The potential of targeted IL-4 therapy for the comorbidity of atopic dermatitis and attention-deficit/hyperactivity disorder in children via the skin-brain axis.

Abstract

Although Atopic Dermatitis (AD) and Attention-Deficit/Hyperactivity Disorder (ADHD) frequently coexist in children, the underlying mechanisms remain unclear. The "Skin-Brain Axis"(SBA) hypothesis, based on the shared ectodermal origin of the skin and the central nervous system(CNS), provides a theoretical foundation for communication between AD and ADHD. However, standardized biomarkers and direct clinical validation are currently lacking. Interleukin-4 (IL-4), a key cytokine driving skin inflammation in AD, may theoretically influence CNS development via the SBA, thereby contributing to the pathophysiology of ADHD; but this hypothesis has not yet been validated in humans. Based on the SBA, the review integrates the dual role of IL-4 in the pathogenesis of AD and ADHD, explores the possibility of IL-4 acting as a bridging signal between peripheral skin inflammation and neurodevelopmental abnormalities, and summarizes existing clinical and preclinical evidence for IL-4-targeted therapies for AD-ADHD comorbidity, while also highlighting current gaps in evidence and limitations in application. Future research should include prospective clinical trials with neurocognitive assessment and brain imaging as endpoints, using direct neuroimmune effects and indirect effects (such as itch relief and improved sleep) as reference indicators, to systematically evaluate the feasibility of IL-4 inhibitors in controlling neurobehavioral symptoms and provide a practical research pathway for clinical translation.