Markers of Systemic Metabolic Dysfunction in Vitiligo and Their Potential Role in Disease Pathogenesis: A Narrative Review.

<h4>Background</h4>Vitiligo is a chronic autoimmune disease characterized by the progressive destruction of melanocytes, resulting in depigmented skin macules. While traditionally viewed as a cutaneous disorder driven by a specific CD8⁺ T cell-mediated interferon-γ (IFN-γ) signature, emerging research suggests that vitiligo may be a systemic condition linked to metabolic syndrome (MetS) and broader metabolic dysregulation.<h4>Methods</h4>This review synthesizes current experimental and clinical evidence regarding systemic metabolic alterations in vitiligo. We analyzed studies investigating disruptions in glucose utilization, lipid profile imbalances, and amino acid metabolism, alongside their mechanistic links to oxidative stress and immune activation.<h4>Results</h4>Evidence indicates that metabolic dysfunction, including aberrant glucose metabolism and lipid alterations, precedes or exacerbates immune mobilization. Key systemic factors such as advanced glycation end-products (AGEs), proinflammatory adipokines and reduced protective factors (vitamins and small antioxidants) create a permissive environment for melanocyte apoptosis. Furthermore, some studies concerning metabolic profiling reveal that systemic biomarkers (e.g., homocysteine, total cholesterol, LDL/HDL ratio, and urinary metabolites) correlate with disease activity and treatment response.<h4>Conclusions</h4>Vitiligo involves a complex interplay between systemic metabolic shifts and cutaneous autoimmunity. Integrating metabolic profiling into clinical practice offers a transformative approach for identifying subclinical abnormalities, discovering biomarkers for early diagnosis, and developing personalized management strategies that address the disease beyond its dermatological manifestations.