Plasma cytokines distinguish clinical phenotypes of atopic dermatitis

Background: Atopic dermatitis (AD) is a heterogeneous disease with several pheno- and endotypes. Distinct cytokine and lymphocyte patterns have already been described in pediatric AD but data integrating immunological and detailed clinical features remain scarce. Objective: To explore cytokine clusters in pediatric AD and examine their relation to clinical features, allergen sensitization and immune cell subsets, aiming to identify immunological signatures linked to disease phenotypes. Methods: 42 children with AD (median age 3.6 years, 64% male, mean SCORAD 45) were included. Plasma cytokines were measured using a multiplex panel and clustered unsupervised by CytoMod. Associations with age, disease severity, eosinophils, allergen sensitizations and peripheral B/T cell subsets were assessed. Results: Six cytokine clusters were identified, two showed distinct clinical associations: Cluster 1 (T cell co-signaling molecules): Associated with younger age, lower total IgE and milder AD. Expression correlated with B cell maturation, but this was age-dependent. Cluster 5 (Th2 cytokines): Expression increased with age and was associated with higher blood eosinophils, sensitization to inhalant allergens and more severe AD. Within this cluster, CCL17 correlated most strongly with SCORAD ( ρ = 0.67, p< 0.001). A CCL17-driven upregulation of CD4+CD25+ICOS+ T cells remained significant after age adjustment. Conclusion: Two phenotypes of pediatric AD emerged, linked to distinct cytokine clusters. CCL17 was identified as a central marker connecting cytokine expression, disease severity and T cell activation. While the role of CCL17 in AD is well known, to our knowledge this is the first pediatric study combining detailed clinical features, allergen sensitization, cytokine profiling and B/T cell subsets in peripheral blood. Future work will extend this approach to other atopic diseases such as allergic asthma to investigate shared and differential cytokine pathways between skin and lung, aiming to better understand the mechanisms underlying atopic multimorbidity. Publication History Article published online: 26 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany