The Neuro-Immuno-Cutaneous-Endocrine (Nice) Model: Biological Mechanisms linking Psychological Stress and Skin Diseases

Abstract

Psychological stress is increasingly recognized as an important modifier of dermatological disease activity. Advances in psychoneuroimmunology have demonstrated that the skin functions as an active neuroimmunoendocrine organ capable of responding to both environmental and psychological stressors. These discoveries have culminated in the development of the Neuro-Immuno-Cutaneous-Endocrine (NICE) model, which provides a comprehensive framework for understanding the biological mechanisms connecting stress and skin diseases. The objective was to review current evidence regarding the neuroendocrine, immunological, inflammatory, and microbiological pathways involved in stress-related skin disease and to discuss future developments in precision psychodermatology. Regarding the methods, a narrative review of the literature was performed using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases. Landmark studies, systematic reviews, meta-analyses, and recent publications addressing psychodermatology, psychoneuroimmunology, skin–brain interactions, biomarkers, microbiome science, and precision medicine were analyzed. The results showed that Psychological stress influences skin physiology through activation of the hypothalamic–pituitary–adrenal axis, sympathetic nervous system stimulation, neurogenic inflammation, mast cell activation, cytokine dysregulation, epidermal barrier impairment, oxidative stress, and microbiome alterations. These interconnected mechanisms form the basis of the NICE model and contribute to the pathogenesis of numerous inflammatory and autoimmune dermatological disorders. Emerging evidence suggests that biomarkers of stress, microbiome profiling, artificial intelligence, and digital health technologies may facilitate the development of personalized psychodermatological care. To conclude, the NICE model provides a robust biological framework for understanding the bidirectional relationship between psychological stress and skin disease. Future advances in systems biology, biomarker discovery, and precision medicine are expected to transform psychodermatology into a predictive and individualized discipline.