Eosinophilic Esophagitis Cases Research Articles

Real-world assessment of anaphylaxis and eosinophilic esophagitis with 12 SQ house dust mite SLIT-tablet sublingual immunotherapy

Sublingual immunotherapy (SLIT) with 12 SQ house dust mile SLIT-tablet (HDM SLIT-tablet) for dust mite-induced perennial allergic rhinitis is reported as effective and safe. Although serious allergic reactions (SARs) and eosinophilic esophagitis (EoE) have infrequently occurred under trial conditions, the safety of HDM SLIT-tablet challenge under real-world conditions is unknown. Our aim was to estimate the incidence of SARs and EoE due to HDM SLIT-tablet challenge. Through use of administrative data from Kaiser Permanente Southern California, this prospective observational study identified patients newly administered HDM SLIT-tablet with follow-up until SLIT discontinuation or end of study. Suspected cases of SARs and EoE were detected by using International Classification of Diseases, 10th Revision, diagnosis and Current Procedural Terminology procedure codes and medication dispensing records. A3-member clinical review committee of allergists adjudicated suspected reactions. The incidence rate of confirmed SARs and EoE per 1000 person years of exposure were determined. A total of 521 patients (93.9% adult and 6.1% pediatric) were exposed to HDM SLIT-tablet challenge from January 2018 through May 2023, for 440.4 person years of exposure. The patients' average age (SD) was 39.3 (14.1) years, 58.7% were female, 44.3% were non-Hispanic White, 40.3% had asthma, and 15.0% had gastroesophageal reflux disease. ASAR occurred in 1 adult patient, and during initial HDM SLIT-tablet challenge, SARs occurred in 2 pediatric adolescents, for an overall incidence of 6.8 SARs per 1000 patient years (95% CI= 2.2-21.1). EoE occurred in 1 adult patient, for an overall incidence of 2.3 cases of EoE per 1000 patient years (95% CI= 0.3-16.1). This real-world study demonstrated that SARs and EoE were infrequent events with HDM SLIT-tablet use, supporting the safety of HDM SLIT-tablets and need for physician supervision with initial challenge.

Expression of CD25, mast cell markers and T-cell markers in eosinophilic esophagitis

While eosinophilic esophagitis (EOE) is defined by histologic presence of eosinophils, a few studies have established the presence of mast cells in EOE and even shown their correlation with symptom persistence despite resolution of eosinophils. Expression of aberrant mast cell markers CD25 and CD2 have not been studied in EOE. This study quantifies the number of hotspot cells per high power field expressing CKIT/CD117, tryptase, CD25, CD2 and CD3 by immunohistochemical stains in endoscopic esophageal biopsies of the following three cohorts: (1) established and histologically confirmed EOE, (2) suspected EOE with biopsies negative for eosinophils, and (3) no history of or suspicion for EOE with histologically unremarkable biopsies. In this study, mast cells were highlighted by CKIT and tryptase in EOE, and not seen in other clinically mimicking cases. There were also significantly higher densities of CD25 and pan-T-cell marker staining in EOE cases. These findings suggest an inflammatory cellular milieu in EOE, beyond just eosinophils, that can be demonstrated by immunohistochemistry, and that invite further study into the role that these cells may play in EOE.

Baseline Peripheral Eosinophil Count Independently Predicts Proton Pump Inhibitor Response in Eosinophilic Esophagitis.

To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE). PPI leads to histologic remission in ~50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in ~50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear. This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable). One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037). Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission.

Proton pump inhibitors, antibiotics, and atopy increase the risk of eosinophilic esophagitis in children with esophageal atresia.

To determine whether proton pump inhibitor (PPI)exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA). A retrospective chart review of children with EA from January 1, 2005 to December31, 2020 was undertaken at Sydney Children's Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression. Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR],7.317; 95% confidence interval [CI],2.244-23.742), family history of atopy (aOR,3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR,1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort. Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.

Understanding of Eosinophilic Esophagitis in Children - A Comprehensive Study on Epidemiology, Clinical Manifestations, Diagnosis and Innovative Treatment Modalities

Introduction:&#x0D; In the late 1960s, probable cases of eosinophilic esophagitis (EoE) emerged, initially linked to esophageal rings and congenital causes or gastroesophageal reflux disease (GERD). Doubts about the GERD association arose due to poor responses to antisecretory therapy. EoE is now a significant pediatric health concern, impacting 1 to 7 cases per 10,000 children.&#x0D; Purpose of the Study:&#x0D; This study aims to comprehensively explore EoE's epidemiology, etiology, subtypes, clinical manifestations, diagnostic methods, and treatment modalities.&#x0D; Materials and Methods:&#x0D; The study employs a cross-sectional analysis of pediatric EoE patients, utilizing endoscopic evaluation and histological assessment. Three distinct EoE subtypes are identified based on pathogenic characteristics. Clinical manifestations, diagnostic methods, and treatments, including endoscopy, are examined.&#x0D; Results:&#x0D; Clinical manifestations span a broad spectrum in the pediatric population. Diagnostic methods include endoscopy, esophageal manometry, impedance-pH monitoring, capsule endoscopy, and string tests. Three distinct EoE subtypes are identified with unique characteristics. Treatment modalities involve dietary management, proton pump inhibitors, topical corticosteroids, biologic therapies, allergen immunotherapy, and endoscopic interventions.&#x0D; Conclusion:&#x0D; Formerly associated with GERD, EoE is now a significant pediatric health concern. The study underscores the importance of comprehensive diagnostic approaches and diverse treatment modalities, including promising biologic therapies and allergen immunotherapy. Understanding these aspects is crucial for effective management and improved outcomes in patients.

Vitamin D Levels as a Potential Modifier of Eosinophilic Esophagitis Severity in Adults.

Vitamin D deficiency is associated with atopic and immune-mediated diseases but has not been extensively assessed in eosinophilic esophagitis (EoE). We aimed to assess if vitamin D levels in newly diagnosed EoE patients were lower than in non-EoE controls and examine levels in relation to EoE clinical features. This secondary analysis of a prospective cohort study used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained and stored at -80oC. Serum 25-hydroxy-vitamin D3 (25(OH)D3) was measured by ELISA. Levels for cases and controls were compared at baseline. Within cases, 25(OH)D3 levels were compared for clinical, endoscopic, and histologic measures. We analyzed 40 EoE and 40 non-EoE controls. Mean serum 25(OH)D3 level was slightly lower in EoE patients than controls (30.9 ± 15.3 ng/mL vs. 35.9 ± 15.4; p = 0.15). After controlling for age, sex, and race, adjusted levels were 10.8 ng/mL lower in EoE patients (95% CI: -19.0, -2.5), but 25(OH)D3 deficiency (< 20ng/mL) was similar in cases and controls (20% vs. 15%; p = 0.56). Levels of 25(OH)D3 were not associated with differences in clinical or endoscopic features of EoE, and EREFS and eosinophil counts did not significantly correlate with 25(OH)D3 levels (R of -0.28 [p = 0.08] and - 0.01 [p = 0.93], respectively). 25(OH)D3 levels were lower in EoE cases with lamina propria fibrosis (23.2 ± 9.6 vs. 45.0 ± 17.7; p = 0.03). After adjusting for age, sex, and race, 25(OH)D3 levels were lower in EoE cases than controls, but deficiency was not common. 25(OH)D3 levels were generally similar across most EoE disease features.

Peripheral Blood IL5RA Gene Expression as a Diagnostic Biomarker for Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus, often diagnosed late because of its challenging symptoms and costly and invasive diagnostic methods.1,2 To address the need for more accessible biomarkers in EoE,3 we aimed to investigate the potential of whole-blood RNA expression as a noninvasive biomarker for diagnosing and monitoring EoE, hypothesizing that genetic signatures in blood could distinguish EoE cases, correlate with disease activity, and predict treatment responses.

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE), a chronic disease with significant patient and health care burden, has increased rapidly in incidence across many countries. Elucidating risk factors for disease development is a priority for health care practitioners and patients. To evaluate the association of maternal and infant use of antibiotics and acid suppressants with the development of EoE. This was a population-based, case-control study of pediatric EoE (1996-2019) in Denmark using pathology, prescription, birth, inpatient, and outpatient health registry data and with complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. Study data were analyzed from September 2020 to August 2023. Maternal and infant use of antibiotics and acid suppressants, examining medication class, timing, and frequency of use. Development of EoE. Included in the study was a total of 392 cases and 3637 sex- and year of birth-matched controls with a median (IQR) age of 11.0 (6.0-15.0) years, 2772 male individuals (68.8%), and 1257 female individuals (31.2%). Compared with children with no antibiotic prescriptions filled during infancy, those with any use of an antibiotic had an associated 40% increase in risk of EoE (adjusted odds ratio [aOR], 1.4; 95% CI, 1.1-1.7). Those with 3 or more prescriptions had an associated 80% increase in risk of EoE (aOR, 1.8; 95% CI, 1.3-2.5). Frequency of maternal antibiotic use was associated with an increased risk (1 prescription: aOR, 1.4; 95% CI, 1.0-1.8; 3≤ prescriptions: aOR, 2.1; 95% CI, 1.4-3.2). Risk was highest for use in the third trimester and in the first 6 months from birth. Any acid suppressant use in infancy was associated with increased risk of EoE (aOR, 15.9; 95% CI, 9.1-27.7). Restriction of cases to those diagnosed at 5 years or older yielded similar results (aOR, 11.6; 95% CI, 5.5-24.8). For maternal use, 3 or more prescriptions were associated with an increased risk of EoE for her offspring (aOR, 5.1; 95% CI, 1.8-14.8). Maternal and infant antibiotic use were associated with increased risk of developing EoE, in a dose-response manner, and the magnitude of association was highest for exposure near the time of delivery. Increased risk was also observed with maternal and infant acid suppressant use. Exposure during early life, a period of known developmental susceptibility, may confer the greatest risk and opportunity for risk mitigation.

A Case of Eosinophilic Esophagitis Presented with Hematemesis

A Case of Eosinophilic Esophagitis Presented with Hematemesis

Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients.

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 segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features.

Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders

Achalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiologic support for this hypothesis, we identified patients with achalasia in the Utah Population Database, and explored their frequency of having EoE and other allergic disorders. We used International Classification of Diseases codes to identify patients with achalasia and allergic disorders including EoE, asthma, atopic dermatitis, contact dermatitis, allergic rhinitis, allergic conjunctivitis, hives/urticaria, and anaphylaxis. We calculated relative risk (RR) for each allergic disorder by comparing the number observed in patients with achalasia with the expected number in individuals matched for birthyear and sex, and we performed subanalyses for patients age ≤40 versus age >40 years. Among 844 patients with achalasia identified (55% female; median age at diagnosis, 58 years), 402 (47.6%) had ≥1 allergic disorder. Fifty-five patients with achalasia (6.5%) had EoE (1.67 EoE cases expected), for a RR of 32.9 (95% confidence interval, 24.8-42.8; P < .001). In 208 patients with achalasia age ≤40 years, the RR for EoE was 69.6 (95% confidence interval, 46.6-100.0; P < .001). RR also was increased significantly for all other allergic disorders evaluated (all greater than 3-fold higher than population rates). Achalasia is strongly associated with EoE and other allergic disorders. These data support the hypothesis that achalasia sometimes might have an allergic etiology.

Prevalence of elderly eosinophilic esophagitis and their clinical characteristics

Background and Aims Eosinophilic esophagitis (EoE) is predominantly found in middle-aged men among adults. There are few reports about EoE in the elderly, despite an ageing population. The study aimed to define the prevalence and clinical characteristics of EoE amongst older adults. Methods Elderly patients (defined as those ≥65 years) were compared to younger adults (18–64) in terms of clinical characteristics (age, gender, presenting symptoms, comorbidities), histological activity (eosinophil count), treatment modality and response to treatment. A pre- existing prospectively generated database of all EoE patients presenting to our department between February 2010 and December 2022 was interrogated. 309 patients who underwent endoscopy and esophageal biopsy and were found to have ≥15 eosinophils/HPF were defined as having EoE and were included for study. Statistical analyses were performed using Fisher’s extract test or Mann–Whitney U test. Results 309 cases of EoE were recorded, mean age 45.7, range (21–88 years), of which20 patients were aged 65 years and over. Compared to younger patients, those aged ≥65 had more medical comorbidities (15 [75%] vs 111[38%], p = 0.002), and instead a non-significant trend toward less fibrosis (0.25 vs 0.46, p = 0.117). Although rate of cases required topical steroid (TCS) therapy was similar, none received repeated or maintenance TCS therapy in elderly. Conclusion In our cohort, only 20 patients (6%) were aged 65 years or older, suggesting that EoE is uncommon in the elderly. The clinical characteristics of EoE in the older age group were similar to the younger patients. Future studies with prospective data collection may determine if EoE disappears with age, or if the younger mean age is reflective of an increasing prevalence in recent years, that may be realized in the elderly EoE population in the future.

Impact of environmental factors on the epidemiology of eosinophilic esophagitis in southwestern Europe (2007-2020).

Eosinophilic esophagitis (EoE) is a disease characterized by symptoms of esophageal dysfunction and at least 15 eosinophils/hpf in the esophagus. Other systemic and local causes of esophageal eosinophilia should be excluded. The study objectives were to examine the annual epidemiology of EoE for 14 consecutive years, investigate whether there is a relationship between the count of aeroallergens and the incidence of EoE for 12 years, evaluate whether there are family ties between the patients with EoE, and determine whether there are cases of EoE that are triggered or exacerbated by pollens. We conducted a prospective, descriptive, and analytic study in patients with EoE for 14 years (2007-2020). The study variables were age, sex, relatives with EoE, time of evolution of the symptoms until diagnosis of the disease, and symptoms. We examined incidence and prevalence, annual counts of aeroallergens for 12 years, and number of diagnoses per year (in 2007-2020). We studied patients with active EoE (in April-July) and EoE in remission (in August-March) for 2 consecutive years. Exacerbations were investigated by measuring symptoms using a visual analog scale of 1 to 10. Of the 366 patients with EoE (studied from 2007 to 2020), 83.5% were atopic, with respiratory allergy and 28% had a food allergy. Their mean age was 35 years. The time of evolution of the symptoms was more than 6 years. Only 11% of the patients had a degree of kinship. Of the 366 patients, 87% had dysphagia, 27% had had impactions, and 12.5% had other symptoms of esophageal dysfunction. We found a positive correlation between the incidence of EoE and Platanaceae pollens. We did not detect any case of EoE triggered or exacerbated by pollens. The epidemiology of EoE in southwestern Europe continues to grow. We have corroborated the relevant impact of the environment on genetics. Future studies will clarify the possible relevance of Platanaceae pollens in the increased epidemiology of EoE. The role of grass and Oleaceae pollens in triggering EoE is limited by having a short pollination in time.

Prenatal, Intrapartum, and Neonatal Factors Increase the Risk of Eosinophilic Esophagitis.

Early-life exposures have been associated with an increased risk of eosinophilic esophagitis (EoE); however, most studies to date have been conducted at referral centers and are subject to recall bias. By contrast, we conducted a nationwide, population-based and registry-based case-control study of prenatal, intrapartum, and neonatal exposures, using data collected prospectively through population-based Danish health and administrative registries. We ascertained all EoE cases in Denmark (birth years 1997-2018). Cases were sex and age matched to controls (1:10) using risk-set sampling. We obtained data on prenatal, intrapartum, and neonatal factors, i.e., pregnancy complications, mode of delivery, gestational age at delivery, birthweight (expressed as a z-score), and neonatal intensive care unit (NICU) admission. We used conditional logistic regression to compute the crude and adjusted odds ratios (aOR) of EoE in relation to each prenatal, intrapartum, and neonatal factor, thus providing an estimate of incidence density ratios with 95% confidence intervals (CI). In the 393 cases and 3,659 population controls included (median age at index date, 11 years [interquartile range, 6-15]; 69% male), we observed an association between gestational age and EoE, peaking at 33 vs 40 weeks (aOR 3.6 [95% CI 1.8-7.4]), and between NICU admission and EoE (aOR 2.8 [95% CI 1.2-6.6], for a NICU hospitalization of 2-3 weeks vs no admission). In interaction analyses, we observed a stronger association between NICU admission and EoE in infants born at term than in preterm infants (aOR 2.0 [95% CI 1.4-2.9] for term infants and aOR 1.0 [95% CI 0.5-2.0] for preterm infants). We also observed an association between pregnancy complications and EoE (aOR 1.4 [95% CI 1.0-1.9]). Infants who were very growth restricted at birth had an increased rate of EoE (aOR 1.4 [95% CI: 1.0-1.9] for a z-score of -1.5 vs a z-score of 0). Mode of delivery was not associated with EoE. Prenatal, intrapartum, and neonatal factors, particularly preterm birth and NICU admission, were associated with development of EoE. Further research is needed to elucidate the mechanisms underlying the observed associations.

Eosinophilic esophagitis in children: Experience in diagnosis, clinical observation in a multidisciplinary hospital

This study presented the characteristics of seven patients with eosinophilic esophagitis from age 1 year and 2 months to age 17 years and 4 months. The follow-up duration ranged from 1 to 7.5 years.&#x0D; Disease onset was observed at different ages: aged 2 years (n=6) and 2 months (n=1). The period between the occurrences of the first symptom to diagnosis ranged from 3 months to 9 years. In one patient, the symptoms were associated with cows milk allergy, whereas the cause was not identified in other cases. Allergic diseases (i.e., atopic dermatitis, allergic rhinitis, and asthma) were observed in six patients.&#x0D; Treatment was provided according to the clinical guidelines. Six patients were prescribed topical steroids (budesonide) and an empirical elimination diet. One patient was prescribed only with an empirical elimination diet due to the steroid phobia of the parents. However, the ineffectiveness of the diet was the basis for topical steroid prescription. During the follow-up, a relapse was observed in two patients who required repeated treatments.&#x0D; A clinical case of eosinophilic esophagitis in a 6-year-old child, with 7.5 years of follow-up, was described. According to the anamnesis, the patient visited a gastroenterologist 4 years after the onset of dysphagia symptoms. Endoscopy revealed cicatricial stenosis of the upper third of the esophagus (grades 23). A morphological study of the esophageal mucosa, which was performed after repeated endoscopic bougienage and a 5-month course of antisecretory therapy was deemed ineffective, revealed massive eosinophilic infiltration. Eosinophilic esophagitis was confirmed based on the anamnesis, clinical symptoms, and endoscopic and morphological data. An elimination diet and topical corticosteroids (budesonide) were prescribed. Following the treatment, the patient showed significant improvements. Subsequently, during the follow-up, a relapse of eosinophilic esophagitis was diagnosed twice (with an interval of 2.3 and 2.5 years), which required topical steroids (case 1) and proton pump inhibitors (case 2).&#x0D; This paper highlights the importance of a multidisciplinary approach, involving an allergist-immunologist, pediatrician, gastroenterologist, endoscopist, and pathologist, in the management of eosinophilic esophagitis in children.

Does eosinophilic esophagitis exist in India?

Eosinophilic esophagitis (EoE) has evolved over the last three decades with a better understanding of the natural course of the disease. The prevalence of EoE is higher in Western countries with increasing reports of the incidence of EoE in the east. There is less data on EoE in India. We have noticed an increase in the number of cases of EoE diagnosed in our center over the last few years. In this study, all patients with high clinical suspicion of EoE were included and prospectively evaluated with endoscopic features and esophageal biopsies. Seventeen of 73 patients were diagnosed with EoE based on clinical, endoscopic and histopathologic features. One patient was lost to follow-up and 16 of the 17 patients were initiated on standard-of-care treatment and followed up for a minimum of fourweeks. Treatment with proton pump inhibitors with six-food elimination diet is highly effective in most patients with afew patients requiring systemic steroids and endoscopic treatment. In conclusion, this study highlights that EoE exists in India with varied manifestations and a high index of clinical suspicion is necessary for diagnosis. It also emphasizes the need for increasing awareness of the entity of EoE, among both patients and doctors. Further, large-scale, multi-centric population-based studies are necessary to estimate the prevalence in our country.

A150 MODERATE AGREEMENT IN ENDOSCOPIC DISEASE SCORING OF PEDIATRIC EOSINOPHILIC ESOPHAGITIS AMONG PEDIATRIC GASTROENTEROLOGISTS IN CANADA

Abstract Background Endoscopy is an important tool in assessing the severity of gastrointestinal diseases including Eosinophilic Esophagitis (EoE). Agreement regarding endoscopy outcomes is important when using tools such as the Endoscopic Reference Score for EoE (EREFS). Purpose Our goal was to determine interrater and intrarater agreement of EREFS among Canadian pediatric gastroenterologists. Method Survey-based study of interrater and intrarater reliability amongst pediatric gastroenterologists with interest in pediatric EoE. Participants were sourced from the Canadian Pediatric EoE Network. Participants were asked how many years of training they’ve had with endoscopy for pediatric EoE and their comfort in disease scoring for pediatric EoE. Pediatric EoE cases were identified from the pediatric EoE registry at the Stollery Children’s Hospital with an endoscopic video associated with each case. Participants were asked to score each video using the EREFS questionnaire for the proximal, middle and distal segments of the esophagus. 15 endoscopic videos were evaluated, with 3 cases provided each week over a period of 5 weeks. Additional data included ratings of the video quality and endoscopy quality. Of 15 cases, 12 were unique cases, distributed evenly in severity between no active disease to severe disease. 3 cases were repeated to assess intrarater reliability. The maximum grade of the proximal, middle and distal segments of the esophagus for each component endoscopic finding (edema, rings, exudates, furrows, strictures) were used for reliability calculations. Fleiss Kappa was calculated for all EREFS items and for each component endoscopic finding. Cohen’s Kappa was calculated to assess intrarater reliability. Result(s) Fifteen participants were recruited for the study. The participants had a median of 12 years (IQR: 7, 19) of clinical experience in endoscopy for pediatric EoE. The majority of participants were “comfortable” (i.e., 4 on 5-point scale) with EREFS scoring for pediatric EoE. Fleiss Kappa for all EREFS items was 0.481. For each component endoscopic finding (edema, rings, exudates, furrows, strictures), Fleiss Kappa was 0.365, 0.293, 0.548, 0.263, 0.445 respectively. Cohen’s Kappa had a median of 0.620 (IQR: 0.593, 0.704). The majority of raters rated video quality and endoscopy quality as “good” (i.e., 4 on 5-point scale). Conclusion(s) There is moderate interrater reliability in EREFS scoring for pediatric EoE. Interrater reliability was between fair to moderate for each component endoscopic finding. Intrarater reliability was good. This study shows there is room for improvement in disease scoring for pediatric EoE. This could be in the form of additional training, expert-defined conventions, or centralized reading which have reduced variability in endoscopic reporting for adult GI disease in past studies and could be used in a follow-up study to attempt to improve agreement. Additionally, incorporating EREFS into routine clinical practice may increase agreement amongst endoscopists. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Genome-wide admixture and association analysis identifies African ancestry–specific risk loci of eosinophilic esophagitis in African Americans

Eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease, is linked to multiple genetic risk factors, but studies have focused on populations of European ancestry. Few studies have assessed Black or African American (AA) populations for loci involved in EoE susceptibility. We performed admixture mapping (AM) and genome-wide association study (GWAS) of EoE using participants from AA populations. We conducted AM and GWAS of EoE using 137 EoE cases and 1465 healthy controls from the AA population. Samples were genotyped using molecular evolutionary genetics analysis (MEGA). Genotype imputation was carried out with the Consortium on Asthma Among African-Ancestry Populations in the Americas (CAAPA) reference panel using the Michigan Imputation Server. Global and local ancestry inference was carried out, followed by fine mapping and RNA sequencing. After quality control filtering, over 6,000,000 variants were tested by logistic regression adjusted for sex, age, and global ancestry. The global African ancestry proportion was found to be significantly lower among cases than controls (0.751 vs 0.786, P= .012). Case-only AM identified 3 significant loci (9p13.3, 12q24.22-23, and 15q11.2) associated with EoE, of which 12q24.22-23 and 9p13.3 were further replicated in the case-control analysis, with associations observed with African ancestry. Fine mapping and multiomic functional annotations prioritized the variants rs11068264 (FBXW8) and rs7307331 (VSIG10) at 12q24.23 and rs2297879 (ARHGEF39) at 9p13.3. GWAS identified 1 genome-wide significant locus at chromosome 1p22.3 (rs17131726, DDAH1) and 10 other suggestive loci. Most GWAS variants were low-frequency African ancestry-specific variants. RNA sequencing revealed that esophageal DDAH1 and VSIG10 were downregulated and ARHGEF39 upregulated among EoE cases. GWAS and AM for EoE in AA revealed that African ancestry-specific genetic susceptibility loci exist at 1p22.3, 9p13.3, and 12q24.23, providing evidence of ancestry-specific inheritance of EoE. More independent genetic studies of different ancestries for EoE are needed.

PREVALENCE OF ALLERGIES ON PEDIATRIC PATIENTS WITH ATOPIC DERMATITIS AND EOSINOPHILIC ESOPHAGITIS

<h3>Introduction</h3> One of the most common allergic diseases in the population is atopic dermatitis (AD), which is sometimes associated with cases of Eosinophilic Esophagitis (EoE). Both, EoE and AD are often associated with other forms of allergy spectrum diseases such as asthma, rhinitis, conjunctivitis, sensitization to foods or pollens, and others. The purpose of this study is to identify and compare the prevalence of the most common allergies and comorbidities in pediatric patients with AD and EoE in the southern region of Puerto Rico. <h3>Methods</h3> A cross-sectional record review of 138 patients from ages 1-18 years old at an allergist/immunologist outpatient clinic in Ponce, Puerto Rico, with epicutaneous and RAST IgE-specific test from December 2016 to 2021. <h3>Results</h3> In dietary allergies nuts, peanuts, soya beans and walnuts had statistical significance with prevalence in patients with EoE compared to AD. The most prevalent in patients with AD were eggs (36.0%), milk (32.8%), wheat (16.8%), and peanuts (11.2%). In the case of EoE, the most frequent food allergies were peanuts (36.4%) and soya bean (27.3%); eggs, almonds, nuts, and wheat had the same percentages of patients (18.2%). <h3>Conclusion</h3> When our data was analyzed and compared to that of the United States, atopic dermatitis showed the same trend as reported across the states. In contrast, the prevalence of sensitivities to the most common allergens was reported differently in our studies in patients with EoE. More patients may be evaluated to reassess dietary restrictions for patients with EoE in Puerto Rico.

Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.