Vitiligo: current medical and scientific understanding.

Vitiligo is a relatively common acquired skin depigmentary disease with a complex presentation, therapy, and etiology. Both the prognosis and therapeutic response for patients with vitiligo is unpredictable. Multiple current therapies exist however the efficacy of these are not optimal. The cause of vitiligo appears to be a combination of genetic effects in both the immune system and the melanocyte itself with a precipitating factor instigating their interaction and resulting in the melanocyte destruction. Headway is being made in understanding the etiology of vitiligo that should culminate in new and improved therapies.

The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer.

BACKGROUND: Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate. OBJECTIVES: To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women. METHODS: Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face. RESULTS: Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35-68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use. CONCLUSIONS: The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.

'VIT1', a novel gene associated with vitiligo.

To define genes associated with the pigmentary disorder vitiligo, gene expression was compared in non-lesional melanocytes cultured from three vitiligo patients and from three control melanocyte cultures by differential display. A basic local alignment search tool search did not reveal homology of six differentially expressed cDNA fragments to previously identified expressed sequence tags; thus, one was used to screen a melanocyte cDNA library. The underlying VIT1 gene maps to chromosome 2p16. The 3' portion of the VIT1 message is complementary to the 3' end of hMSH6 mRNA, enabling the formation of RNA-RNA hybrids, which may interfere with G/T mismatch repair function. Moreover, the aligned cDNA sequence revealed an open reading frame identical to a hypothetical protein expressed in brain, with a similarity to Drosophila calmodulin, and containing a zinc-finger motif partially identical to N-recognin. Expression of ORF mRNA was confirmed for multiple skin cell types, suggesting its importance for skin physiology.

The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase activity.

It has been known for several decades that cutaneous depigmentation, i.e., contact/occupational vitiligo, can be caused by some phenolic derivatives that have a similar structure to tyrosine. Among these phenolic depigmenting agents, 4-tertiary butylphenol is the most potent. The cutaneous depigmentation induced by phenolic derivatives results from the loss of functional melanocytes. Tyrosinase is a melanocyte specific copper-containing enzyme that catalyzes the conversion of the amino acid tyrosine, through a complex series of intermediates, to melanin. In this study we tested the hypothesis that the cytotoxicity induced by 4-tertiary butylphenol is mediated by tyrosinase and occurs via an apoptotic process. Melanocyte cultures derived from African-American and Caucasian donors exhibiting a 3-fold difference in tyrosinase activity and 14-fold difference in melanin content demonstrate comparable concentration-dependent sensitivity to 4-tertiary butylphenol. In addition, cultures of dermal fibroblasts and epidermal keratinocytes exhibited similar and reduced sensitivity, respectively, to 4-tertiary butylphenol compared with autologous melanocytes. Two melanoma cell lines, one melanotic and one amelanotic lacking the expression of both tyrosinase protein and activity, when transfected with the tyrosinase cDNA, exhibited no alteration in its sensitivity to 4-tertiary butylphenol. These data suggest that 4-tertiary butylphenol cytotoxicity is not mediated via tyrosinase. Melanocytes treated with 4-tertiary butylphenol, however, did exhibit plasma membrane blebbing, DNA fragmentation, and phosphatidylserine relocalization indicating that 4-tertiary butylphenol induced melanocyte destruction occurs by an apoptotic process.

Vitiligo.

Vitiligo involves a progressive loss of melanocytes from the epidermis and hair follicles. Milky-white patches appear resulting in cosmetic disfiguration that is most apparent in dark-skinned individuals. The disease is further classified according to distribution pattern and extent of depigmentation. The presence of several clinical subtypes may reflect the diversity in causative factors. To select appropriate therapeutic measures it is important to distinguish vitiligo from other disorders that affect melanocyte function. Although vitiligo has a characteristic clinical appearance and histological features, the presence of early or atypical lesions often requires the exclusion of other disorders such as postinflammatory hypopigmentation and piebaldism. Multiple hypotheses have been put forward to explain vitiligo. An inherited tendency to develop depigmentation may involve the inherent aberrancies that have been observed in nonlesional vitiligo melanocytes in vivo as well as in vitro. These abnormalities potentially render vitiliginous melanocytes more vulnerable to assaults from extracellular factors. Such factors include keratinocyte physiology, extracellular matrix composition, humoral and cellular immunity, and environmental agents. Therapies aimed at repopulation of lesional skin include phototherapy, application of topical corticosteroids, and transplantation of skin or skin cells. Moreover, micropigmentation or camouflage can be used to restore a pigmented appearance to lesional skin. In patients in which vitiligo affects extensive areas of the body, depigmentation may be the treatment of choice. In all, this acquired pigmentary disorder can be treated in a variety of ways and should not be regarded as an untreatable affliction.

Establishment of proliferative, pure cultures of pigmented chicken melanocytes from neural tubes.

In order to obtain pure cultures of chicken melanocytes, neural tubes were excised from 22-somite stage embryos and placed in culture dishes to allow melanoblasts to migrate out and proliferate. The growth of contaminating cells was inhibited by maintaining the primary cultures in low-calcium and low-magnesium medium supplemented with 32 nM 12-O-tetradecanoylphorbol-13-acetate (TPA). Subsequently the pure cultures of melanocytes were maintained in Ham's F-10 medium supplemented with TPA. The population doubling time was approximately 12 h. The cell density at confluency in medium containing 32 nM TPA, 80 nM TPA, or 32 nM TPA plus 1 nM cholera toxin was 3.4, 5.6, or 8.3 X 10(4) cells/cm2, respectively. The melanocytes were highly pigmented and had tyrosinase activities ranging from 0.7-5.0 mU/mg protein.