Longitudinal Enrichment of Eosinophilic Esophagitis in Children with AD: The MPAACH Cohort.

Introduction: The atopic march refers to the natural history of the sequential development of atopic dermatitis (AD), food allergy (FA), asthma and allergic rhinitis (AR) in childhood, but there is significant heterogeneity in the timing and order of disease presentation. Eosinophilic esophagitis (EoE) is an emerging food-induced inflammatory disease of the esophagus that shares clinical and immunologic features, genetic susceptibility and comorbidities with other march members. We sought to investigate the incidence and prevalence of EoE in a cohort of children with AD and elucidate the individual trajectories of sensitization and allergic comorbidity development. Methods: We evaluated 700 children participating in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort. FA was defined as parental report of a physician diagnosis. AR was defined by a positive skin prick test to ≥1 aeroallergen and symptoms. Asthma was defined by pulmonary function testing and symptoms according to ATS criteria. Participants were classified as having EoE if they had ≥15 eosinophils per high-power field in at least one esophageal biopsy. Results: Of the 700 children in MPAACH, 10 developed EoE, all after AD onset. The cumulative incidence of EoE in MPAACH was 0.7% by age 2, 0.7% between ages 2 and 5, and 1.6% between ages 5 and 8. The prevalence of EoE in MPAACH is 1.4% (95%CI 0.5-2.3%) and the median age at EoE diagnosis was 3.7 years (interquartile range (IQR): 1.8-6.5). Despite no difference in skin barrier quality or AD severity, children with EoE were more likely to have food sensitization (60% vs. 28%, p=0.039) and FA (70% vs. 13%, p<0.001). 90% of children with EoE had ≥1 allergic comorbidity compared to 49% of the MPAACH cohort (p=0.009). Of these 9, 6 developed FA and/or AR prior to their EoE diagnosis and 3 children developed FA, AR, and/or asthma after EoE onset. Conclusions: Our data support the inclusion of EoE as a fifth member of the march, with new incidence estimates showing enrichment in children with AD, underscoring early-life AD as a risk factor for EoE. The higher prevalence of food sensitization and FA despite no difference in skin barrier quality or AD severity suggests the esophagus as the site of allergen penetration independent of the skin. These data support screening for EoE symptoms in children with early allergic manifestations.