Objective: Eosinophilic enteritis (EoN) remains underrecognized because of nonspecific symptoms and difficulty obtaining deep small intestinal biopsies. We evaluated the diagnostic utility of double-balloon enteroscopy (DBE)-guided multisite biopsy and explored tissue and blood eosinophil thresholds distinguishing EoN from non-EoN conditions. Methods: This single-center retrospective cohort included consecutive patients who underwent DBE with small intestinal biopsies (January 2021–December 2024). Biopsies were obtained from up to six predefined segments (duodenum, upper/lower jejunum, upper/lower ileum, terminal ileum). EoN diagnosis required abdominal pain and/or diarrhea, exclusion of competing diagnoses, and small intestinal biopsy-proven eosinophilic infiltration. Peripheral eosinophil percentage and computed tomography findings were recorded. The primary outcome was the extent of small intestinal eosinophil infiltration in patients with EoN. Secondary outcomes were the peripheral blood eosinophil count, clinical background, and exploratory comparisons with non-EoN cases. Results: Eighteen patients were included (5 EoN, 13 non-EoN). Computed tomography showed small intesinal wall edema in three patients with EoN. Peripheral eosinophil counts were significantly higher in EoN (median, 15.2% vs. 1.9%; P < 0.01). Across 83 biopsy specimens (25 EoN, 58 non-EoN), patient-level peak eosinophil counts were greater in EoN (median, 77/HPF 22–213 vs. 23/HPF 12–111; P < 0.01). All patients with EoN had at least one segment with ≥50 eosinophils/HPF, while two with non-EoN reached this threshold. No DBE-related serious adverse events occurred. Conclusions: EoN exhibits significantly greater eosinophil infiltration than non-EoN. DBE-guided multisite biopsy enables accurate recognition of EoN. Prospective multicenter studies are needed to refine site-specific thresholds and standardize HPF reporting.
Yamashina et al. (2026) studied this question.