{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T13:33:44Z","timestamp":1788010424053,"version":"build-2784847793"},"reference-count":50,"publisher":"Mattioli1885","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Introduction: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.<\/jats:p>","DOI":"10.5826\/dpc.1504a5329","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:22:08Z","timestamp":1761916928000},"page":"5329","source":"Crossref","is-referenced-by-count":3,"title":["Skin-Immune-Neuro-Gastro-Endocrine (SINGE) System: Lighting the Fire on Atopic Dermatitis Research"],"prefix":"10.5826","volume":"15","author":[{"given":"Meshi","family":"Paz","sequence":"first","affiliation":[{"name":"Tulane University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7600-0152","authenticated-orcid":false,"given":"Peter","family":"Lio","sequence":"first","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University; Medical Dermatology Associates of Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27750","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"10.5826\/dpc.1504a5329_ref1","doi-asserted-by":"crossref","unstructured":"Afshari M, Kolackova M, Rosecka M, \u010celakovsk\u00e1 J, Krejsek J. 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