Helicobacter pylori as a potential cause of reversible esophageal eosinophilia

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Cohen, Tzippora Shalem, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6570424/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 Purpose Helicobacter pylori (HP) infects up to half of the global population, though its prevalence is declining due to improved hygiene and eradication therapies. In contrast, eosinophilic esophagitis (EoE) incidence is rising, potentially linked to the hygiene hypothesis. Studies suggest an inverse relationship between HP and EoE, but esophageal eosinophilia (EE) can arise from various causes, including infections. The aim of this study was to examine the association between HP and EE and the effect of HP eradication. Methods We conducted a retrospective observational study of patients aged 1–21 years diagnosed with EE (> 15 eosinophils/high power field [HPF]) between 2019 and 2024 at Shamir Medical Center, Israel. Gastric biopsies confirmed HP infection, followed by eradication therapy and repeat endoscopy. Data included demographics, medical history, endoscopic findings, HP eradication success, and esophageal histology. Results Among 97 patients with EE, 70.1% were male, and the mean age was 10.46 ± 5.79 years. HP infection was present in 23 (23.7%) patients, with successful eradication in 11 (47.8%). Basal cell hyperplasia (BCH) was more frequent in HP-positive patients (60.9% vs. 36.5%, P = 0.039). Other features were similar. EE resolved in 4 (36.4%) of successfully eradicated patients. Patients with EE resolution were younger, less likely male, and had fewer atopic conditions. Conclusions HP infection may contribute to esophageal epithelial remodeling as indicated by increased BCH. In some children, HP-associated EE may be reversible. HP diagnosis and eradication should be considered before confirming EoE, particularly in younger patients with mild eosinophilia and no macroscopic EoE findings. Helicobacter pylori Eosinophilic esophagitis Esophageal eosinophilia Basal cell hyperplasia Figures Figure 1 What is Known? Helicobacter pylori (HP) infection is common in children, though its prevalence is declining in developed countries. There is an inverse association between HP infection and eosinophilic esophagitis (EoE), suggesting a potential immunomodulatory effect. Current guidelines for EoE and HP management do not recommend routine HP testing or eradication in patients with esophageal eosinophilia (EE). What is New? In a retrospective cohort, over third of HP-positive children who underwent eradication therapy experienced resolution of EE, suggesting that HP may contribute to transient esophageal eosinophilia. Younger patients with lower eosinophil counts were more likely to show EE resolution, raising the possibility of a distinct, non-EoE eosinophilic response. Basal cell hyperplasia (BCH) was significantly more frequent in patients with both EoE and HP infection compared to EoE alone, suggesting that HP may contribute to epithelial remodeling in the esophagus. This finding raises questions about the impact of HP on esophageal histology and its potential role in disease progression. Introduction Helicobacter pylori (HP) infects up to half of the world's population ( 1 ). The prevalence varies substantially according to age, ethnicity, geographic region, associated diseases, socioeconomic status and hygiene conditions. The global prevalence has been decreasing due to improvements in the two last aforementioned causes and due to eradication therapies as a further contributor ( 1 – 4 ). On the contrary, the incidence of eosinophilic esophagitis (EoE) is increasing worldwide, with both environmental and genetic factors involved in its pathogenesis. One of the suggested theories for EoE development is the hygiene hypothesis which leads to an imbalance between T helper 1 (Th1) and T helper 2 (Th2) mediated immune responses ( 5 ), since allergic conditions are common comorbidities. While EoE involves Th2 mediated immune response, HP involves the Th1 mediated response ( 6 ). The rapid decrease in HP prevalence may contribute to this imbalance, with a hyper-activated Th2 response, and therefore to the rising incidence of EoE. This is supported by inverse correlation between HP infection and EoE reported by various studies ( 7 ). However, when encountering esophageal eosinophilia (EE), one must exclude other etiologies before EoE diagnosis is made, including infections ( 8 ). HP should be considered in the differential diagnosis of gastrointestinal (GI) tissue eosinophilia both in the stomach and in other parts of the GI tract ( 9 ). A possible explanation for EE secondary to HP infection is gastric acid hypersecretion during early HP antral-predominant infection causing esophageal barrier injury and secondary inflammation including eosinophilic response. Despite knowledge regarding the inverse correlation between HP infection and EoE, there is a lack of comprehensive studies investigating the relationship between EE, when already present, and HP infection and eradication. We aimed to address this gap by examining the presence of HP in pediatric and young adult patients with EE and the effect of its eradication on such eosinophilia in this population. Materials and methods We conducted a retrospective observational study at Shamir Medical Center, Israel, evaluating pediatric and young adult patients (aged 1–21 years) diagnosed with EE between 2019 and 2024. EE was defined as the presence of ≥ 15 eosinophils per high-power field (HPF) on esophageal biopsy from any level, obtained during upper endoscopy. Patients were categorized into two groups based on HP status, determined by histological evaluation of gastric antrum and/or corpus biopsies, including Giemsa stain in all samples and immunohistochemistry when inconclusive. Demographic characteristics, clinical symptoms at diagnosis, and endoscopic and histologic findings were collected and compared between HP-positive and HP-negative patients. A subset of HP-positive patients underwent eradication therapy, after which a follow-up endoscopy with repeat esophageal and gastric biopsies was performed under no medicinal or dietary treatment, timed at least a month following completion of eradication. We assessed the resolution of EE post-eradication, defined as less than 15 eosinophils per HPF in all esophageal biopsies, and analyzed clinical and histological changes in this subgroup. All other patients with EE were treated according to EoE guidelines ( 8 ). Ethics statement: The study was approved by the ethics committee of the Shamir medical center IRB no ASF-0192-24. This study was exempt from obtaining patient consent as it involved retrospective data analysis with de-identified records, in accordance with the regulations of the Institutional Review Board. Statistical analysis: Categorical variables were summarized as frequency and percentages. The distribution of the continuous variables was evaluated using histograms. Normally distributed continuous variables were reported as means and SD, while other variables were reported as median and IQR. Categorical variables were compared using chi test of Fisher exact test and continuous and ordinal variables using independent student t- test, ANOVA, Mann Whitny test or Kruskal Wallis test. P-values < 0.05 were considered significant. The analysis was performed using SPSS 26.0. Results Ninety-seven patients, aged 1–21 years, were diagnosed with EE during the years 2019–2024 in the Shamir medical center. Sixty-eight (70.1%) were males and the mean age at diagnosis was 10.46 ± 5.79 years. Overall, 54 (55.7%) of the patients had an atopic background and the most common clinical presenting symptoms were dysphagia or eating problems (49, 50.5%) and nausea and/or vomiting (45, 46.4%), followed by abdominal pain (28, 28.9%), food impaction (19, 19.6%), chest pain or heartburn (9, 9.3%) and failure to thrive or weight loss (8, 8.2%). Esophageal endoscopic findings included furrows in 70 (72.2%) patients, exudates in 46 (47.4%) patients and trachealization in 20 (20.6%). Esophageal stricture was diagnosed in only 2 patients (2.1%). Microscopically, mean esophageal eosinophilic counts per HPF were highest in the lower esophagus (38.35 ± 32.57), followed by mid-esophagus (36.87 ± 32.94) and upper esophagus (31.81 ± 37.58). The mean maximal eosinophilic count was 50.89 ± 33.71 per HPF. Data shown in Tables 1 , 2 . Twenty-three (23.7%) patients in our cohort had a concomitant HP infection. Twelve (52.2%) were given recommendations for HP eradication, which was successful in 11 (91.7%). Data shown in Fig. 1 . Demographic and clinical features were similar between HP-positive and HP-negative groups (Table 1 ), as well as endoscopic and microscopic features (Table 2 ), excluding basal cell hyperplasia (BCH) which was more common in HP-positive patients (60.9% compares with 36.5%, P = 0.039). Table 1 Demographic and clinical features among HP-positive and HP-negative EE patients All EE patients (n = 97) HP-positive (n = 23) HP-negative (n = 74) Significance Mean age (years) 10.46 ± 5.79 10.83 ± 5.73 10.35 ± 53.84 P = 0.715 Male sex (%) 68 (70.1%) 17 (73.9%) 51 (68.9%) P = 0.648 Atopic features Asthma (%) 21 (21.6%) 16 (21.7%) 5 (21.6%) P = 1 Food allergy (%) 39 (40.2%) 8 (35.8%) 31 (41.9%) P = 0.544 Atopic dermatitis (%) 18 (18.6%) 2 (8.7%) 16 (21.6%) P = 0.226 Other atopy (%) 17 (17.5%) 4 (17.4%) 13 (17.6%) P = 1 Clinical symptoms Abdominal pain (%) 28 (28.9%) 6 (21.6%) 22 (29.7%) P = 0.736 Chest pain / heartburn (%) 9 (9.3%) 4 (19%) 5 (5.8%) P = 0.209 Nausea and/or vomiting (%) 45 (46.4%) 8 (34.8%) 37 (50%) P = 0.201 Dysphagia / eating problems 49 (50.5%) 15 (65.2%) 34 (45.9%) P = 0.106 Food impaction (%) 19 (19.6%) 5 (21.7%) 14 (18.9%) P = 0.769 Weight loss / failure to thrive (%) 8 (8.2%) 4 (17.4%) 4 (5.4%) P = 0.088 Table 2 Endoscopic and microscopic features among HP-positive and HP-negative EE patients All EE patients (n = 97) HP-positive (n = 23) HP-negative (n = 74) Significance Endoscopic features Trachealization (%) 20 (20.6%) 2 (8.7%) 18 (24.3%) P = 0.143 Exudates (%) 46 (47.4%) 10 (43.5%) 36 (48.6%) P = 0.664 Furrows (%) 70 (72.2%) 13 (56.5%) 57 (77%) P = 0.055 Stricture (%) 2 (2.1%) 0 (0%) 2 (2.7%) P = 1 Microscopic features Eosinophil count (mean) Lower esophagus 38.35 ± 32.57 44.65 ± 48.23 36.65 ± 27.06 P = 0.842 Mid-esophagus 36.87 ± 32.94 38.48 ± 41.96 36.36 ± 29.83 P = 0.855 Upper esophagus 31.81 ± 37.58 43.68 ± 55.18 28.59 ± 30.95 P = 0.551 Maximal eosinophilic count (mean) 50.89 ± 33.71 55.09 ± 46.69 49.58 ± 28.82 P = 0.888 Basal cell hyperplasia (%) 41 (42.3%) 14 (60.9%) 27 (36.5%) P = 0.039 Eosinophilic microabscesses (%) 10 (10.3%) 4 (17.4%) 6 (8.1%) P = 0.241 Among 11 HP-positive patients who underwent successful HP eradication, EE resolution was observed in 4 (36.4%) on follow-up endoscopy (Fig. 1 ), as well as in the 1 (9.1%) patient without successful HP eradication, despite the lack of proper long term EoE treatment. Although small sample size limited statistical analysis, patients with EE resolution were younger (median 6 years, IQR 5.5–13.5, vs. median 16 years, IQR 8–17), were less likely to be of male gender, and had less frequent atopic background (40 vs. 71.4% for both). Clinically, these patients presented more commonly with chest pain or heartburn (40% vs. 14.3%) and none presented with food impaction (compared with 42.9%). Data shown in Table 3 . Table 3 Demographic and clinical features among EE patients receiving HP eradication EE resolution (n = 5) No EE resolution (n = 7) Median age (years) 6 (IQR 5.5–13.5) 16 (IQR 7–17) Male sex (%) 2 (40%) 5 (71.4%) Atopic features Asthma (%) 0 (0%) 2 (28.6%) Food allergy (%) 1 (20%) 4 (57.1%) Atopic dermatitis (%) 0 (0%) 1 (14.3%) Allergic rhinitis (%) 1 (20%) 0 (0%) Other atopy (%) 1 (20%) 0 (0%) All (%) 2 (40%) 5 (71.4%) Clinical symptoms Abdominal pain (%) 1 (20%) 3 (42.9%) Chest pain / heartburn (%) 2 (40%) 1 (14.3%) Nausea and/or vomiting (%) 1 (20%) 1 (14.3%) Dysphagia / eating problems 3 (60%) 5 (71.4%) Food impaction (%) 0 (0%) 3 (42.9%) Weight loss / failure to thrive (%) 1 (20%) 2 (28.6%) Esophageal endoscopic features of EoE (trachealization, exudates, furrows or stricture) were noted in only 1 patient with EE resolution (20%) compared with 4 patients (57.1%) without EE resolution. Esophageal and duodenal ulcers were only diagnosed in patients with EE resolution. Presence of nodular gastritis was similar in both groups. Data shown in Table 4 . Microscopically, median esophageal eosinophilic counts per HPF were lower in patients with EE resolution compared with patients without EE resolution in all esophageal levels; 6 (IQR 0–73) vs. 39.5 (IQR 9–95) in lower esophagus, 18 (IQR 8-26.5) vs. 41 (IQR 20–60) in mid-esophagus, and 6.5 (IQR 0-78.25) vs. 50 (41–150) in upper esophagus. Similar findings were noted in median maximal eosinophilic count between the two groups with 26 (IQR 19.5–76) eosinophils per HPF in patients with EE resolution compared with 50 (IQR 41–150) in patients without EE resolution. Data shown in Table 4 . Table 4 Endoscopic and microscopic features among EE patients receiving HP eradication EE resolution (n = 5) No EE resolution (n = 7) Endoscopic features Trachealization (%) 0 (0%) 1 (14.3%) Exudates (%) 1 (20%) 3 (42.9%) Furrows (%) 1 (20%) 3 (42.9%) Stricture (%) 0 (0%) 0 (0%) All EoE esophageal features (%) 1 (20%) 4 (57.1%) Esophageal ulcer (%) 1 (20%) 0 (0%) Nodular gastritis (%) 2 (40%) 4 (57.1%) Duodenal ulcer (%) 1 (20%) 0 (%) Microscopic features Eosinophil count (median) Lower esophagus 6 (IQR 0–73) 39.5 (IQR 9–95) Mid-esophagus 18 (IQR 8-26.5) 41 (IQR 20–60) Upper esophagus 6.5 (IQR 0-78.25) 50 (IQR 0-150) Maximal eosinophilic count (median) 26 (IQR 19.5–76) 50 (IQR 41–150) Basal cell hyperplasia (%) 2 (40%) 3 (42.9%) Eosinophilic microabscesses (%) 1 (20%) 1 (14.3%) In patients with EE resolution, the highest eosinophilic count was noted only in the mid (3, 60%) or lower (2, 40%) esophagus while in patients with no EE resolution it was noted most commonly in the upper esophagus (3, 42.9%) and in 2 patients (28.6%) it was evenly distributed on all esophageal levels (Table 5 ). Other microscopic findings were similar between the groups. Table 5 Location of maximal esophageal eosinophilic count among EE patients receiving HP eradication Esophageal level of maximal eosinophilic count EE resolution (n = 5) No EE resolution (n = 7) Upper esophagus 0 (0%) 3 (42.9%) Mid-esophagus 3 (60%) 1 (14.3%) Lower esophagus 2 (40%) 0 (0%) Evenly distributed in lower and mid-esophagus 0 (0%) 1 (14.3%) Evenly distributed in all esophageal levels 0 (0%) 2 (28.5%) Discussion Our study explored the relationship between HP infection and EE in pediatric patients. While we found no significant differences in clinical presentation or disease characteristics between HP-positive and HP-negative groups at diagnosis, an intriguing observation emerged from the small subset of HP-positive patients who successfully underwent eradication therapy. Among these 11 patients, 4 exhibited resolution of EE and did not progress to EoE. Similar findings were observed in 1 additional patient who underwent unsuccessful HP eradication attempt. Although our sample size was insufficient for statistical analysis, this trend suggests that HP eradication or attenuation may play a role in resolving EE in select patients, particularly younger children lacking macroscopic findings suggestive of EoE and with lower eosinophil counts. Shah et al. conducted a meta-analysis demonstrating that HP exposure was associated with decreased odds of EoE, possibly due to HP’s immunomodulatory effects ( 7 ). However, our study suggests that HP infection can be a possible massacre for the diagnosis of EoE. In our study BCH was significantly more frequent in patients with both EE and HP infection compared to those with EE alone (60.9% vs. 36.5%, p = 0.039). BCH is a hallmark histologic feature of EoE, reflecting epithelial remodeling due to chronic inflammation and increased esophageal mucosal turnover. However, its higher prevalence in HP-positive patients raises several intriguing questions about the interplay between HP infection and esophageal epithelial changes ( 10 ). One possible explanation for this association is that HP-induced gastric acid hypersecretion, particularly in the early stages of infection, may exacerbate esophageal injury, leading to increased basal cell proliferation as part of the mucosal repair process. HP infection is known to affect acid production dynamically—while chronic infection may lead to hypochlorhydria, early HP infection, especially in antral-predominant cases, has been associated with increased acid output ( 11 ). This could contribute to esophageal epithelial stress, thereby amplifying BCH. Another potential mechanism is HP’s impact on the esophageal immune environment. HP infection has been shown to modulate immune responses, shifting the balance between Th1 and Th2 pathways ( 12 ). Since BCH in EoE is thought to be driven by epithelial cytokines such as IL-13 and TGF-β, it is possible that HP infection alters the inflammatory milieu, further stimulating epithelial proliferation ( 13 ). This hypothesis aligns with findings from studies showing that epithelial remodeling in EoE is not solely dependent on eosinophil-mediated damage but also influenced by broader immune dysregulation. Additionally, HP-related cytokine signaling might contribute to BCH development. HP infection has been associated with increased expression of pro-inflammatory mediators such as IL-6 and TNF-α, which can promote epithelial hyperplasia and barrier dysfunction ( 14 ). If similar inflammatory pathways are active in the esophageal epithelium, HP could potentiate epithelial remodeling in patients predisposed to EoE. Currently, there are no recommendation in EoE management guidelines advocating for routine HP eradication in patients with EE ( 8 ). Furthermore, the updated ESPGHAN/NASPGHAN guidelines for HP management emphasize the importance of appropriate diagnosis and treatment of HP infection in children, and reducing the rates of unnecessary eradication. These guidelines highlight HP’s complex interactions with the gastrointestinal immune system but do not provide recommendations regarding its potential role in EE or EoE development ( 15 ). Given our findings, future guideline revisions may need to consider whether HP testing should be incorporated into the diagnostic workup of pediatric patients with EE. As a result, HP-positive patients with EE may be mistakenly diagnosed with EoE and subjected to long-term management strategies meant for a chronic, immune-mediated disease. This misclassification has significant implications. Patients labeled with EoE often face unnecessary dietary restrictions, frequent endoscopic monitoring, and prolonged pharmacologic therapy, including proton pump inhibitors (PPIs) and corticosteroids ( 16 ). The potential misdiagnosis is particularly relevant given the common use of PPIs in EoE management ( 17 ). While PPIs are effective for some patients with EE, their long-term use in HP-positive individuals can be problematic. PPIs alter gastric acid secretion, which may promote HP expansion into the gastric corpus, potentially worsening gastritis and increasing the risk of atrophic gastric changes ( 18 ), and even precancerous lesions ( 19 ). In HP-infected patients, prolonged acid suppression could, paradoxically, worsen gastrointestinal pathology rather than provide benefit. Given these concerns, clinicians should carefully assess HP status before initiating long-term PPI therapy for presumed EoE. A key strength of our study is its novel contribution to the understanding of EE and its potential reversibility following HP eradication. This is one of the first studies to investigate whether HP infection may transiently cause EE and whether its eradication could prevent the misdiagnosis of EoE. Additionally, our study cohort was histologically confirmed, ensuring reliable identification of EE and HP infection. Furthermore, all patients underwent a repeat upper endoscopy post-eradication to confirm the resolution of EE with biopsies from three levels of the esophagus as per EoE guidelines ( 20 ). However, our study also has limitations. The small sample size, particularly within the HP eradication group, limited our ability to perform statistical analysis. As a retrospective study, we were also unable to control for potential confounding factors such as dietary exposures, atopic conditions, or other inflammatory triggers that might influence EE. Furthermore, we lacked long-term follow-up to determine whether EE resolution in HP-eradicated patients was sustained over time or if eosinophilia recurred. Future prospective studies with larger cohorts and extended follow-up are needed to validate these findings and clarify the potential causal relationship between HP eradication and EE resolution. Additionally, our study was conducted in Israel, a country with a relatively high prevalence of HP compared to Western nations where HP rates are declining. This limits the generalizability of our findings to populations with lower HP prevalence, where the impact of HP on EE may be less pronounced. Future studies in diverse geographic regions with varying HP prevalence are necessary to determine whether our findings are applicable to broader populations ( 21 ). In conclusion, our findings suggest that HP infection may contribute to EE in some pediatric and young adult patients and that its eradication or attenuation may lead to histologic resolution in select cases. Given the potential for misdiagnosis and unnecessary chronic treatment, HP testing should be considered in pediatric patients with EE, particularly younger individuals with mild eosinophilia and nonspecific endoscopic findings. Additionally, careful consideration should be given to the use of PPIs in HP-positive patients with EE, as acid suppression may exacerbate HP-related pathology. Future research should aim to clarify whether HP-induced EE represents a transient, self-limited condition or a potential precursor to EoE in certain individuals. If a true link between HP eradication and EE resolution is established, this could lead to modifications in diagnostic algorithms, ultimately preventing unnecessary lifelong EoE diagnoses and treatments in misclassified patients. Abbreviations BCH, Basal cell hyperplasia; EE, Esophageal eosinophilia; EoE, Eosinophilic esophagitis; HP, Helicobacter pylori; HPF, High power field Declarations Competing Interests and Funding: No funds, grants, or other support was received. The authors have no competing interests to declare that are relevant to the content of this article. Author Contribution A.A, N.M and Y.B collected the data.A.B conducted the statistical analysis.A.A and N.M wrote the main manuscript.T.S, E.B and D.C reviewed and contributed significantly to the manuscript, Data Availability Data is available for delivery by corresponding author by request. References Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153(2):420–9. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. 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Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem. Epidemiol Infect. 2019;147:e276. 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-6570424","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454791928,"identity":"7b30685a-21c6-4335-817e-fc2f8f827406","order_by":0,"name":"Nimrod Moss Ophir","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtklEQVRIiWNgGAWjYFACHoYDDAwSciDmgQekaDEGa0kgVgsIJDaASKK08Ev3HjxcucMifX7Y4YdAW+zkdBsIaJGccy7h4NkzErkbb6cZALUkG5sdIKDF4EaOwcHGNqCW2QkgLQcStxGrJd1wdvoH0rQkyEvnEGmL5JwzYC2GG6RzCg4kGBDhF37pHuOPjW118vKz0zd/+FBhJ0dQC4MEzIVglQaElCNrkW8gRvUoGAWjYBSMSAAAVuJHbnVyTG8AAAAASUVORK5CYII=","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Nimrod","middleName":"Moss","lastName":"Ophir","suffix":""},{"id":454791929,"identity":"c100a997-1e61-4e10-a01e-c312b1dcd6c7","order_by":1,"name":"Anton Bermont","email":"","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Anton","middleName":"","lastName":"Bermont","suffix":""},{"id":454791930,"identity":"d5d536dd-5fce-42a8-8001-8b1fafa0d3eb","order_by":2,"name":"Daniel L. Cohen","email":"","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"L.","lastName":"Cohen","suffix":""},{"id":454791931,"identity":"aefeb97f-bbf3-4d8c-bae1-71d746ce4c89","order_by":3,"name":"Tzippora Shalem","email":"","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Tzippora","middleName":"","lastName":"Shalem","suffix":""},{"id":454791932,"identity":"b8e9b598-8304-4cd1-bd08-16734c569a5e","order_by":4,"name":"Yael Ben Haim","email":"","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yael","middleName":"Ben","lastName":"Haim","suffix":""},{"id":454791933,"identity":"37b1a4bd-1a6c-4ff9-b6d2-a8be534f2302","order_by":5,"name":"Efrat Broide","email":"","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Efrat","middleName":"","lastName":"Broide","suffix":""},{"id":454791934,"identity":"237466a6-5d5f-4e30-821a-e06646fa0bb0","order_by":6,"name":"Adi Eindor-Abarbanel","email":"","orcid":"","institution":"Shamir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Adi","middleName":"","lastName":"Eindor-Abarbanel","suffix":""}],"badges":[],"createdAt":"2025-05-01 08:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6570424/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6570424/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82583379,"identity":"62d4abe2-2a9a-47d4-b494-5b0f15802268","added_by":"auto","created_at":"2025-05-13 06:50:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":12265,"visible":true,"origin":"","legend":"\u003cp\u003eStudy\u003cstrong\u003e \u003c/strong\u003epopulation flowchart\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6570424/v1/544eeaae7082b45d0b391351.png"},{"id":89242609,"identity":"65f040e5-3fbf-4a4e-90c4-39696ed63f1f","added_by":"auto","created_at":"2025-08-17 21:16:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":643484,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6570424/v1/502c8cee-b47d-44b6-96d8-b88df2161ccc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Helicobacter pylori as a potential cause of reversible esophageal eosinophilia","fulltext":[{"header":"What is Known?","content":"\u003cul\u003e\n \u003cli\u003e\u003cem\u003eHelicobacter pylori\u003c/em\u003e (HP) infection is common in children, though its prevalence is declining in developed countries. There is an inverse association between HP infection and eosinophilic esophagitis (EoE), suggesting a potential immunomodulatory effect.\u003c/li\u003e\n \u003cli\u003eCurrent guidelines for EoE and HP management do not recommend routine HP testing or eradication in patients with esophageal eosinophilia (EE).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is New?\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eIn a retrospective cohort, over third of HP-positive children who underwent eradication therapy experienced resolution of EE, suggesting that HP may contribute to transient esophageal eosinophilia. Younger patients with lower eosinophil counts were more likely to show EE resolution, raising the possibility of a distinct, non-EoE eosinophilic response.\u003c/li\u003e\n \u003cli\u003eBasal cell hyperplasia (BCH) was significantly more frequent in patients with both EoE and HP infection compared to EoE alone, suggesting that HP may contribute to epithelial remodeling in the esophagus. This finding raises questions about the impact of HP on esophageal histology and its potential role in disease progression.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eHelicobacter pylori\u003c/em\u003e (HP) infects up to half of the world's population (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The prevalence varies substantially according to age, ethnicity, geographic region, associated diseases, socioeconomic status and hygiene conditions. The global prevalence has been decreasing due to improvements in the two last aforementioned causes and due to eradication therapies as a further contributor (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOn the contrary, the incidence of eosinophilic esophagitis (EoE) is increasing worldwide, with both environmental and genetic factors involved in its pathogenesis. One of the suggested theories for EoE development is the hygiene hypothesis which leads to an imbalance between T helper 1 (Th1) and T helper 2 (Th2) mediated immune responses (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), since allergic conditions are common comorbidities. While EoE involves Th2 mediated immune response, HP involves the Th1 mediated response (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The rapid decrease in HP prevalence may contribute to this imbalance, with a hyper-activated Th2 response, and therefore to the rising incidence of EoE. This is supported by inverse correlation between HP infection and EoE reported by various studies (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, when encountering esophageal eosinophilia (EE), one must exclude other etiologies before EoE diagnosis is made, including infections (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). HP should be considered in the differential diagnosis of gastrointestinal (GI) tissue eosinophilia both in the stomach and in other parts of the GI tract (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). A possible explanation for EE secondary to HP infection is gastric acid hypersecretion during early HP antral-predominant infection causing esophageal barrier injury and secondary inflammation including eosinophilic response.\u003c/p\u003e \u003cp\u003eDespite knowledge regarding the inverse correlation between HP infection and EoE, there is a lack of comprehensive studies investigating the relationship between EE, when already present, and HP infection and eradication. We aimed to address this gap by examining the presence of HP in pediatric and young adult patients with EE and the effect of its eradication on such eosinophilia in this population.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eWe conducted a retrospective observational study at Shamir Medical Center, Israel, evaluating pediatric and young adult patients (aged 1\u0026ndash;21 years) diagnosed with EE between 2019 and 2024. EE was defined as the presence of \u0026ge;\u0026thinsp;15 eosinophils per high-power field (HPF) on esophageal biopsy from any level, obtained during upper endoscopy.\u003c/p\u003e \u003cp\u003ePatients were categorized into two groups based on HP status, determined by histological evaluation of gastric antrum and/or corpus biopsies, including Giemsa stain in all samples and immunohistochemistry when inconclusive. Demographic characteristics, clinical symptoms at diagnosis, and endoscopic and histologic findings were collected and compared between HP-positive and HP-negative patients.\u003c/p\u003e \u003cp\u003eA subset of HP-positive patients underwent eradication therapy, after which a follow-up endoscopy with repeat esophageal and gastric biopsies was performed under no medicinal or dietary treatment, timed at least a month following completion of eradication. We assessed the resolution of EE post-eradication, defined as less than 15 eosinophils per HPF in all esophageal biopsies, and analyzed clinical and histological changes in this subgroup. All other patients with EE were treated according to EoE guidelines (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEthics statement:\u003c/p\u003e \u003cp\u003e The study was approved by the ethics committee of the Shamir medical center IRB no ASF-0192-24. This study was exempt from obtaining patient consent as it involved retrospective data analysis with de-identified records, in accordance with the regulations of the Institutional Review Board.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eCategorical variables were summarized as frequency and percentages. The distribution of the continuous variables was evaluated using histograms. Normally distributed continuous variables were reported as means and SD, while other variables were reported as median and IQR. Categorical variables were compared using chi test of Fisher exact test and continuous and ordinal variables using independent student t- test, ANOVA, Mann Whitny test or Kruskal Wallis test. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered significant. The analysis was performed using SPSS 26.0.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eNinety-seven patients, aged 1\u0026ndash;21 years, were diagnosed with EE during the years 2019\u0026ndash;2024 in the Shamir medical center. Sixty-eight (70.1%) were males and the mean age at diagnosis was 10.46\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.79 years. Overall, 54 (55.7%) of the patients had an atopic background and the most common clinical presenting symptoms were dysphagia or eating problems (49, 50.5%) and nausea and/or vomiting (45, 46.4%), followed by abdominal pain (28, 28.9%), food impaction (19, 19.6%), chest pain or heartburn (9, 9.3%) and failure to thrive or weight loss (8, 8.2%). Esophageal endoscopic findings included furrows in 70 (72.2%) patients, exudates in 46 (47.4%) patients and trachealization in 20 (20.6%). Esophageal stricture was diagnosed in only 2 patients (2.1%). Microscopically, mean esophageal eosinophilic counts per HPF were highest in the lower esophagus (38.35\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;32.57), followed by mid-esophagus (36.87\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;32.94) and upper esophagus (31.81\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;37.58). The mean maximal eosinophilic count was 50.89\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;33.71 per HPF. Data shown in Tables \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTwenty-three (23.7%) patients in our cohort had a concomitant HP infection. Twelve (52.2%) were given recommendations for HP eradication, which was successful in 11 (91.7%). Data shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Demographic and clinical features were similar between HP-positive and HP-negative groups (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), as well as endoscopic and microscopic features (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), excluding basal cell hyperplasia (BCH) which was more common in HP-positive patients (60.9% compares with 36.5%, P\u0026thinsp;=\u0026thinsp;0.039).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical features among HP-positive and HP-negative EE patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll EE patients (n\u0026thinsp;=\u0026thinsp;97)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHP-positive (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHP-negative (n\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.46\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.83\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.35\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;53.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.715\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (70.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (73.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (68.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.648\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eAtopic features\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (21.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (21.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFood allergy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (40.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (35.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (41.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtopic dermatitis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (21.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.226\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther atopy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (21.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (29.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.736\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest pain / heartburn (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (9.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea and/or vomiting (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysphagia / eating problems\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (50.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (65.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (45.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFood impaction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.769\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight loss / failure to thrive (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEndoscopic and microscopic features among HP-positive and HP-negative EE patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAll EE patients (n\u0026thinsp;=\u0026thinsp;97)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHP-positive (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHP-negative (n\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eEndoscopic features\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTrachealization (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (24.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eExudates (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (47.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFurrows (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (72.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (56.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57 (77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eStricture (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eMicroscopic features\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eEosinophil count (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.35\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;32.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.65\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;48.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.65\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;27.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.842\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMid-esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.87\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;32.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.48\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;41.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.36\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;29.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.855\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpper esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.81\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;37.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.68\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;55.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.59\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;30.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMaximal eosinophilic count (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.89\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;33.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.09\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;46.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.58\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;28.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.888\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBasal cell hyperplasia (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (42.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (60.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27 (36.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEosinophilic microabscesses (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (8.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.241\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong 11 HP-positive patients who underwent successful HP eradication, EE resolution was observed in 4 (36.4%) on follow-up endoscopy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), as well as in the 1 (9.1%) patient without successful HP eradication, despite the lack of proper long term EoE treatment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAlthough small sample size limited statistical analysis, patients with EE resolution were younger (median 6 years, IQR 5.5\u0026ndash;13.5, vs. median 16 years, IQR 8\u0026ndash;17), were less likely to be of male gender, and had less frequent atopic background (40 vs. 71.4% for both). Clinically, these patients presented more commonly with chest pain or heartburn (40% vs. 14.3%) and none presented with food impaction (compared with 42.9%). Data shown in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical features among EE patients receiving HP eradication\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEE resolution (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo EE resolution (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (IQR 5.5\u0026ndash;13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (IQR 7\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAtopic features\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFood allergy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtopic dermatitis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAllergic rhinitis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther atopy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest pain / heartburn (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea and/or vomiting (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysphagia / eating problems\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFood impaction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight loss / failure to thrive (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEsophageal endoscopic features of EoE (trachealization, exudates, furrows or stricture) were noted in only 1 patient with EE resolution (20%) compared with 4 patients (57.1%) without EE resolution. Esophageal and duodenal ulcers were only diagnosed in patients with EE resolution. Presence of nodular gastritis was similar in both groups. Data shown in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eMicroscopically, median esophageal eosinophilic counts per HPF were lower in patients with EE resolution compared with patients without EE resolution in all esophageal levels; 6 (IQR 0\u0026ndash;73) vs. 39.5 (IQR 9\u0026ndash;95) in lower esophagus, 18 (IQR 8-26.5) vs. 41 (IQR 20\u0026ndash;60) in mid-esophagus, and 6.5 (IQR 0-78.25) vs. 50 (41\u0026ndash;150) in upper esophagus. Similar findings were noted in median maximal eosinophilic count between the two groups with 26 (IQR 19.5\u0026ndash;76) eosinophils per HPF in patients with EE resolution compared with 50 (IQR 41\u0026ndash;150) in patients without EE resolution. Data shown in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEndoscopic and microscopic features among EE patients receiving HP eradication\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEE resolution (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo EE resolution (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eEndoscopic features\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTrachealization (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eExudates (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFurrows (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eStricture (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAll EoE esophageal features (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEsophageal ulcer (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNodular gastritis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDuodenal ulcer (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eMicroscopic features\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eEosinophil count (median)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (IQR 0\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.5 (IQR 9\u0026ndash;95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMid-esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (IQR 8-26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (IQR 20\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpper esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.5 (IQR 0-78.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (IQR 0-150)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMaximal eosinophilic count (median)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (IQR 19.5\u0026ndash;76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (IQR 41\u0026ndash;150)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBasal cell hyperplasia (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEosinophilic microabscesses (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn patients with EE resolution, the highest eosinophilic count was noted only in the mid (3, 60%) or lower (2, 40%) esophagus while in patients with no EE resolution it was noted most commonly in the upper esophagus (3, 42.9%) and in 2 patients (28.6%) it was evenly distributed on all esophageal levels (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Other microscopic findings were similar between the groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLocation of maximal esophageal eosinophilic count among EE patients receiving HP eradication\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEsophageal level of maximal eosinophilic count\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEE resolution (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo EE resolution (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMid-esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEvenly distributed in lower and mid-esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEvenly distributed in all esophageal levels\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (28.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study explored the relationship between HP infection and EE in pediatric patients. While we found no significant differences in clinical presentation or disease characteristics between HP-positive and HP-negative groups at diagnosis, an intriguing observation emerged from the small subset of HP-positive patients who successfully underwent eradication therapy. Among these 11 patients, 4 exhibited resolution of EE and did not progress to EoE. Similar findings were observed in 1 additional patient who underwent unsuccessful HP eradication attempt. Although our sample size was insufficient for statistical analysis, this trend suggests that HP eradication or attenuation may play a role in resolving EE in select patients, particularly younger children lacking macroscopic findings suggestive of EoE and with lower eosinophil counts. \u003cem\u003eShah et al.\u003c/em\u003e conducted a meta-analysis demonstrating that HP exposure was associated with decreased odds of EoE, possibly due to HP\u0026rsquo;s immunomodulatory effects (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, our study suggests that HP infection can be a possible massacre for the diagnosis of EoE.\u003c/p\u003e \u003cp\u003eIn our study BCH was significantly more frequent in patients with both EE and HP infection compared to those with EE alone (60.9% vs. 36.5%, p\u0026thinsp;=\u0026thinsp;0.039). BCH is a hallmark histologic feature of EoE, reflecting epithelial remodeling due to chronic inflammation and increased esophageal mucosal turnover. However, its higher prevalence in HP-positive patients raises several intriguing questions about the interplay between HP infection and esophageal epithelial changes (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). One possible explanation for this association is that HP-induced gastric acid hypersecretion, particularly in the early stages of infection, may exacerbate esophageal injury, leading to increased basal cell proliferation as part of the mucosal repair process. HP infection is known to affect acid production dynamically\u0026mdash;while chronic infection may lead to hypochlorhydria, early HP infection, especially in antral-predominant cases, has been associated with increased acid output (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). This could contribute to esophageal epithelial stress, thereby amplifying BCH.\u003c/p\u003e \u003cp\u003eAnother potential mechanism is HP\u0026rsquo;s impact on the esophageal immune environment. HP infection has been shown to modulate immune responses, shifting the balance between Th1 and Th2 pathways (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Since BCH in EoE is thought to be driven by epithelial cytokines such as IL-13 and TGF-β, it is possible that HP infection alters the inflammatory milieu, further stimulating epithelial proliferation (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This hypothesis aligns with findings from studies showing that epithelial remodeling in EoE is not solely dependent on eosinophil-mediated damage but also influenced by broader immune dysregulation. Additionally, HP-related cytokine signaling might contribute to BCH development. HP infection has been associated with increased expression of pro-inflammatory mediators such as IL-6 and TNF-α, which can promote epithelial hyperplasia and barrier dysfunction (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). If similar inflammatory pathways are active in the esophageal epithelium, HP could potentiate epithelial remodeling in patients predisposed to EoE.\u003c/p\u003e \u003cp\u003eCurrently, there are no recommendation in EoE management guidelines advocating for routine HP eradication in patients with EE (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Furthermore, the updated \u003cem\u003eESPGHAN/NASPGHAN guidelines\u003c/em\u003e for HP management emphasize the importance of appropriate diagnosis and treatment of HP infection in children, and reducing the rates of unnecessary eradication. These guidelines highlight HP\u0026rsquo;s complex interactions with the gastrointestinal immune system but do not provide recommendations regarding its potential role in EE or EoE development (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Given our findings, future guideline revisions may need to consider whether HP testing should be incorporated into the diagnostic workup of pediatric patients with EE. As a result, HP-positive patients with EE may be mistakenly diagnosed with EoE and subjected to long-term management strategies meant for a chronic, immune-mediated disease. This misclassification has significant implications. Patients labeled with EoE often face unnecessary dietary restrictions, frequent endoscopic monitoring, and prolonged pharmacologic therapy, including proton pump inhibitors (PPIs) and corticosteroids (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe potential misdiagnosis is particularly relevant given the common use of PPIs in EoE management (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). While PPIs are effective for some patients with EE, their long-term use in HP-positive individuals can be problematic. PPIs alter gastric acid secretion, which may promote HP expansion into the gastric corpus, potentially worsening gastritis and increasing the risk of atrophic gastric changes (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), and even precancerous lesions (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In HP-infected patients, prolonged acid suppression could, paradoxically, worsen gastrointestinal pathology rather than provide benefit. Given these concerns, clinicians should carefully assess HP status before initiating long-term PPI therapy for presumed EoE.\u003c/p\u003e \u003cp\u003eA key strength of our study is its novel contribution to the understanding of EE and its potential reversibility following HP eradication. This is one of the first studies to investigate whether HP infection may transiently cause EE and whether its eradication could prevent the misdiagnosis of EoE. Additionally, our study cohort was histologically confirmed, ensuring reliable identification of EE and HP infection. Furthermore, all patients underwent a repeat upper endoscopy post-eradication to confirm the resolution of EE with biopsies from three levels of the esophagus as per EoE guidelines (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, our study also has limitations. The small sample size, particularly within the HP eradication group, limited our ability to perform statistical analysis. As a retrospective study, we were also unable to control for potential confounding factors such as dietary exposures, atopic conditions, or other inflammatory triggers that might influence EE. Furthermore, we lacked long-term follow-up to determine whether EE resolution in HP-eradicated patients was sustained over time or if eosinophilia recurred. Future prospective studies with larger cohorts and extended follow-up are needed to validate these findings and clarify the potential causal relationship between HP eradication and EE resolution. Additionally, our study was conducted in Israel, a country with a relatively high prevalence of HP compared to Western nations where HP rates are declining. This limits the generalizability of our findings to populations with lower HP prevalence, where the impact of HP on EE may be less pronounced. Future studies in diverse geographic regions with varying HP prevalence are necessary to determine whether our findings are applicable to broader populations (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn conclusion, our findings suggest that HP infection may contribute to EE in some pediatric and young adult patients and that its eradication or attenuation may lead to histologic resolution in select cases. Given the potential for misdiagnosis and unnecessary chronic treatment, HP testing should be considered in pediatric patients with EE, particularly younger individuals with mild eosinophilia and nonspecific endoscopic findings. Additionally, careful consideration should be given to the use of PPIs in HP-positive patients with EE, as acid suppression may exacerbate HP-related pathology.\u003c/p\u003e \u003cp\u003eFuture research should aim to clarify whether HP-induced EE represents a transient, self-limited condition or a potential precursor to EoE in certain individuals. If a true link between HP eradication and EE resolution is established, this could lead to modifications in diagnostic algorithms, ultimately preventing unnecessary lifelong EoE diagnoses and treatments in misclassified patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBCH,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBasal cell hyperplasia; EE, Esophageal eosinophilia; EoE, Eosinophilic esophagitis; HP, Helicobacter pylori; HPF, High power field\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eCompeting Interests\u003c/strong\u003e \u003cp\u003eand Funding: No funds, grants, or other support was received. The authors have no competing interests to declare that are relevant to the content of this article.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.A, N.M and Y.B collected the data.A.B conducted the statistical analysis.A.A and N.M wrote the main manuscript.T.S, E.B and D.C reviewed and contributed significantly to the manuscript,\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is available for delivery by corresponding author by request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153(2):420\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEusebi LH, Zagari RM, Bazzoli F. Epidemiology of Helicobacter pylori infection. Helicobacter. 2014;19 Suppl 1:1\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark JS, Jun JS, Seo J-H, Youn H-S, Rhee K-H. Changing prevalence of Helicobacter pylori infection in children and adolescents. Clin Exp Pediatr. 2021;64(1):21\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRenz H, Bl\u0026uuml;mer N, Virna S, Sel S, Garn H. The immunological basis of the hygiene hypothesis. Chem Immunol Allergy. 2006;91:30\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagheri N, Salimzadeh L, Shirzad H. The role of T helper 1-cell response in Helicobacter pylori-infection. Microb Pathog. 2018;123:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah SC, Tepler A, Peek RMJ, Colombel J-F, Hirano I, Narula N. Association Between Helicobacter Pylori Exposure and Decreased Odds of Eosinophilic Esophagitis-A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2019;17(11):2185\u0026ndash;2198.e3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDhar A, Haboubi HN, Attwood SE, Auth MKH, Dunn JM, Sweis R, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. 2022;71(8):1459\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapadopoulou A, Amil-Dias J, Auth MK-H, Chehade M, Collins MH, Gupta SK, et al. Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2024;78(1):122\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhelan KA, Godwin BC, Wilkins B, Elci OU, Benitez A, DeMarshall M, et al. Persistent Basal Cell Hyperplasia Is Associated With Clinical and Endoscopic Findings in Patients With Histologically Inactive Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2020;18(7):1475\u0026ndash;1482.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagheri N, Salimzadeh L, Shirzad H. The role of T helper 1-cell response in Helicobacter pylori-infection. Microb Pathog. 2018;123(June):1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRochman M, Azouz NP, Rothenberg ME. Epithelial origin of eosinophilic esophagitis. J Allergy Clin Immunol. 2018;142(1):10\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu B, Xiang L, Peppelenbosch MP, Fuhler GM. Overlapping cytokines in H. pylori infection and gastric cancer: A tandem meta-analysis. Front Immunol. 2023;14:1125658.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoman M, Jones NL, Bontems P, Carroll MW, Czinn SJ, Gold BD, et al. Updated joint ESPGHAN/NASPGHAN guidelines for management of Helicobacter pylori infection in children and adolescents (2023). J Pediatr Gastroenterol Nutr. 2024;(May):1\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLucendo AJ, L\u0026oacute;pez-S\u0026aacute;nchez P. Targeted Therapies for Eosinophilic Gastrointestinal Disorders. BioDrugs. 2020;34(4):477\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuti\u0026eacute;rrez-Junquera C, Fern\u0026aacute;ndez-Fern\u0026aacute;ndez S, Dom\u0026iacute;nguez-Ortega G, Vila Miravet V, Garc\u0026iacute;a-Puig R, La Orden-Izquierdo E, et al. Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy. J Pediatr Gastroenterol Nutr. 2023;76(2):191\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Z, Wu C, Li L, Wang Z, Xie H, He X, et al. Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis. Saudi J Gastroenterol Off J Saudi Gastroenterol Assoc. 2017;23(4):222\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaziri A, Juniku-Shkololli A, Gashi Z, Berisha D, Haziri A. Helicobacter pylori infection and precancerous lesions of the stomach. Med Arh. 2010;64(4):248\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Bortoli N, Visaggi P, Penagini R, Annibale B, Baiano Svizzero F, Barbara G, et al. The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring. Dig liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2024;56(7):1173\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuhsen K, Sinnereich R, Beer-Davidson G, Nassar H, Abu Ahmed W, Cohen D, et al. Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem. Epidemiol Infect. 2019;147:e276.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Helicobacter pylori, Eosinophilic esophagitis, Esophageal eosinophilia, Basal cell hyperplasia","lastPublishedDoi":"10.21203/rs.3.rs-6570424/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6570424/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003e \u003cem\u003eHelicobacter pylori\u003c/em\u003e (HP) infects up to half of the global population, though its prevalence is declining due to improved hygiene and eradication therapies. In contrast, eosinophilic esophagitis (EoE) incidence is rising, potentially linked to the hygiene hypothesis. Studies suggest an inverse relationship between HP and EoE, but esophageal eosinophilia (EE) can arise from various causes, including infections. The aim of this study was to examine the association between HP and EE and the effect of HP eradication.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective observational study of patients aged 1\u0026ndash;21 years diagnosed with EE (\u0026gt;\u0026thinsp;15 eosinophils/high power field [HPF]) between 2019 and 2024 at Shamir Medical Center, Israel. Gastric biopsies confirmed HP infection, followed by eradication therapy and repeat endoscopy. Data included demographics, medical history, endoscopic findings, HP eradication success, and esophageal histology.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 97 patients with EE, 70.1% were male, and the mean age was 10.46\u0026thinsp;\u0026plusmn;\u0026thinsp;5.79 years. HP infection was present in 23 (23.7%) patients, with successful eradication in 11 (47.8%). Basal cell hyperplasia (BCH) was more frequent in HP-positive patients (60.9% vs. 36.5%, P\u0026thinsp;=\u0026thinsp;0.039). Other features were similar. EE resolved in 4 (36.4%) of successfully eradicated patients. Patients with EE resolution were younger, less likely male, and had fewer atopic conditions.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHP infection may contribute to esophageal epithelial remodeling as indicated by increased BCH. In some children, HP-associated EE may be reversible. HP diagnosis and eradication should be considered before confirming EoE, particularly in younger patients with mild eosinophilia and no macroscopic EoE findings.\u003c/p\u003e","manuscriptTitle":"Helicobacter pylori as a potential cause of reversible esophageal eosinophilia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 06:49:59","doi":"10.21203/rs.3.rs-6570424/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":"7097b52e-956e-4a44-89b7-462ef9fa2450","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-17T21:08:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 06:49:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6570424","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6570424","identity":"rs-6570424","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}