Distinct trajectories of childhood atopic dermatitis are associated with differences in long-term inflammatory and cardiometabolic disease risks

Florian Thaçi, Philip Curman, Katja Bieber, Henning Olbrich, Diamant Thaçi, Ralf J. Ludwig

medRxiv 2025.08.18.25333898; doi: https://doi.org/10.1101/2025.08.18.25333898

This article is a preprint and has not been certified by peer review. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

Abstract

Importance Atopic dermatitis (AD) is a common childhood inflammatory skin disease which occurs frequently in the early childhood and is later linked to type 2 diseases but also other systemic comorbidities. The role of different AD-disease trajectories on long-term health outcomes remains unclear, as prior studies have rarely conducted direct comparisons between distinct AD trajectories.

Objective To assess how different childhood AD trajectories - persistent, transient - or none, are associated with long-term risks of other type 2 inflammatory diseases (T2IDs), autoimmune diseases, and cardiometabolic disorders by performing all pairwise comparisons to identify trajectory-specific risk patterns.
Design Retrospective cohort study using US TriNetX Analyses included propensity-score matching, sensitivity analyses, and subgroup (sex and ancestry) stratification.

Setting Multicenter, population-based network of electronic health records from diverse US healthcare organizations.

Participants Children with AD onset before age of two were grouped by disease trajectory (persistent or transient) and compared with matched non-AD controls.

Exposures AD trajectory phenotype (persistent vs transient) or no AD.

Main outcomes and measures Hazard ratios (HRs) for T2IDs, autoimmune diseases, cardiovascular risk factors, venous thromboembolism (VTE), and major adverse cardiovascular events (MACE).

Risks of comorbid outcomes in children with persisting,
transient, or no atopic dermatitis (AD).

Results Persistent AD was associated with increased risk of T2IDs (HR 2.11, 95%-CI 2.01– 2.21), autoimmune diseases (HR 1.68, 1.60–1.76), and cardiovascular risk factors (HR 1.38, 1.22–1.56), but not VTE or MACE. Compared with transient, persistent AD conferred higher risk across most outcomes. EoE risk was especially elevated in females and children with Black or African American ancestry; other sex- or racial disparities were limited.

Conclusions and relevance Persistent childhood AD is associated with a substantial long-term inflammatory and cardiometabolic burden, whereas the risk conferred by transient AD appears minimal. These findings underscore the prognostic importance of disease trajectory and support timely disease activity-adapted interventions in children.

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