松永 佳世子

Background: Solar lentigines (SLs) are characterized by hyperpigmented macules, commonly seen on sun-exposed areas of the skin. Although it has been reported that an increase in the number of melanocytes and epidermal melanin content was observed in the lesions, the following questions remain to be answered: (1) Is acceleration of melanogenesis in the epidermis caused by an increased number of melanocytes or the high melanogenic potential of each melanocyte? (2) Why does the number of melanocytes increase? Objective: To elucidate the pathogenic mechanism of SLs by investigating the number, melanogenic potential and proliferation status of the melanocyte lineage in healthy skin and SL lesions. Methods: Immunostaining for melanocyte lineage markers (tyrosinase, MART-1, MITF, and Frizzled-4) and a proliferation marker, Ki67, was performed on skin sections, and the obtained images were analyzed by image analysis software. Results: The expression level of tyrosinase to MART-1 of each melanocyte was significantly higher in SL lesions than healthy skin. The numbers of melanocytes in the epidermis, melanoblasts in the hair follicular infundibulum and melanocyte stem cells in the bulge region were increased in SL; however, no significant difference was observed in the Ki67-positive rate of these cells. Conclusion: The melanogenic potential of each melanocyte was elevated in SL lesions. It was suggested that the increased number of melanocytes in the SL epidermis might be attributed to the abnormal increase of melanocyte stem cells in the bulge. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Background: Solar lentigines (SLs) are characterized by hyperpigmented macules, commonly seen on sun-exposed areas of the skin. Although it has been reported that an increase in the number of melanocytes and epidermal melanin content was observed in the lesions, the following questions remain to be answered: (1) Is acceleration of melanogenesis in the epidermis caused by an increased number of melanocytes or the high melanogenic potential of each melanocyte? (2) Why does the number of melanocytes increase? Objective: To elucidate the pathogenic mechanism of SLs by investigating the number, melanogenic potential and proliferation status of the melanocyte lineage in healthy skin and SL lesions. Methods: Immunostaining for melanocyte lineage markers (tyrosinase, MART-1, MITF, and Frizzled-4) and a proliferation marker, Ki67, was performed on skin sections, and the obtained images were analyzed by image analysis software. Results: The expression level of tyrosinase to MART-1 of each melanocyte was significantly higher in SL lesions than healthy skin. The numbers of melanocytes in the epidermis, melanoblasts in the hair follicular infundibulum and melanocyte stem cells in the bulge region were increased in SL; however, no significant difference was observed in the Ki67-positive rate of these cells. Conclusion: The melanogenic potential of each melanocyte was elevated in SL lesions. It was suggested that the increased number of melanocytes in the SL epidermis might be attributed to the abnormal increase of melanocyte stem cells in the bulge. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

ゴム関連アレルゲン陽性の職業性接触皮膚炎側に対する加硫促進剤非含有ゴム(VAF)手袋の有用性について検討した。thiuram mixに陽性反応を呈した27例を対象とした。VAF手袋を4週間使用した。手湿疹の増悪因子が多い職業では医療従事者8例、美容師2例、清掃員2例、栄養士1例、飲食店転院1例、農業従事者1例、工場作業員1例、自転車販売修理員1例、専業主婦3例、少ない職業では会社員2例、学生2例、無職(引退後)2例、修道女1例であった。既往歴はアトピー性皮膚炎4例、気管支喘息5例、花粉症7例、アレルギー性鼻炎3例、手湿疹22例、既往歴なしが2例であった。OHSIは27例中24例においで点数が減少(すなわち手湿疹が軽快した)または不変となり、点数が増加した(すなわち手湿疹が増悪した)のは3例で、有意差を認めた。アンケートでは否定的な意見は少なく、良いあるいは普通と答え例が多かった。

ニトリルラテックスゴム手袋の皮膚感作性に影響する化学物質について検討した。加硫促進剤を必要としない新型ニトリル手袋の製品化に成功した。加硫促進剤非含有の新型ニトリル手袋と、比較のために現在市販されている従来方法で加硫したニトリル手袋2種類(A、B)を用いた。新型ニトリル手袋からは加硫促進剤由来成分は検出しなかった。従来ニトリル手袋A、BからはP&TGC-MSで加硫促進剤の分解物を検出し、薄層クロマトグラフィーによってジエチルジチオカルバミン酸亜鉛およびジ-n-ブチルジチオカルバミン酸亜鉛が含まれていることが明らかとなった。従来ニトリル手袋Aと新型ニトリルとで皮膚感作性試験では低濃度領域で明らかな差が見られ、新型ニトリルでは感作性が低減していた。

Concurrent reactivation of herpes simplex and varicella zoster viruses is rare. Here, we describe the case of an elderly patient with herpes labialis and herpes zoster manifesting as a right-side facial eruption with vesicles and crusting. The loop-mediated isothermal amplification (LAMP) assay demonstrated the presence of both herpes simplex virus type 1 and varicella zoster virus in swab samples taken from the face, which was confirmed by real-time PCR, suggesting concurrent reactivation of both viruses. The use of the LAMP assay in the present case indicates its usefulness in the diagnosis of atypical herpes infections. © 2014 S. Karger AG, Basel.

Objectives: We investigated the facial skin microbiota of Japanese acne patients. Methods: Skin swab samples were obtained from 100 acne patients and 28 healthy controls to evaluate Propionibacterium and Staphylococcus spp. using a culture method. Malassezia spp. were evaluated using a non-culture method. Antibiotic resistance of Propionibacterium spp. was also examined. Results: Acne patients and controls did not show significant differences in Propionibacterium and Staphylococcus spp. populations. However, the number of Malassezia globosa from patients was greater than that from controls. Moreover, the number of Propionibacterium spp. from patients carrying antibiotic-resistant strains was significantly greater than that from patients not carrying them. Conclusions: The present study characterized the facial skin microbiota of Japanese acne patients, suggesting a correlation between acne and quantitative differences in Malassezia microbiota. It was also found that the antibiotic resistance of Propionibacterium spp. may affect its abundance in the skin. (C) 2013 S. Karger AG, Basel

目的:2010年5月に日本で発売開始されたパッチテストテープ6種とジャパニーズスタンダードアレルゲン2008のアレルゲン6種の陽性率を比較した。結果:両アレルゲンを貼布した401例を検討した結果、6種のアレルゲンすべての陽性一致率は60.4%で、ジャパニーズスタンダードアレルゲン2008のみ陽性であったのは14.4%、パッチテストテープのみ陽性であったのは25.2%であった。陽性一致率は硫酸ニッケル64.5%、塩化コバルト46.7%、重クロム酸カリウム60.0%、チメロサール64.0%であった。ホルムアルデヒドは両アレルゲンに陽性であった症例は認めず、メルカプトミックス陽性は1例ありメルカプトベンゾチアゾールにも陽性であった。結論:パッチテストテープはパッチテスト試薬として有用であるが、アレルゲンの種類が少なくパネルシートの発売が待たれる。(著者抄録)

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized disease characterized by elevated serum IgG4 levels, tissue infiltration rich in IgG4(+) plasma cells. We report on a case which was first considered as pseudolymphoma from the histopathological analysis, but finally diagnosed as IgG4-related skin lesions. As the morphological features of cutaneous involvement of IgG4-RD are consistent with those of cutaneous pseudolymphoma, we tried immunostaining past potential cases of IgG4-RD. Thirty-two skin specimens (15 men and 17 women; mean age, 53years) diagnosed as having pseudolymphoma were retrieved from the archives to conduct hematoxylin-eosin, IgG and IgG4 staining. Out of the 32 cases of cutaneous pseudolymphoma, germinal center formation was seen in 22 cases, and moderate-severe fibrosis was seen in seven cases. Eleven cases showed more than 10 IgG4(+) plasma cell infiltration/high-power field, and among these 11 cases, seven cases (22%) showed A ratio of IgG4(+)/IgG(+) cells of more than 40%. Thus, out of the 32 cases of cutaneous pseudolymphomas, two cases (6.3%) satisfied IgG4-RD histopathological diagnostic criteria. As clinical presentations and histopathological features of skin involvement of IgG4-RD are analogous to cutaneous B-cell pseudolymphoma, careful identification is required through systemic examination, serum IgG4 measurement and other means.

2010年11月から2011年5月の間に藤田保健衛生大学病院,りかこ皮フ科クリニックおよび神戸大学医学部附属病院を受診したアトピー性皮膚炎,小児乾燥性皮膚炎,光線過敏症などの患者の中で口唇の乾燥を有する50例に対し,口唇の保湿と遮光を目的として「ノブリップケアクリームUV」を4週間使用した。試験開始および終了時に口唇の皮膚所見を得るとともに角層水分量と経表皮水分蒸散量を測定し,さらに新しい皮膚生理機能の評価としてテープストリッピングにより採取した角層細胞の有核細胞数とTNF-αおよびTSLPを測定した。50例中,3例が被験者の嗜好などの自己都合にて使用を中止したため47例を評価対象とした。有害事象としては,1例において口唇の軽度の鱗屑と皮膚表面の硬化感(ごわごわした感じ)を被験者自身が自覚したものの使用を継続した。皮膚所見においては,乾燥,鱗屑,亀裂,紅斑および縦皺において有意な改善を認めた。また従来の機器測定による角層水分量と経表皮水分蒸散量では有意な変化は認めなかったが,テープストリッピングにより得た角層細胞において,有核細胞数とTNF-αおよびTSLPの有意な減少を認めた。これらの結果から,試験に供した「ノブリップケアクリームUV」は,口唇の乾燥した皮膚症状を改善することが明らかとなった。また口唇は口腔粘膜との移行部位であり凹凸や弾力性および呼吸などにより水分量や蒸散量の正確な計測の難しさがあった。テープストリッピングによる角層解析は採取が簡単で安定した結果を得ることができ,臨床症状の改善に合致した皮膚生理機能の客観的評価として有用と考えた。(著者抄録)

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized disease characterized by elevated serum IgG4 levels, tissue infiltration rich in IgG4(+) plasma cells. We report on a case which was first considered as pseudolymphoma from the histopathological analysis, but finally diagnosed as IgG4-related skin lesions. As the morphological features of cutaneous involvement of IgG4-RD are consistent with those of cutaneous pseudolymphoma, we tried immunostaining past potential cases of IgG4-RD. Thirty-two skin specimens (15 men and 17 women; mean age, 53years) diagnosed as having pseudolymphoma were retrieved from the archives to conduct hematoxylin-eosin, IgG and IgG4 staining. Out of the 32 cases of cutaneous pseudolymphoma, germinal center formation was seen in 22 cases, and moderate-severe fibrosis was seen in seven cases. Eleven cases showed more than 10 IgG4(+) plasma cell infiltration/high-power field, and among these 11 cases, seven cases (22%) showed A ratio of IgG4(+)/IgG(+) cells of more than 40%. Thus, out of the 32 cases of cutaneous pseudolymphomas, two cases (6.3%) satisfied IgG4-RD histopathological diagnostic criteria. As clinical presentations and histopathological features of skin involvement of IgG4-RD are analogous to cutaneous B-cell pseudolymphoma, careful identification is required through systemic examination, serum IgG4 measurement and other means.

Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method with a high specificity, efficiency and speed. No reports exist regarding the usefulness of LAMP for clinically suspected skin infections caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The aim of this study was to evaluate the clinical usefulness of LAMP in the diagnosis of common cutaneous alpha herpesvirus (HSV type 1 and 2, and VZV) infections. LAMP and real-time polymerase chain reaction (PCR) were performed using swab samples collected from 106 patients with clinically suspected alpha herpesvirus skin infections. The results of LAMP performed with DNA extraction did not differ from those performed without DNA extraction. The sensitivity of LAMP tested against real-time PCR was 96% in herpes simplex, 78% in eczema herpeticum, 93% in herpes zoster and 100% in varicella. No viral DNA was detected by LAMP in all negative real-time PCR samples. Viral DNA load was significantly lower in samples with false-negative LAMP results than in the LAMP-positive samples. LAMP enables confirmation of clinically suspected cutaneous HSV and VZV infections. However, the sensitivity of LAMP is lower than real-time PCR. The accuracy of LAMP may increase if sufficient viral DNA is obtained from lesions. LAMP performed without DNA extraction remains sensitive; thus, LAMP represents a quick and economical method for the diagnosis of common alpha herpesvirus skin infections.

AIM: This preliminary study investigated genomic biomarkers for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), related to three antiepileptic drugs, zonisamide, phenobarbital and phenytoin. PATIENTS & METHODS: HLA class I and HLA-DRB1 loci were genotyped for Japanese patients with zonisamide-, phenobarbital- or phenytoin-induced SJS/TEN (n = 12, 8 and 9, respectively) and for healthy Japanese volunteers (n = 2878). RESULTS: Carrier frequencies of HLA-A*02:07 in patients with zonisamide-induced SJS/TEN and in the general Japanese population were 41.7 and 6.81%, respectively. Carrier frequencies of HLA-B*51:01 in patients with phenobarbital- and phenytoin-induced SJS/TEN and in controls were 75.0, 55.6 and 15.2%, respectively. HLA-A*02:07 and HLA-B*51:01, in a dominant model, were significantly associated with zonisamide- and phenobarbital-induced SJS/TEN, respectively (Pc = 0.0176 and 0.0042, respectively). CONCLUSION: Our data suggest that HLA-A*02:07 and HLA-B*51:01 are potential biomarkers for zonisamide- and phenobarbital-induced SJS/TEN, respectively, in Japanese individuals.

Hydroquinone (HQ) is a chemical compound that inhibits the functions of melanocytes and has long been known for its skin-whitening effect. According to previous studies, the Tyrosinase (Tyr) activity inhibitory effect and melanocyte-specific cell toxicity are known depigmenting mechanisms; however, details of the underlying mechanisms are unknown. Arbutin (Arb) is also known for its Tyr activity inhibitory effect and is commonly used as a skin-whitening agent. However, the detailed depigmenting mechanism of Arb is also not yet fully understood. Few studies have attempted to elucidate the effects of HQ and Arb on undifferentiated melanocytes. In this study, we examined the effects of HQ and Arb throughout each stage of differentiation of melanocytes using a mouse embryonic stem cell (ESC) culture system to induce melanocytes. The results showed that HQ in particular downregulated the early stage of differentiation, in which neural crest cells were generated, and the late stage of differentiation, in which melanogenesis became active. On the other hand, Arb had no effect on the differentiation of melanocytes, and only suppressed melanogenesis by specifically suppressing elevations in Tyr expression in the late stage of differentiation.