The term "exposome" describes the totality of exposures to which an individual is subjected from conception to death. It includes both external and internal factors as well as the human body's response to these factors. Current exposome research aims to understand the effects all factors have on specific organs, yet today, the exposome of human skin has not received major attention and a corresponding definition is lacking. This review was compiled with the collaboration of European scientists, specialized in either environmental medicine or skin biology. A comprehensive review of the existing literature was performed using PubMed. The search was restricted to exposome factors and skin aging. Key review papers and all relevant, epidemiological, in vitro, ex vivo and clinical studies were analyzed to determine the key elements of the exposome influencing skin aging. Here we propose a definition of the skin aging exposome. It is based on a summary of the existing scientific evidence for the role of exposome factors in skin aging. We also identify future research needs which concern knowledge about the interaction of distinct exposomal factors with each other and the resulting net effects on skin aging and suggest some protective measures.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence‐based and expert‐based recommendations (S1 level).

Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo.

The shorter wavelengths of the visible light spectrum have been recently reported to induce a long-lasting hyperpigmentation but only in melano-competent individuals. Here, we provide evidence showing that OPN3 is the key sensor in melanocytes responsible for hyperpigmentation induced by the shorter wavelengths of visible light. The melanogenesis induced through OPN3 is calcium dependent and further activates CAMKII followed by CREB, extracellular signal-regulated kinase, and p38, leading to the phosphorylation of MITF and ultimately to the increase of the melanogenesis enzymes: tyrosinase and dopachrome tautomerase. Furthermore, blue light induces the formation of a protein complex that we showed to be formed by tyrosinase and dopachrome tautomerase. This multimeric tyrosinase/tyrosinase-related protein complex is mainly formed in dark-skinned melanocytes and induces a sustained tyrosinase activity, thus explaining the long-lasting hyperpigmentation that is observed only in skin type III and higher after blue light irradiation. OPN3 thus functions as the sensor for visible light pigmentation. OPN3 and the multimeric tyrosinase/tyrosinase-related protein complex induced after its activation appear as new potential targets for regulating melanogenesis but also to protect dark skins against blue light in physiological conditions and in pigmentary disorders.

Summary: Melasma is a common hyperpigmentary disorder. The impact on the quality of life of affected individuals is well demonstrated, demanding new therapeutic strategies. However, the treatment of melasma remains highly challenging. Melasma is often considered as the main consequence of female hormone stimulation on a predisposed genetic background. Although these two factors do contribute to this acquired pigmentary disorder, the last decade has revealed several other key players and brought new pieces to the complex puzzle of the pathophysiology of melasma. Here, we summarize the latest evidence on the pathophysiology of melasma, and we suggest that melasma might be a photoaging skin disorder affecting genetically predisposed individuals. Such data must be taken into consideration by clinicians as they could have a profound impact on the treatment and the prevention of melasma.

Abstract: Everyone knows and seems to agree that melanocytes are there to generate melanin – an intriguing, but underestimated multipurpose molecule that is capable of doing far more than providing pigment and UV protection to skin (1). What about the cell that generates melanin, then? Is this dendritic, neural crest‐derived cell still serving useful (or even important) functions when no‐one looks at the pigmentation of our skin and its appendages and when there is essentially no UV exposure? In other words, what do epidermal and hair follicle melanocytes do in their spare time – at night, under your bedcover? How much of the full portfolio of physiological melanocyte functions in mammalian skin has really been elucidated already? Does the presence or absence of melanoctyes matter for normal epidermal and/or hair follicle functions (beyond pigmentation and UV protection), and for skin immune responses? Do melanocytes even deserve as much credit for UV protection as conventional wisdom attributes to them? In which interactions do these promiscuous cells engage with their immediate epithelial environment and who is controlling whom? What lessons might be distilled from looking at lower vertebrate melanophores and at extracutaneous melanocytes in the endeavour to reveal the ‘secret identity’ of melanocytes? The currentControversiesfeature explores these far too infrequently posed, biologically and clinically important questions. Complementing a companion viewpoint essay on malignant melanocytes (2), this critical re‐examination of melanocyte biology provides a cornucopia of old, but under‐appreciated concepts and novel ideas on the slowly emerging complexity of physiological melanocyte functions, and delineates important, thought‐provoking questions that remain to be definitively answered by future research.