Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. Depigmenting compounds should act selectively on hyperactivated melanocytes, without short-or long-term side-effects, and induce a permanent removal of undesired pigment. Since 1961 hydroquinone, a tyrosinase inhibitor, has been introduced and its therapeutic efficacy demonstrated, and other whitening agents specifically acting on tyrosinase by different mechanisms have been proposed. Compounds with depigmenting activity are now numerous and the classification of molecules, based on their mechanism of action, has become difficult. Systematic studies to assess both the efficacy and the safety of such molecules are necessary. Moreover, the evidence that bleaching compounds are fairly ineffective on dermal accumulation of melanin has prompted investigations on the effectiveness of physical therapies, such as lasers. This review which describes the different approaches to obtain depigmentation, suggests a classification of whitening molecules on the basis of the mechanism by which they interfere with melanogenesis, and confirms the necessity to apply standardized protocols to evaluate depigmenting treatments.

Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005)(2006)(2007)(2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may stimulate the secretion of cytokines, such as interleukin (IL)-6 and IL-8 by follicular keratinocytes and IL-8 and -12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL-1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5a-dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future. Biology of sebaceous glandsThe sebaceous gland is a holocrine gland, and its secretion is formed by the complete disintegration of the glandular cells. Excreting sebum is the major function of sebaceous glands (1), and increased sebum excretion is a major concurrent event that parallels the development of acne lesions. With the development of human sebaceous gland experimental models for in vitro studies (2-5), considerable progress has been made in our understanding of many new

SummaryAn overview of agents causing hypopigmentation in human skin is presented. The review is organized to put forward groups of biological and chemical agents. Their mechanisms of action cover (i) tyrosinase inhibition, maturation and enhancement of its degradation; (ii) Mitf inhibition; (iii) downregulation of MC1R activity; (iv) interference with melanosome maturation and transfer; (v) melanocyte loss, desquamation and chemical peeling. Tyrosinase inhibition is the most common approach to achieve skin hypopigmentation as this enzyme catalyses the rate-limiting step of pigmentation. Despite the large number of tyrosinase inhibitors in vitro, only a few are able to induce effects in clinical trials. The gap between in-vitro and in-vivo studies suggests that innovative strategies are needed for validating their efficacy and safety. Successful treatments need the combination of two or more agents acting on different mechanisms to achieve a synergistic effect. In addition to tyrosinase inhibition, other parameters related to cytotoxicity, solubility, cutaneous absorption, penetration and stability of the agents should be considered. The screening test system is also very important as keratinocytes play an active role in modulating melanogenesis within melanocytes. Mammalian skin or at least keratinocytes/melanocytes co-cultures should be preferred rather than pure melanocyte cultures or soluble tyrosinase.

Due to its interface function between the body and the environment, the skin is chronically exposed to both endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species (ROS). There is compelling evidence that oxidative stress is involved in the damage of cellular constituents, such as DNA, cell membrane lipids or proteins. To protect the skin against the over-load of oxidant species, it contains a well-organised system of both chemical and enzymatic antioxidant which are able to work in a synergistic manner. Skin antioxidant network protects cells against oxidative injury and prevent the production of oxidation products, such as 4-hydroxy-2-nonenal or malonaldehyde, which are able to induce protein damage, apoptosis or release of pro-inflammatory mediators, such as cytokines. When oxidative stress overwhelms the skin antioxidant capacity the subsequent modification of cellular redox apparatus leads to an alteration of cell homeostasis and a generation of degenerative processes. Topical application or oral administration of antioxidants has been recently suggested as preventive therapy for skin photoaging and UV-induced cancer. The recognition that ROS can act as second messengers in the induction of several biological responses, such as the activation of NF-kB or AP-1, the generation of cytokines, the modulation of signalling pathways, etc., has led many researchers to focus on the possible effects of antioxidants in many pathological processes. The recent demonstration that the peroxisome proliferators-activated receptors, whose natural ligands are polyunsaturated fatty acids and theirs oxidation products, have a central role in the induction of some skin diseases, such as psoriasis or acne, has indicated new links between free radicals and skin inflammation. Based on these findings, the review summarises the possible correlations between antioxidant imbalance, lipid oxidative breakage and skin diseases, from both a pathological and therapeutic points of view.

Summary During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term ‘vitiligo’ be used as an umbrella term for all non-segmental forms of vitiligo, including ‘mixed vitiligo’ in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.

Subscribe to PCMR and stay up-to-date with the only journal committed to publishing basic research in melanoma and pigment cell biology As a member of the IFPCS or the SMR you automatically get online access to PCMR. Sign up as a member today at www.ifpcs.org or at www.societymelanomaresarch.org SummaryDespite considerable advances in the past decade, melanin research still suffers from the lack of universally accepted and shared nomenclature, methodologies, and structural models. This paper stems from the joint efforts of chemists, biochemists, physicists, biologists, and physicians with recognized and consolidated expertise in the field of melanins and melanogenesis, who critically reviewed and experimentally revisited methods, standards, and protocols to provide for the first time a consensus set of recommended procedures to be adopted and shared by researchers involved in pigment cell research. The aim of the paper was to define an unprecedented frame of reference built on cutting-edge knowledge and state-of-the-art methodology, to enable reliable comparison of results among laboratories and new progress in the field based on standardized methods and shared information.

Vitiligo is the most common depigmenting disorder, which affects 0.5-1% of the worldwide population, causing disfigurement and serious disturbances in well being. There is a current lack of consensus in definition and methods of assessment of this disorder, which makes it generally impossible to compare the outcomes of different studies of the same treatment. This report summarizes the work carried out by the Vitiligo European Task Force to propose a consensus definition of the disease and to assess treatment outcomes using a system which combines analysis of extent, stage of disease (staging), and disease progression (spreading). In summary, extent is evaluated using the rule of 9. Staging is based on cutaneous and hair pigmentation in vitiligo patches, and the disease is staged 0-3 (revised version) on the largest macule in each body region, except hands and feet, which are assessed separately and globally as one unique area. Assessment of spreading is based on Wood's lamp examination of the same largest macule in each body area. Wood's lamp is useful for a combined assessment of staging and spreading in the same selected area. This study reports a workshop which validated the clinical use of the assessment form performed at several European University clinics, and showed an overall good concordance among panelists using the proposed scoring system. This system can be easily handled in clinical practice. However, variations between scorer profiles indicate a need for training to decrease interobserver variability. Further steps are envisaged, namely: (i) build a global index including staging and spreading for the initial assessment of vitiligo patients, usable as a guidance for therapeutic indications and prognosis, which could be interpreted as an equivalent of the TNM (tumor, node, metastasis) system for cancer; (ii) implement large-scale tests necessary for clinical trials (to check reproducibility and sensitivity); (iii) carry out studies of automated devices to assess extent more accurately; (iv) set up a teaching tool for scoring vitiligo, which could be posted on a website; and (v) set up an international conference on classifying, staging and scoring vitiligo, through the IFPCS Special Interest Group on Vitiligo.

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