Abstract
Acne vulgaris is one of the most prevalent chronic inflammatory skin diseases worldwide, characterized by marked clinical heterogeneity, fluctuating disease course, and strong sensitivity to environmental and lifestyle factors. The exposome, encompassing lifelong environmental, lifestyle, psychosocial, microbial, and intrinsic exposures, offers an integrative framework for re-conceptualizing acne as an environmentally modulated inflammatory disease. This review synthesizes external and internal exposomal drivers of acne, including pollution, radiation, climate and occupational factors, diet, smoking, cosmetics, psychosocial stress, and microbial ecosystems. We highlight the sebaceous gland as a central exposome sensor that integrates metabolic, immune, microbial, and neuroendocrine signals. Genetic susceptibility, epigenetic reprogramming, and non-coding RNA networks are key modifiers translating environmental exposures into persistent inflammatory and metabolic responses within the pilosebaceous unit. Importantly, adopting a health equity and social determinants of health (SDOH) perspective, we emphasize how structural and socioeconomic inequalities shape exposome burden, disease severity, and access to care. We propose that exposome-informed, low-cost, community-level prevention strategies, combined with evidence-based therapies, offer a pragmatic and equitable approach to acne management. Integrating molecular mechanisms with real-world and equity considerations, this framework advances understanding of acne pathophysiology and supports translation into more inclusive clinical practice.