Food antigen consumption and disease activity affect food-specific IgG4 levels in patients with eosinophilic esophagitis (EoE).

INTRODUCTION: High levels of serum food-specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics. METHODS: This was a case-control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE-negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels. RESULTS: The analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p = .30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p = .24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p = .01) and the presence of sIgE to milk (OR 4.23; p = .008). CONCLUSION: Serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non-EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study.

Food-induced immediate response of the esophagus in pediatric eosinophilic esophagitis.

BACKGROUND: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. METHODS: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. RESULTS: A total of 78 patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in 16.7% of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). CONCLUSIONS: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE?

Oral immunotherapy (OIT) may induce eosinophilic esophagitis (EoE). Proton pump inhibitors (PPIs) are an effective treatment for EoE. However, the effect of PPI treatment is not well established in patients with EoE induced by OIT. Our primary aim was to compare the clinical, endoscopic, and histological response rates to PPIs in children with EoE induced by OIT (EoE+OIT) versus EoE patients without OIT (EoE-OIT). The secondary aims are to describe the clinical and histological features of EoE+OIT. Demographic, clinical, endoscopic, and histological findings of patients with EoE in the gastroenterology clinic at Shamir Medical Center between March 2015 and December 2022 were collected. Comparisons were performed between EoE+OIT and EoE-OIT patients. The study included 42 children (74% male, mean age 11.2), of whom 31 had EoE-OIT and 11 had EoE+OIT. There were no significant differences between groups regarding sex, comorbidities, symptoms, or endoscopic and histological characteristics at diagnosis. All 42 children were treated with PPIs after diagnosis with or without diet changes. The rates of any clinical response were 83.9% and 90.1% in the EoE-OIT group and EoE+OIT group, respectively (p = 1.0). The rate of any endoscopic response was 74.2% for EoE-OIT and 81.8% for EoE+OIT (p = 0.54). Histologically, PPIs were even more effective in the EoE+OIT group, where only 18.2% had no histological response at all compared to 51.6% in the EoE-OIT group (p = 0.1). CONCLUSION: PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. WHAT IS KNOWN: • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). WHAT IS NEW: • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.

Eosinophilic esophagitis: A review of the pediatric population and consideration of upcoming therapies.

Eosinophilic esophagitis (EoE) is a disease entity that has become increasingly recognized in the pediatric population over the last decade and was first recognized as early as 1990. EoE is a clinicopathologic diagnosis with signs and symptoms varying between age groups. The clinical presentation of EoE is variable ranging from milder nonspecific symptoms, such as abdominal pain, vomiting, and dyspepsia, to more severe presentations such as failure to thrive, dysphagia and even food impaction and is dependent on age of diagnosis 2. There is growing body of evidence with regards to the pathophysiology, diagnostic modalities, and treatment options for EoE in the past decade. In this review article, we aim to discuss the disease burden, pathophysiology, diagnostic strategies, and currently available treatment options for EoE based on existing literature.

Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy.

BACKGROUND: The relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia. PATIENTS AND METHODS: All enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined. KEY RESULTS: Twenty consecutive patients (65% female, age range: 21-84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy. CONCLUSIONS AND INFERENCES: Submucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.

Needs Assessment for Eosinophilic Esophagitis Education in School Nurses.

Over the past 2 decades, eosinophilic esophagitis (EoE) has become increasingly recognized as a common cause of gastrointestinal morbidity in children. A mainstay of treatment is food avoidance, which must be implemented in both the home and school settings for school-aged children. The aim of this study is to assess school nurses' familiarity with EoE with regard to food avoidance and treatment in the school setting. We conducted a 19-question online survey of 60 school nurses (elementary through high school) recruited from Dauphin, Lebanon, and Lancaster Counties in Pennsylvania. Results indicated that 62% of respondents were familiar with EoE. However, only 22% felt comfortable distinguishing between symptoms of EoE and food-dependent anaphylaxis. Almost all respondents (97%) were interested in learning more about EoE. We report significantly increased familiarity with food-dependent anaphylaxis in comparison with EoE among school nurses. There is an interest and need for increasing education on EoE.

Food-induced immediate response of the esophagus-A newly identified syndrome in patients with eosinophilic esophagitis.

BACKGROUND: Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as "food-induced immediate response of the esophagus" (FIRE), observed in EoE patients. METHODS: Food-induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. RESULTS: Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P < .01) and in those with high allergic comorbidity. Food-induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03). CONCLUSIONS: Food-induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.

Eosinophilic gastrointestinal disorders and allergen immunotherapy: Lights and shadows.

Allergic diseases, such as IgE-mediated food allergy, asthma, and allergic rhinitis, are relevant health problems worldwide and show an increasing prevalence. Therapies for food allergies are food avoidance and the prompt administration of intramuscular epinephrine in anaphylaxis occurring after accidental exposure. However, allergen immunotherapy (AIT) is being investigated as a new potential tool for treating severe food allergies. Effective oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) induce desensitization and restore immune tolerance to the causal allergen. While immediate side effects are well known, the long-term effects of food AIT are still underestimated. In this regard, eosinophilic gastrointestinal disorders (EGIDs), mainly eosinophilic esophagitis, have been reported as putative complications of OIT for food allergy and sublingual immunotherapy (SLIT) for allergic asthma and rhinitis. Fortunately, these complications are usually reversible and the patient recovers after AIT discontinuation. This review summarizes current knowledge on the possible causative link between eosinophilic gastrointestinal disorders and AIT, highlighting recent evidence and controversies.

Emerging drugs for eosinophilic esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is rare but incidence and prevalence is increasing. EoE is characterized by eosinophilic inflammation of the esophagus causing gastrointestinal symptoms such as abdominal pain, vomiting, reflux, dysphagia, and food impactions. If untreated, remodeling and fibrosis of the esophagus can occur and stricture formation may result. Current treatment options are limited to food-restriction diets or medications including proton pump inhibitors (PPIs) or swallowed corticosteroids. Significant progress has been made in understanding the underlying mechanisms of EoE allowing for development of drugs that target specific points in EoE pathways. Investigation of these drugs is early with few controlled studies, but many show promise as future treatments. Areas covered: This review will provide an up to date discussion of current therapies and investigational drugs for EoE. Articles used in this review were retrieved from PubMed. Ongoing or completed clinical trials were obtained through clinicaltrials.gov and review of the PharmaProjects database. Expert Opinion: Multiple therapeutic targets have been identified and several have shown efficacy. Work is needed to define appropriate trial outcome measures. Collaboration between government agencies, patient advocacy groups, and investigator-led consortia is critical for completing new clinical trials which should pave the way for new therapies in clinical practice.

Efficacy of Atopy Patch Testing in Directed Dietary Therapy of Eosinophilic Esophagitis: A Pilot Study.

BACKGROUND: Atopy patch testing (APT) has shown potential for predicting dietary food triggers in studies of children and adolescents with eosinophilic esophagitis (EoE). AIMS: To assess the efficacy of APT in adults with EoE. METHODS: We conducted a prospective open-label pilot study of patients ≥ 18 years old with diagnosis of EoE at Mayo Clinic in Rochester, Minnesota, from November 2014 to January 2016. All patients underwent patch testing using intact food products, followed by a six food elimination diet and stepwise food reintroduction. Response to elimination diet was assessed with serial endoscopy with biopsies as well as clinical symptoms. APT results were directly compared to elimination diet results for assessment of efficacy. Correlation between clinical symptoms, endoscopic score, and histology was also qualitatively evaluated. RESULTS: Fifty percent of the patients had a positive APT, while only 16% had an APT result confirmed histologically during food reintroduction. Sensitivity of APT was calculated to be 5.9%, with specificity of 92.0%. Furthermore, we found significant qualitative inter-patient heterogeneity in the correlation between clinical symptoms, EREFS score, and histology. CONCLUSIONS: APT does not reliably predict food triggers identified by food elimination diet in adult patients with EoE. As a result, APT does not have a clear role in the evaluation of patients with EoE.

Eosinophilic Esophagitis in Children.

PURPOSE OF REVIEW: EoE is a significant cause of gastrointestinal morbidity affecting 1:2000. Patients with EoE typically have multiple atopic comorbidities, and additionally, many patients with EoE can be controlled well with elimination diets. The purpose of this review is to summarize the care of pediatric eosinophilic esophagitis patients. RECENT FINDINGS: EoE represents a distinct clinical syndrome which is characterized by esophageal dysfunction and eosinophil-predominant inflammation of the esophageal mucosa. Patients with EoE can present with varying symptoms depending on their age; in this review, we review the presenting features of eosinophilic esophagitis in children as well as a diagnostic algorithm for EoE. The mucosal inflammation in EoE is driven by exposure to food antigens in many patients with EoE. Therefore, for the majority of patients, the mainstays of treatment remain food elimination diets or swallowed steroids. This review summarizes the diagnostic approach to eosinophilic esophagitis (EoE) in pediatric patients, focusing on the importance of accurate diagnosis and selection of appropriate therapy.

Prostaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus.

Eosinophilic esophagitis is characterized by eosinophil-predominant inflammation in the esophagus. How eosinophils migrate and infiltrate into the esophagus, however, is less clear. Our previous study demonstrated that mast cell activation led to eosinophil infiltration in the esophagus. Prostaglandin D2 (PGD2) is an important mediator released from activated mast cells. The present study aims to determine whether PGD2 induces eosinophil infiltration into the esophagus via a d-type prostanoid receptor 2 (DP2) receptor-dependent mechanism. Using an in vivo guinea pig model, PGD2, d-type prostanoid receptor 1 (DP1) agonist, or DP2 agonist were injected into the esophagus. Esophageal tissues were removed 2 hours after injections and proceeded to either hematoxylin-eosin (HE) staining or immunofluorescent staining of eosinophil major basic protein (MBP) to compare each treatment-induced eosinophil infiltration in the esophagus. In a separate study, ovalbumin (OVA)-sensitized guinea pigs were pretreated with either DP2 or DP1 antagonists, followed by inhalation of OVA to induce mast cell activation. Esophageal tissues were then processed for immunofluorescent staining of MBP. PGD2 injection in the esophagus led to an increase of eosinophil infiltration in esophageal epithelium at the injection site as revealed by HE staining. Increased infiltration of eosinophils was further confirmed by the increased presence of MBP-labeled immunopositive (MBP-LI) cells in esophageal epithelium. Injection with DP2 agonist 15(R)-PGD2, but not DP1 agonist BW 245C, mimicked the PGD2-induced response. In OVA-sensitized animals, antigen inhalation increased MBP-LI cells in esophageal epithelium. Pretreatment with DP2 antagonist BAY-u3405, but not DP1 antagonist BW 868C, inhibited the antigen inhalation-induced increase of MBP-LI cells in esophageal epithelium. These data support the hypothesis that PGD2 induces eosinophil trafficking into the esophageal epithelium via a DP2-mediated pathway, suggesting a role of DP2 antagonist in the prevention of eosinophilic esophagitis.

A Mouse Model for Eosinophilic Esophagitis (EoE).

Eosinophilic esophagitis (EoE) is an emerging chronic T helper type 2 (Th2)-associated, allergic, and immune-mediated disease, characterized histologically by eosinophil-predominant mucosal inflammation and clinically by esophageal dysfunction. Over the past years, the prevalence of EoE has dramatically increased globally. Until recently, most studies of EoE focused on using human biopsies, which are also used for diagnostic purposes, or esophageal epithelial cell lines, which led to major advances in the understanding of EoE. Despite this, a robust mouse model that mimics human disease is still crucial for both understanding disease pathogenesis and as a preclinical model for testing future therapeutics. Herein, we describe a highly reproducible and robust model of EoE that can be performed using wild-type mice by ear sensitization with oxazolone (OXA) followed by intraesophageal challenges. Experimental EoE elicited by OXA mimics the main histopathological features of human EoE, including intraepithelial eosinophilia, epithelial and lamina propria thickening, basal cell hyperplasia, and fibrosis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of EoE in mice using oxazolone Support Protocol 1: Preparing the mouse esophagus for histological analysis Support Protocol 2: Assessment of epithelial and lamina propria thickness using H&E staining Support Protocol 3: Assessment of eosinophilic infiltration using anti-MBP and basal cell proliferation using anti-Ki-67 staining Support Protocol 4: Flow cytometry of mouse esophageal samples Support Protocol 5: ELISA on protein lysates of esophageal samples.

Inflammatory Causes of Dysphagia in Children.

Gastroesophageal reflux (GER) and eosinophilic esophagitis (EoE) are the most common inflammatory causes of pediatric dysphagia, but several other less prevalent conditions should be considered. These conditions can affect one or several aspects of the swallowing process. In some inflammatory conditions dysphagia may be an early symptom. Esophagoscopy and instrumental swallow studies are often needed to determine the underlying diagnosis and best treatment plan. In some inflammatory conditions dysphagia can portend a worse outcome and need for more aggressive treatment of the underlying condition. Consultations with speech language pathology, gastroenterology, dietetics, allergy/immunology and/or rheumatology are often needed to optimize management.

IgE and non-IgE food allergy: A review of immunological mechanisms.

Background: Food allergic (FA) conditions have been classified as immunoglobulin E (IgE) and non-IgE-mediated reactions that affect as many as 8% of young children and 2% of adults in Western countries, and their prevalence seems to be rising. Although the immunologic basis of IgE-mediated FA is well established, the mechanisms that govern non-IgE-mediated FA are not well understood and are marked by a paucity of comprehensive insights. Objective: The purpose of the present report is to examine the current classification and epidemiology of non-IgE-mediated FA, the latest immunologic mechanisms that underlie the three most commonly cited non-IgE FA conditions, viz., eosinophilic esophagitis, food protein-induced enterocolitis, and food protein-induced allergic proctocolitis, and explore what allergist/immunologists in practice should be aware of with regard to the condition. Methods: An extensive research was conducted in medical literature data bases by applying terms such as FA, non-IgE allergy, tolerance, unresponsiveness, cytokines, CD4+ T helper cell pathways, and key cytokine pathways involved in FA. Results: Current evidence now supports the view that immune dysregulation and cytokine-induced inflammation are the fundamental bases for both IgE- and non-IgE-mediated FA. The existing non-IgE-related FA literature is mostly characterized by a relative dearth of mechanistic information in contrast to IgE-mediated FA, in which the immunologic underpinnings as a T helper type 2 directed entity are well established. Although the need for future methodologic research and adherence to rigorous scientific protocols is essential, it is also necessary to acknowledge past contributions that have given much to our understanding of the condition. In the present report, a novel signature cytokine-based classification of IgE-mediated and non-IgE-mediated allergy is proposed that may offer a novel template for future research in the field of non-IgE-mediated FA. Conclusion: The present report provides an overview of the current classification and frequency of IgE- and non-IgE-mediated FAs, and offers insights and potential solutions to address lingering questions, particularly when concerning the latest immunologic mechanisms that underlie the pathogenesis of non-IgE-mediated FA. Although some progress has been made in recent years toward making diagnostic and treatment options available for these conditions, there still remain many lingering questions and concerns to be addressed, which can be fully understood by future research.

Dupilumab Leads to Clinical Improvements including the Acquisition of Tolerance to Causative Foods in Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Disorders.

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.

EoE behaves as a unique Th2 disease: a narrative review.

Background and Objective: To highlight and interpret two significant differences between eosinophilic esophagitis (EoE), a type 2 helper cell (Th2) disease, and three other representative Th2 diseases. EoE, asthma, atopic dermatitis (AD), chronic rhinosinusitis (CRS) and other Th2 diseases employ epithelial alarmins to recognize triggers, share a prototypical inflammatory cascade, and respond to glucocorticoids. However, EoE also has several distinguishing characteristics which may be explained by a distinct pathophysiologic mechanism. Methods: The following report consist of four related narrative reviews which combine comprehensive PubMed and Google searches. Two reviews were performed to identify and contrast all eligible studies describing serologic markers in EoE compared to asthma, AD, and CRS. Two additional reviews then compare the responses to parenteral biological therapies in EoE and in the same representative Th2 diseases. Key Content and Findings: Comprehensive literature searches definitively differentiate the absence of serologic markers in EoE compared to their identification in the other representative Th2 diseases. Similarly, a summary of therapeutic trials demonstrates that while EoE is unable to clinically respond to a variety of parenteral biological therapies, asthma, AD and CRS are very effectively treated with this same approach. A novel pathophysiology for EoE is proposed, and the emerging literature that support its existence is summarized. Conclusions: The fundamental properties described in this narrative regarding serologic signaling and response to parenteral therapy in EoE could be explained if EoE employs a unique application of the Th2 pathway. One potential mechanism consistent with these observations is that EoE employs exclusively esophageal mucosal constituents to initiate and generate the prototypical Th2 cascade and the fibrostenotic changes that follow.

Development of an Oral Isoliquiritigenin Self-Nano-Emulsifying Drug Delivery System (ILQ-SNEDDS) for Effective Treatment of Eosinophilic Esophagitis Induced by Food Allergy.

Isoliquiritigenin (ILQ) is a natural flavonoid with various pharmacological activities. In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also evaluated. Combined surfactants and co-surfactants were screened, and the optimal formulation of ILQ-SNEDDS was determined according to droplet size, droplet dispersity index (DDI), and drug loading. The formulation was composed of ethyl oleate (oil phase), Tween 80 & Cremophor EL (surfactant, 7:3), and PEG 400 & 1,2-propylene glycol (cosurfactant, 1:1), with a mass ratio of 3:6:1. Its physicochemical properties, including drug loading, droplets' size, Zeta potential, appearance, and Fourier transform infrared (FTIR) spectroscopy, were characterized. In vitro release profile, in situ intestinal absorption, and in vivo pharmacokinetics were applied to confirm the improvement of oral ILQ bioavailability by NEDDS. Finally, the efficacy of ILQ-SNEDDS in the treatment of food allergy-induced eosinophilic esophagitis (EOE) was further evaluated. When the ILQ drug loading was 77.9 mg/g, ILQ-SNEDDS could self-assemble into sub-spherical uniform droplets with an average size of about 33.4 ± 2.46 nm (PDI about 0.10 ± 0.05) and a Zeta potential of approximately -10.05 ± 3.23 mV. In situ intestinal absorption showed that optimized SNEDDS significantly increased the apparent permeability coefficient of ILQ by 1.69 times, and the pharmacokinetic parameters also confirmed that SNEDDS sharply increased the max plasma concentration and bioavailability of ILQ by 3.47 and 2.02 times, respectively. ILQ-SNEDDS also significantly improved the apparent signs, allergic index, hypothermia and body weight of EoE model mice. ILQ-SNEDDS treatment significantly reduced the levels of inflammatory cytokines, such as TNF-α, IL-4, and IL-5, and the level of PPE-s-IgE in serum, and significantly inhibited the expression of TGF-ß1 in esophageal tissue. SNEDDS significantly improved the solubility and bioavailability of ILQ. Additionally, ILQ-SNEDDS treatment attenuated symptomatology of EoE model mice, which was associated with inhibiting the production of TH2 inflammatory cytokines and PPE-s-IgE and the expression of TGF-ß1. The above results shows that ILQ-SNEDDS has great potential as a good candidate for the treatment of eosinophilic esophagitis.

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry.

Rationale: 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. Methods: 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. Results: 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. Conclusions: 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.