigs sensitized to ovalbumin with or without subsequent oral exposure to ovalbumin to produce eosinophilic esophagitis lesions for comparison to non-allergic controls.

Ease of eosinophil quantitation was analyzed, and varied by histochemical stain, to determine whether stain selection increased accuracy and efficiency of evaluation. Noticeable differences in color contrast between intracytoplasmic granules, surrounding tissue, and cellular components aided detection and identification of eosinophils and mast cells with Astra Blue/New Vital Red and Toluidine Blue, respectively. For eosinophils, Congo Red and H&E were adequate, while Luna and Sirius Red presented challenges for quantitation.

In this case, rapid and reliable characterization of porcine esophageal allergy models was made possible by using Astra Blue/New Vital Red for eosinophils and Toluidine Blue for mast cells.

The Index of Severity for Eosinophilic Esophagitis (I-SEE) grades eosinophilic esophagitis (EoE) severity across several domains. We assessed associations between EoE features and severity by I-SEE at diagnosis, and baseline I-SEE and outcomes following topical corticosteroids (tCS).

We conducted a retrospective cohort study of newly diagnosed EoE patients. Data were extracted to complete the I-SEE at diagnosis. Disease activity was categorized as mild (I-SEE 1-6), moderate (I-SEE 7-14), or severe (I-SEE ≥15). We compared baseline characteristics by I-SEE category. We assessed if baseline I-SEE associated with treatment response in patients treated with tCS.

Of 1312 patients, there were 657 (50%), 461 (35%), and 194 (15%) with mild, moderate, and severe disease by I-SEE, respectively. Baseline scores were similar for children (8.5 ± 6.6) and adults (8.8 ± 6.5) (P = .37). Compared with mild or moderate disease, patients with severe disease were younger (23.8 ± 19.8 years for severe vs 28.0 ± 19.7 years for mild vs 30.3 ± 17.0 years for moderate; P < .001), had lower body mass index (21.6 ± 7.1 kg/m2 vs 24.4 ± 7.0 kg/m2 vs 25.7 ± 6.8 kg/m2; P < .001), and had longer symptom length preceding diagnosis (9.3 ± 10.5 years vs 5.9 ± 7.5 years vs 7.2 ± 7.9 years; P < .001). The baseline category associated with tCS response, with severe patients less likely to have histologic response (49% vs 55% vs 64%; P = .03 for <15 eosinophils per high-power field) and symptomatic responses, while also having the highest post-treatment eosinophilic esophagitis endoscopic reference scores.

I-SEE correlated with baseline features in a large EoE cohort, performed similarly in children and adults, and associated with post-treatment responses to tCS. These data support that I-SEE provides prognostic data and suggest that severe disease may benefit from intensive upfront management.

Real-world data on the impact of eosinophilic esophagitis (EoE) in patients are limited. This study assessed clinical characteristics, healthcare resource utilization (HCRU), symptoms, comorbidities, and quality of life (QoL) of EoE patients.

The multicountry cross-sectional survey, Adelphi EoE Disease Specific Programme™, collected physician and patient-reported data on clinical characteristics, HCRU, symptoms, comorbidities, and QOL of EoE patients with past/current proton pump inhibitor use and ongoing dysphagia-related symptoms (September to December 2020) at study entry.

Physicians provided clinical characteristics, symptom, comorbidity, and HCRU data for 412 patients (12-17 years: 8%; ≥18 years: 92%); and 161 of these patients (12-17 years: 6%; ≥18 years: 94%) provided symptom and QOL data. Of the 412 patients, 67% were male, with a mean (SD) age of 37.0 (15.3) years. Overall, 74% of patients were currently being treated with corticosteroids (12-17 years: 88%; ≥18 years: 73%); 25% of patients had a history of esophageal dilations (12-17 years: 19%; ≥18 years: 26%); and 30% of patients had EoE-related emergency room visit (12-17 years: 31%; ≥18 years: 30%) in the last year. Among the 161 patients, heartburn (69%) was the most commonly reported symptom; the greatest negative impacts on QOL were reported for dysphagia-related anxiety, social activities involving food, and maintaining friendships (EoE Impact Questionnaire scores [1-5, low to high impact]: 1.6-2.2 for both age groups).

EoE patients continued to experience disease burden despite receiving treatment, highlighting the high unmet need for effective disease management in this population.

Eosinophilic esophagitis (EoE) and atopic dermatitis (AD) are two known and sometimes comorbid type 2 helper cell-mediated diseases. EoE shares clinical features, immunologic pathways, susceptibility loci, and risk with atopic conditions including food allergies (food allergies), asthma, allergic rhinitis (AR), and AD. These conditions share an impaired immunological response against a range of antigens or allergens, leading to CD4+ Th2 differentiation and overproduction of immunoglobulin E (IgE). The emerging coexistence of EoE and AD presents a compelling area of study. Both diseases manifest on stratified squamous epithelium along the skin-gut continuum and have overlapping treatment algorithms that include avoidance of triggers, topical steroids, and dupilumab. This narrative review highlights the clinical and immunologic nuances underlying these two conditions and sheds light on potential new research and therapeutic avenues.

Edible coatings are a combination of substances that are applied onto foods to enhance their shelf life and that can be consumed by humans. Coatings are often composed of a combination of proteins, lipids, and/or polysaccharides and can contain plasticizers to increase flexibility and elongation. Surfactants and emulsifiers are sometimes added to decrease surface water activity and prevent moisture loss. The ideal edible coating slows the loss of desirable flavor volatiles and water vapor as well as restricts the exchange of gases, creating a modified atmosphere but not creating anaerobic conditions, all while not adding off-flavors to the food. In this review, the different components used in edible films and coatings are examined, along with their benefits and weaknesses. Additionally, this study reviews possible safety issues associated with consuming ingredients used in edible films and coatings. Edible films and coatings are more successful when multiple ingredients are used together to create a good moisture and gas barrier, thus creating the possibility for interactions. Most, but not all, ingredients used in edible films and coatings do not pose a risk to people when consumed at the levels present in coatings. Thus, it is imperative to review and consider new data on the safety of ingredients used in coatings.

Esophagitis is a frequent, but at the molecular level poorly characterized condition with diverse underlying etiologies and treatments. Correct diagnosis can be challenging due to partially overlapping histological features. By proteomic profiling of routine diagnostic FFPE biopsy specimens (n = 55) representing controls, Reflux- (GERD), Eosinophilic-(EoE), Crohn's-(CD), Herpes simplex (HSV) and Candida (CA)-esophagitis by LC-MS/MS (DIA), we identified distinct signatures and functional networks (e.g. mitochondrial translation (EoE), immunoproteasome, complement and coagulations system (CD), ribosomal biogenesis (GERD)), and pathogen-specific proteins for HSV and CA. Moreover, combining these signatures with histological parameters in a machine learning model achieved high diagnostic accuracy (100% training set, 93.8% test set), and supported diagnostic decisions in borderline/challenging cases. Applied to a young patient representing a use case, the external GERD diagnosis could be revised to CD and ICAM1 was identified as highly abundant therapeutic target. This resulted in CyclosporinA as a personalized treatment recommendation by the local multidisciplinary molecular inflammation board. Our integrated AI-assisted morphoproteomic approach allows deeper insights in disease-specific molecular alterations and represents a promising tool in esophagitis-related precision medicine.

Background: Eosinophilic esophagitis (EoE) is a disease characterized by eosinophilic inflammation of the esophagus and associated esophageal dysfunction with increasing worldwide prevalence. Clinical presentation is nonspecific and varies with age, with limited studies in the pediatric population. Objective: Our study aimed to compile clinical phenotypes, esophagogastroduodenoscopy findings, and treatment response of EoE in a tertiary pediatric center, and to examine factors associated with the response of treatment. Methods: In this retrospective study, we reviewed the medical records of 824 patients diagnosed with EoE at Children's Hospital of Michigan from 2011 to 2021. Data collected included a demographic profile, symptoms, esophagogastroduodenoscopic and histopathologic findings, treatment modalities, response, and compliance. We then performed a multivariable logistic regression to assess the associating factors that influenced the treatment response rate. Results: A high proportion of males and coexisting allergic conditions were observed in the patients with EoE, with the most common presentation of vomiting in children and of abdominal pain in adolescents. Among 656 of the 824 patients who had follow-up esophagogastroduodenoscopy, treatment response rates varied among modalities, with proton-pump inhibitor treatment exhibiting the highest response rate, at 60.8%, followed by diet modification (50%) and topical steroid treatment (43.5%). Significant predictors of normal endoscopic findings at follow-up included female gender, normal endoscopic appearance, good compliance to treatment, and absence of topical steroids in the treatment regimen. There were no significant differences in outcomes observed for targeted elimination led by a skin-prick test or specific immunoglobulin E test. Medication compliance did not significantly differ among the treatment options. Conclusion: Managing EoE in pediatric patients poses significant challenges, which emphasizes the need for multidisciplinary care to achieve treatment response effectively. The findings underscore the complexity of managing EoE and the need for individualized treatment approaches. Further research is warranted to elucidate the underlying mechanisms and optimize management strategies for pediatric patients with EoE.

The spectrum of non-IgE mediated conditions includes well-defined conditions like Food Protein-Induced Enterocolitis Syndrome (FPIES), Eosinophilic Oesophagitis (EoE), Food Protein-Induced Enteropathy, and Food Protein-Induced Allergic Proctocolitis, but also the more controversial food protein-induced dysmotility disorders like food protein-induced gastroesophageal reflux disease (FPGORD) and food protein-induced constipation (FPC). Typically, non-IgE mediated reactions are delayed, with symptom onset from hours to days after exposure to a culprit food. The diagnosis is mostly clinical, and food elimination followed by reintroduction is the primary diagnostic method. Apart from EoE, the diagnosis of these conditions remains challenging, and there is a need to develop specific diagnostic tests. Acute FPIES presents with distinct symptoms, but misdiagnosis is common due to poor recognition. In contrast, some presentations, particularly FPGORD and FPC, overlap with the common, often benign disorders of gut-brain interaction, previously known as functional gastrointestinal disorders. This raises concerns about overdiagnosis and can lead to an unnecessary restrictive diet in infants and breastfeeding mothers. A systematic approach to an elimination diet and the support of a registered dietitian/nutritionist are recommended to ensure nutritional adequacy, suitable alternatives, promote timely introductions when appropriate, support breastfeeding where required as well as prevent nutritional deficiencies and feeding difficulties. This publication aims to provide an update on the spectrum of non-IgE-mediated food allergic conditions and intends to provide clinicians with practical guidance on the diagnosis and management of each condition. The authors acknowledge the need for further research in a range of areas to inform best evidence-based practice.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus with rising prevalence. Dupilumab (DUPI), a monoclonal antibody that targets the interleukin-4 receptor α, has shown promise as a treatment option. We conducted a systematic review and network meta-analysis of randomized controlled trials searching the PubMed/Medline database, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials (CENTRAL), and the medRxiv preprint server up to 31 July 2024, assessing DUPI's efficacy and optimal dosing in the treatment of EoE. Finally, three randomized-controlled trials comprising 470 participants, including 102 children under 12 years of age, were included in the qualitative synthesis. Both high-exposure (HE-DUPI, 300 mg weekly) and low-exposure (LE-DUPI, 300 mg biweekly) regimens achieved significant histologic remission relative to placebo (OR = 26.88, 95% CI 11.98-60.29 for LE-DUPI; OR = 29.15, 95% CI 13.68-62.12 for HE-DUPI). Although overall adverse events were comparable between groups, HE-DUPI was associated with a notable increase in serious adverse events. These findings suggest that DUPI is effective in promoting histologic remission in EoE, with LE-DUPI emerging as a preferred option for balancing efficacy and safety. This study highlights the efficacy and safety profiles of different dosing regimens and pediatric groups. Further studies are warranted to explore long-term outcomes and identify patient subgroups that may derive the greatest benefit from DUPI therapy.

Dupilumab is the only FDA-approved medication for eosinophilic esophagitis (EoE). Clinical trials have shown its effectiveness in alleviating symptoms and decreasing inflammation associated with EoE. However, real-world data on its efficacy is still limited.

We searched multiple databases for articles reporting the outcomes of dupilumab for the treatment of EoE and conducted a meta-analysis.

Five retrospective studies including 209 subjects (mean age: 22.12±12.01 y and 61.24% males) were analyzed. The pooled outcome for symptom improvement with dupilumab was 89.2% [95% Cl: 68.0%-97.0%; I2=58%]. Peak eosinophil count improved markedly postdupilumab [pre: 47.13 (95% Cl: 45.5-48.67; I2=98%) vs. post: 6.44 (95% Cl: 0.72-13.60; I2=98%) eos/hpf, P<0.001]. There was a significant reduction in Endoscopic Reference Score (EREFS) [pre: 4.10 (95% Cl: 1.74-6.43; I2=95%) vs. post: 0.77 (95% Cl: 0.14-1.7; I2=95%), P<0.001]. The mean duration of treatment and follow-up was 5.66±1.14 months. The most common adverse event reported was a pain due to injection, which was controlled with local anesthetics.

Our study shows that in a real-world scenario, administration of dupilumab for EoE induces histologic and endoscopic remission and symptomatic improvement. Hence, dupilumab can be considered a treatment option for EoE, especially in resistant cases. Future studies should evaluate its long-term effectiveness for preventing esophageal fibrosis/stricture and long-term side effect profile. Furthermore, cost-effectiveness analysis is warranted to help establish its role as a potential first-line treatment strategy.

Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID), based on the involved gastrointestinal organs. The present survey was performed to provide an overview of the current status of the epidemiology, diagnosis, and treatment of EGID in Asia.

Responses to the questionnaire were obtained from 228 doctors at various institutions in eight Asian countries. The questionnaire consisted of 52 questions on EoE and non-EoE EGID.

Responses to questionnaire were obtained from 228 doctors from eight countries. The most common participation facilities were university hospitals, followed by public hospitals, private hospitals, and private clinics. 1-10 were the most frequent patients per year in each institution for both EoE and non-EoE-EGID. The 30s and 40s are common age groups for both EoE and non-EoE-EGID. Although endoscopic findings vary among countries, 15 or more eosinophil infiltrations in high-power fields as a diagnostic criterion are used in all countries for EoE. As treatments, the prescription rates of Proton pump inhibitor, diet, topical and systemic steroids, and biologics were similar among the eight countries in EoE. Non-EoE-EGID showed a similar trend to EoE in epidemiology, symptoms, diagnosis, and treatment.

The questionnaire survey partially revealed the current status of the epidemiology, symptoms, diagnosis, and treatment of EGID in Asian countries.