Eosinophilic Esophagitis Research Articles

Health State Utility is Substantially Reduced With an Increasing Burden of Patient-Reported Symptoms in Eosinophilic Esophagitis.

We aimed to estimate health state utility in eosinophilic esophagitis (EoE) by histologic activity and assess association with disease parameters. In this cross-sectional study, we measured health state utility by time trade-off and assessed symptoms with the EoE Symptom Activity Index. In 51 adults with EoE, the mean utility was 0.91 (95% CI 0.86, 0.95). Utility was numerically worse in patients with dilation or a smaller stricture diameter. With each ten-point improvement in EoE Symptom Activity Index, utility increased by 0.03 (95% CI 0.01, 0.05). EoE is associated with reduced health state utility, with symptoms most strongly predicting valuation.

Reflux, eosinophilic esophagitis, and celiac disease - the blurred lines.

Gastroesophageal reflux disease (GERD) is a commonly recognized cause of dysphagia. Conversely, eosinophilic esophagitis (EoE) and celiac disease are rarer and often overlooked as dysphagia culprits. Overlap between these conditions complicates diagnosis and delays appropriate treatment. This review aims to clarify the distinctive dysphagia characteristics in each condition, explore potential overlaps, and offer guidance on differentiation. Recent studies have advanced our understanding of dysphagia mechanisms in GERD, EoE, and celiac disease, particularly in characterizing disordered motility and dysphagia's natural history. While upper endoscopy, biopsies, and manometry remain crucial in dysphagia assessment, novel diagnostic tools are emerging. New insights highlight the significance of cytokine-induced mucosal injury in all three conditions, revealing potential connections where mucosal damage in one disorder may contribute to the development of others. GERD, EoE, and celiac disease can coexist and present with similar symptoms. Distinguishing between them often entails upper endoscopy, esophageal biopsies, pH testing, and celiac serologies. EoE should be considered when GERD patients fail proton pump inhibitor therapy or when celiac patients have persistent esophageal symptoms despite a gluten-free diet. Consider celiac disease if dysphagia accompanies iron deficiency anemia, malabsorptive diarrhea, or osteoporosis. Recognizing the potential overlap between these conditions is crucial for guiding clinical evaluation and therapy.

TEMPORAL TREND OF INCIDENCE AND PREVALENCE OF EOSINOPHILIC ESOPHAGITIS IN ASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

There are limited epidemiological studies on eosinophilic esophagitis (EoE) in Asia. We studied the temporal trend of EoE in Asia, the presenting symptoms and association with atopic diseases. Literature search on PubMed, Embase, MEDLINE, Scopus, and Web of Science was performed to retrieve studies published between 1980 and 2023 that reported the prevalence or incidence of EoE in Asia. We employed the random effects model to estimate the pooled incidence and prevalence. I2 index and Cochran Q test were used to assess heterogeneity. Subgroup analyses were conducted for study types, different regions, years of examination, and age groups. The proportion of atopic diseases amongst patients with EoE was described. 25 studies from Asia were included. The pooled prevalence of EoE was 33.5 cases per 100,000 inhabitants in population-based studies and 11.0 cases per 1000 patients/visitors in hospital-based studies. The incidence rate among children was 12.3 cases per 1,000 patients/visitors, whereas for adults it was only 0.2 cases per 1,000 patients/visitors. Amongst population-based studies, there was an increase in prevalence from 19.8 per 100,000 in 2005-2009 to 73.0 per 100,000 in 2015-2019. Similar upward trend was observed in hospital-based studies conducted during the same time period. Patients with EoE commonly presented with dysphagia (36.3%) and nausea and vomiting (34.6%). History of atopy was reported in 57.2% of EoE patients in Asia. The prevalence and incidence of EoE in Asia have been rising over the past decades. Due to the limited number of Asian studies and variations in subjects' sources, caution should be exercised when interpreting these results.

Eosinophilic gastrointestinal disorders and the role for the epithelium in pathogenesis and treatment.

This review aims to provide an overview of the current understanding of eosinophilic gastrointestinal disorders (EGIDs) and the role of the epithelium in influencing disease pathogenesis to inform and devise future therapeutic strategies. Changes in epithelial cell structure, functions, and integrity are observed in EGIDs. In eosinophilic esophagitis (EoE), the esophageal epithelium has been shown to play key roles in perpetuating the inflammatory response in EoE through the expression of pro-inflammatory cytokines and immunological cell-surface proteins. Similar mechanisms appear to exist in the other EGIDs, including eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Because of the increasing rarity of each non-EoE EGID, research focusing on how the epithelium is modulating disease in each lower gastrointestinal compartment is still in its rudimentary stages. While there has been significant progress in understanding the role of the epithelium in EoE, further research is needed to obtain a better understanding of the mechanisms mediating epithelial-immune crosstalk in non-EoE EGIDs. Using EoE-epithelial cell research to inform future EGID investigations could lead to the development of new therapeutic interventions, such as targeted therapies to restore epithelial barrier function and reduce inflammation, to improve rare disease-patient quality of life.

Advances in omics data for eosinophilic esophagitis: moving towards multi-omics analyses.

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus characterized by eosinophil accumulation and has a growing global prevalence. EoE significantly impairs quality of life and poses a substantial burden on healthcare resources. Currently, only two FDA-approved medications exist for EoE, highlighting the need for broader research into its management and prevention. Recent advancements in omics technologies, such as genomics, epigenetics, transcriptomics, proteomics, and others, offer new insights into the genetic and immunologic mechanisms underlying EoE. Genomic studies have identified genetic loci and mutations associated with EoE, revealing predispositions that vary by ancestry and indicating EoE's complex genetic basis. Epigenetic studies have uncovered changes in DNA methylation and chromatin structure that affect gene expression, influencing EoE pathology. Transcriptomic analyses have revealed a distinct gene expression profile in EoE, dominated by genes involved in activated type 2 immunity and epithelial barrier function. Proteomic approaches have furthered the understanding of EoE mechanisms, identifying potential new biomarkers and therapeutic targets. However, challenges in integrating diverse omics data persist, largely due to their complexity and the need for advanced computational methods. Machine learning is emerging as a valuable tool for analyzing extensive and intricate datasets, potentially revealing new aspects of EoE pathogenesis. The integration of multi-omics data through sophisticated computational approaches promises significant advancements in our understanding of EoE, improving diagnostics, and enhancing treatment effectiveness. This review synthesizes current omics research and explores future directions for comprehensively understanding the disease mechanisms in EoE.

Real-World Effectiveness and Use of Dupilumab in Eosinophilic Esophagitis.

Dupilumab, the first US Food and Drug Administration-approved treatment for eosinophilic esophagitis (EoE), lacks real-world data on use and effectiveness. We conducted a retrospective cohort study of 70 patients with EoE prescribed dupilumab, comparing prescriber type, indication, follow-up, and response. Indications varied with gastroenterologists commonly prescribing for treatment-refractory cases and allergists as first-line therapy. Endoscopic assessment was lacking in 25.9%, but those with follow-up showed high histologic remission (92.3% first-line and 85% previous treatment failure). Dupilumab demonstrates effectiveness across EoE severity, including milder disease without previous treatment failure. Improving follow-up and assessing cost-effectiveness will help clarify its role in the treatment algorithm.

Allergen immunotherapy and eosinophilic esophagitis: friends or foes?

The connection between eosinophilic esophagitis (EoE) and food and airborne allergens is complex. Exposure to allergens (mainly food) is often the trigger for EoE flares. The development of EoE has been described as a side effect of allergen immunotherapy, especially oral immunotherapy (OIT, with food allergens), while isolated cases of EoE have been reported during sublingual immunotherapy (SLIT, with extracts of aeroallergens). EoE is currently recognized as a common side effect of OIT, while a solid correlation between SLIT and EoE is missing. Animal models have been developed to study the pathophysiological link between sensitization to aeroallergens and the induction of EoE and will probably provide an interpretation of why there are cases of EoE developed during SLIT. Recent findings in animal models suggest a genetic connection to EoE development after sensitization and re-exposure to airborne allergens. Subcutaneous allergen immunotherapy does not have a causative effect on EoE; on the contrary, a beneficial effect on EoE has been reported. Moreover, epicutaneous immunotherapy with a vector containing milk has also been used to treat children with milk-induced EoE. Discovering the immune links between allergens and EoE will further guide the proper use of allergen immunotherapy and help define future strategies for the management of EoE.

Utility of Endoscopy in the Control of Specific Immunotherapy With Pollen in Seasonal Eosinophilic Esophagitis

Utility of Endoscopy in the Control of Specific Immunotherapy With Pollen in Seasonal Eosinophilic Esophagitis

Novel Technique to Diagnose Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD), which is commonly encountered in clinical practice, has become increasingly prevalent in Asia in recent years. Definitive diagnosis of GERD requires upper gastrointestinal endoscopy and ambulatory pH monitoring and is therefore challenging. Endoscopic lesions are usually not incorporated into the diagnostic criteria, and pH monitoring is expensive, complicated, and uncomfortable for patients. Studies have investigated novel methods for diagnosis of GERD. Mucosal integrity, evaluated by mucosal admittance or impedance, is impaired in GERD owing to microscopic epithelial changes. Measurement of mucosal integrity is simple and can be performed endoscopically. Mucosal impedance has been investigated as a method to differentiate between GERD, non-GERD, and eosinophilic esophagitis, and mucosal admittance provides evidence to support diagnosis of GERD. Further research on these novel techniques is warranted to incorporate these into the diagnostic modalities used for GERD.

Clinical-pathological correlation of endoscopic findings in eosinophilic esophagitis in the pediatric population.

Eosinophilic esophagitis (EoE) is an immunologic disorder of the esophagus with an increasing incidence in our region of 8.1 cases per 100,000 inhabitants per year. It is characterized by dysphagia, and its diagnosis requires esophagoscopy with biopsies for histopathological analysis, which macroscopically reveals certain characteristic endoscopic findings, though their diagnostic utility remains uncertain. The correlation between these endoscopic findings and the histopathological diagnosis of EoE continues to be a subject of controversy in the pediatric population. This study evaluates the clinical-pathological association of different endoscopic abnormalities in EoE. We conducted an analytical study of patients under 15 years old who underwent esophagoscopy due to highly suspicious symptoms of EoE at a pediatric hospital between 2015 and 2022.

Effectiveness of treatment with budesonide orodispersible tablets in 76 patients with eosinophilic oesophagitis – real-life experience from the population-based DanEoE cohort

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.

Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study.

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.

Successful novel use of dupilumab for gastrointestinal involvement of idiopathic hypereosinophilic syndrome: case report and review of the literature.

Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia leading to organ damage. Gastrointestinal involvement is the third most common manifestation. We present a patient with idiopathic HES with secondary eosinophilic esophagitis (EoE), gastritis, and enteritis, corticosteroids-dependent, azathioprine- and mepolizumab-refractory. The patient achieved clinical and histopathologic remission following dupilumab treatment. A 28year-old female presented with chronic episodic nausea and emesis since childhood and initial diagnosis of primary eosinophilic gastrointestinal disease (EGID), improved with corticosteroids, refractory to azathioprine. She was found to have peripheral eosinophilia and multifactorial anemia, with iron, B12, and folate deficiencies. Esophageal, gastric, duodenal, and terminal ileum biopsies showed significant eosinophilic infiltrate. Bone marrow biopsy at age 31 confirmed HES diagnosis. By age 32, she became total parental nutrition (TPN)-dependent. She failed trials of benralizumab and mepolizumab [anti-interleukin (IL)-5 inhibitors], and cromolyn (mast-cell stabilizer). After developing new esophageal stricture, we initiated dupilumab (IL-4/13 inhibitor), recently FDA-approved for EoE. After 9weeks, esophageal stricture, gut tissue eosinophilia, and prior intestinal ulcerations resolved. She ceased TPN and is tolerating a non-restricted diet, with complete symptom resolution. Our patient's complete remission with dupilumab shows promise for broadening its use in treating GI involvement in HES, along with primary EGIDs.

A cost-of-illness study of eosinophilic esophagitis in Italy: assessing direct and indirect costs

BackgroundEosinophilic esophagitis (EoE) is a chronic and progressive type 2 inflammatory disease affecting the esophagus. Its prevalence has increased in recent years due to increased awareness, evolving clinical guidelines, and heightened sensitivity among healthcare professionals managing the condition. The exact causes behind EoE’s development remain unknown, and its clinical presentation varies, often leading to significant diagnostic delays depending on the age at which symptoms manifest. Consequently, achieving long-term disease control through heightened awareness becomes imperative. EoE generates a significant clinical burden, resulting in substantial economic consequences for patients, healthcare systems, and society. This study aimed to assess the economic and social impacts on EoE patients within the Italian context.MethodsA cost-of-illness analysis was conducted from two perspectives: the National Health System (NHS) and the societal perspective. This analysis encompassed direct healthcare, indirect healthcare, and non-healthcare costs. Data were collected and assessed through a survey administered to a panel of expert clinicians and EoE-affected patients.ResultsManaging EoE incurs a significant burden on healthcare systems, amounting to €6,852.28 per patient per year. The primary cost component appears to be direct costs, comprising 60.73% of the total cost per patient for this condition, while indirect costs contribute to 29.68% of the overall management expenses.ConclusionThis analysis underscores a substantial financial burden on both the healthcare system and patients affected by eosinophilic esophagitis. It emphasizes the imperative need for a continuous and combined effort from clinicians, patients, and families to promptly recognize symptoms and adaptive behavior to mitigate diagnostic delays.

Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids.

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.

Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers.

Eosinophilic Esophagitis (EoE) is a chronic inflammatory condition of the esophagus triggered by food and aeroallergens. There is a need for noninvasive biomarkers that reliably detect EoE in patients with cardinal symptoms and predict treatment response to reduce endoscopic evaluations. Nonasthmatic patients 18 years or above with suspected or diagnosed EoE, gastroesophageal reflux disease (GERD), and control individuals with indication for endoscopy were enrolled prospectively between November 2020 and May 2022. Participants underwent body plethysmography with fractionated exhaled nitric oxide (FeNO) level measurement. Besides, serum and fecal biomarkers were measured by ELISA. A follow-up examination was scheduled after treatment initiation in patients with active EoE. The median FeNO level in active EoE (20 ppb) was higher compared with GERD (15 ppb, P=0.038) and control individuals (14 ppb, P=0.046). Median FeNO did not significantly differ in EoE patients who underwent follow-up assessment after treatment response (20 ppb vs. 18 ppb, P=0.771). Serum EDN, ECP, and the absolute eosinophil blood count (AEC) were elevated in active EoE compared with control individuals but not compared with GERD except for AEC. Serum EDN, ECP and AEC decreased in EoE in remission at follow-up assessment. None of the fecal biomarkers was elevated in active EoE or during treatment. Assessment of FeNO may have diagnostic value in differentiating patients with active EoE from non-EoE patients but is not a suitable marker for monitoring disease activity. Serum EDN, ECP, TARC, and AEC levels are emerging as potential candidates for monitoring disease activity in EoE.

Somatic, emotional, and gastrointestinal symptom severity are increased among children and adolescents with COVID-19.

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.

232. EPIDEMIOLOGY OF EOSINOPHILIC ESOPHAGITIS IN JAPAN: A POPULATION-BASED STUDY

Abstract Backgrounds Eosinophilic esophagitis (EoE) has been increasingly diagnosed in Western countries whilst there have been few general population-based studies in Asia. In addition, risk factors for EoE have not been examined completely. The aim of the study was to investigate the epidemiology and risk factors of EoE in Japanese general population. Methods We analyzed an employer-based health insurance claim database from January 2005 to September 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. We calculated the incidence and prevalence of EoE using Poisson regression and binomial distribution with exact methods respectively. Using 10 times more matched controls for EoE cases, a nested case-control study identified potential risk factors for adult EoE. Results Of 15,200,895 individuals, 1,010 EoE cases were identified. The incidence and prevalence of EoE were 2.82 (95% CI 2.44–3.26) per 100,000 person-years and 10.68 (95% CI 10.01–11.37) per 100,000 people in 2022. Both rates had dramatically increased since 2017. smoking was associated with a 59% risk reduction of EoE whereas constant alcohol consumption was associated with a 63% increase in the risk of EoE. EoE was not associated with either body mass index or health-related diseases such as hypertension, diabetes mellitus, hyperuricemia, and dyslipidemia. Conclusion The incidence and prevalence of EoE in Japan has steadily increased over the past two decades. Nevertheless, EoE remains less common in Japan compared to Western countries. Factors contributing to the epidemiology of EoE on a global basis may improve our understanding of the contribution of genetic and environmental risk factors. In light of potential risk factors, further study is warranted to investigate whether lifestyle intervention can improve the management of EoE.

404. REAL-WORLD TREATMENT PATTERN OF EOSINOPHILIC ESOPHAGITIS IN JAPAN

Abstract Background Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration in the esophageal epithelium that causes esophageal dysfunction-related symptoms. The treatment for EoE includes acid suppressants (proton pump inhibitors (PPIs) or potassium competitive acid blocker (P-CAB)), topical corticosteroid (TCS), and diet therapy. In addition, biologics (i.e. dupilumab) have been recently approved for EoE in the US. However, the appropriate initial and maintenance therapy for EoE have not been established yet. Therefore, the aim of the study was to investigate the treatment pattern of EoE and its association with fibrostenosis in Japan. Methods We investigated prescription pattern for EoE analyzing an employer-based health insurance claim database from 2005 to 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. The initial treatment of interest for EoE included PPIs, P-CAB, and TCS (swallowed inhaled CS). The initial treatment for EoE was defined as these drugs prescribed within two months from the index date of EoE diagnosis. The discontinuation rates of initial PPIs or P-CAB were analyzed using Kaplan-Meier method. The discontinuation of treatment was defined as no treatment following within 90 days from the prescription of the previous treatment. Results Overall, 984 EoE patients (45 years old [38-52], male 747 [75.9%]) were ultimately analyzed. Most of the initial treatment for EoE was acid suppressants (PPIs [323 54.9%], P-CAB [241, 41%]), followed by TCS (13, 2.2%) and combination therapy of PPIs or P-CAB and TCS (11, 1.9%). PPIs or P-CAB discontinued in approximately 50% and 70% of the cases at approximately 150 days and 720 days respectively from the start of the initial therapy. The switching to the second-line therapy from the initial PPIs or P-CAB rarely happened. During the observation period, no EoE patients developed esophageal stenosis. Conclusion PPIs or P-CAB were most prescribed as the initial treatment for EoE in Japan. In addition, more than half of EoE patients discontinued such initial therapy within 2 years without fibrostenotic complication. These findings indicate that EoE that can respond to initial acid suppressants therapy does not necessarily require the maintenance therapy to prevent esophageal fibrostenosis.

Persistent Desmoglein-1 downregulation and Periostin accumulation in histologic remission of Eosinophilic Esophagitis

BackgroundPatients with Eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite histologic remission. ObjectiveTo characterize persisting molecular alterations in pediatric patients with EoE using tissue transcriptomics and proteomics. MethodsEsophageal biopsies (n=247) collected prospectively during 189 endoscopies from pediatric patients with EoE (N=36, up to 11 follow-up endoscopies) and pediatric controls (N=44, single endoscopies) were subjected to bulk transcriptomics (n=96) and proteomics (n=151). Intercellular junctions (Desmoglein-1/-3, Desmoplakin, E-cadherin) and epithelial-to-mesenchymal transition (EMT, Vimentin:E-cadherin ratio) were assessed by immunofluorescence staining. ResultsActive EoE (≥15 eosinophils/hpf), inactive EoE (<15 eosinophils/hpf) and deep remission EoE (0 eosinophils/hpf) were diagnosed in 107/185, 78/185 and 41/185 biopsies, respectively. Among the dysregulated genes (up-/downregulated 310/112) and proteins (up-/downregulated 68/16) between active EoE and controls, 17 genes and 6 proteins remained dysregulated in inactive EoE. Using persistently upregulated genes (n=9) and proteins (n=3) only, such as ALOX15, CXCL1, CXCL6, CTSG, CDH26, PRRX1, CLC, EPX, and POSTN was sufficient to separate inactive EoE, as well as deep remission biopsies from control tissue. While 32 differentially expressed genes persisted in deep remission of EoE compared to controls, the proteome normalized except for persistently upregulated Periostin (POSTN). Epithelial-mesenchymal transition normalized in inactive EoE, whereas desmosome recovery remained impaired due to Desmoglein-1 downregulation. ConclusionThe analysis of molecular changes shows persistent EoE-associated esophageal dysregulation despite histologic remission. These data expand our understanding of inflammatory processes and possible mechanisms that underlie tissue remodeling in EoE.