Different effects of five depigmentary compounds,rhododendrol, raspberry ketone,monobenzone, rucinol and AP736 on melanogenesis and viability of human epidermal melanocytes

Numerous medications are used to treat hyperpigmentation. However, several reports have indicated that repeated application of some agents, such as rhododendrol (RD), raspberry ketone (RK) and monobenzone (MB), can be toxic to melanocytes. Although these agents had severe side effects in human trials, no current in vitro methods can predict the safety of such drugs. This study assessed the in vitro effects of five depigmentary compounds including leukoderma‐inducing agents. In particular, we determined the effects of different concentrations and exposure times of different depigmentary agents on cell viability and melanogenesis in the presence and absence of ultraviolet B (UVB) radiation. Concentrations of RD, RK and MB that inhibit melanogenesis are similar to concentrations that are cytotoxic; however, concentrations of rucinol (RC) and AP736 that inhibit melanogenesis are much lower than concentrations that are cytotoxic. Furthermore, the concentrations that cause toxic effects depend on exposure duration, and prolonged exposure to RD, RK and MB had more cytotoxic effects than prolonged exposure to RC and AP736. The cytotoxic effects of RD and RK appear to be mediated by apoptosis due to increased expression of caspase‐3 and caspase‐8; UVB radiation increased the cytotoxicity of these agents and also increased caspase activity. Our results indicate that different leukoderma‐inducing compounds have different effects on the viability of normal epidermal melanocytes and suggest that the in vitro assay used here can be used to predict whether an investigational compound that induces leukoderma may lead to adverse effects in human trials.     

Postburn leukoderma successfully treated with topical daylight psoralen UVA therapy

Postburn leukoderma is challenging to treat with different surgical and nonsurgical treatments resulting in variable outcomes. We report a case of a 56‐year‐old female with postburn leukoderma treated successfully with topical daylight psoralen UVA therapy for 6 months. The treatment was well tolerated and showed excellent improvement. In conclusion, we report the successful use of topical daylight PUVA for postburn leukoderma with almost complete repigmentation. This is a simple, convenient, and cheap nonsurgical treatment option.     

Spontaneous Contraction of Leukodermic Patches in Waardenburg Syndrome

Waardenburg Syndrome is an autosomal dominantly inherited disorder with variable penetrance (1–5). It is a rare disorder with an estimated frequency of 1:20,000 in Kenya (East Africa) and 1:40,000, in the Netherlands presenting with or without deafness. The frequency with deafness is lower, estimated at 1:50,000 to 1:212,000 (1, 2). The major characteristic features are as follows, with reported incidences in parenthesis: 1) Dystopia canthorum (99%); 2) synophrys (17%–69%); 3) broad nasal root (78%); 4) depigmentation of hair, skin, or both (17%–58% with white forelock); 5) heterochromic or hypochromic irides (greater than 20%); 6) congenital deafness (9%–38%) (1–7). Genetic heterogeneity has led to classification of affected families as type I, with dystopia canthorum, or type II, without dystopia canthorum (2, 6). Piebaldism and Woolf's Syndrome can present with pigmentary changes which are similar to Waardenburg Syndrome (2, 3, 8). Woolf's Syndrome also includes deafness (9). However, the distinguishing structural ophthomologic abnormalities of dystopia canthorum, broad nasal root, and synophrys are not found in either piebaldism or Woolf's Syndrome (2, 3, 8, 9). The congenital patterns of leukoderma in both piebaldism and Waardenburg Syndrome has been believed to be stable throughout the lifetime of the affected individuals (2, 10). We report an otherwise typical family with Waardenburg Syndrome, type I, in which 2 members atypically demonstrate spontaneous pigmentation and contraction of congenital leukodermic patches. To our knowledge, this has not been previously reported in Waardenburg Syndrome (1, 2, 6, 10).     

Frontiers and controversies in the pathobiology of vitiligo: separating the wheat from the chaff

Abstract:  The pathogenesis of vitiligo is complex and not well understood. Genes play a role in all aspects of vitiligo pathogenesis, and studies are ongoing to identify these genes and understand their biology. There is a body of interlocking, compelling evidence supporting an autoimmune basis for most or all cases of generalized vitiligo. The development of an autoimmune disease generally involves three components; the immune system, environmental triggers and other exogenous precipitating factors, and the target tissue. In vitiligo, precipitating factors could induce melanocyte damage in genetically susceptible individuals and consequent cell death, loss of tolerance, and induction of melanocyte-directed autoimmunity. Future research will more precisely define the multiple biological events that regulate development of vitiligo.     

威灵仙致接触性皮炎后色素异常

报告1例威灵仙致接触性白斑和色素性接触性皮炎。患者男，34岁。外敷威灵仙5个月后左腕关节屈侧皮肤出现色素减退斑、周围不规则色素沉着斑8个月。皮肤科检查：左腕关节屈侧皮肤见面积约4cm×4cm大不规则白斑，其周围有宽度不同、颜色均一的色素沉着斑，边界清楚。其他部位皮肤未见白斑或色素沉着斑。行威灵仙乙醇和水提物斑贴试验均为阳性。诊断：威灵仙致接触性白斑和色素性接触性皮炎。     

Management of resistant halo nevi

Background: Halo nevus (HN) is a rare dermatologic disorder characterized by typical whitish rim surrounding an existing melanocytic nevus resembling halo. It is a cosmetic problem that may be linked to vitiligo, and it is advised to remove these nevi in order to avoid development of vitiligo.

Objectives: The aim of the present study is to evaluate the cosmetic outcome after nevus removal and leukoderma dermabrasion with epithelial graft followed by narrow-band ultraviolet B (NB-UVB) phototherapy as management of resistant halo nevi and avoidance of development of vitiligo.

Patients and Methods: Ten patients with persisting halo nevi were selected as candidates in this study. Superficial dermabrasion was carried out using proper diamond fraises on depigmented rim and then punch biopsy probes with suitable size were used to harvest the nevus. Thiersch graft was prepared and applied on the dermabraded depigmented area. After 1 week of the procedure, patients were exposed to NB-UVB twice weekly and were followed up for 3 months.

Results: Repigmentation was noticed in 2 weeks and was nearly fully accomplished in all 10 patients within the 3-month period. No other vitiligo lesions developed during this period in all patients except for one case.

Conclusion: Excision of Sutton’s nevus with combined dermabrasion and Thiersch grafting followed by phototherapy is a good aesthetic maneuver in treating halo nevi and helps in avoiding further vitiligo depigmentation.     

中波紫外线治疗色素减退性皮肤病

目的：探讨在黄种人中应用中波紫外线(UVB)治疗色素减退性皮肤病的方法、效果及影响因素。方法：应用中波紫外线治疗白癜风、妊娠纹、色素减退性瘢痕等色素减退性皮肤病共40例。结果：中波紫外线治疗色素减退性皮肤病的有效率分别为：白癜风60％；妊娠纹80％；色素减退性瘢痕60％；三种疾病的治疗效果无统计学差异。治疗效果与皮损面积有关，面积较小者治疗效果较好，不良反应较轻。结论：中波紫外线是一种安全有效的治疗常见色素减退性皮肤病的方法。     

Guide for medical professionals (i.e. dermatologists) for the management of Rhododenol‐induced leukoderma

Because some users develop depigmentation after the use of melanogenesis‐inhibiting products containing the quasi‐drug ingredient Rhododenol, Japanese Dermatological Association (JDA) established a Special Committee on the Safety of Cosmetics Containing Rhododenol on July 17, 2013 and management guide for dermatologists has been updated on the website in order to delineate the diagnostic criteria for Rhododenol‐induced leukoderma and provides a broad guide for standard treatment based on current knowledge. This guide is produced on the basis of the guide (version 7) updated on June 20, 2014 in the website. Rhododenol‐induced leukoderma refers to depigmentation of varying severity that develops after the use of cosmetics containing Rhododenol, mainly at the site of use. In most cases, repigmentation of part or all the affected area is evident after discontinuation. Histopathologically cellular infiltration around the hair follicles and melanophages are present in most cases. The number of melanocytes in the lesion is declined but not totally absent in most cases. Rhododenol itself is a good substrate for tyrosinase, resulting in the formation of Rhododenol metabolites (e.g., Rhododenol quinone). Melanocytes are damaged by Rhododenol metabolites during the subsequent metabolic process. The continued use of cosmetics containing Rhododenol thus induces tyrosinase activity‐dependent cytotoxicity in melanocytes in the epidermis at application sites, resulting in decreasing the amount of melanin produced by melanocytes; the addition of some other factor to this process is believed to subsequently cause the decrease or disappearance of melanocytes themselves from the epidermis.