Refractory Eosinophilic Duodenal Bulb Ulcer Associated with Helicobacter pylori Eradication in Children: A Multicenter Study

Refractory Eosinophilic Duodenal Bulb Ulcer Associated with Helicobacter pylori Eradication in Children: A Multicenter Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Refractory Eosinophilic Duodenal Bulb Ulcer Associated with Helicobacter pylori Eradication in Children: A Multicenter Study Zhiheng Huang, Ping Li, Ying Zhou, Min Ji, Yangyang Ma, Yingying Meng, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8090557/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted 16 You are reading this latest preprint version Abstract Background and aims: Refractory eosinophilic duodenal bulb ulcers (REDU) that develop following Helicobacter pylori (HP) eradication are rarely recognized. This study aimed to investigate the REDU in pediatric populations after HP eradication. Methods This multicenter retrospective analysis was conducted on children admitted to the gastroenterology department of three children’s hospitals from January 1, 2016, to August 31, 2025. Eligible pediatric cases diagnosed with REDU across the three centers were included. For the REDU group, clinical characteristics, laboratory tests, endoscopic findings, HP treatment strategies, and follow-up data were analyzed. Results Thirty patients (mean age 10.0 ± 3.4 years) were diagnosed with REDU, including 19 with HP eradication-related REDU and 11 with idiopathic REDU. Compared with the HP-induced DBU control group, the HP eradication-related REDU group had higher rates of anemia, elevated peripheral blood eosinophils (EOS) count, endoscopic giant DBU, bulbar stenosis, repeated endoscopies, and HP eradication therapies (all P < 0.01). REDU patients presented with punched-out DBU featuring a clean, thin white base; 76.7% (23/30) of REDU patients had giant DBU. Before treatment, among the entire REDU cohort, 9 patients had pathological EOS counts ≥ 100 cells/high-power field (HPF), and another 9 had ≥ 50 cells/HPF. Serum cytokine assay showed that IL-8 was significantly elevated. All patients were treated with dietary avoidance and proton pump inhibitor (PPI) therapy. Recurrence was common, occurring in 9 of 16 patients (56.2%) following PPI dose reduction or discontinuation (median interval: 50.0 [35.0, 120.0] days). Conclusions HP eradication may associate with REDU in children via eosinophilic infiltration, emphasizing the need for systematic monitoring of immune-related complications post-eradication. Health sciences/Diseases Health sciences/Gastroenterology Health sciences/Medical research Biological sciences/Microbiology refractory duodenal ulcer Helicobacter pylori eosinophilic gastrointestinal disorders proton pump inhibitor children Figures Figure 1 Figure 2 Figure 3 Introduction Helicobacter pylori (HP), a Gram-negative bacterium, remains a pivotal focus in clinical gastroenterology, with well-established links to peptic ulcer disease, including gastric and duodenal ulcers [1]. Our prior research validated the safety and efficacy of four HP eradication regimens and characterized long-term gut microbiota shifts[2], which has advanced clinical management and solidified HP eradication as a cornerstone of therapy for HP-associated diseases. Eosinophilic gastrointestinal diseases (EGIDs) encompass a heterogeneous group of disorders defined by abnormal eosinophil (EOS) infiltration in the gastrointestinal tract, which triggers inflammatory cascades that manifest as symptoms ranging from mild discomfort to severe complications (e.g., vomiting, abdominal pain, anemia, and growth retardation)—a condition particularly prevalent in pediatric populations [3,4]. Emerging evidence reveals a complex interplay between HP and EGIDs. Epidemiological studies consistently demonstrate an inverse association: lower HP prevalence in patients with eosinophilic gastritis (EGE) or eosinophilic esophagitis (EoE) compared to healthy controls, suggesting a potential protective role of HP in mitigating chronic immune-mediated diseases[5]. This "protective effect" is hypothesized to stem from the ability of HP to shift mucosal immunity toward a Th1-dominated response, thereby suppressing Th2-mediated pathways that are central to the pathogenesis of EGIDs. Conversely, a growing body of reports links successful HP eradication to the de novo onset or exacerbation of eosinophilic conditions, including refractory eosinophilic duodenal bulb ulcers (REDU) [6,7]. This paradox—where eradication of a pathogen (HP) linked to ulcer disease precipitates a distinct, immune-mediated ulcer phenotype—raises critical questions regarding the long-term consequences of HP clearance, particularly in children with developing immune systems. Despite their rarity, these REDU cases pose significant diagnostic and therapeutic challenges, with their pathophysiology remaining poorly understood—a knowledge gap amplified by the paucity of pediatric data in this field. To date, research on the post-eradication development of REDU (distinct from HP-associated DBU) remains limited, particularly in pediatric cohorts. This multicenter study aims to address this gap by characterizing the clinical features, endoscopic findings, pathological mechanisms, and management strategies of this understudied condition, with implications for optimizing clinical practice in pediatric gastroenterology. Methods Data Sources This study was approved by the Ethics Committee of the Children’s Hospital of Fudan University (Shanghai, China; IRB No.: 2024 (248)). All methods were performed in accordance with the relevant guidelines and regulations Written informed consent was obtained from the parents of all participants prior to study initiation. Pediatric patients were recruited retrospectively between January 1, 2016, and August 31, 2025, and their electronic medical records were reviewed to assess eligibility. The inclusion and exclusion criteria Inclusion criteria: ① Diagnosis of duodenal bulb ulcer (DBU) (a subtype of peptic ulcer) confirmed by endoscopy, with documentation of ulcer location, size, number, and recurrence interval. ② Pathological evidence of EOS counts ≥ 50 cells per high-power field (HPF) in duodenal bulb biopsies [3]. ③ Documentation of HP testing (e.g., ¹³C urea breath test [¹³C UBT], rapid urease test [RUT], pathological examination); HP eradication therapy was administered to all patients with positive HP test results. Exclusion criteria Patients with intestinal tuberculosis, inflammatory bowel disease, parasitic infections, eosinophilic leukemia, primary immunodeficiencies, non-steroidal anti-inflammatory drug (NSAID)-induced reactions, or other confounding conditions were excluded. REDU was defined as refractory eosinophilic duodenal bulb ulcers that either persisted at the first follow-up endoscopy or initially resolved but relapsed during subsequent follow-ups [8]. These REDU cases were divided into 2 subgroups based on their HP infection status:​ Group A HP eradication-associated REDU group​ Definition Patients with definitive evidence of HP infection (e.g., positive ¹³C urea breath test [¹³C UBT], positive rapid urease test [RUT], or positive pathological examination), who developed DBU within 8 weeks after completing HP eradication therapy and met the diagnostic criteria for REDU as defined above. Group B Idiopathic REDU group​ Definition Patients with no definitive evidence of HP infection (all HP detection tests were negative), no other identified causes of ulcers (e.g., NSAID use, autoimmune diseases), and who met the diagnostic criteria for REDU. Group C Control group. Thirty-eight children at the same period with HP-associated DBU who underwent HP eradication therapy and achieved successful DBU healing were randomly selected. These patients were matched to Group A by age (± 2 years), gender, and HP eradication regimen to ensure they had the same exposure (i.e., HP eradication) but a different outcome (i.e., no post-eradication ulcer recurrence) Laboratory and Genetic Assessments During ulcer recurrence, the following parameters were evaluated: peripheral blood EOS count, erythrocyte sedimentation rate (ESR), serum albumin level, serum specific IgE level, immunoglobulin G4 (IgG4) level, and humoral/cellular immunity profiles. For the REDU group, thirty-four serum cytokines were measured using a Luminex 200 instrument (Millipore) with a ThermoFisher ProcartaPlex multiplex immunoassay kit (cat. no.: EPXR340-12167-901), including macrophage inflammatory protein-1α (MIP-1α), MIP-1β, stromal cell-derived factor-1α (SDF-1α), interleukin-27 (IL-27), IL-1β, IL-2, IL-4, IL-5, interferon gamma-induced protein 10 (IP-10), IL-6, IL-7, IL-8, IL-10, Eotaxin, IL-12p70, IL-13, IL-17A, IL-31, IL-1 receptor antagonist (IL-1RA), CCL5/regulated on activation, normal T cell expressed and secreted (RANTES), interferon-γ (IFN-γ), granulocyte–macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), TNF-β, IFN-α, monocyte chemoattractant protein-1 (MCP-1), IL-9, growth-related oncogene alpha (GRO-α), IL-1α, IL-23, IL-15, IL-18, IL-21, and IL-22. Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene polymorphisms were analyzed via polymerase chain reaction (PCR). The metabolic phenotypes of CYP2C19 included extensive metabolizers (EM), intermediate metabolizers (IM), poor metabolizers (PM), rapid metabolizers (RM), and ultrarapid metabolizers (UM). Endoscopic and Histopathological Evaluation Upper gastrointestinal endoscopy (gastroscopy) and lower gastrointestinal endoscopy (colonoscopy) were performed under deep sedation. Biopsies of the duodenal bulb and gastric antral mucosa were collected for pathological examination and EOS counting. Colonoscopy with mucosal biopsies was performed to rule out duodenal ulcers secondary to systemic diseases. Duodenal bulb ulcers with a diameter of ≥ 2 cm observed during endoscopy were defined as giant DBU, as described in previous studies [9]. Statistical analysis Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]) depending on their distribution, while categorical variables were expressed as frequencies (percentages). Differences between the HP eradication-associated REDU group (Group A) and the HP eradication-control group (Group C) were analyzed using the chi-square (χ²) test for categorical variables and the independent samples t-test and the Mann–Whitney test for continuous variables. Binary logistic regression was employed to explore the risk factors of REDU.Statistical significance was set at P < 0.05. All statistical analyses were performed using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). Results Patient Baseline Characteristics Of 53 initially reviewed cases of suspected REDU, 30 were enrolled after applying the exclusion criteria (23 cases were excluded: 12 with insufficient pathological data, 9 with subthreshold EOS counts [< 50 cells/HPF], and 2 with comorbidities [Crohn’s disease and Henoch-Schönlein purpura]). A total of 30 enrolled patients with REDU were divided into two subgroups: Group A (HP eradication-associated REDU, 19 cases) and Group B (idiopathic REDU, 11 cases). An additional 38 children with HP-induced DBU who had achieved successful cure after HP eradication therapy were randomly selected as the control group (Group C). The REDU cohort (n = 30) comprised 27 males and 3 females (male-to-female ratio: 9:1; mean age: 10.0 ± 3.4 years; age range: 5–15 years Symptom duration ranged from 1 day to 6 years, with abdominal pain being the most common primary presenting symptom, median duration 24.0[7.5,30.0] month (Table 1 ). Seventeen patients (56.7% of the REDU cohort) presented with anemia, among whom three had severe anemia (with the lowest hemoglobin level of 57 g/L) accompanied by melena, requiring blood transfusion. Refractory duodenal bulb ulcers were the primary reason for repeated hospital visits. Table 1 The symptom for REDU patients first visit hospital Characteristic REDU Age (y) 10.0 ± 3.4 Body weight(kg) 34.3 ± 12.8 Gender Male: n (%) 27(90) Female: n (%) 3(10) Symptom Abdominal pain: n (%) 24 (80) Vomit: n (%) 2 (6.7) Hematemesis: n (%) 2 (6.7) Melena: n (%) 2 (6.7) Anemia: n (%) 19 (63.3) Pale: n (%) 4 (13.3) Chest distress: n (%) 1 (3.3) Malnutrition: n (%) 18 (60) Data are expressed as number (%) for categorical variables or median (range) for continuous variables HP: Helicobacter pylori; N: number; EDU: refractory eosinophilic duodenal bulb ulcers; y: year For the REDU cohort, the median body mass index (BMI, kg/m²) was 15.6, with an IQR of [15.0, 17.0]. Malnutrition was prevalent in the REDU cohort: 10 patients (33.3%) had a BMI z-score between − 1 and − 2 SD, 6 patients (20.0%) had a BMI z-score between − 2 and − 3 SD, and 1 patient (3.3%) had a BMI z-score < -3 SD. Comparison of Characteristics Between HP Eradication-Associated REDU (Group A) and HP-Associated DBU Control (Group C) The characteristics of the HP eradication-associated REDU group (Group A) and the HP-associated DBU control group (Group C) are compared in Table 2 . Abdominal pain was also the most common chief complaint in both groups. The time interval from HP treatment to the onset of REDU is 14.7 ± 8.8 months. The time interval between the diagnosis of HP infection and the negative result in ¹³C UBT re-examination is 9.3 ± 7.0 months. For the Group C, the time interval of the last follow-up was 3.0 (2.0, 11.5) months. No symptoms were reported in Group C, so no further follow-up visits to the gastroenterology department were conducted. Table 2 Comparison of Characteristics Between HP- eradication-associated REDU group and HP eradication-control group Characteristic HP- eradication-associated REDU group(n = 19) HP eradication-control group(n = 38) P value Age (y) 11.2 ± 3.0 11.4 ± 2.2 0.82 Body weight 38.8 ± 11.3 47.5 ± 16.3 0.02 Gender Male: n (%) 17(89.5) 31(81.6) 0.44 Female: n (%) 2(9.5) 7(18.4) Chief complain Abdominal pain: n (%) 15 (78.9) 24(63.2) 0.22 Anemia: n (%) 13(68.4) 4(10.5) 0.00 Melena: n (%) 1(5.3) 1(2.6) 0.61 Vomiting: n (%) 1(5.3) 3(7.9) 0.714 Ulcer In first gastroscopy Giant Duodenal bulb ulcer: n (%) 17 (89.5) 4(10.5) 0.00 Gastric Antrum ulcer: n (%) 2 (10.5) 4(10.5) 1.00 Duodenal bulb stenosis: n (%) 9 (47.4) 1 (2.6) 0.00 laboratory examination Blood EOS count (IQR) cells/µL 480[410,820] 140[77.5,245.0] 0.00 Hb (g/L) 87.0[70.0,122.0] 136.0[123.5,142.0] 0.00 Alb (g/L) 42.9 ± 3.2 44.4 ± 2.5 0.08 WBC (10^9/L) 7.5 ± 2.8 7.4 ± 2.4 0.88 Repeated endoscopy examination: n 7.8 ± 4.3 2.6 ± 1.3 0.00 Repeated HP eradication therapy : n [ IQR] 1.0[1.0,3.0] 1.0[1.0,1.0] 0.00 EOS : eosinophils; HP: Helicobacter pylori; n:number;REDU: refractory eosinophilic duodenal bulb ulcers; y: year. After gastroscopic diagnosis of HP-induced duodenal bulb ulcer, patients in Group A and Group C immediately received eradication therapy. Compared with the Group C, the HP eradication-associated REDU group (Group A) had a significantly higher incidence of anemia, giant DBU, and elevated peripheral blood EOS counts (all P < 0.01). Additionally, Group A had a higher need for repeated HP eradication therapy (42.1% vs. 2.6%, P < 0.01). The number of endoscopic examinations was also compared between the two groups. Compared with Group C, Group A required a significantly higher number of endoscopic examinations (median: 7.0 [IQR: 4.0, 11.0] vs. 2.0 [IQR: 2.0, 2.0], P < 0.001) (Table 2 ). For Group A (HP eradication-associated REDU), the median number of HP eradication courses per patient was 1.0 [IQR: 1.0, 2.5]. Binary logistic regression analysis revealed that an elevated peripheral blood EOS percentage (P = 0.008; odds ratio [OR] = 0.08, 95% confidence interval [CI]: 0.008–0.289) and the number of endoscopic examinations (P = 0.019; OR = 0.428, 95% CI: 0.210–0.869) were significant factors influencing the cure outcome of REDU. HP infection was confirmed in 8 patients via serum HP antibody testing, 9 patients via RUT, 3 patients via pathological examination of gastric mucosa biopsies, and 4 patients via ¹³C UBT. The HP eradication regimens administered to Group A patients included amoxicillin-based triple therapy (6 patients), bismuth-based quadruple therapy (16 patients), and high-dose amoxicillin-proton pump inhibitor (PPI) dual therapy (1 patient). Laboratory Findings Among the entire REDU cohort (n = 30), 19 patients (63.3%) had anemia, with a mean hemoglobin (Hb) level of 96.6 ± 25.6 g/L. When comparing Group A (HP eradication-associated REDU) and Group B (idiopathic REDU), no significant difference in mean Hb level was observed (Group A: 96.8 ± 26.9 g/L vs. Group B: 106.1 ± 23.0 g/L, P = 0.029). In the REDU cohort, the median serum IgE level was 393.0 kU/L (IQR: 61.7–655.8 kU/L; reference range: 0–300 kU/L), and the mean peripheral blood EOS count was 518.0 ± 349.0 cells/µL (reference range: 60–300 cells/µL). With respect to serum IgE levels and peripheral blood EOS counts, no significant differences were detected between Group A and Group B (all P > 0.05). In the REDU cohort, the mean erythrocyte sedimentation rate (ESR) was 17.6 ± 14.0 mm/h (reference range: 0–21 mm/h), the mean serum IgG4 level was 1.64 ± 1.29 g/L (reference range: 0.012–1.699 g/L), the mean serum albumin level was 42.6 ± 3.3 g/L (reference range: 35–55 g/L), and the mean serum prealbumin level was 201.5 ± 41.8 mg/L (reference range: 200–400 mg/L). No significant differences in ESR, serum IgG4 level, serum albumin level, or serum prealbumin level were observed between Group A and Group B (all P > 0.05). All 30 patients in the REDU cohort underwent specific allergen testing, among whom 28 (93.3%) tested positive. Of these 28 allergen-positive patients, 24 (85.7%) had food allergies—specifically, 15 (62.5% of food-allergic patients) were sensitized to cow’s milk protein, 13 (54.2%) to egg white, and 8 (33.3%) to egg yolk—and 11 (39.3% of allergen-positive patients) had dust mite sensitivity. For HP-associated DBU control group, allergen information is lacking due to disease testing and medical ethics restrictions. Serum cytokines were assayed in the REDU cohort(n=?). The median serum IL-8 level was significantly elevated to 361.2 pg/mL (IQR: 92.8–613.4 pg/mL; reference range: 0.0–47 pg/mL). Nine patients (30.0% of the REDU cohort) had elevated serum levels of both MIP-1α (reference range: 0.0–21 pg/mL) and MIP-1β (reference range: 0.0–147 pg/mL), while five patients (16.7%) had elevated serum levels of both IL-10 (reference range: 0.0–3.0 pg/mL) and TNF-α (reference range: 0.0–14 pg/mL). Additionally, one patient (3.3%) had an elevated serum IL-4 level (84.8 pg/mL; reference range: 0–45 pg/mL), and another patient (3.3%) had an elevated serum IL-5 level (41.2 pg/mL; reference range: 0–17 pg/mL). CYP2C19 gene polymorphisms were analyzed in 24 patients from the REDU cohort, and the metabolic phenotypes were as follows: 12 (50.0%) IM, 8 (34.8%) NM, 3 (13.0%) PM, and 1 (4.3%) RM. Endoscopic and Pathologic Findings Endoscopic findings of patients in the REDU cohort are summarized in Table 3 and Fig. 1 . Among patients with REDU, 13 (13/30) had ulcers located in the postbulbar duodenum, 12 (12/30) in the anterior wall of the duodenal bulb, and 5 (5/30) in the greater curvature of the duodenal bulb; of these patients, 3 had "kissing ulcers”. Eosinophilic duodenal bulb ulcers (in both Group A and Group B) were characterized by large, shallow, pan-like lesions covered with a clean, thin white exudate—distinct from HP-associated DBU (Group C), which typically featured a dirty ulcer base (Fig. 1 A, 1 I). Regarding giant DBU, 17 patients (89.5% of Group A) had giant DBU, compared with 6 patients (54.5% of Group B) (P < 0.001). Twenty-eight patients (93.3% of the REDU cohort) underwent colonoscopy, which revealed terminal ileitis in 13 patients (46.4% of colonoscopy recipients) and proctocolitis in 8 patients (28.6%). Fourteen patients (46.7% of the REDU cohort) underwent capsule endoscopy, with findings including enteritis (6 patients, 42.9% of capsule endoscopy recipients), duodenal ulcer (2 patients, 14.3%), normal findings (4 patients, 28.6%), and capsule impaction secondary to duodenal bulb stenosis (2 patients, 14.3%). Table 3 The endoscopic findings in all REDU patients Endoscopic Findings Duodenal Bulb N (%) Duodenal descending Part N (%) Gastric Body N (%) Gastric Antrum N (%) Esophagus N (%) Ulcer 30 (100) 0 (0) 0 (0) 4 (13.3) 2 (6.6) Stenosis 13(43.3) 0 (0) 0 (0) 0 (0) 0 (0) Edema 13 (43.3) 0 (0) 2(6.6) 3 (10.0) 6 (20) Erosion 7 (23.3) 1 (3.3) 0 (0) 4(13.3) 1 (3.3) Bleeding 1 (3.3) 0 (0) 0 (0) 1 (3.3) 0 (0) N: number; REDU: refractory eosinophilic duodenal bulb ulcers All patients in the REDU cohort underwent repeated gastroscopy due to persistent abdominal pain or for ulcer surveillance. Follow-up gastroscopy revealed that 21 patients (70.0%) had persistent duodenal bulb ulcers, 13 patients (43.3%) had duodenal bulb stenosis, and 4 patients (13.3%) had duodenal mucosal erosion. Pathologically, pre-treatment duodenal bulb biopsies from the REDU cohort showed EOS counts of ≥ 100 cells/HPF in 17 patients (56.7%) and ≥ 50 cells/HPF in 13 patients (43.3%). Gastric antrum biopsies showed EOS ≥ 100/HPF (3 patients) and ≥ 30/HPF (8 patients). For EOS count per HPF in the duodenal bulb and gastric antrum, no statistically Gastric antral biopsies showed EOS counts of ≥ 100 cells/HPF in 3 patients (10.0%) and ≥ 30 cells/HPF in 8 patients (26.7%). No statistically significant difference in EOS counts per HPF was observed between Group A and Group B, either in the duodenal bulb ( P = 0.16) or in the gastric antrum ( P = 0.70).In the last follow-up, after post-treatment, duodenal EOS counts decreased significantly (pre-treatment: 100.0 [IQR: 60.0, 100.0]/HPF vs. post-treatment: 20.0 [IQR: 2.0, 88.0]/HPF; P < 0.01), while gastric antrum EOS counts showed no significant change (pre-treatment: 2.0 [IQR: 0.0, 52.0]/HPF vs. post-treatment: 0.0 [IQR: 0.0, 4.3]/HPF; P = 0.08).. The typical pathological picture of these patients was shown in Fig. 2 . Radiological Findings Twenty-four patients underwent enhanced abdominal CT: 23 showed duodenal bulb wall thickening with abnormal mucosal enhancement, and 8 had gastric antral mucosal thickening. The typical imagological picture of these patients was shown in Fig. 3 . Treatment and Follow-up For these patients with REDU, treatment included dietary avoidance (100%), PPIs (100%), glucocorticoids (46.7%), immunosuppressants (azathioprine/methotrexate, 33.3%), antihistamines (16.7%), and montelukast (40%) ( Table 3 ). All patients received PPIs for a median duration of 20.5 [IQR: 11.3, 35.0] months; Seven patients received glucocorticoids for a median duration of 2.5[IQR:2.0,4.5] months; Thirty patients (100%) received food avoidance plus PPI treatment, 14 patients (46.7%) received food avoidance plus PPI plus glucocorticoid treatment, and 5 patients (17.7%) received food avoidance plus PPI plus glucocorticoid plus immunosuppressive agent treatment. Recurrence occurred in 7 patients, 6 of whom had PPI dose reduction or discontinuation (median interval from adjustment to recurrence: 50.0 [IQR: 35.0, 120.0] days). For patients in the REDU cohort, at the last follow-up visit, 29 remained on PPI therapy, while 3 had persistent positive HP antibodies. Eleven patients achieved ulcer healing, with 8 of these patients responding to treatment consisting of prednisolone tapering combined with immunosuppressants and PPI maintenance therapy. In contrast, 8 patients had persistent ulcers despite the use of multiple treatment strategies. Discussion HP infection is highly prevalent in children, yet post-eradication EGIDs remain underreported. As far as we know, this study presents the largest pediatric cohort to date of REDU following HP eradication, shedding light on this underrecognized phenomenon. Fujita et al. first reported a 14-year-old boy with exacerbation of eosinophilic duodenal ulcer after HP eradication, managed with PPIs. [7,10]. Our study expands this evidence to 30 pediatric cases, 19 of whom developed persistent or worsening symptoms (including malnutrition, anemia, and hemorrhagic ulcers) after HP eradication. Thirteen cases(13/30)of REDU were located in the postbulbar duodenum. This finding emphasizes the need to consider EGID in pediatric patients with persistent or recurrent ulcers post-HP eradication, particularly those with eosinophilic infiltration of the duodenal bulb.[11,12] The severity of HP infection-induced pediatric DBU may be closely associated with adverse outcomes such as REDU. Our study found that compared with Group C (children with HP-induced DBU who achieved cure), Group A (REDU post-HP eradication) had higher rates of giant DBU, anemia, elevated peripheral EOS, and subsequent duodenal bulb stenosis. Additionally, Group A required more frequent HP eradication therapy and repeated gastroscopies to monitor disease status. Notably, even with negative post-eradication HP tests, the patients in Group A had persistent EOS infiltration and recurrent ulcers in the duodenal bulb, posing significant therapeutic challenges. Therefore, HP eradication in pediatric patients with HP-associated DBU requires prudence, and the optimal regimen should be selected based on individual patient characteristics. Interestingly, we observed striking phenotypic differences between HP-associated ulcers and eosinophilic post-eradication ulcers—differences that have clinical implications for diagnosis. Eosinophilic post-eradication ulcers differ from HP-associated ulcers in three key ways: (1) clean vs. dirty ulcer base [13]. (2) shallow, pan-shaped vs. deep, irregular lesions; (3) less surrounding mucosal edema [14]. Capsule endoscopy is limited here due to stenosis-related capsule impaction and inability to obtain biopsies, reinforcing upper gastrointestinal endoscopy with biopsy as the gold standard for diagnosis. The pathogenesis of EGIDs- beyond eosinophilic involvement- remains incompletely understood, but current research highlights multifactorial mechanisms involving IgE-mediated and cell-mediated responses[15]. These include T-helper-2 (Th2) cytokines (IL-4, IL-5, IL-13) and chemokines, which collectively promote eosinophil recruitment and activation in the gastrointestinal tract[16]. Thirty-four cytokines involved in Th1, Th2, and Th17 pathways were measured in this study and we found a dramatically increase of IL-8 level in these patients with eosinophilic duodenal bulb ulcers. Eosinophils can activate neutrophils, inducing the release of superoxide and IL-8 [17]. A prior study reported a 12.2-fold upregulation of IL-8 in the inflamed esophageal mucosa of adult patients with EoE (P < 0.001)[18]. The detection of IL-8 levels may serve as an indicator for judging the exacerbation or alleviation of diseases. The exact mechanism underlying REDU (with eosinophilia) post-HP eradication remains unclear, but one proposed hypothesis involves HP’s role in modulating gastrointestinal mucosal immunity[19]. HP infection typically elicits a Th1-dominated immune response, which suppresses Th2 cytokines associated with EoE. Eradication may shift this balance toward Th2 dominance, fostering EOS infiltration and triggering EGID symptoms.[20]. In EGID patients, elevated serum IgE levels are commonly observed.[21] The impact of HP effect the production of IgE produced by B Cells. HP infection may also influence IgE production by B cells: HP-induced Th1 responses (predominantly secreting IFN-γ) inhibit Th2 responses, thereby reducing B cell differentiation into IgE-secreting plasma cells This also explains why IgE levels are usually not high in HP infections and may be inversely correlated with allergic reactions[20,22]. Our findings suggest HP eradication may disrupt immune homeostasis, promoting eosinophilic inflammation in the duodenal bulb. Our findings—elevated serum IgE, peripheral blood EOS count and high allergen positivity in REDU patients—support the hypothesis that HP eradication disrupts immune homeostasis, promoting eosinophilic inflammation in the duodenal bulb. Upper gastrointestinal endoscopy with duodenal bulb biopsy is essential for diagnosing REDU post-HP eradication. Most of our REDU patients had giant duodenal bulb ulcers, which developed or persisted after HP eradication. Notably, our REDU cohort had higher peripheral EOS counts (median: 491.2 cells/µL) than previously reported in pediatric EGID studies. No definitive treatment guidelines for eosinophilic duodenal ulcers exist. [12,23]. In our cohort, PPIs relieved symptoms but had a high recurrence rate (56.2%, 9/16) upon dose reduction or discontinuation. This is consistent with our finding that 50% of REDU patients carried CYP2C19 IM/PM genotypes—genotypes associated with reduced PPI metabolism and efficacy. Meta-analyses have also linked CYP2C19 IM/PM status to reduced PPI efficacy in peptic ulcers. Dietary avoidance is a standard conservative treatment for EGIDs[24]. In our study, all REDU patients received dietary avoidance plus PPIs, so we could not assess the efficacy of dietary avoidance alone. Glucocorticoids provided rapid symptom relief but required combination with immunosuppressants to prevent relapse—mirroring management strategies for inflammatory bowel disease [25]. This study has several limitations. First, despite being a multicenter study, the rarity of REDU resulted in a relatively small sample size, which may introduce selection bias Second, as a retrospective study, some data (e.g., long-term follow-up of growth parameters, the allergic history in control group) were incomplete. Third, we did not conduct in-depth mechanistic studies (e.g., gut microbiota profiling or Th1/Th2 cytokine signaling pathway analysis). These limitations should be addressed in future prospective, large-cohort studies.[14,26]. Conclusion This multicenter study establishes a clinical link between HP eradication and REDU in children, mediated by immune dysregulation—characterized by elevated serum IL-8, peripheral eosinophilia, and marked EOS infiltration of the duodenal bulb. Clinicians should monitor EOS levels in post-eradication refractory ulcers. Further research into HP-immune-microbiota interactions may identify novel targets for EGID therapy. Declarations Author Contributions ZH and PL conceived the study and drafted the manuscript. YZ, XW, XZ, MJ, YM, SNW, CZ, LW, JL, ZT, and ZJ collected data. PS contributed to the statistical analyses. YH and YHW designed the study and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript. Acknowledgments We acknowledge the patients and their parents for their help for this study. Funding This research was supported by the grants from the National Key Research and Development Program of China 2023YFC2706501 and Shanghai Science and Technology Innovation Action Plan 23Y11905100. Ethics Statement This study was approved by the Ethics Committee of the Children’s Hospital of Fudan University (Shanghai, China; IRB No.: 2024 (248)). Consent Written informed consent was obtained from all parents. Conflicts of Interest The authors declare no conflicts of interest. Data availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. ORCID Ying Huang: https://orcid.org/0000-0002-4931-4006 References Chey WD, Howden CW, Moss SFet al. . ACG Clinical Guideline: Treatment of Helicobacter pylori Infection Am J Gastroenterol . 2024;119:1730-1753. Zhou Y, Ye Z, Wang Yet al. . Comparison of four different regimens against Helicobacter pylori as a first-line treatment: A prospective, cross-sectional, comparative, open trial in Chinese children Helicobacter . 2020;25:e12679; Zhou Y, Ye Z, Lu Jet al. . Long-term changes in the gut microbiota after 14-day bismuth quadruple therapy in penicillin-allergic children Helicobacter . 2020;25:e12721. Papadopoulou A, Amil-Dias J, Auth MKet al. . Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis J Pediatr Gastroenterol Nutr . 2024;78:122-152. Quinn LA, Burger C, Nguyen Bet al. . Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia Am J Gastroenterol . 2024;119:1298-1308. von Arnim U, Wex T, Link Aet al. . Helicobacter pylori infection is associated with a reduced risk of developing eosinophilic oesophagitis Aliment Pharmacol Ther . 2016;43:825-830; Furuta K, Adachi K, Aimi Met al. . Case-control study of association of eosinophilic gastrointestinal disorders with Helicobacter pylori infection in Japan J Clin Biochem Nutr . 2013;53:60-62; Spinelli I, Porcari S, Esposito Cet al. . Meta-Analysis: Inverse Association Between Helicobacter pylori Infection and Eosinophilic Oesophagitis Aliment Pharmacol Ther . 2025;61:1096-1109. Zhou Y, Ye Z, Wang Yet al. . Long-term changes in the gut microbiota after triple therapy, sequential therapy, bismuth quadruple therapy and concomitant therapy for Helicobacter pylori eradication in Chinese children Helicobacter . 2021;26:e12809. Fujita Y, Tominaga K, Tanaka T, Ishida K, Yoshihara S. Eosinophilic Duodenal Ulcer Exacerbation after Helicobacter pylori Eradication in a 14-Year-Old Boy Tohoku J Exp Med . 2022;257:153-156. Yeh PJ, Chen CC, Chao HCet al. . The trends of pediatric duodenal ulcer and predictors of recurrence J Formos Med Assoc . 2024;123:1070-1077. Tang Z, Shi J, Ji M, Shi P, Huang Z, Huang Y. The characteristics of 83 giant peptic ulcers in Chinese children: Evaluation and follow-up Saudi J Gastroenterol . 2018;24:360-364. Fujita Y, Tominaga K, Ishida K, Masuyama H, Yoshihara S. Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer with Esophageal Involvement: A Pediatric Case Tohoku J Exp Med . 2022;257:309-313. Yamazaki K, Sakashita T, Iwata Het al. . A case of a teenage boy with eosinophilic gastroenteritis with esophageal involvement developing a hemorrhagic duodenal ulcer Clin J Gastroenterol . 2015;8:179-185. Licari A, Votto M, D'Auria E, Castagnoli R, Caimmi SME, Marseglia GL. Eosinophilic Gastrointestinal Diseases in Children: A Practical Review Curr Pediatr Rev . 2020;16:106-114. Kobayashi S, Tsunoda T, Umetsu S, Inui A, Fujisawa T, Sogo T. Clinical features of pediatric eosinophilic gastroenteritis Pediatr Int . 2022;64:e15322. Tsuge M, Shigehara K, Uda Ket al. . Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature Allergy Asthma Clin Immunol . 2023;19:103. Dellon ES. Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis Am J Gastroenterol . 2022;117:697-700. Migliorisi G, Mastrorocco E, Dal Buono Aet al. . Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review J Clin Med . 2024;13. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease Nat Rev Immunol . 2013;13:9-22. Arias A, Vicario M, Bernardo Det al. . Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis Clin Transl Gastroenterol . 2018;9:147. Homan M, Jones NL, Bontems Pet al. . Updated joint ESPGHAN/NASPGHAN guidelines for management of Helicobacter pylori infection in children and adolescents (2023) J Pediatr Gastroenterol Nutr . 2024;79:758-785. Shah SC, Tepler A, Peek RM, Jr., Colombel JF, Hirano I, Narula N. Association Between Helicobacter pylori Exposure and Decreased Odds of Eosinophilic Esophagitis-A Systematic Review and Meta-analysis Clin Gastroenterol Hepatol . 2019;17:2185-2198 e2183. Kobayashi T, Hayashi T, Torii-Goto Aet al. . Exploration of useful clinical laboratory values as diagnostic criteria for eosinophilic gastroenteritis Eur J Gastroenterol Hepatol . 2024;36:292-297. Doulberis M, Kountouras J, Rogler G. Reconsidering the "protective" hypothesis of Helicobacter pylori infection in eosinophilic esophagitis Ann N Y Acad Sci . 2020;1481:59-71. Dellon ES, Gupta SK. Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases Immunol Allergy Clin North Am . 2024;44:397-406. Chehade M, Doerfler B, Atkins D. Dietary Management of Non-EoE Eosinophilic Gastrointestinal Diseases Immunol Allergy Clin North Am . 2024;44:383-396. Kubo K, Kimura N, Mabe K, Matsuda S, Tsuda M, Kato M. Eosinophilic Gastroenteritis-associated Duodenal Ulcer Successfully Treated with Crushed Budesonide Intern Med . 2020;59:2249-2254. Taniguchi R, Nambu R, Ichimura K, Yoshida M, Hara T, Iwama I. Achievement of duodenal ulcer remission by vedolizumab in children with eosinophilic gastroenteritis Clin J Gastroenterol . 2025;18:278-281. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 16 Dec, 2025 Reviews received at journal 15 Dec, 2025 Reviews received at journal 14 Dec, 2025 Reviews received at journal 11 Dec, 2025 Reviews received at journal 10 Dec, 2025 Reviewers agreed at journal 04 Dec, 2025 Reviewers agreed at journal 04 Dec, 2025 Reviewers agreed at journal 03 Dec, 2025 Reviewers agreed at journal 03 Dec, 2025 Reviewers agreed at journal 03 Dec, 2025 Reviewers agreed at journal 03 Dec, 2025 Reviewers invited by journal 03 Dec, 2025 Editor assigned by journal 01 Dec, 2025 Editor invited by journal 14 Nov, 2025 Submission checks completed at journal 13 Nov, 2025 First submitted to journal 13 Nov, 2025 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. 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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-8090557","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":555516271,"identity":"fbe69fec-ac8f-431b-94b4-17a727ba0181","order_by":0,"name":"Zhiheng Huang","email":"","orcid":"","institution":"Children's Hospital of Fudan University, National Children's Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zhiheng","middleName":"","lastName":"Huang","suffix":""},{"id":555516272,"identity":"485f2ad5-f2a5-4d7a-a81c-1f42b47023d1","order_by":1,"name":"Ping Li","email":"","orcid":"","institution":"Children's Hospital of Fudan 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1","display":"","copyAsset":false,"role":"figure","size":632440,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEndoscopic Images of DBU\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. Image of case 2, Duodenal bulb ulcer (DBU) during HP infection; B. Healing of the DBU following HP eradication; C, D: Recurrence of the DBU after omeprazole dose reduction. E. Image of the 3rd recurrence of the DBU in Case 3 after omeprazole dose reduction. F. Healing of the DBU after treatment with 40 mg omeprazole. G. Recurrence of the DBU after omeprazole dose reduction. H. Healing of the DBU under maintenance therapy with reduced-dose omeprazole combined with azathioprine. I. Image of the DBU in case 10 caused by HP infection; J. Scar formation after omeprazole administration. K. Recurrence of the DBU after omeprazole dose reduction. L. Healing of the DBU under maintenance therapy with reduced-dose omeprazole combined with azathioprine.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8090557/v1/71c9a3a432747c9219967265.png"},{"id":97892672,"identity":"4f669285-8297-4b5c-83b7-a6c037b4facd","added_by":"auto","created_at":"2025-12-10 15:17:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1065678,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistological findings of duodenal bulb biopsy specimens from patients with eosinophilic duodenal bulb ulcer (DBU).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. Case 2: Hematoxylin-Eosin (HE) staining demonstrating HP-associated chronic inflammation (red oval indicates HP-like Gram-negative bacilli; magnification: 400×);\u003cbr\u003e\nB. Case 2: Case 2: Pre-treatment duodenal bulb mucosa with marked eosinophilic infiltration (≈90 eosinophils [EOS]/high-power field [HPF]; magnification: 200×);;\u003cbr\u003e\nC.Case 2: Post-treatment duodenal bulb mucosa with reduced EOS count per HPF (200×);\u003cbr\u003e\nD, E. Case 3: Pre-treatment duodenal mucosa with severe eosinophilic infiltration: D (≈100 EOS/HPF) and E (≈50 EOS/HPF); magnification: 200×for both;\u003cbr\u003e\nF. Case 3: Post-treatment duodenal mucosa (omeprazole 40 mg/day + azathioprine 1 mg/kg/day) with near-resolution of eosinophilic infiltration (≈2 EOS/HPF; magnification: 200×);\u003cbr\u003e\nG. Case 10: Methylene blue staining of gastric antral glandular crypts showing small short rod-shaped HP (red oval, 400×);\u003cbr\u003e\nH. Case 10: Pre-treatment duodenal mucosa with severe eosinophilic infiltration (≈100 EOS/HPF; magnification: 200×);\u003c/p\u003e\n\u003cp\u003eI. post-treatment duodenal mucosa (omeprazole + azathioprine) showing reduced EOS infiltration (400×).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8090557/v1/0446186818e4547b9f99886e.png"},{"id":97687771,"identity":"d9a8ab18-a9da-424e-b81b-64f2e692015b","added_by":"auto","created_at":"2025-12-08 10:29:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":501694,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAbdominal enhanced CT examination of eosinophilic DBU\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA and B: Thickening of the duodenal bulb (large arrow) and descending part (small arrow) in case 10, with improvement after treatment.\u003cbr\u003e\nC: Thickening of the duodenal bulb (large arrow) in case 3.\u003cbr\u003e\nD: Thickening of the duodenal bulb (large arrow) in case 18.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8090557/v1/2866c6b4ec905d426549700b.png"},{"id":101690524,"identity":"7e8de73b-1048-495b-83db-785d8e1d3e16","added_by":"auto","created_at":"2026-02-02 16:04:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3275812,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8090557/v1/4e96f332-1d3a-4fd2-b994-a5dd2d672d17.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Refractory Eosinophilic Duodenal Bulb Ulcer Associated with Helicobacter pylori Eradication in Children: A Multicenter Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHelicobacter pylori (HP), a Gram-negative bacterium, remains a pivotal focus in clinical gastroenterology, with well-established links to peptic ulcer disease, including gastric and duodenal ulcers [1]. Our prior research validated the safety and efficacy of four HP eradication regimens and characterized long-term gut microbiota shifts[2], which has advanced clinical management and solidified HP eradication as a cornerstone of therapy for HP-associated diseases.\u003c/p\u003e\u003cp\u003eEosinophilic gastrointestinal diseases (EGIDs) encompass a heterogeneous group of disorders defined by abnormal eosinophil (EOS) infiltration in the gastrointestinal tract, which triggers inflammatory cascades that manifest as symptoms ranging from mild discomfort to severe complications (e.g., vomiting, abdominal pain, anemia, and growth retardation)\u0026mdash;a condition particularly prevalent in pediatric populations [3,4].\u003c/p\u003e\u003cp\u003eEmerging evidence reveals a complex interplay between HP and EGIDs. Epidemiological studies consistently demonstrate an inverse association: lower HP prevalence in patients with eosinophilic gastritis (EGE) or eosinophilic esophagitis (EoE) compared to healthy controls, suggesting a potential protective role of HP in mitigating chronic immune-mediated diseases[5]. This \"protective effect\" is hypothesized to stem from the ability of HP to shift mucosal immunity toward a Th1-dominated response, thereby suppressing Th2-mediated pathways that are central to the pathogenesis of EGIDs.\u003c/p\u003e\u003cp\u003eConversely, a growing body of reports links successful HP eradication to the de novo onset or exacerbation of eosinophilic conditions, including refractory eosinophilic duodenal bulb ulcers (REDU) [6,7]. This paradox\u0026mdash;where eradication of a pathogen (HP) linked to ulcer disease precipitates a distinct, immune-mediated ulcer phenotype\u0026mdash;raises critical questions regarding the long-term consequences of HP clearance, particularly in children with developing immune systems. Despite their rarity, these REDU cases pose significant diagnostic and therapeutic challenges, with their pathophysiology remaining poorly understood\u0026mdash;a knowledge gap amplified by the paucity of pediatric data in this field.\u003c/p\u003e\u003cp\u003eTo date, research on the post-eradication development of REDU (distinct from HP-associated DBU) remains limited, particularly in pediatric cohorts. This multicenter study aims to address this gap by characterizing the clinical features, endoscopic findings, pathological mechanisms, and management strategies of this understudied condition, with implications for optimizing clinical practice in pediatric gastroenterology.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData Sources\u003c/h2\u003e\u003cp\u003e This study was approved by the Ethics Committee of the Children\u0026rsquo;s Hospital of Fudan University (Shanghai, China; IRB No.: 2024 (248)). All methods were performed in accordance with the relevant guidelines and regulations Written informed consent was obtained from the parents of all participants prior to study initiation. Pediatric patients were recruited retrospectively between January 1, 2016, and August 31, 2025, and their electronic medical records were reviewed to assess eligibility.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eThe inclusion and exclusion criteria\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eInclusion criteria:\u003c/h2\u003e\u003cp\u003e① Diagnosis of duodenal bulb ulcer (DBU) (a subtype of peptic ulcer) confirmed by endoscopy, with documentation of ulcer location, size, number, and recurrence interval.\u003c/p\u003e\u003cp\u003e② Pathological evidence of EOS counts\u0026thinsp;\u0026ge;\u0026thinsp;50 cells per high-power field (HPF) in duodenal bulb biopsies [3].\u003c/p\u003e\u003cp\u003e③ Documentation of HP testing (e.g., \u0026sup1;\u0026sup3;C urea breath test [\u0026sup1;\u0026sup3;C UBT], rapid urease test [RUT], pathological examination); HP eradication therapy was administered to all patients with positive HP test results.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eExclusion criteria\u003c/strong\u003e\u003cp\u003ePatients with intestinal tuberculosis, inflammatory bowel disease, parasitic infections, eosinophilic leukemia, primary immunodeficiencies, non-steroidal anti-inflammatory drug (NSAID)-induced reactions, or other confounding conditions were excluded.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eREDU\u003c/b\u003e was defined as refractory eosinophilic duodenal bulb ulcers that either persisted at the first follow-up endoscopy or initially resolved but relapsed during subsequent follow-ups [8].\u003c/p\u003e\u003cp\u003eThese REDU cases were divided into 2 subgroups based on their HP infection status:​\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eGroup A\u003c/strong\u003e\u003cp\u003eHP eradication-associated REDU group​\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDefinition\u003c/strong\u003e\u003cp\u003ePatients with definitive evidence of HP infection (e.g., positive \u0026sup1;\u0026sup3;C urea breath test [\u0026sup1;\u0026sup3;C UBT], positive rapid urease test [RUT], or positive pathological examination), who developed DBU within 8 weeks after completing HP eradication therapy and met the diagnostic criteria for REDU as defined above.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003cp\u003eIdiopathic REDU group​\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDefinition\u003c/strong\u003e\u003cp\u003ePatients with no definitive evidence of HP infection (all HP detection tests were negative), no other identified causes of ulcers (e.g., NSAID use, autoimmune diseases), and who met the diagnostic criteria for REDU.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eGroup C\u003c/strong\u003e\u003cp\u003eControl group.\u003c/p\u003e\u003c/p\u003e\u003cp\u003eThirty-eight children at the same period with HP-associated DBU who underwent HP eradication therapy and achieved successful DBU healing were randomly selected. These patients were matched to Group A by age (\u0026plusmn;\u0026thinsp;2 years), gender, and HP eradication regimen to ensure they had the same exposure (i.e., HP eradication) but a different outcome (i.e., no post-eradication ulcer recurrence)\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLaboratory and Genetic Assessments\u003c/h3\u003e\n\u003cp\u003eDuring ulcer recurrence, the following parameters were evaluated: peripheral blood EOS count, erythrocyte sedimentation rate (ESR), serum albumin level, serum specific IgE level, immunoglobulin G4 (IgG4) level, and humoral/cellular immunity profiles. For the REDU group, thirty-four serum cytokines were measured using a Luminex 200 instrument (Millipore) with a ThermoFisher ProcartaPlex multiplex immunoassay kit (cat. no.: EPXR340-12167-901), including macrophage inflammatory protein-1α (MIP-1α), MIP-1β, stromal cell-derived factor-1α (SDF-1α), interleukin-27 (IL-27), IL-1β, IL-2, IL-4, IL-5, interferon gamma-induced protein 10 (IP-10), IL-6, IL-7, IL-8, IL-10, Eotaxin, IL-12p70, IL-13, IL-17A, IL-31, IL-1 receptor antagonist (IL-1RA), CCL5/regulated on activation, normal T cell expressed and secreted (RANTES), interferon-γ (IFN-γ), granulocyte\u0026ndash;macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), TNF-β, IFN-α, monocyte chemoattractant protein-1 (MCP-1), IL-9, growth-related oncogene alpha (GRO-α), IL-1α, IL-23, IL-15, IL-18, IL-21, and IL-22. Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene polymorphisms were analyzed via polymerase chain reaction (PCR). The metabolic phenotypes of CYP2C19 included extensive metabolizers (EM), intermediate metabolizers (IM), poor metabolizers (PM), rapid metabolizers (RM), and ultrarapid metabolizers (UM).\u003c/p\u003e\n\u003ch3\u003eEndoscopic and Histopathological Evaluation\u003c/h3\u003e\n\u003cp\u003eUpper gastrointestinal endoscopy (gastroscopy) and lower gastrointestinal endoscopy (colonoscopy) were performed under deep sedation. Biopsies of the duodenal bulb and gastric antral mucosa were collected for pathological examination and EOS counting. Colonoscopy with mucosal biopsies was performed to rule out duodenal ulcers secondary to systemic diseases. Duodenal bulb ulcers with a diameter of \u0026ge;\u0026thinsp;2 cm observed during endoscopy were defined as giant DBU, as described in previous studies [9].\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (interquartile range [IQR]) depending on their distribution, while categorical variables were expressed as frequencies (percentages). Differences between the HP eradication-associated REDU group (Group A) and the HP eradication-control group (Group C) were analyzed using the chi-square (χ\u0026sup2;) test for categorical variables and the independent samples t-test and the Mann\u0026ndash;Whitney test for continuous variables. Binary logistic regression was employed to explore the risk factors of REDU.Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePatient Baseline Characteristics\u003c/h2\u003e\u003cp\u003eOf 53 initially reviewed cases of suspected REDU, 30 were enrolled after applying the exclusion criteria (23 cases were excluded: 12 with insufficient pathological data, 9 with subthreshold EOS counts [\u0026lt;\u0026thinsp;50 cells/HPF], and 2 with comorbidities [Crohn\u0026rsquo;s disease and Henoch-Sch\u0026ouml;nlein purpura]). A total of 30 enrolled patients with REDU were divided into two subgroups: Group A (HP eradication-associated REDU, 19 cases) and Group B (idiopathic REDU, 11 cases). An additional 38 children with HP-induced DBU who had achieved successful cure after HP eradication therapy were randomly selected as the control group (Group C).\u003c/p\u003e\u003cp\u003eThe REDU cohort (n\u0026thinsp;=\u0026thinsp;30) comprised 27 males and 3 females (male-to-female ratio: 9:1; mean age: 10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 years; age range: 5\u0026ndash;15 years Symptom duration ranged from 1 day to 6 years, with abdominal pain being the most common primary presenting symptom, median duration 24.0[7.5,30.0] month (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Seventeen patients (56.7% of the REDU cohort) presented with anemia, among whom three had severe anemia (with the lowest hemoglobin level of 57 g/L) accompanied by melena, requiring blood transfusion. Refractory duodenal bulb ulcers were the primary reason for repeated hospital visits.\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\u003eThe symptom for REDU patients first visit hospital\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eREDU\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (y)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody weight(kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27(90)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSymptom\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal pain: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (80)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomit: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHematemesis: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMelena: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnemia: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (63.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePale: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChest distress: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalnutrition: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (60)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eData are expressed as number (%) for categorical variables or median (range) for continuous variables\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eHP: Helicobacter pylori; N: number; EDU: refractory eosinophilic duodenal bulb ulcers; y: year\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFor the REDU cohort, the median body mass index (BMI, kg/m\u0026sup2;) was 15.6, with an IQR of [15.0, 17.0]. Malnutrition was prevalent in the REDU cohort: 10 patients (33.3%) had a BMI z-score between \u0026minus;\u0026thinsp;1 and \u0026minus;\u0026thinsp;2 SD, 6 patients (20.0%) had a BMI z-score between \u0026minus;\u0026thinsp;2 and \u0026minus;\u0026thinsp;3 SD, and 1 patient (3.3%) had a BMI z-score \u0026lt; -3 SD.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eComparison of Characteristics Between HP Eradication-Associated REDU (Group A) and HP-Associated DBU Control (Group C)\u003c/h2\u003e\u003cp\u003eThe characteristics of the HP eradication-associated REDU group (Group A) and the HP-associated DBU control group (Group C) are compared in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Abdominal pain was also the most common chief complaint in both groups. The time interval from HP treatment to the onset of REDU is 14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8 months. The time interval between the diagnosis of HP infection and the negative result in \u0026sup1;\u0026sup3;C UBT re-examination is 9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0 months. For the Group C, the time interval of the last follow-up was 3.0 (2.0, 11.5) months. No symptoms were reported in Group C, so no further follow-up visits to the gastroenterology department were conducted.\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\u003eComparison of Characteristics Between HP- eradication-associated REDU group and HP eradication-control group\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\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHP- eradication-associated REDU group(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHP eradication-control group(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (y)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.82\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody weight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17(89.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31(81.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(18.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChief complain\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal pain: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (78.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24(63.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnemia: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13(68.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMelena: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(5.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomiting: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(5.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.714\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUlcer In first gastroscopy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGiant Duodenal bulb ulcer: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (89.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastric Antrum ulcer: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuodenal bulb stenosis: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (47.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003elaboratory examination\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood EOS count (IQR) cells/\u0026micro;L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e480[410,820]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e140[77.5,245.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87.0[70.0,122.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e136.0[123.5,142.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlb (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC (10^9/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRepeated endoscopy examination: n\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRepeated HP eradication therapy\u003c/b\u003e: \u003cb\u003en [ IQR]\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0[1.0,3.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.0[1.0,1.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eEOS : eosinophils; HP: Helicobacter pylori; n:number;REDU: refractory eosinophilic duodenal bulb ulcers; y: year.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAfter gastroscopic diagnosis of HP-induced duodenal bulb ulcer, patients in Group A and Group C immediately received eradication therapy. Compared with the Group C, the HP eradication-associated REDU group (Group A) had a significantly higher incidence of anemia, giant DBU, and elevated peripheral blood EOS counts (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Additionally, Group A had a higher need for repeated HP eradication therapy (42.1% vs. 2.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The number of endoscopic examinations was also compared between the two groups. Compared with Group C, Group A required a significantly higher number of endoscopic examinations (median: 7.0 [IQR: 4.0, 11.0] vs. 2.0 [IQR: 2.0, 2.0], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFor Group A (HP eradication-associated REDU), the median number of HP eradication courses per patient was 1.0 [IQR: 1.0, 2.5]. Binary logistic regression analysis revealed that an elevated peripheral blood EOS percentage (P\u0026thinsp;=\u0026thinsp;0.008; odds ratio [OR]\u0026thinsp;=\u0026thinsp;0.08, 95% confidence interval [CI]: 0.008\u0026ndash;0.289) and the number of endoscopic examinations (P\u0026thinsp;=\u0026thinsp;0.019; OR\u0026thinsp;=\u0026thinsp;0.428, 95% CI: 0.210\u0026ndash;0.869) were significant factors influencing the cure outcome of REDU.\u003c/p\u003e\u003cp\u003eHP infection was confirmed in 8 patients via serum HP antibody testing, 9 patients via RUT, 3 patients via pathological examination of gastric mucosa biopsies, and 4 patients via \u0026sup1;\u0026sup3;C UBT. The HP eradication regimens administered to Group A patients included amoxicillin-based triple therapy (6 patients), bismuth-based quadruple therapy (16 patients), and high-dose amoxicillin-proton pump inhibitor (PPI) dual therapy (1 patient).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eLaboratory Findings\u003c/h2\u003e\u003cp\u003eAmong the entire REDU cohort (n\u0026thinsp;=\u0026thinsp;30), 19 patients (63.3%) had anemia, with a mean hemoglobin (Hb) level of 96.6\u0026thinsp;\u0026plusmn;\u0026thinsp;25.6 g/L. When comparing Group A (HP eradication-associated REDU) and Group B (idiopathic REDU), no significant difference in mean Hb level was observed (Group A: 96.8\u0026thinsp;\u0026plusmn;\u0026thinsp;26.9 g/L vs. Group B: 106.1\u0026thinsp;\u0026plusmn;\u0026thinsp;23.0 g/L, P\u0026thinsp;=\u0026thinsp;0.029). In the REDU cohort, the median serum IgE level was 393.0 kU/L (IQR: 61.7\u0026ndash;655.8 kU/L; reference range: 0\u0026ndash;300 kU/L), and the mean peripheral blood EOS count was 518.0\u0026thinsp;\u0026plusmn;\u0026thinsp;349.0 cells/\u0026micro;L (reference range: 60\u0026ndash;300 cells/\u0026micro;L). With respect to serum IgE levels and peripheral blood EOS counts, no significant differences were detected between Group A and Group B (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the REDU cohort, the mean erythrocyte sedimentation rate (ESR) was 17.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0 mm/h (reference range: 0\u0026ndash;21 mm/h), the mean serum IgG4 level was 1.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29 g/L (reference range: 0.012\u0026ndash;1.699 g/L), the mean serum albumin level was 42.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3 g/L (reference range: 35\u0026ndash;55 g/L), and the mean serum prealbumin level was 201.5\u0026thinsp;\u0026plusmn;\u0026thinsp;41.8 mg/L (reference range: 200\u0026ndash;400 mg/L). No significant differences in ESR, serum IgG4 level, serum albumin level, or serum prealbumin level were observed between Group A and Group B (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eAll 30 patients in the REDU cohort underwent specific allergen testing, among whom 28 (93.3%) tested positive. Of these 28 allergen-positive patients, 24 (85.7%) had food allergies\u0026mdash;specifically, 15 (62.5% of food-allergic patients) were sensitized to cow\u0026rsquo;s milk protein, 13 (54.2%) to egg white, and 8 (33.3%) to egg yolk\u0026mdash;and 11 (39.3% of allergen-positive patients) had dust mite sensitivity. For HP-associated DBU control group, allergen information is lacking due to disease testing and medical ethics restrictions.\u003c/p\u003e\u003cp\u003eSerum cytokines were assayed in the REDU cohort(n=?). The median serum IL-8 level was significantly elevated to 361.2 pg/mL (IQR: 92.8\u0026ndash;613.4 pg/mL; reference range: 0.0\u0026ndash;47 pg/mL). Nine patients (30.0% of the REDU cohort) had elevated serum levels of both MIP-1α (reference range: 0.0\u0026ndash;21 pg/mL) and MIP-1β (reference range: 0.0\u0026ndash;147 pg/mL), while five patients (16.7%) had elevated serum levels of both IL-10 (reference range: 0.0\u0026ndash;3.0 pg/mL) and TNF-α (reference range: 0.0\u0026ndash;14 pg/mL). Additionally, one patient (3.3%) had an elevated serum IL-4 level (84.8 pg/mL; reference range: 0\u0026ndash;45 pg/mL), and another patient (3.3%) had an elevated serum IL-5 level (41.2 pg/mL; reference range: 0\u0026ndash;17 pg/mL).\u003c/p\u003e\u003cp\u003eCYP2C19 gene polymorphisms were analyzed in 24 patients from the REDU cohort, and the metabolic phenotypes were as follows: 12 (50.0%) IM, 8 (34.8%) NM, 3 (13.0%) PM, and 1 (4.3%) RM.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eEndoscopic and Pathologic Findings\u003c/h2\u003e\u003cp\u003eEndoscopic findings of patients in the REDU cohort are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among patients with REDU, 13 (13/30) had ulcers located in the postbulbar duodenum, 12 (12/30) in the anterior wall of the duodenal bulb, and 5 (5/30) in the greater curvature of the duodenal bulb; of these patients, 3 had \"kissing ulcers\u0026rdquo;. Eosinophilic duodenal bulb ulcers (in both Group A and Group B) were characterized by large, shallow, pan-like lesions covered with a clean, thin white exudate\u0026mdash;distinct from HP-associated DBU (Group C), which typically featured a dirty ulcer base (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eI). Regarding giant DBU, 17 patients (89.5% of Group A) had giant DBU, compared with 6 patients (54.5% of Group B) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Twenty-eight patients (93.3% of the REDU cohort) underwent colonoscopy, which revealed terminal ileitis in 13 patients (46.4% of colonoscopy recipients) and proctocolitis in 8 patients (28.6%). Fourteen patients (46.7% of the REDU cohort) underwent capsule endoscopy, with findings including enteritis (6 patients, 42.9% of capsule endoscopy recipients), duodenal ulcer (2 patients, 14.3%), normal findings (4 patients, 28.6%), and capsule impaction secondary to duodenal bulb stenosis (2 patients, 14.3%).\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\u003eThe endoscopic findings in all REDU 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\" colname=\"c1\"\u003e\u003cp\u003eEndoscopic Findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDuodenal Bulb N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDuodenal descending Part N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGastric Body N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eGastric Antrum N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eEsophagus N (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUlcer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (100)\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (6.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStenosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13(43.3)\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEdema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (43.3)\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\u003e2(6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErosion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.3)\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\u003e4(13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.3)\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eN: number; REDU: refractory eosinophilic duodenal bulb ulcers\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAll patients in the REDU cohort underwent repeated gastroscopy due to persistent abdominal pain or for ulcer surveillance. Follow-up gastroscopy revealed that 21 patients (70.0%) had persistent duodenal bulb ulcers, 13 patients (43.3%) had duodenal bulb stenosis, and 4 patients (13.3%) had duodenal mucosal erosion. Pathologically, pre-treatment duodenal bulb biopsies from the REDU cohort showed EOS counts of \u0026ge;\u0026thinsp;100 cells/HPF in 17 patients (56.7%) and \u0026ge;\u0026thinsp;50 cells/HPF in 13 patients (43.3%). Gastric antrum biopsies showed EOS\u0026thinsp;\u0026ge;\u0026thinsp;100/HPF (3 patients) and \u0026ge;\u0026thinsp;30/HPF (8 patients). For EOS count per HPF in the duodenal bulb and gastric antrum, no statistically Gastric antral biopsies showed EOS counts of \u0026ge;\u0026thinsp;100 cells/HPF in 3 patients (10.0%) and \u0026ge;\u0026thinsp;30 cells/HPF in 8 patients (26.7%). No statistically significant difference in EOS counts per HPF was observed between Group A and Group B, either in the duodenal bulb (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16) or in the gastric antrum (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.70).In the last follow-up, after post-treatment, duodenal EOS counts decreased significantly (pre-treatment: 100.0 [IQR: 60.0, 100.0]/HPF vs. post-treatment: 20.0 [IQR: 2.0, 88.0]/HPF; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), while gastric antrum EOS counts showed no significant change (pre-treatment: 2.0 [IQR: 0.0, 52.0]/HPF vs. post-treatment: 0.0 [IQR: 0.0, 4.3]/HPF; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08).. The typical pathological picture of these patients was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eRadiological Findings\u003c/h2\u003e\u003cp\u003eTwenty-four patients underwent enhanced abdominal CT: 23 showed duodenal bulb wall thickening with abnormal mucosal enhancement, and 8 had gastric antral mucosal thickening. The typical imagological picture of these patients was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eTreatment and Follow-up\u003c/h2\u003e\u003cp\u003eFor these patients with REDU, treatment included dietary avoidance (100%), PPIs (100%), glucocorticoids (46.7%), immunosuppressants (azathioprine/methotrexate, 33.3%), antihistamines (16.7%), and montelukast (40%) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). All patients received PPIs for a median duration of 20.5 [IQR: 11.3, 35.0] months; Seven patients received glucocorticoids for a median duration of 2.5[IQR:2.0,4.5] months; Thirty patients (100%) received food avoidance plus PPI treatment, 14 patients (46.7%) received food avoidance plus PPI plus glucocorticoid treatment, and 5 patients (17.7%) received food avoidance plus PPI plus glucocorticoid plus immunosuppressive agent treatment. Recurrence occurred in 7 patients, 6 of whom had PPI dose reduction or discontinuation (median interval from adjustment to recurrence: 50.0 [IQR: 35.0, 120.0] days).\u003c/p\u003e\u003cp\u003eFor patients in the REDU cohort, at the last follow-up visit, 29 remained on PPI therapy, while 3 had persistent positive HP antibodies. Eleven patients achieved ulcer healing, with 8 of these patients responding to treatment consisting of prednisolone tapering combined with immunosuppressants and PPI maintenance therapy. In contrast, 8 patients had persistent ulcers despite the use of multiple treatment strategies.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eHP infection is highly prevalent in children, yet post-eradication EGIDs remain underreported. As far as we know, this study presents the largest pediatric cohort to date of REDU following HP eradication, shedding light on this underrecognized phenomenon.\u003c/p\u003e\u003cp\u003eFujita et al. first reported a 14-year-old boy with exacerbation of eosinophilic duodenal ulcer after HP eradication, managed with PPIs. [7,10]. Our study expands this evidence to 30 pediatric cases, 19 of whom developed persistent or worsening symptoms (including malnutrition, anemia, and hemorrhagic ulcers) after HP eradication. Thirteen cases(13/30)of REDU were located in the postbulbar duodenum. This finding emphasizes the need to consider EGID in pediatric patients with persistent or recurrent ulcers post-HP eradication, particularly those with eosinophilic infiltration of the duodenal bulb.[11,12]\u003c/p\u003e\u003cp\u003eThe severity of HP infection-induced pediatric DBU may be closely associated with adverse outcomes such as REDU. Our study found that compared with Group C (children with HP-induced DBU who achieved cure), Group A (REDU post-HP eradication) had higher rates of giant DBU, anemia, elevated peripheral EOS, and subsequent duodenal bulb stenosis. Additionally, Group A required more frequent HP eradication therapy and repeated gastroscopies to monitor disease status. Notably, even with negative post-eradication HP tests, the patients in Group A had persistent EOS infiltration and recurrent ulcers in the duodenal bulb, posing significant therapeutic challenges. Therefore, HP eradication in pediatric patients with HP-associated DBU requires prudence, and the optimal regimen should be selected based on individual patient characteristics.\u003c/p\u003e\u003cp\u003eInterestingly, we observed striking phenotypic differences between HP-associated ulcers and eosinophilic post-eradication ulcers\u0026mdash;differences that have clinical implications for diagnosis. Eosinophilic post-eradication ulcers differ from HP-associated ulcers in three key ways: (1) clean vs. dirty ulcer base [13]. (2) shallow, pan-shaped vs. deep, irregular lesions; (3) less surrounding mucosal edema [14]. Capsule endoscopy is limited here due to stenosis-related capsule impaction and inability to obtain biopsies, reinforcing upper gastrointestinal endoscopy with biopsy as the gold standard for diagnosis.\u003c/p\u003e\u003cp\u003eThe pathogenesis of EGIDs- beyond eosinophilic involvement- remains incompletely understood, but current research highlights multifactorial mechanisms involving IgE-mediated and cell-mediated responses[15]. These include T-helper-2 (Th2) cytokines (IL-4, IL-5, IL-13) and chemokines, which collectively promote eosinophil recruitment and activation in the gastrointestinal tract[16]. Thirty-four cytokines involved in Th1, Th2, and Th17 pathways were measured in this study and we found a dramatically increase of IL-8 level in these patients with eosinophilic duodenal bulb ulcers. Eosinophils can activate neutrophils, inducing the release of superoxide and IL-8 [17]. A prior study reported a 12.2-fold upregulation of IL-8 in the inflamed esophageal mucosa of adult patients with EoE (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001)[18]. The detection of IL-8 levels may serve as an indicator for judging the exacerbation or alleviation of diseases.\u003c/p\u003e\u003cp\u003eThe exact mechanism underlying REDU (with eosinophilia) post-HP eradication remains unclear, but one proposed hypothesis involves HP\u0026rsquo;s role in modulating gastrointestinal mucosal immunity[19]. HP infection typically elicits a Th1-dominated immune response, which suppresses Th2 cytokines associated with EoE. Eradication may shift this balance toward Th2 dominance, fostering EOS infiltration and triggering EGID symptoms.[20]. In EGID patients, elevated serum IgE levels are commonly observed.[21] The impact of HP effect the production of IgE produced by B Cells. HP infection may also influence IgE production by B cells: HP-induced Th1 responses (predominantly secreting IFN-γ) inhibit Th2 responses, thereby reducing B cell differentiation into IgE-secreting plasma cells This also explains why IgE levels are usually not high in HP infections and may be inversely correlated with allergic reactions[20,22]. Our findings suggest HP eradication may disrupt immune homeostasis, promoting eosinophilic inflammation in the duodenal bulb. Our findings\u0026mdash;elevated serum IgE, peripheral blood EOS count and high allergen positivity in REDU patients\u0026mdash;support the hypothesis that HP eradication disrupts immune homeostasis, promoting eosinophilic inflammation in the duodenal bulb.\u003c/p\u003e\u003cp\u003eUpper gastrointestinal endoscopy with duodenal bulb biopsy is essential for diagnosing REDU post-HP eradication. Most of our REDU patients had giant duodenal bulb ulcers, which developed or persisted after HP eradication. Notably, our REDU cohort had higher peripheral EOS counts (median: 491.2 cells/\u0026micro;L) than previously reported in pediatric EGID studies.\u003c/p\u003e\u003cp\u003e No definitive treatment guidelines for eosinophilic duodenal ulcers exist. [12,23]. In our cohort, PPIs relieved symptoms but had a high recurrence rate (56.2%, 9/16) upon dose reduction or discontinuation. This is consistent with our finding that 50% of REDU patients carried CYP2C19 IM/PM genotypes\u0026mdash;genotypes associated with reduced PPI metabolism and efficacy. Meta-analyses have also linked CYP2C19 IM/PM status to reduced PPI efficacy in peptic ulcers. Dietary avoidance is a standard conservative treatment for EGIDs[24]. In our study, all REDU patients received dietary avoidance plus PPIs, so we could not assess the efficacy of dietary avoidance alone. Glucocorticoids provided rapid symptom relief but required combination with immunosuppressants to prevent relapse\u0026mdash;mirroring management strategies for inflammatory bowel disease [25].\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, despite being a multicenter study, the rarity of REDU resulted in a relatively small sample size, which may introduce selection bias Second, as a retrospective study, some data (e.g., long-term follow-up of growth parameters, the allergic history in control group) were incomplete. Third, we did not conduct in-depth mechanistic studies (e.g., gut microbiota profiling or Th1/Th2 cytokine signaling pathway analysis). These limitations should be addressed in future prospective, large-cohort studies.[14,26].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis multicenter study establishes a clinical link between HP eradication and REDU in children, mediated by immune dysregulation\u0026mdash;characterized by elevated serum IL-8, peripheral eosinophilia, and marked EOS infiltration of the duodenal bulb. Clinicians should monitor EOS levels in post-eradication refractory ulcers. Further research into HP-immune-microbiota interactions may identify novel targets for EGID therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZH and PL conceived the study and drafted the manuscript. YZ, XW, XZ, MJ, YM, SNW, CZ, LW, JL, ZT, and ZJ collected data. PS contributed to the statistical analyses. YH and YHW designed the study and\u0026nbsp;revised\u0026nbsp;the manuscript critically for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the patients and their parents for their help for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the grants from the National Key Research and Development Program of China 2023YFC2706501 and Shanghai Science and Technology Innovation Action Plan 23Y11905100.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Children\u0026rsquo;s Hospital of Fudan University (Shanghai, China; IRB No.: 2024 (248)).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all parents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eORCID\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYing Huang: https://orcid.org/0000-0002-4931-4006\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChey WD, Howden CW, Moss SFet al. . ACG Clinical Guideline: Treatment of Helicobacter pylori Infection \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. 2024;119:1730-1753.\u003c/li\u003e\n\u003cli\u003eZhou Y, Ye Z, Wang Yet al. . Comparison of four different regimens against Helicobacter pylori as a first-line treatment: A prospective, cross-sectional, comparative, open trial in Chinese children \u003cem\u003eHelicobacter\u003c/em\u003e. 2020;25:e12679; Zhou Y, Ye Z, Lu Jet al. . Long-term changes in the gut microbiota after 14-day bismuth quadruple therapy in penicillin-allergic children \u003cem\u003eHelicobacter\u003c/em\u003e. 2020;25:e12721.\u003c/li\u003e\n\u003cli\u003ePapadopoulou A, Amil-Dias J, Auth MKet al. . Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis \u003cem\u003eJ Pediatr Gastroenterol Nutr\u003c/em\u003e. 2024;78:122-152.\u003c/li\u003e\n\u003cli\u003eQuinn LA, Burger C, Nguyen Bet al. . Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. 2024;119:1298-1308.\u003c/li\u003e\n\u003cli\u003evon Arnim U, Wex T, Link Aet al. . Helicobacter pylori infection is associated with a reduced risk of developing eosinophilic oesophagitis \u003cem\u003eAliment Pharmacol Ther\u003c/em\u003e. 2016;43:825-830; Furuta K, Adachi K, Aimi Met al. . Case-control study of association of eosinophilic gastrointestinal disorders with Helicobacter pylori infection in Japan \u003cem\u003eJ Clin Biochem Nutr\u003c/em\u003e. 2013;53:60-62; Spinelli I, Porcari S, Esposito Cet al. . Meta-Analysis: Inverse Association Between Helicobacter pylori Infection and Eosinophilic Oesophagitis \u003cem\u003eAliment Pharmacol Ther\u003c/em\u003e. 2025;61:1096-1109.\u003c/li\u003e\n\u003cli\u003eZhou Y, Ye Z, Wang Yet al. . Long-term changes in the gut microbiota after triple therapy, sequential therapy, bismuth quadruple therapy and concomitant therapy for Helicobacter pylori eradication in Chinese children \u003cem\u003eHelicobacter\u003c/em\u003e. 2021;26:e12809.\u003c/li\u003e\n\u003cli\u003eFujita Y, Tominaga K, Tanaka T, Ishida K, Yoshihara S. Eosinophilic Duodenal Ulcer Exacerbation after Helicobacter pylori Eradication in a 14-Year-Old Boy \u003cem\u003eTohoku J Exp Med\u003c/em\u003e. 2022;257:153-156.\u003c/li\u003e\n\u003cli\u003eYeh PJ, Chen CC, Chao HCet al. . The trends of pediatric duodenal ulcer and predictors of recurrence \u003cem\u003eJ Formos Med Assoc\u003c/em\u003e. 2024;123:1070-1077.\u003c/li\u003e\n\u003cli\u003eTang Z, Shi J, Ji M, Shi P, Huang Z, Huang Y. The characteristics of 83 giant peptic ulcers in Chinese children: Evaluation and follow-up \u003cem\u003eSaudi J Gastroenterol\u003c/em\u003e. 2018;24:360-364.\u003c/li\u003e\n\u003cli\u003eFujita Y, Tominaga K, Ishida K, Masuyama H, Yoshihara S. Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer with Esophageal Involvement: A Pediatric Case \u003cem\u003eTohoku J Exp Med\u003c/em\u003e. 2022;257:309-313.\u003c/li\u003e\n\u003cli\u003eYamazaki K, Sakashita T, Iwata Het al. . A case of a teenage boy with eosinophilic gastroenteritis with esophageal involvement developing a hemorrhagic duodenal ulcer \u003cem\u003eClin J Gastroenterol\u003c/em\u003e. 2015;8:179-185.\u003c/li\u003e\n\u003cli\u003eLicari A, Votto M, D\u0026apos;Auria E, Castagnoli R, Caimmi SME, Marseglia GL. Eosinophilic Gastrointestinal Diseases in Children: A Practical Review \u003cem\u003eCurr Pediatr Rev\u003c/em\u003e. 2020;16:106-114.\u003c/li\u003e\n\u003cli\u003eKobayashi S, Tsunoda T, Umetsu S, Inui A, Fujisawa T, Sogo T. Clinical features of pediatric eosinophilic gastroenteritis \u003cem\u003ePediatr Int\u003c/em\u003e. 2022;64:e15322.\u003c/li\u003e\n\u003cli\u003eTsuge M, Shigehara K, Uda Ket al. . Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature \u003cem\u003eAllergy Asthma Clin Immunol\u003c/em\u003e. 2023;19:103.\u003c/li\u003e\n\u003cli\u003eDellon ES. Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. 2022;117:697-700.\u003c/li\u003e\n\u003cli\u003eMigliorisi G, Mastrorocco E, Dal Buono Aet al. . Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review \u003cem\u003eJ Clin Med\u003c/em\u003e. 2024;13.\u003c/li\u003e\n\u003cli\u003eRosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease \u003cem\u003eNat Rev Immunol\u003c/em\u003e. 2013;13:9-22.\u003c/li\u003e\n\u003cli\u003eArias A, Vicario M, Bernardo Det al. . Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis \u003cem\u003eClin Transl Gastroenterol\u003c/em\u003e. 2018;9:147.\u003c/li\u003e\n\u003cli\u003eHoman M, Jones NL, Bontems Pet al. . Updated joint ESPGHAN/NASPGHAN guidelines for management of Helicobacter pylori infection in children and adolescents (2023) \u003cem\u003eJ Pediatr Gastroenterol Nutr\u003c/em\u003e. 2024;79:758-785.\u003c/li\u003e\n\u003cli\u003eShah SC, Tepler A, Peek RM, Jr., Colombel JF, Hirano I, Narula N. Association Between Helicobacter pylori Exposure and Decreased Odds of Eosinophilic Esophagitis-A Systematic Review and Meta-analysis \u003cem\u003eClin Gastroenterol Hepatol\u003c/em\u003e. 2019;17:2185-2198 e2183.\u003c/li\u003e\n\u003cli\u003eKobayashi T, Hayashi T, Torii-Goto Aet al. . Exploration of useful clinical laboratory values as diagnostic criteria for eosinophilic gastroenteritis \u003cem\u003eEur J Gastroenterol Hepatol\u003c/em\u003e. 2024;36:292-297.\u003c/li\u003e\n\u003cli\u003eDoulberis M, Kountouras J, Rogler G. Reconsidering the \u0026quot;protective\u0026quot; hypothesis of Helicobacter pylori infection in eosinophilic esophagitis \u003cem\u003eAnn N Y Acad Sci\u003c/em\u003e. 2020;1481:59-71.\u003c/li\u003e\n\u003cli\u003eDellon ES, Gupta SK. Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases \u003cem\u003eImmunol Allergy Clin North Am\u003c/em\u003e. 2024;44:397-406.\u003c/li\u003e\n\u003cli\u003eChehade M, Doerfler B, Atkins D. Dietary Management of Non-EoE Eosinophilic Gastrointestinal Diseases \u003cem\u003eImmunol Allergy Clin North Am\u003c/em\u003e. 2024;44:383-396.\u003c/li\u003e\n\u003cli\u003eKubo K, Kimura N, Mabe K, Matsuda S, Tsuda M, Kato M. Eosinophilic Gastroenteritis-associated Duodenal Ulcer Successfully Treated with Crushed Budesonide \u003cem\u003eIntern Med\u003c/em\u003e. 2020;59:2249-2254.\u003c/li\u003e\n\u003cli\u003eTaniguchi R, Nambu R, Ichimura K, Yoshida M, Hara T, Iwama I. Achievement of duodenal ulcer remission by vedolizumab in children with eosinophilic gastroenteritis \u003cem\u003eClin J Gastroenterol\u003c/em\u003e. 2025;18:278-281.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"refractory duodenal ulcer, Helicobacter pylori, eosinophilic gastrointestinal disorders, proton pump inhibitor, children","lastPublishedDoi":"10.21203/rs.3.rs-8090557/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8090557/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and aims:\u003c/h2\u003e\u003cp\u003eRefractory eosinophilic duodenal bulb ulcers (REDU) that develop following Helicobacter pylori (HP) eradication are rarely recognized. This study aimed to investigate the REDU in pediatric populations after HP eradication.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis multicenter retrospective analysis was conducted on children admitted to the gastroenterology department of three children\u0026rsquo;s hospitals from January 1, 2016, to August 31, 2025. Eligible pediatric cases diagnosed with REDU across the three centers were included. For the REDU group, clinical characteristics, laboratory tests, endoscopic findings, HP treatment strategies, and follow-up data were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThirty patients (mean age 10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 years) were diagnosed with REDU, including 19 with HP eradication-related REDU and 11 with idiopathic REDU. Compared with the HP-induced DBU control group, the HP eradication-related REDU group had higher rates of anemia, elevated peripheral blood eosinophils (EOS) count, endoscopic giant DBU, bulbar stenosis, repeated endoscopies, and HP eradication therapies (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). REDU patients presented with punched-out DBU featuring a clean, thin white base; 76.7% (23/30) of REDU patients had giant DBU. Before treatment, among the entire REDU cohort, 9 patients had pathological EOS counts\u0026thinsp;\u0026ge;\u0026thinsp;100 cells/high-power field (HPF), and another 9 had\u0026thinsp;\u0026ge;\u0026thinsp;50 cells/HPF. Serum cytokine assay showed that IL-8 was significantly elevated. All patients were treated with dietary avoidance and proton pump inhibitor (PPI) therapy. Recurrence was common, occurring in 9 of 16 patients (56.2%) following PPI dose reduction or discontinuation (median interval: 50.0 [35.0, 120.0] days).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eHP eradication may associate with REDU in children via eosinophilic infiltration, emphasizing the need for systematic monitoring of immune-related complications post-eradication.\u003c/p\u003e","manuscriptTitle":"Refractory Eosinophilic Duodenal Bulb Ulcer Associated with Helicobacter pylori Eradication in Children: A Multicenter Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 10:29:26","doi":"10.21203/rs.3.rs-8090557/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-16T12:37:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-15T07:54:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-14T15:13:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-11T06:15:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-10T11:03:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124690317578835259380731913313629264430","date":"2025-12-05T00:31:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"242770284817417041644010352043711616680","date":"2025-12-04T06:36:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"178714095673259957920304499742571405115","date":"2025-12-04T04:14:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131294817332232837454705584656245071845","date":"2025-12-03T22:55:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55743741788078695633794835360380604197","date":"2025-12-03T19:17:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19111504758346101411059254244648105164","date":"2025-12-03T17:26:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-03T15:35:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-01T14:10:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-14T14:00:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-13T12:24:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-13T12:20:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1db97282-109d-40c5-806a-3c0c00917b23","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":59125094,"name":"Health sciences/Diseases"},{"id":59125095,"name":"Health sciences/Gastroenterology"},{"id":59125096,"name":"Health sciences/Medical research"},{"id":59125097,"name":"Biological sciences/Microbiology"}],"tags":[],"updatedAt":"2026-02-02T16:01:34+00:00","versionOfRecord":{"articleIdentity":"rs-8090557","link":"https://doi.org/10.1038/s41598-026-37351-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-01-29 15:58:08","publishedOnDateReadable":"January 29th, 2026"},"versionCreatedAt":"2025-12-08 10:29:26","video":"","vorDoi":"10.1038/s41598-026-37351-y","vorDoiUrl":"https://doi.org/10.1038/s41598-026-37351-y","workflowStages":[]},"version":"v1","identity":"rs-8090557","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8090557","identity":"rs-8090557","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}