Very Early Onset Eosinophilic Esophagitis Is Common, Responds to Standard Therapy, and Demonstrates Enrichment for CAPN14 Genetic Variants

Abstract

To determine if very early onset eosinophilic esophagitis (V-EoE) represents a separate disease endotype, with worse clinical features and prognosis, distinct molecular properties, and specific risk factors, compared with that of later-onset pediatric eosinophilic esophagitis (L-EoE).In this study, researchers included patients diagnosed with eosinophilic esophagitis (EoE) at the age of ≤12 months (V-EoE: n = 57) and at the age of 14 to 18 years (L-EoE: n = 70). The diagnostic criteria for EoE included symptoms of esophageal dysfunction or inflammation and at least 15 eos/hpf in distal esophageal biopsy despite proton pump inhibitor use.A single-center retrospective chart review was focused on demographics and clinical history. Pretreatment histologic and gross endoscopic features were graded by using the EoE Histology Scoring System and the EoE Endoscopic Reference Score. RNA was extracted from a cohort of 15 pretreatment patients and analyzed via the EoE Diagnostic Panel, which is used to distinguish EoE from gastroesophageal reflux. With genetic analysis, the researchers examined whether single-nucleotide polymorphisms in CAPN14 and TSLP were associated with age of diagnosis.EoE was most commonly diagnosed at the age of 0 to 24 months. The V-EoE group was more likely to present with feeding issues, weight concerns, and vomiting, compared with that of dysphagia in the L-EoE group. Patients with V-EoE were more likely to have a history of cesarean delivery. Dietary restriction was more likely to be the initial and successful therapy in in the V-EoE group, whereas the L-EoE group was more likely to respond to swallowed steroids. Histologic remission was sustained in patients with V-EoE and was less common in patients with L-EoE, likely due to therapy nonadherence. The V-EoE group demonstrated higher levels of inflammation on histology, whereas esophageal strictures and fibrosis were more common in the L-EoE group. EDP molecular expression was similar between the 2 groups. Genetic analysis–identified single-nucleotide polymorphisms in CAPN14 were associated with V-EoE.V-EoE is associated with unique clinical, histologic, and genetic features. The increased incidence of cesarean delivery in patients with V-EoE may indicate a role of early-life dysbiosis. Patients with V-EoE can be managed successfully with standard therapy and achieve sustained remission. Fibrostenosis and esophageal dilation were more likely in L-EoE.V-EoE is a clinically important entity, requiring prompt recognition and diagnosis to initiate treatment. In a patient with recurrent emesis, feeding difficulties, and poor weight gain, consider endoscopy to evaluate for EoE. Risk factors include cesarean delivery and CAPN14 variants. Successful management of V-EoE can be attained with standard therapy and may prevent late-stage complications related to esophageal remodeling.