松永 佳世子

Background: Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol. Objective: To investigate the mechanism underlying the depigmentation caused by rhodbdendrol-containing cosmetics, this study was performed. Methods: The mechanism above was examined using more than dozen of fnelanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect rhododendrol and its metabolites in the presence of tyrosinase. Results: Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the rhododendrol-induced melanocyte impairment. Hydroxyl-rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity. Conclusion: The generation of a tyrosinase-catalyzed hydroxyl-metabolite is one of the causes for the diminishnient of the melanocyte viability by rhododendrol. (C) 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Bipolar radiofrequency (RF) technology is developed based on fractional thermolysis, and the literature concerning the efficacy of the rejuvenation and treatment of acne scars has been reported in Europe and the United States of America. Therefore, we examined bipolar RF treatment using fractional thermolysis to evaluate the efficacy and safety of the treatment of Asian photo-aging skin, particularly wrinkles' and sagging.' Ten Japanese women (mean age: 58.6, skin type III-IV) received three fractional bipolar RF treatments every 4-6weeks. For the objective evaluation, we evaluated the improvement of the wrinkles on the forehead, lateral canthus (crow's feet) and lower eyelid, and the sagging of the nasolabial fold using digital photographs captured using Visia. For the subjective evaluation, the participants were asked to describe the improvements observed in the wrinkles on the forehead, lateral canthus (crow's feet) and lower eyelid, and sagging nasolabial fold and to evaluate the level pain experienced using a 10-point VAS score. The objective evaluation in each category showed significant improvements in the wrinkles on the lateral canthus (crow's feet) and lower eyelid. As for the nasolabial fold, 60% of the subjects showed improvements, scoring from good to excellent (51-100% improvement), although there was a little improvement of the wrinkle on the forehead. Similar improvements were observed in the subjective evaluation. During each treatment, oedema and erythema were observed in all participants, but the oedema disappeared the following day in all cases. However, mild erythema persisted for an average of 3.1days. Micro debris disappeared after an average of 5.2days. The participants were satisfied, as we allowed them to apply make-up the next day. There were no other severe adverse reactions observed during the treatment. The 10-point VAS score was 3.8, and no participants dropped out due to discomfort. Little improvement was observed in the forehead wrinkles in either the objective or the subjective evaluation. The results obtained in this study indicate that fractional bipolar RF is an effective and safe treatment for the wrinkling' and sagging' of Asian photo-aging skin.

本邦で、4-(4-ヒドロキシフェニル)-2-ブタノール(ロドデノール)を2%含有する化粧品使用者において、他のメラニン生成抑制物質含有化粧品に比べて高頻度に脱色素斑が発生することが判明し、2013年7月に製造販売業者によって自主回収が発表された。本事例の脱色素斑症例は、2014年6月時点で18,909名と発表されている。日本皮膚科学会は、ロドデノール(RD)誘発性脱色素斑の臨床所見と疫学的な特徴を明らかにするために、RD含有医薬品部外品の使用後に生じた脱色素斑を主訴に受診した患者を対象に、2013年7月から9月にかけて全国一次調査を行い、1,338人の調査票を解析した。脱色素斑は96%で製品使用部位に概ね一致していたが、4%では製品使用部位以外にも白斑を認めた。色素脱失部位は顔面(92.9%)、頸部(58.8%)が好発部位であった。色素脱失については、完全か不完全かで3型に分類した。その結果、不完全脱色素斑42%、完全脱色素斑17%、混在28%であった。また、43.8%が炎症を伴うものであった。85%の症例では臨床的に特発性尋常性白斑と区別できないと回答された。本調査によってRD誘発性脱色素斑症例の臨床・疫学的な実態を明らかにした。今後、二次調査で疾患の経過、予後について検討する。(著者抄録)

目的:2011年の当科における持参香粧品による接触皮膚炎および原因製品の動向を明らかにすることを目的とした。方法:2011年に香粧品による接触皮膚炎の疑いで当科を受診した症例に対し、パッチテスト(以下PT)を施行した。PTは患者が持参した香粧品とJapanease standard allergens 2008および化粧品関連アレルゲンを貼布した。判定は72時間または1週間後International Contact Dermatitis Research Group基準で+以上を陽性とした。結果:68例にPTを施行した。香粧品のPTが陽性で臨床的に関連性があると考えられた症例は12例で、原因製品は17製品であった。原因製品の内訳は染毛剤が8製品と最も多く、ついで保湿剤とシャンプーが各3製品、日焼け止めクリーム、ファンデーション、マスカラ、フェイスクリーム、アイクリームが各1製品であった。結論:2011年は当科において新規アレルゲンとしてアルガニアスピノサ核エキスとココイルグルタミン酸ナトリウムを認めた。(著者抄録)

近年、加水分解小麦(グルパール19S)含有石鹸使用後に発症した小麦アレルギー症例についての報告が多くなされている。そこで今回、当科を2010年〜2012年に受診し、同石鹸使用に起因する小麦アレルギーと診断された9症例について初診時の症状とその後の経過について検討した。症例は全例女性で、平均年齢は44.7歳であった。2013年9月現在全例で小麦を摂取しており、完全に小麦摂取を避けている症例はなかった。通常量の摂取が可能となった症例は5例であったが、そのうちの3例は食後の運動を避けていた。少量の小麦であれば摂取可能な症例は4例であり、そのうちの3例はときに症状の出現をみている。小麦およびグルテン特異的IgE抗体は全例陰性化した。グルパール19S特異的IgE抗体は多くの症例で低下傾向ではあるが、現在も5例で陽性であった。以上より、今後も注意深い経過観察が必要と考えた。(著者抄録)

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

It has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB-induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR-1x HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear -catenin-positive McSCs were increased as compared to non-irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of -catenin, was significantly upregulated in McSCs of UVB-irradiated mice. The Wnt1 expression and the number of nuclear -catenin-positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte-related genes including Dct in early-passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.

Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

Chemically induced depigmentation of the skin, which occurs following exposure (application or inhalation) to a depigmenting agent, is a disease with clinical findings similar to vitiligo. Recently, skin depigmentation possibly resulting from exposure to 4-(4-hydroxyphenyl)-2-butanol (HPB) was reported in humans. However, the role of HPB as the causative material of this skin depigmentation was not clear. To evaluate whether HPB has the potential for skin depigmentation, we characterized its effects on the skin of pigmented guinea pigs. Following exposure to 30% HPB 3 times/day for about 20 days, we found that obvious skin depigmentation was induced in brown and black guinea pigs. In the depigmented skin, there was a marked reduction in melanin pigment, and decreased numbers of DOPA and S-100 positive epidermal melanocytes were observed histologically. In addition, the depigmentation gradually recovered spontaneously and the number of melanocytes in the skin also increased after terminating the application of HPB. Complete re-pigmentation needed 31 to 70 days to return to the original baseline level. These data indicate that skin depigmentation is induced by the toxicity of HPB to epidermal melanocytes, and that the induced skin depigmentation can recover by terminating the application of HPB.

日本人尋常性ざ瘡に対する過酸化ベンゾイル(BPO)ゲルの有効性および安全性に関する試験について、プラセボを対照としたランダム化、二重盲検、並行群間比較、多施設共同で実施した。その結果、2.5%BPOゲル群および5%BPOゲル群はプラセボ群と比べ、炎症性皮疹数および非炎症性皮疹数の減少率が有意に高かった。また、安全性についても問題がないと考えられたことから、2.5%BPOゲルおよび5%BPOゲルは尋常性ざ瘡患者の治療薬として有用であると考えられた。