The Exposome in Melasma: A Comprehensive Review of Etiology, Mechanisms, and Implications for Management

Abstract: Melasma is a common pigmentary skin disorder characterised by symmetrical brownish patches on the face, which significantly impacts patients’ quality of life. This article provides a comprehensive review of the latest research progress on melasma from the perspective of the exposome, a dynamic interactive model. The exposome encompasses all environmental exposures and their biological responses experienced by an individual throughout their lifespan. We systematically explore the synergistic pathogenic mechanisms of endogenous exposures (such as hormonal levels, oxidative stress, thyroid dysfunction, vitamin D metabolism and psychological stress) alongside specific exogenous exposures (such as ultraviolet, visible light radiation, air pollution, pharmacological agents, dietary habits and skincare practices) and general exogenous exposures (such as climate change) in the pathogenesis of melasma. This article reveals how multiple exposure factors converge on key pathways such as the MITF/AhR signaling axis, oxidative stress cycles, and the POMC neuroendocrine pathway, collectively driving the sustained activation of melanocytes and pigmentation. Traditional therapies primarily target already formed pigmentation, with limitations including high recurrence rates and addressing symptoms rather than root causes. Based on the exposome concept, future clinical management strategies need to shift towards proactive, comprehensive health management throughout the entire process. This includes thorough assessment of individual exposure risks, enhanced full-spectrum photoprotection, skin barrier repair, lifestyle adjustments (such as stress management, regular routines and antioxidant-rich diets), as well as combined reparative treatments. This review aims to integrate existing evidence to provide new perspectives on the aetiology of melasma and offer insights for developing personalised prevention and treatment strategies. Keywords: melasma, exposome, ultraviolet radiation, oxidative stress, estrogen, air pollution