Persistent Pain in Pediatric Eosinophilic Esophagitis: Evidence for a Distinct Clinical Subtype

Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven inflammatory esophageal disease associated with diverse symptoms, including pain, which has received little attention.

We performed a retrospective, case-control study of 1,097 patients with EoE treated at Cincinnati Children's Hospital. Patients with documented, persistent EoE-associated pain were identified using a validated natural language processing algorithm. Following systematic review and abstraction of the electronic health record of patients with EoE-associated persistent pain (EoEp+) and no documented EoE-associated pain (EoEp-), a nested subgroup of confirmed subjects (n = 47 per group) was examined for clinical features and esophageal gene expression.

Clinically significant EoEp+ represented 4.3% of EoE subjects. Demographics, disease activity including eosinophil levels, and dysphagia were similar between groups; however, patients with EoEp+ were older at initial presentation (13.01 vs. 7.997 years, p < 0.028). Within the EoEp+ phenotype, duration of EoE care is associated with increasing endoscopy burden over time (r = 0.68, p < 0.0001). Subjects with EoEp+ most commonly experienced abdominal pain-38% isolated pain and 62% with additional gastrointestinal symptoms-and experienced more polytherapy (p = 0.0020), treatment alteration (p = 0.027), and comorbid conditions than subjects with EoEp-. Gene expression analyses revealed decreased ALOX15 levels in EoEp+ esophageal biopsies, particularly in remission cases (p = 0.0062).

Persistent pain in pediatric EoE is associated with a distinct clinical profile, characterized by greater treatment complexity, increased comorbid conditions, and dysregulated ALOX15 expression. These findings suggest that persistent pain in EoE identifies a clinically meaningful candidate endotype and highlights the need for targeted management strategies.