Ineffective Esophageal Motility Defined by Chicago Classification v4.0 Identifies a Clinically and Endoscopically Relevant Phenotype in Eosinophilic Esophagitis.

BACKGROUNDS: Esophageal motility abnormalities may contribute to symptoms in eosinophilic esophagitis (EoE), but most available evidence is based on Chicago Classification version 3.0 (CCv3.0). AIM: We evaluated the prevalence and clinical relevance of motility disorders defined according to CCv4.0 in patients with EoE. METHODS: We retrospectively included consecutive untreated patients with EoE who underwent upper endoscopy and high-resolution manometry at four Italian tertiary centers between 2016 and 2024. Manometric tracings were reanalyzed according to both CCv3.0 and CCv4.0. Associations between ineffective esophageal motility (IEM), symptoms, diagnostic delay, and Endoscopic Reference System (EREFS) findings were assessed. RESULTS: 106 patients were included in the analysis. CCv4.0 identified IEM in 15 patients (14.2%), compared with 29 (27.4%) using CCv3.0, while normal motility increased from 60.4% to 75.5%. Food impaction occurred in 14/15 patients with CCv4.0-defined IEM. CCv4.0-defined IEM was independently associated with food impaction (OR 6.92, 95% CI 1.37-34.94; p = 0.019), whereas CCv3.0-defined IEM was not. According to CCv4.0, IEM was strongly associated with both inflammatory (93.3% vs. 57.5%; OR 10.35, 95% CI 1.30-82.55; p = 0.008) and fibrostenotic endoscopic phenotypes (73.3% vs. 35.0%; OR 5.11, 95% CI 1.49-17.53; p = 0.009), whereas no significant associations were observed using CCv3.0. CONCLUSIONS: CCv4.0 reduces the prevalence of IEM and identifies a more clinically and endoscopically relevant hypomotility phenotype in EoE, characterized by a strong association with food impaction and both inflammatory and fibrostenotic endoscopic features. These findings support the clinical relevance of the more stringent CCv4.0 criteria for functional phenotyping in EoE.