Skin-Immune-Neuro-Gastro-Endocrine (SINGE) System: Lighting the Fire on Atopic Dermatitis Research

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by pruritic, dry, eczematous lesions. Traditionally regarded primarily as a cutaneous disorder influenced by genetic and environmental factors, AD is increasingly recognized as a multisystem condition involving immune, microbial, and neuroendocrine interactions.

This review proposes the Skin-Immune-Neuro-Gastro-Endocrine (SINGE) network as a comprehensive framework to explore the interconnected pathophysiology of AD. The aim is to highlight how changes across various systems contribute to disease development, presentation, and treatment.

A comprehensive review of current literature was performed, examining the roles of skin barrier dysfunction, immune signaling, neuroendocrine pathways, and gut microbial dysbiosis. These domains were integrated into a unified model that describes bidirectional interactions and their clinical implications.

The SINGE model reveals that epidermal barrier disruption activates a cascade of immune responses. Microbial dysbiosis, in concert with the gut-skin axis, further exacerbates AD symptoms, highlighting how alterations in one organ affect the other. Neuroinflammation further contributes to AD symptoms by perpetuating the itch-scratch cycle. Neuroendocrine factors amplify the inflammatory dysregulation, particularly through endocrine involvement involving cortisol signaling in the hypothalamic-pituitary-adrenal (HPA) axis and the paradoxical inflammatory effects on the skin barrier. Together, these intertwined pathways perpetuate the chronic inflammation and skin barrier dysfunction in AD.

By examining these elements as an intricate, intertwined system, the SINGE network reframes AD as a multisystem condition. This apprach not only shifts the understanding of the disease, but also serves as a foundation for exploration of targeted therapies.