Risk Of Eosinophilic Esophagitis Research Articles

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.

Perinatal Environmental Risks for Eosinophilic Esophagitis: A Systemic Review and Meta-Analysis.

There are limited data on the association of eosinophilic esophagitis (EoE) and environmental risk factors. The aim of this study was to determine the potential associations between perinatal risk factors and EoE. A search was conducted for relevant studies published up to December 12th, 2023, using MEDLINE, EMBASE, Scopus, Web of Sciences, and Cochrane databases. Risk ratioswith the 95% confidence interval (CI) were estimated using a random-effects model. Case-control or cohort studies that determined perinatal environmental factors within the first year of life and their association with EoE were included. Six case-control studies were included in the analysis. Six studies (2,087 EoE and 6,786 controls) were included for risk of infant antibiotic use with a pooled risk ratio of 1.30 (95%CI: 1.11-1.52,I2 = 76%), and five studies were included for cesarean section with a pooled risk ratio of 1.22 (95%CI: 1.10-1.34, I2 = 5%). There were three studies for breastfeeding with a pooled risk ratio of 1.07 (95%CI:1.00-1.15, I2 = 0%); five studies were included for preterm birth with a pooled risk ratio of 1.52 (95%CI: 1.14-2.04, I2 = 48%). There were three studies for neonatal intensive care unit admission with a pooled risk ratio of 1.75 (95% CI: 1.41-2.18, I2 = 0%). Publication bias was found between EoE and infant antibiotic use and cesarean section, but not for EoE and preterm birth, neonatal care unit admission, or breastfeeding. This meta-analysis suggests a weak association between antibiotic use during the first year of life, cesarean section, preterm birth, and neonatal intensive care unit admission and a possible risk of EoE. Further studies are warranted to confirm these findings as they may be indirect associations rather than causal.

A clinical predictive model identifies pediatric patients at risk for eosinophilic esophagitis

BackgroundIdentifying children needing endoscopic evaluation for suspected eosinophilic esophagitis (EoE) is crucial for prompt diagnosis and management. AimsWe aimed to develop a clinical prediction tool to distinguish children with EoE from children without the disease before endoscopy. MethodsWe conducted a retrospective case-control study of children undergoing upper endoscopy at a tertiary care center. Clinical characteristics before endoscopy were extracted from 380 EoE cases and 380 controls without EoE. We built a predictive model for case-control status and performed age-stratified analyses. ResultsAfter multivariable analysis, history of adaptive eating behaviors, food allergy, food impaction, male sex, and regurgitation were independently associated with EoE, and abdominal pain and failure to thrive with control status (AUC 0.81). Food allergy and male sex were predictors of EoE across all ages. Regurgitation and adaptive eating behaviors were specific to EoE in early (0–5 years) (AUC 0.74) and middle childhood (6–11 years) (AUC 0.82), while dysphagia and food impaction were specific to EoE in the adolescence (12–17 years) (AUC 0.87). ConclusionWe determined age-specific clinical features that predict EoE with good discrimination in a pediatric population before endoscopy. Validation of this model in an independent population can confirm the utility of this tool.

Causality of Helicobacter pylori infection on eosinophilic esophagitis and potential pathogenesis: a Mendelian randomization study.

Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE. Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.

An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission.

Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand-receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.

Association of celiac disease with eosinophilic esophagitis: Nationwide register-based cohort study with sibling analyses

Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE). We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings. Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n= 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding. The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51). In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.

A Comprehensive Global Population-Based Analysis on the Coexistence of Eosinophilic Esophagitis and Inflammatory Bowel Disease.

We explored inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) coexistence using a global dataset. Investigating their epidemiology, risks, and impact, we aimed to enhance the understanding of concurrent diagnoses and patient outcomes. A retrospective population-based cohort study was conducted using deidentified patient data from the TriNetX database (2011-2022). We estimated the incidence and prevalence of EoE in patients with IBD, including both Crohn's disease (CD) and ulcerative colitis (UC), and vice versa. Risks of select immune-mediated conditions and disease complications were compared among patients with EoE, IBD, or concurrent diagnoses. Our results included 174,755 patients with CD; 150,774 patients with UC; and 44,714 patients with EoE. The risk of EoE was significantly higher among patients with CD (prevalence ratio [PR] 11.2) or UC (PR 8.7) compared with individuals without IBD. The risk of IBD was higher in patients with EoE (CD: PR 11.6; UC: PR 9.1) versus those without EoE. A propensity-matched analysis of IBD patients revealed that, when comparing patients with and without EoE, the relative risk of immune-mediated comorbidities was significantly greater for celiac disease, IBD-related inflammatory conditions, eczema and asthma (CD: n = 1896; UC: n = 1231; p < 0.001). Patients with a concurrent diagnosis of EoE and IBD had a higher composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.14, p < 0.005; UC: aHR 1.17, p < 0.01) and lower risk of food bolus impaction (aHR 0.445, p = 0.0011). Simultaneous EoE and IBD increased IBD-related complications risk, needing more treatment (glucocorticoids, biologic therapy, abdominal surgery), while reducing EoE-related issues like food bolus impaction.

Systematic identification of genotype-dependent enhancer variants in eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p<5×10-8) and 27 additional loci of suggestive significance (5×10-8<p<1×10-5). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal. To systematically interrogate the gene regulatory activity of these variants, we designed a massively parallel reporter assay (MPRA) containing the alleles of each variant within their genomic sequence context cloned into a GFP reporter library. Analysis of reporter gene expression in TE-7, HaCaT, and Jurkat cells revealed cell-type-specific gene regulation. We identify 32 allelic enhancer variants, representing 6 genome-wide significant EoE loci and 7 suggestive EoE loci, that regulate reporter gene expression in a genotype-dependent manner in at least one cellular context. By annotating these variants with expression quantitative trait loci (eQTL) and chromatin looping data in related tissues and cell types, we identify putative target genes affected by genetic variation in individuals with EoE. Transcription factor enrichment analyses reveal possible roles for cell-type-specific regulators, including GATA3. Our approach reduces the large set of EoE-associated variants to a set of 32 with allelic regulatory activity, providing functional insights into the effects of genetic variation in this disease.

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.

Prior hospital-based infection and risk of eosinophilic esophagitis in a Swedish nationwide case-control study.

Eosinophilic esophagitis (EoE) is an increasingly common, largely food allergen-driven disease characterized by dysphagia. Prior infections are known to associate with other loss of tolerance diseases such as autoimmunity. We aimed to determine if antecedent infection was associated with later EoE development. We performed a case-control study of all patients with biopsy-verified EoE diagnosed between 2000 and 2017 in Sweden (n=1587) and matched to 5 general population controls (n=7660). Cases were identified using histopathology codes from the Epidemiology Strengthened by histopathology Reports in Sweden study, a validated cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals for antecedent infections from patients seen at hospital-based outpatient clinics or inpatients. In secondary analyses, we compared EoE patients with their full siblings to further reduce residual confounding. 564 (35.7%) EoE patients and 1793 (23.4%) matched controls had an earlier record of infection. This corresponded to a 2-fold increased risk of infections in EoE patients (OR 2.01; 95%CI: 1.78-2.27). ORs for earlier gastrointestinal or respiratory infection were 2.73 (n=128 EoE, 268 control; 95%CI: 2.17-3.41) and 1.89 (n=305 EoE, 960 control; 95%CI: 1.63-2.20), respectively. Having an EoE diagnosis was linked to a 3.39-fold increased odds of sepsis (n=14 EoE, 21 control; 95%CI: 1.68-6.65). Individuals with EoE were also more likely to have had an infection compared to their non-EoE siblings (n=427 EoE, 593 control; OR=1.57; 95%CI=1.30-1.89). In this nationwide cohort study, prior infection, was associated with subsequent EoE. Risks were particularly high after sepsis, and gastrointestinal or respiratory infections.

Oral Immunotherapy and Risk of Eosinophilic Esophagitis in Children: 15 Years' Experience.

Oral immunotherapy (OIT) is an effective treatment for children with persistent food allergy, and has concerns about its safety, including eosinophilic esophagitis (EoE). The aim of this study was to evaluate the prevalence of EoE in a large cohort of children who underwent OIT in our center, and to determine if there were any clinical, endoscopic, or histologic differences depending on the food employed for the OIT. A retrospective study was performed over a 15-year period (2005-2020). Children who underwent cow's milk (CM), egg, and/or peanut OIT and developed EoE were included. Six hundred and seven OIT were carried out (277 CM-OIT, 322 egg-OIT, and 8 peanut-OIT). Seventeen patients (2.8%) had a confirmed histologic diagnosis of EoE with a higher prevalence for patients who underwent CM-OIT (3.9%) than egg-OIT (2.2%). Symptoms suggestive of EoE and a confirmed diagnosis occurred at median times of 25 and 36 months, respectively, after the build-up phase of the OIT was completed. Choking, abdominal pain, and dysphagia were the most frequent symptoms and lamina propria fibrosis was observed in 41.2% of patients. No significant differences in clinical symptoms, endoscopic, or histologic findings between patients under CM or egg-OIT were found. One-third of patients reported mild symptoms suggestive of EoE before the OIT. EoE appears to be a rare but important adverse event that can occur even years after OIT. Validated questionnaires to screen EoE before the OIT and in the follow-up of these patients may be the main tool for an early diagnosis.

283. DOES PROTON PUMP INHIBITOR EXPOSURE INCREASE THE RISK OF DEVELOPING EOSINOPHILIC ESOPHAGITIS IN CHILDREN WITH ESOPHAGEAL ATRESIA?

Abstract Children with esophageal atresia (EA) receive proton pump inhibitors (PPIs) long-term due to gastroesophageal reflux disease susceptibility. They have also demonstrated greater susceptibility to eosinophilic esophagitis (EoE) compared to the general pediatric population. No studies have investigated EoE risk factors in EA. This study aimed to determine whether PPI exposure and early-life factors are associated with an increased risk for subsequent EoE development in children with EA. A retrospective chart review was undertaken at a paediatric hospital in Sydney, Australia. The study cohort consisted of children with EA who had their repair and/or follow-up at this hospital between 1 January 2005 and 31 December 2020. Children with EA and EoE (cases) were matched (1:2) with those with only EA (controls), for sex, prematurity and presence of long-gap, to compare PPI exposure. Other early-life factors were analysed without matching, using simple and multivariable logistic regression. Of the 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EA and EoE received PPI for significantly higher durations (p = 0.018) and at significantly higher cumulative doses (p = 0.017) than children with EA but no EoE. Food allergy (adjusted odds ratio [aOR], 10.515; 95% confidence interval [CI], 2.659–41.581), family history of atopy (aOR, 5.312; 95% CI, 1.575–17.911) and infantile antibiotic exposure (aOR, 1.048; 95% CI, 1.011–1.086) were also significantly associated with an increased risk of developing EoE in the EA cohort. Longer durations of PPI exposure and exposure to higher cumulative doses of PPI were both associated with the subsequent development of EoE in children with EA. Other early life factors such as atopic family history, food allergy and infantile antibiotic exposure were also significantly associated with an increased risk of developing EoE in children with EA.

A genome-wide association meta-analysis identifies new eosinophilic esophagitis loci

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus marked by eosinophilic infiltration. Cumulative evidence indicates that the risk of EoE involves the complex interplay of both genetic and environmental factors. Because only a few genetic loci have been identified in EoE, the genetic underpinning of EoE remains largely elusive. We sought to identify genetic loci associated with EoE. Four EoE cohorts were genotyped using the Illumina single nucleotide polymorphism array platform, totaling 1,930 cases and 13,634 controls of European ancestry. Genotype imputation was performed with the Michigan Imputation Server using the Trans-Omics for Precision Medicine reference panel including whole-genome sequencing data from more than 100,000 individuals. Meta-analysis was conducted to identify potential novel genetic loci associated with EoE. Our study identified 11 new genome-wide significant loci, of which 6 are common variant loci, including 5q31.1 (rs2106984, P= 4.16×10-8; odds ratio [OR], 1.26, RAD50), 15q22.2 (rs2279293, P= 1.23×10-10; OR, 0.69, RORA), and 15q23 (rs56062135, P= 2.91×10-11; OR, 1.29, SMAD3), which have been previously associated with allergic conditions. Interestingly, a low-frequency synonymous mutation within the MATN2 gene was identified as the most significant single nucleotide polymorphism at the 8q22.1 locus. We also identified 5 sex-specific loci in the EoE cases, including an inflammatorybowel disease-associated locus at 9p24.1 (rs62541556, P= 4.4×10-8; OR, 1.11, JAK2). Our findings demonstrate shared genetic underpinnings between EoE and other immune-mediated diseases and provide novel candidate genes for therapeutic target identification and prioritization.

Increased risk of eosinophilic esophagitis with poor environmental quality as measured by the Environmental Quality Index.

Geographic differences in eosinophilic esophagitis (EoE) prevalence suggest the possibility that environmental exposures contribute to EoE pathogenesis. We aimed to examine the association between environmental quality and risk of EoE, using the Environmental Quality Index (EQI), which provides quantification of environmental quality in five domains: air, land, water, built, and sociodemographic for all counties in the United States. To do this, we performed a case-control study in a large pathology database. EoE cases were defined by ≥15 eosinophils per high-power field with other pathologic diagnoses excluded; controls did not have EoE. The pathology data were geocoded and linked with the EQI by county of residence. Logistic regression was used to estimate odds ratio (OR and 95% confidence interval [CI]) of EoE with overall EQI and for each domain, after adjusting for sex, age, and proportion minority race or ethnicity at the county level (higher EQI score indicates worse environmental quality). Of 29,802 EoE cases and 593,329 controls analyzed, odds of EoE were highest in the worst quintile of EQI (OR 1.25; 95% CI: 1.04-1.50), which was largely explained by poor scores in the water domain (OR: 1.33; 1.17-1.50). Conversely, odds of EoE were reduced with higher scores in the air domain (OR: 0.87, 0.74-1.03) and land domain (OR 0.87; 0.76-0.99). Poor EQI, mostly reflected by poor water quality, was associated with increased odds of EoE, while poor air and land quality were inversely associated with EoE. Additional work to identify specific water pollutants that may have an etiologic role in EoE may be warranted.

Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes

Eosinophilic esophagitis (EoE) is an emerging, chronic, rare allergic disease associated with marked eosinophil accumulation in the esophagus. Previous genome-wide association studies have provided strong evidence for 3 genome-wide susceptibility loci. We sought to replicate known and suggestive EoE genetic risk loci and conduct a meta-analysis of previously reported data sets. An EoE-Custom single-nucleotide polymophism (SNP) Chip containing 956 candidate EoE risk single-nucleotide polymorphisms was used to genotype 627 cases and 365 controls. Statistical power was enhanced by adding 1959 external controls and performing meta-analyses with 2 independent EoE genome-wide association studies. Meta-analysis identified replicated association and genome-wide significance at 6 loci: 2p23 (2 independent genetic effects) and 5q22, 10p14, 11q13, and 16p13. Seven additional loci were identified at suggestive significance (P< 10-6): 1q31, 5q23, 6q15, 6q21, 8p21, 17q12, and 22q13. From these risk loci, 13 protein-coding EoE candidate risk genes were expressed in a genotype-dependent manner. EoE risk genes were expressed in disease-relevant cell types, including esophageal epithelia, fibroblasts, and immune cells, with some expressed as a function of disease activity. The genetic risk burden of EoE-associated genetic variants was markedly larger in cases relative to controls (P< 10-38); individuals with the highest decile of genetic burden had greater than 12-fold risk of EoE compared with those within the lowest decile. This study extends the genetic underpinnings of EoE, highlighting 13 genes whose genotype-dependent expression expands our etiologic understanding of EoE and provides a framework for a polygenic risk score to be validated in future studies.

S0710 Epidemiology of Eosinophilic Esophagitis in Inflammatory Bowel Disease and General Population: A Population-Based Study

INTRODUCTION: Some chronic immune-mediated diseases like Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have similar pathogenesis. Recent studies have shown that both the prevalence and incidence of EoE and IBD are rising in developed countries. However, only few case reports on concurrent EoE and IBD were published and only limited data is available describing the epidemiology. Our objective was to evaluate the prevalence and associated comorbidities of concurrent EoE and IBD. METHODS: We performed a population-based study using IBM EXPLORYS, a HIPPA-enabled web platform that includes over 65 million patient data, pooled from multiple healthcare systems with distinct electronic health records. The prevalence of EoE in patients with IBD and in general population without IBD was compared. The IBD patient group was further stratified into Crohn's disease and Ulcerative colitis groups. Prevalence was calculated per 100,000 patients. Patient characteristics like age, gender and co-morbid immune-mediated disorders like celiac disease, asthma, and eczema were compared between patients with and without EoE in Crohn's disease, UC and the general population. Data were analyzed with R statistical software (RStudio, Inc. Boston, MA). RESULTS: A total of 197,050 patients with IBD and 64,095,520 without IBD were identified. Among the 197,050 cohorts with IBD, 100,780 (51%) had CD and 96,270 (49%) had UC. EoE prevalence is significantly higher in the IBD group compared to the general population (533 vs. 47, P < 0.0001). There was a significant difference in the prevalence of EoE between Crohn's disease and UC group (575 vs. 488, P = 0.008). The proportion of patients between age 18–65 years was significantly higher in EoE all 3 groups. A significant association of asthma and eczema with EoE was noted in all three groups. CONCLUSION: The risk of EoE is significantly higher among IBD patients, both Crohn's disease and UC. Concurrent diagnoses of EoE and IBD might modify the risk of IBD- and EoE-related complications. Studies to evaluate the mechanisms underlying the observation are needed.Table 1.: Prevalence and characteristics of patients with Eosinophilic esophagitis (EoE) associated with Crohn's disease, Ulcerative colitis and in general population

Pathogenesis of Eosinophilic Esophagitis: A Comprehensive Review of the Genetic and Molecular Aspects.

Eosinophilic esophagitis (EoE) is a relatively new condition described as an allergic-mediated disease of the esophagus. Clinically, it is characterized by dysphagia, food impaction, and reflux-like symptoms. Multiple genome-wide association studies (GWAS) have been conducted to identify genetic loci associated with EoE. The integration of numerous studies investigating the genetic polymorphisms in EoE and the Mendelian diseases associated with EoE are discussed to provide insights into the genetic risk of EoE, notably focusing on CCL26 and CAPN14. We focus on the genetic loci investigated thus far, and their classification according to whether the function near the loci is known. The pathophysiology of EoE is described by separately presenting the known function of each cell and molecule, with the major contributors being eosinophils, Th2 cells, thymic stromal lymphopoietin (TSLP), transforming growth factor (TGF)-β1, and interleukin (IL)-13. This review aims to provide detailed descriptions of the genetics and the comprehensive pathophysiology of EoE.

Review - Helicobacter pylori and non-malignant upper gastro-intestinal diseases.

This review takes into account recent publications focusing on the relationship betweenHelicobacter pyloriinfection and non-malignant diseases of the upper gastro-intestinal tract. The authors have summarized current knowledge on associations between the Hpylori infection and non-malignant upper GI conditions including gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis (EOE), peptic ulcer disease (PUD), Hpylori gastritis, celiac disease and functional dyspepsia. In the field of GERD, current data focusing on different locations of Hpylori infection detect significant differences between antrum- and corpus predominant gastritis explainable by different changes in acid secretion in different gastric niches. High volume studies from Sweden and Brazil underline the safety of Hpylori eradication concerning the risk of Barret's esophagus or adenocarcinoma. The relationship betweenHpylori infection and EOE remains uncertain, but current data supports the concept of expected positive and protective effects of Hpylori exposure reducing the risk of EOE. Analyzing biomarkers might be helpful to identify subjects under risk for the development of precancerous lesions after H pylori infection, where microRNAs, IL-9 and IL-4, and also Tc17/9 and Th17/9 and microbiota profiles showed promising results to identify subgroups under risk.

Early life factors are associated with risk for eosinophilic esophagitis diagnosed in adulthood.

Early life exposures have been associated with pediatric eosinophilic esophagitis (EoE), but it is unknown if a similar association is present in adults. We aimed to assess the association between early life risk factors and development of EoE in adulthood. To do this, we conducted a case-control study which was nested within a prospective cohort study of adults undergoing outpatient endoscopy. Cases of EoE were diagnosed per consensus guidelines; controls did not meet these criteria. Subjects and their mothers were contacted to collect information on four key early life exposures: antibiotics taken during the first year of life, Cesarean delivery, preterm delivery (≤37weeks' gestation), and neonatal intensive care unit (NICU) admission. We calculated the odds of EoE given in each exposure and assessed agreement between subjects and their mothers. For the 40 cases and 40 controls enrolled, we observed a positive association between each of the early life exposures and development of EoE (antibiotics in infancy, OR = 4.64, 95% CI = 1.63-13.2; Cesarean delivery, OR = 3.08, 95% CI = 0.75-12.6; preterm delivery, OR = 2.92, 95% CI = 0.71-12.0; NICU admission, OR = 4.00, 95% CI = 1.01-15.9). Results were unchanged after adjusting for potential confounders, though only early antibiotic use had CIs that did not cross 1.0. Moderate to strong agreement was observed between 54 subject-mother pairs (antibiotics, K = 0.44, P = 0.02; Cesarean delivery, K = 1.0, P < 0.001; preterm delivery, K = 0.80, P < 0.001; NICU, K = 0.76, P < 0.001). In sum, antibiotics in infancy was significantly associated with increased risk of EoE diagnosed in adulthood, while positive trends were seen with other early life factors such as Cesarean delivery, preterm delivery, and NICU admission. This may indicate persistent effects of early life exposures and merits additional study into conserved pathogenic mechanisms.

A Model Using Clinical and Endoscopic Characteristics Identifies Patients at Risk for Eosinophilic Esophagitis According to Updated Diagnostic Guidelines

Updated diagnostic guidelines for eosinophilic esophagitis (EoE) have eliminated the requirement for a proton pump inhibitor (PPI) trial, but there are no models to identify patients with EoE based on these new criteria. We aimed to develop a predictive model for diagnosis of EoE based on the updated EoE diagnostic guidelines. We performed a secondary analysis of a prospective study of adult patients referred for outpatient esophagogastroduodenoscopy at University of North Carolina who had symptoms of esophageal dysfunction; patients with prevalent EoE were excluded. We analyzed data from 206 EoE cases (mean age 40.1, 62.6% male, 93.2% white) and 306 controls (mean age 52.3, 37.9% male, 79.7% white). We built predictive models for case-control status, using clinical, endoscopic, and histologic features, and defining EoE by either the new or historical definition of PPI non-response. Model discrimination was assessed by the area under the receiver-operator characteristic curve (AUC). Before endoscopy, younger age, male sex, history of atopic condition or food allergy, and dysphagia identified patients with EoE with an AUC of 0.83. When we included endoscopy findings suggestive of EoE, the model identified patients with EoE with an AUC of 0.92; this increased to 0.99 when histology was included. We developed a model to identify patients with EoE, without a trial of PPIs, based on updated diagnostic guidelines. Clinical features and endoscopic findings identified patients with EoE with an AUC of 0.92-even without histologic data and in the absence of dysphagia. This model can be used to select patients with upper gastrointestinal symptoms but without dysphagia for early diagnostic endoscopy. The model can also be used to identify cases of EoE when eosinophil counts are greater than 15 in biopsies but other causes of esophageal eosinophilia cannot necessarily be excluded.