The atopic march describes the natural development of atopic dermatitis (AD), IgE-mediated food allergy (FA), asthma, and allergic rhinitis (AR). The relationship between eosinophilic esophagitis (EoE) and the atopic march is unknown. METHODS: Utilizing a primary care birth cohort of 130,457 children (entered age <1-year, followed > _24-months), we performed case-control analysis with propensity score-matched controls to establish if presence of AD, FA, asthma, and AR modify risk of developing EoE. RESULTS: 139 children developed EoE during the observation period (prevalence 0.11%). After adjustment, male gender (OR 2.7, 95%CI [1.9-4.0]) and white race (OR 2.4 [1.5-3.9]) were risk factors for EoE. Peak age of EoE diagnosis was 2.7-years, as compared with 0.4-years, 1-year, 1.1years, and 4.1-years for AD, FA, asthma, and AR, respectively. AD, FA, and asthma independently increased risk of EoE (HR [95%CI] of 2.7 [1.9-4.0], 8.9 [6.3-12.4], and 2.2 [1.6-3.1], respectively). Conversely, presence of EoE significantly increased risk of subsequent AR (HR 3.8, [1.4-2.7]). The cumulative effect of atopic conditions on risk of subsequent EoE was also significant (HR [95%CI] of 3.9 [2.6-5.7] for one-condition, 6.5 [4.3-9.9] for two-conditions, 9.8 [5.8,16.8] for three-conditions, and 12.2 [5.0-30.0] for four-conditions). p< _0.001 for all associations. CONCLUSIONS: Peak incidence of EoE occurs after that of AD, FA, and asthma, and is statistically concurrent with AR, fitting with known associations between these conditions. AD, FA and asthma independently and cumulatively increase risk of subsequent EoE, while EoE increases risk of subsequent AR. Our findings indicate that EoE is a late manifestation of the atopic march.
