Discrepancy Between Clinical Symptoms and Endoscopic Severity in Eosinophilic Esophagitis: A Retrospective Analysis

Discrepancy Between Clinical Symptoms and Endoscopic Severity in Eosinophilic Esophagitis: A Retrospective Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Discrepancy Between Clinical Symptoms and Endoscopic Severity in Eosinophilic Esophagitis: A Retrospective Analysis Abdulrahman Ahmed Almalaq, Abdulaziz Omar Almasoud, Ebtissam Almeghaiseeb, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6873476/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Eosinophilic esophagitis (EoE) presents with a wide range of clinical symptoms and endoscopic abnormalities. The correlation between clinical symptoms and endoscopic severity remains inconsistent. Objective To assess the relationship between presenting symptoms and endoscopic severity in patients diagnosed with EoE. Methods This retrospective study included patients diagnosed with EoE at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between 2011 and 2021. Symptom profiles and endoscopic findings were analyzed using the validated EREFS scoring system. Mann-Whitney U tests and multivariate regression were used to determine statistical significance. Results A total of 41 patients were included. Dysphagia was the most common symptom (53.7%), followed by abdominal pain (29.3%). The median EREFS score was 3.0 (IQR: 2.0–5.0). Nausea and vomiting were associated with significantly lower endoscopic scores (mean EREFS: 2.0 vs. 3.94, p = 0.015). On multivariate analysis, nausea and vomiting remained independently associated with lower EREFS scores (β = -1.80, p = 0.048). Conclusion Clinical symptoms, particularly nausea and vomiting, do not reliably predict endoscopic severity in EoE. Endoscopic assessment remains essential for accurate disease evaluation and monitoring. Eosinophilic esophagitis EREFS dysphagia endoscopy symptom correlation retrospective study Saudi Arabia Figures Figure 1 Figure 2 Figure 3 Highlights • Symptom severity in eosinophilic esophagitis does not consistently reflect endoscopic disease activity. • Endoscopic scoring using EREFS helps quantify mucosal disease but shows variable correlation with clinical presentation. • Nausea and vomiting may be associated with lower EREFS scores, suggesting a distinct symptom phenotype. • This study provides data from a Middle Eastern population, adding regional context to global EoE findings. • Findings support the need for multimodal assessment in managing EoE patients. Introduction Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal dysfunction and histological eosinophilic infiltration. The diagnosis is made based on clinical symptoms and the presence of at least 15 eosinophils per high power field (eos/hpf) on esophageal biopsy in the absence of secondary causes of eosinophilia [ 1 , 2 ]. The prevalence and incidence of EoE are increasing globally, particularly in Western countries and the Middle East [ 3 ]. EoE may present with a broad range of clinical symptoms, which often differ by age. In adults, dysphagia and food impaction are common, whereas in children, vomiting, abdominal pain, and feeding difficulties are more typical [ 4 ]. However, symptom severity has been shown to not always correlate with histologic or endoscopic disease activity, raising concern about the reliability of clinical symptoms as a standalone indicator of disease severity [ 5 , 6 ]. Several scoring systems have been developed to quantify the extent of endoscopic findings, with the EREFS (Edema, Rings, Exudates, Furrows, Strictures) score being the most widely used and validated [ 7 ]. EREFS provides a standardized approach for endoscopic evaluation of EoE patients and is incorporated into both clinical and research settings. While previous studies have evaluated the correlation between symptoms and histologic or endoscopic severity, results have been inconsistent [ 6 , 8 ]. Some studies demonstrated a modest correlation between dysphagia severity and fibrotic features such as strictures or rings, while others found poor correlation between patient-reported symptoms and endoscopic findings [ 9 ]. These discrepancies may be due to differences in study populations, symptom perception, or disease phenotype. There is a paucity of data from the Middle East exploring the clinical-endoscopic relationship in EoE. Understanding this relationship can improve disease monitoring and therapeutic decision-making. Therefore, we aimed to evaluate the correlation between presenting clinical symptoms and endoscopic severity using EREFS among adult patients diagnosed with EoE at a tertiary referral center in Riyadh, Saudi Arabia. Methods Study Design and Setting This was a retrospective study conducted at Prince Sultan Military Medical City (PSMMC), a tertiary care center in Riyadh, Saudi Arabia. The study was approved by the hospital's Institutional Review Board. Patients and Data Collection We included adult patients (≥ 18 years) diagnosed with EoE between January 2011 and December 2021. Diagnosis was based on symptoms of esophageal dysfunction and histological findings of ≥ 15 eos/hpf on esophageal biopsy. Patients with secondary causes of eosinophilia (e.g., GERD, Crohn’s disease, eosinophilic gastroenteritis) were excluded. Data collected included demographics, presenting symptoms, laboratory findings, and endoscopic findings. Presenting symptoms were categorized as dysphagia, food impaction, abdominal pain, heartburn, nausea, vomiting, and weight loss. Endoscopic findings were assessed and scored retrospectively using the EREFS scoring system based on documented endoscopic reports and images. Statistical Analysis Descriptive statistics were used to summarize the data. Continuous variables were presented as mean ± standard deviation or median (IQR) depending on distribution. Categorical variables were presented as frequencies and percentages. Mann-Whitney U tests were used to compare EREFS scores based on symptom presence. Multivariate linear regression was used to identify independent associations between symptoms and total EREFS score. A p-value < 0.05 was considered statistically significant. All analyses were performed using SPSS version 26.0 (IBM Corp, Armonk, NY). Results A total of 41 patients met the inclusion criteria for this study. The demographic data showed a median age of 32 years (Interquartile Range [IQR]: 21–45), with a predominance of male patients, accounting for 75.6% of the sample. The most frequently reported symptom was dysphagia, observed in 53.7% of the patients, followed by abdominal pain (29.3%), heartburn (24.4%), nausea (19.5%), vomiting (14.6%), food impaction (14.6%), and weight loss (12.2%). The median Eosinophilic Esophagitis Endoscopic Functional Scale (EREFS) score was found to be 3.0 (IQR: 2.0–5.0). (Fig. 1 ) Statistical analysis revealed that patients with nausea and vomiting exhibited significantly lower EREFS scores compared to those without these symptoms, with mean scores of 2.0 vs. 3.94 respectively (p = 0.015). Importantly, multivariate regression analysis identified nausea and vomiting as independent predictors associated with lower EREFS scores (β = -1.80, p = 0.048), even after controlling for age and gender. (Figs. 2 and 3 ) Discussion In this retrospective study of adult EoE patients, we found that presenting symptoms, particularly nausea and vomiting, were associated with lower endoscopic severity as measured by the EREFS score. These findings support previous literature suggesting that clinical symptoms alone are not reliable indicators of endoscopic activity in EoE. Our results are consistent with studies from the United States and Europe showing poor correlation between symptom severity and histologic or endoscopic inflammation [ 5 , 6 ]. For instance, Schoepfer et al. demonstrated that dysphagia severity scores do not consistently correlate with mucosal eosinophilia or endoscopic findings [ 8 ]. Similarly, Dellon et al. showed that EREFS scores improved after treatment despite minimal changes in patient-reported symptoms [ 9 ]. The inverse relationship between nausea/vomiting and EREFS score may reflect a distinct symptom phenotype in EoE or potential overlap with functional gastrointestinal disorders. This observation requires further investigation in larger prospective studies. Our study contributes novel data from a Middle Eastern cohort and reinforces the importance of objective assessment tools such as EREFS in guiding disease management. Given the heterogeneity of EoE presentation, relying on symptoms alone may lead to underestimation of disease activity and suboptimal treatment decisions. Limitations This study has several limitations. Firstly, the cross-sectional design limits our ability to establish causality between eosinophilic esophagitis (EoE) symptoms and endoscopic findings. Secondly, our sample size may restrict the generalizability of our findings to the broader population, as participants were recruited from a single center. Furthermore, potential response biases exist due to the reliance on self-reported symptoms. Lastly, because of the retrospective nature of some aspects of our data collection, not all relevant clinical variables may have been captured, which could affect the interpretation of our results. Conclusion Clinical symptoms in EoE do not consistently predict endoscopic severity. Nausea and vomiting were associated with lower EREFS scores, suggesting a distinct phenotype or overlap with other conditions. Routine endoscopic evaluation using standardized scoring systems remains essential for accurate disease assessment and monitoring. Declarations Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors' contributions AAA and AOA designed the study. AAA collected the data. AAA and MAA analyzed the data. EAM, RAA, and AAA interpreted the results. All authors contributed to drafting and critically revising the manuscript. All authors read and approved the final manuscript. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Human Ethics and Consent to Participate This study was approved by the Institutional Review Board of Prince Sultan Military Medical City, Riyadh, Saudi Arabia. The requirement for informed consent was waived due to the retrospective nature of the study and anonymized data collection. References Liacouras CA, et al. Eosinophilic esophagitis: updated consensus recommendations. J Allergy Clin Immunol. 2011;128(1):3–e206. Dellon ES et al. Updated International Consensus Diagnostic Criteria for EoE: AGREE conference report. Gastroenterology. 2018;155(4):1022–33.e10. Furuta GT, et al. Eosinophilic gastrointestinal diseases: pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2007;120(3):660–7. Lucendo AJ, et al. Eosinophilic esophagitis: a systematic review. Eur J Gastroenterol Hepatol. 2015;27(8):847–56. Dellon ES, et al. Correlation of symptoms with endoscopic findings in adult EoE. Gastrointest Endosc. 2009;70(6):992–8. Moawad FJ, et al. Symptom-based disease monitoring in EoE is not reliable. Am J Gastroenterol. 2014;109(3):350–6. Hirano I, et al. Development and validation of the EREFS system. Gastrointest Endosc. 2013;77(3):322–9. Schoepfer AM, et al. Symptom-based activity index for adults with EoE. Clin Gastroenterol Hepatol. 2014;12(4):635–e421. Dellon ES, et al. Responsiveness of EREFS to treatment of EoE. Clin Gastroenterol Hepatol. 2016;14(2):234–e421. Warners MJ, et al. Symptoms and endoscopic findings do not correlate in adult patients with eosinophilic esophagitis. Gastrointest Endosc. 2017;85(3):533–41. Reed CC, et al. Variability in endoscopic assessment of eosinophilic esophagitis across practice settings. Am J Gastroenterol. 2019;114(2):253–60. Dellon ES. The EREFS system: development, validation, and clinical utility in eosinophilic esophagitis. J Allergy Clin Immunol Pract. 2018;6(5):1483–92. Melgaard D, et al. Clinical relevance of endoscopic findings in eosinophilic esophagitis: a population-based study. Scand J Gastroenterol. 2016;51(6):644–50. Greuter T, et al. Clinical and histologic remission do not align in adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2021;19(6):1107–15. Dellon ES, et al. Assessment of disease activity in eosinophilic esophagitis using EREFS and histologic scoring: development of a composite scoring tool. Clin Gastroenterol Hepatol. 2020;18(9):1975–84. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6873476","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":472986082,"identity":"3ef4cc06-bd05-484e-af60-b2b9a912c455","order_by":0,"name":"Abdulrahman Ahmed Almalaq","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYBACe/kDbBKJDRJy/CBeQgERWgxnJLBbfGywMZZsAGkxIEKLwY0E9p8zG9ISNxwAc4nTwnabt+Fw4ubzqxM/PDBgkOcXO0BAy/0DEC3bbrzdLAF0mOHM2QmEtDDAtJzdANKSYHCbkJabDWzSfxv+526ecXbzD+K03DjAJg20JX0Df+824mwxnJHYBtJiLHGDd5tFgoEEYb/YSyQfk+b9c1iuv//s5ps/Kmzk+aUJaGFgYGyA0BJglRKElCMD/gOkqB4Fo2AUjIKRBAAmQk/QgLko+wAAAABJRU5ErkJggg==","orcid":"","institution":"Prince Sultan Military Medical City","correspondingAuthor":true,"prefix":"","firstName":"Abdulrahman","middleName":"Ahmed","lastName":"Almalaq","suffix":""},{"id":472986085,"identity":"d872394d-e662-4ece-b3e9-030235fc170c","order_by":1,"name":"Abdulaziz Omar Almasoud","email":"","orcid":"","institution":"Prince Sultan Military Medical City","correspondingAuthor":false,"prefix":"","firstName":"Abdulaziz","middleName":"Omar","lastName":"Almasoud","suffix":""},{"id":472986088,"identity":"fd5e52fa-e5c4-45e0-81d1-06ba3bc6a75f","order_by":2,"name":"Ebtissam Almeghaiseeb","email":"","orcid":"","institution":"Prince Sultan Military Medical City","correspondingAuthor":false,"prefix":"","firstName":"Ebtissam","middleName":"","lastName":"Almeghaiseeb","suffix":""},{"id":472986091,"identity":"181e1660-e515-4f01-b45f-bba849a266ae","order_by":3,"name":"Reem Abdullah Alamro","email":"","orcid":"","institution":"Prince Sultan Military Medical City","correspondingAuthor":false,"prefix":"","firstName":"Reem","middleName":"Abdullah","lastName":"Alamro","suffix":""},{"id":472986094,"identity":"4d5fc6d0-3233-431a-a43f-8aff693e9e44","order_by":4,"name":"Mohamad Abdulhadi Alharbi","email":"","orcid":"","institution":"Prince Sultan Military Medical City","correspondingAuthor":false,"prefix":"","firstName":"Mohamad","middleName":"Abdulhadi","lastName":"Alharbi","suffix":""},{"id":472986095,"identity":"42f32d01-730b-4ed0-a6f1-c01000ba4c91","order_by":5,"name":"Abdulrahman Ali Alrobayan","email":"","orcid":"","institution":"Prince Sultan Military Medical City","correspondingAuthor":false,"prefix":"","firstName":"Abdulrahman","middleName":"Ali","lastName":"Alrobayan","suffix":""}],"badges":[],"createdAt":"2025-06-11 15:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6873476/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6873476/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85306083,"identity":"b7d6f6f7-59a1-45ac-8790-de00130c75b7","added_by":"auto","created_at":"2025-06-24 12:48:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39187,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of symptoms among patients diagnosed with Eosinophilic Esophagitis. Dysphagia was the most frequently reported symptom, followed by abdominal pain, heartburn, and others.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6873476/v1/e77f60a7b151fc0be2aab543.png"},{"id":85305649,"identity":"4d55fe86-88b9-48fd-b5ba-2e9c7de3da39","added_by":"auto","created_at":"2025-06-24 12:40:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29679,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of EREFS scores between patients with and without nausea/vomiting. Those experiencing nausea/vomiting had significantly lower EREFS scores.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6873476/v1/60f5f67ba2b2006be8ac7dbd.png"},{"id":85305653,"identity":"e9245cdb-4d6c-4fba-9c25-42776e5acd2f","added_by":"auto","created_at":"2025-06-24 12:40:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":40157,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot showing EREFS scores for individual patients, grouped by presence or absence of nausea/vomiting. Lower scores are more prevalent among patients with these symptoms.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6873476/v1/9d8375b19e87b5be92939b1f.png"},{"id":92860488,"identity":"2d7fd4fe-c7d7-41bf-b14c-c5ef7145ce1a","added_by":"auto","created_at":"2025-10-06 12:09:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":510637,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6873476/v1/831a6223-cda2-48d3-8e96-0115ee0247aa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Discrepancy Between Clinical Symptoms and Endoscopic Severity in Eosinophilic Esophagitis: A Retrospective Analysis","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u0026bull; Symptom severity in eosinophilic esophagitis does not consistently reflect endoscopic disease activity.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Endoscopic scoring using EREFS helps quantify mucosal disease but shows variable correlation with clinical presentation.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Nausea and vomiting may be associated with lower EREFS scores, suggesting a distinct symptom phenotype.\u003c/p\u003e\n\u003cp\u003e\u0026bull; This study provides data from a Middle Eastern population, adding regional context to global EoE findings.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Findings support the need for multimodal assessment in managing EoE patients.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eEosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal dysfunction and histological eosinophilic infiltration. The diagnosis is made based on clinical symptoms and the presence of at least 15 eosinophils per high power field (eos/hpf) on esophageal biopsy in the absence of secondary causes of eosinophilia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The prevalence and incidence of EoE are increasing globally, particularly in Western countries and the Middle East [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEoE may present with a broad range of clinical symptoms, which often differ by age. In adults, dysphagia and food impaction are common, whereas in children, vomiting, abdominal pain, and feeding difficulties are more typical [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, symptom severity has been shown to not always correlate with histologic or endoscopic disease activity, raising concern about the reliability of clinical symptoms as a standalone indicator of disease severity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral scoring systems have been developed to quantify the extent of endoscopic findings, with the EREFS (Edema, Rings, Exudates, Furrows, Strictures) score being the most widely used and validated [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. EREFS provides a standardized approach for endoscopic evaluation of EoE patients and is incorporated into both clinical and research settings.\u003c/p\u003e \u003cp\u003eWhile previous studies have evaluated the correlation between symptoms and histologic or endoscopic severity, results have been inconsistent [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Some studies demonstrated a modest correlation between dysphagia severity and fibrotic features such as strictures or rings, while others found poor correlation between patient-reported symptoms and endoscopic findings [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These discrepancies may be due to differences in study populations, symptom perception, or disease phenotype.\u003c/p\u003e \u003cp\u003eThere is a paucity of data from the Middle East exploring the clinical-endoscopic relationship in EoE. Understanding this relationship can improve disease monitoring and therapeutic decision-making. Therefore, we aimed to evaluate the correlation between presenting clinical symptoms and endoscopic severity using EREFS among adult patients diagnosed with EoE at a tertiary referral center in Riyadh, Saudi Arabia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy Design and Setting\u003c/p\u003e \u003cp\u003e This was a retrospective study conducted at Prince Sultan Military Medical City (PSMMC), a tertiary care center in Riyadh, Saudi Arabia. The study was approved by the hospital's Institutional Review Board.\u003c/p\u003e \u003cp\u003ePatients and Data Collection\u003c/p\u003e \u003cp\u003eWe included adult patients (\u0026ge;\u0026thinsp;18 years) diagnosed with EoE between January 2011 and December 2021. Diagnosis was based on symptoms of esophageal dysfunction and histological findings of \u0026ge;\u0026thinsp;15 eos/hpf on esophageal biopsy. Patients with secondary causes of eosinophilia (e.g., GERD, Crohn\u0026rsquo;s disease, eosinophilic gastroenteritis) were excluded.\u003c/p\u003e \u003cp\u003eData collected included demographics, presenting symptoms, laboratory findings, and endoscopic findings. Presenting symptoms were categorized as dysphagia, food impaction, abdominal pain, heartburn, nausea, vomiting, and weight loss. Endoscopic findings were assessed and scored retrospectively using the EREFS scoring system based on documented endoscopic reports and images.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were used to summarize the data. Continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (IQR) depending on distribution. Categorical variables were presented as frequencies and percentages. Mann-Whitney U tests were used to compare EREFS scores based on symptom presence. Multivariate linear regression was used to identify independent associations between symptoms and total EREFS score. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using SPSS version 26.0 (IBM Corp, Armonk, NY).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 41 patients met the inclusion criteria for this study. The demographic data showed a median age of 32 years (Interquartile Range [IQR]: 21\u0026ndash;45), with a predominance of male patients, accounting for 75.6% of the sample.\u003c/p\u003e \u003cp\u003eThe most frequently reported symptom was dysphagia, observed in 53.7% of the patients, followed by abdominal pain (29.3%), heartburn (24.4%), nausea (19.5%), vomiting (14.6%), food impaction (14.6%), and weight loss (12.2%). The median Eosinophilic Esophagitis Endoscopic Functional Scale (EREFS) score was found to be 3.0 (IQR: 2.0\u0026ndash;5.0). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eStatistical analysis revealed that patients with nausea and vomiting exhibited significantly lower EREFS scores compared to those without these symptoms, with mean scores of 2.0 vs. 3.94 respectively (p\u0026thinsp;=\u0026thinsp;0.015). Importantly, multivariate regression analysis identified nausea and vomiting as independent predictors associated with lower EREFS scores (β = -1.80, p\u0026thinsp;=\u0026thinsp;0.048), even after controlling for age and gender. (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective study of adult EoE patients, we found that presenting symptoms, particularly nausea and vomiting, were associated with lower endoscopic severity as measured by the EREFS score. These findings support previous literature suggesting that clinical symptoms alone are not reliable indicators of endoscopic activity in EoE.\u003c/p\u003e \u003cp\u003eOur results are consistent with studies from the United States and Europe showing poor correlation between symptom severity and histologic or endoscopic inflammation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. For instance, Schoepfer et al. demonstrated that dysphagia severity scores do not consistently correlate with mucosal eosinophilia or endoscopic findings [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Similarly, Dellon et al. showed that EREFS scores improved after treatment despite minimal changes in patient-reported symptoms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe inverse relationship between nausea/vomiting and EREFS score may reflect a distinct symptom phenotype in EoE or potential overlap with functional gastrointestinal disorders. This observation requires further investigation in larger prospective studies.\u003c/p\u003e \u003cp\u003eOur study contributes novel data from a Middle Eastern cohort and reinforces the importance of objective assessment tools such as EREFS in guiding disease management. Given the heterogeneity of EoE presentation, relying on symptoms alone may lead to underestimation of disease activity and suboptimal treatment decisions.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThis study has several limitations. Firstly, the cross-sectional design limits our ability to establish causality between eosinophilic esophagitis (EoE) symptoms and endoscopic findings. Secondly, our sample size may restrict the generalizability of our findings to the broader population, as participants were recruited from a single center. Furthermore, potential response biases exist due to the reliance on self-reported symptoms. Lastly, because of the retrospective nature of some aspects of our data collection, not all relevant clinical variables may have been captured, which could affect the interpretation of our results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eClinical symptoms in EoE do not consistently predict endoscopic severity. Nausea and vomiting were associated with lower EREFS scores, suggesting a distinct phenotype or overlap with other conditions. Routine endoscopic evaluation using standardized scoring systems remains essential for accurate disease assessment and monitoring.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAAA and AOA designed the study. AAA collected the data. AAA and MAA analyzed the data. EAM, RAA, and AAA interpreted the results. All authors contributed to drafting and critically revising the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Prince Sultan Military Medical City, Riyadh, Saudi Arabia. The requirement for informed consent was waived due to the retrospective nature of the study and anonymized data collection.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLiacouras CA, et al. Eosinophilic esophagitis: updated consensus recommendations. J Allergy Clin Immunol. 2011;128(1):3\u0026ndash;e206.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDellon ES et al. Updated International Consensus Diagnostic Criteria for EoE: AGREE conference report. Gastroenterology. 2018;155(4):1022\u0026ndash;33.e10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFuruta GT, et al. Eosinophilic gastrointestinal diseases: pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2007;120(3):660\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLucendo AJ, et al. Eosinophilic esophagitis: a systematic review. Eur J Gastroenterol Hepatol. 2015;27(8):847\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDellon ES, et al. Correlation of symptoms with endoscopic findings in adult EoE. Gastrointest Endosc. 2009;70(6):992\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoawad FJ, et al. Symptom-based disease monitoring in EoE is not reliable. Am J Gastroenterol. 2014;109(3):350\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirano I, et al. Development and validation of the EREFS system. Gastrointest Endosc. 2013;77(3):322\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoepfer AM, et al. Symptom-based activity index for adults with EoE. Clin Gastroenterol Hepatol. 2014;12(4):635\u0026ndash;e421.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDellon ES, et al. Responsiveness of EREFS to treatment of EoE. Clin Gastroenterol Hepatol. 2016;14(2):234\u0026ndash;e421.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWarners MJ, et al. Symptoms and endoscopic findings do not correlate in adult patients with eosinophilic esophagitis. Gastrointest Endosc. 2017;85(3):533\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReed CC, et al. Variability in endoscopic assessment of eosinophilic esophagitis across practice settings. Am J Gastroenterol. 2019;114(2):253\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDellon ES. The EREFS system: development, validation, and clinical utility in eosinophilic esophagitis. J Allergy Clin Immunol Pract. 2018;6(5):1483\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelgaard D, et al. Clinical relevance of endoscopic findings in eosinophilic esophagitis: a population-based study. Scand J Gastroenterol. 2016;51(6):644\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreuter T, et al. Clinical and histologic remission do not align in adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2021;19(6):1107\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDellon ES, et al. Assessment of disease activity in eosinophilic esophagitis using EREFS and histologic scoring: development of a composite scoring tool. Clin Gastroenterol Hepatol. 2020;18(9):1975\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Eosinophilic esophagitis, EREFS, dysphagia, endoscopy, symptom correlation, retrospective study, Saudi Arabia","lastPublishedDoi":"10.21203/rs.3.rs-6873476/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6873476/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEosinophilic esophagitis (EoE) presents with a wide range of clinical symptoms and endoscopic abnormalities. The correlation between clinical symptoms and endoscopic severity remains inconsistent.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo assess the relationship between presenting symptoms and endoscopic severity in patients diagnosed with EoE.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included patients diagnosed with EoE at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between 2011 and 2021. Symptom profiles and endoscopic findings were analyzed using the validated EREFS scoring system. Mann-Whitney U tests and multivariate regression were used to determine statistical significance.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 41 patients were included. Dysphagia was the most common symptom (53.7%), followed by abdominal pain (29.3%). The median EREFS score was 3.0 (IQR: 2.0\u0026ndash;5.0). Nausea and vomiting were associated with significantly lower endoscopic scores (mean EREFS: 2.0 vs. 3.94, p\u0026thinsp;=\u0026thinsp;0.015). On multivariate analysis, nausea and vomiting remained independently associated with lower EREFS scores (β = -1.80, p\u0026thinsp;=\u0026thinsp;0.048).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eClinical symptoms, particularly nausea and vomiting, do not reliably predict endoscopic severity in EoE. Endoscopic assessment remains essential for accurate disease evaluation and monitoring.\u003c/p\u003e","manuscriptTitle":"Discrepancy Between Clinical Symptoms and Endoscopic Severity in Eosinophilic Esophagitis: A Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-24 12:40:18","doi":"10.21203/rs.3.rs-6873476/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c0f1b8b9-0443-4a1a-96d9-7b066bb2d6b0","owner":[],"postedDate":"June 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T12:08:53+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-24 12:40:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6873476","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6873476","identity":"rs-6873476","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}