Very early onset eosinophilic esophagitis is common, responds to standard therapy, and demonstrates enrichment for CAPN14 genetic variants

• Published in: Journal of allergy and clinical immunology 2021-01, Vol.147 (1), p.244-254.e6
• Main Authors: Lyles, John L., Martin, Lisa J., Shoda, Tetsuo, Collins, Margaret H., Trimarchi, Michael P., He, Hua, Kottyan, Leah C., Mukkada, Vincent A., Rothenberg, Marc E.
• Format: Article
• Language: English
• Subjects: ACTG2; Adolescent; Age of Onset; Calpain - genetics; Calpain - immunology; CAPN14; cesarean delivery; EDP; environment; EoEHSS; Eosinophilic Esophagitis - genetics; Eosinophilic Esophagitis - immunology; Eosinophilic Esophagitis - pathology; EREFS; Female; Genetic Variation; genetics; Humans; Infancy; Male; molecular pathogenesis; Retrospective Studies
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2020.10.017

Eosinophilic esophagitis (EoE) is a chronic, food antigen–mediated disease characterized by esophageal dysfunction and intraepithelial eosinophil accumulation. We hypothesized that very early onset EoE (V-EoE) would be enriched for early-life and genetic factors and have worse presentation and prognosis than later-onset pediatric EoE (L-EoE). We conducted a single-site, retrospective review comparing patients diagnosed at age 12 months or less (V-EoE, n = 57) and age 14 to 18 years (L-EoE, n = 70). These patients underwent medical record, EoE Histology Scoring System, Endoscopic Reference Score, and EoE Diagnostic Panel assessment when sample availability permitted. Genetic association used 2 EoE genotype repositories. Data were analyzed using chi-square tests, t tests, Wilcoxon rank-sum tests, Spearman correlations, cluster analysis, and logistic regression. Among pediatric patients with EoE, diagnosis most commonly occurred within early life (0-24 months, 17%). V-EoE was more likely to attain histologic remission via dietary restriction (P < .0001). Basal zone hyperplasia and eosinophil inflammation were greater in V-EoE (P < .05). Esophageal strictures more commonly occurred in L-EoE (P = .03). V-EoE had lower endoscopic scores (P < .05). Molecular expression was very similar between groups. Cesarean delivery was more common in patients with V-EoE (P = .03). Patients with V-EoE demonstrated enrichment of CAPN14 common genetic variants. Early-life diagnosis of EoE is a common occurrence. V-EoE responds to standard therapy without early evidence for complications, suggesting a less severe prognosis than hypothesized. Molecular pathogenesis is preserved between V-EoE and L-EoE. Cesarean delivery and CAPN14 genetic variation likely promote earlier disease development. [Display omitted]