矢上 晶子

経皮感作による食物アレルギーが注目されているが、ラテックス-フルーツ症候群はその先駆けとなった食物アレルギーである。ラテックスアレルギー患者の約半数は食物過敏反応が誘発され、この一連の症状は、天然ゴムラテックス製品に含まれるラテックス蛋白抗原と植物性食品に含有される蛋白抗原との交差反応性に起因しており、原因となる果物や野菜は種の枠を越え、非常に幅広い植物性食品が現在までに報告されている。特に、バナナ、キウイ、クリ、アボカドは症状を誘発する頻度が高く、重篤な即時型アレルギーを誘発することが報告されており、これはラテックス蛋白に含まれるヘベイン様ドメインと、野菜や果物に含まれるクラスIキチナーゼによる交差反応によることが明らかにされている。(著者抄録)

某県の歯科医院と市中病院2施設に対してラテックスアレルギー(LA)に関する意識調査を行なった。回答はA病院勤務者419名、B病院勤務者325名、歯科医院勤務者458名より得られた。今回、この調査結果を2005年に報告された明石らによる全国調査と比較した。ゴム手袋で蕁麻疹を起こすことを知っていた割合は60%から90%になっていた。また、アナフィラキシーを起こす可能性があることを知っていた割合は33%から60%になっていた。一方、果物との交差反応性があることを知っていた割合は10%以下から10〜40%に、更に特定のグループに多いことを知っていた割合は10%以下から約50%と、それぞれ認知度が高くなっていることが確認された。特にLAに関する知識が高かったB病院ではラテックスフリー手袋の使用率が高く、ラテックス手袋使用時もパウダーフリーの割合が高いことが明らかとなった。

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.

Background: Immediate-type wheat allergy caused by a specific hydrolyzed wheat protein (HWP-IWA), Glupearl 19S (GP19S), typically develops food-dependent exercise-induced anaphylaxis (FDEIA), but is different from conventional FDEIA, or simple wheat allergy in many aspects. The skin prick test (SPT) is considered to be the most effective method for diagnosis of HWP-IWA. As SPT is a relatively qualitative method, we developed quantitative and high-throughput test method for HWP-IWA. Methods: An enzyme-linked immunosorbent assay (ELISA)-based GP19S-specific IgE assay was tested using sera from 14 HWP-IWA and five conventional wheat-dependent exercise-induced anaphylaxis (CO-WDEIA) patients, as well as five healthy subjects. Then a validation study at five different institutions was carried out using sera from 10 HWP-IWA and five CO-WDEIA patients, as well as five healthy subjects different from the previous studies. Results: The mean unit values converted from measured absorbance of ELISA were 68.3, 1.3 and 1.1 respectively. Furthermore, the validation study revealed reproducible results across all five institutions, with the standard deviation (SD) being 0.3-0.4 for the healthy group, 0.2-0.6 for the CO-WDEIA group, and 3.8-9.6 for HWP-IWA group except for one case. One case of HWP-IWA was excluded from analysis due to the high SD of 53.3 units, indicating that samples with a unit value > 100.0 will affect inter-laboratory reproducibility. Conclusions: Our findings suggest that the ELISA-based GP19S-specific IgE assay can be used to test HWP-IWA using venous blood samples, except for those with a unit value > 100.0.

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.

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

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.

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.

Morphea is a type of localized scleroderma. It is a skin disease involving the development of fibrosis in the dermis and subcutaneous fat tissue beneath without a visceral lesion, and the cause is still unclear. An involvement of epithelial-mesenchymal transition (EMT) has been reported as a cause of tissue fibrosis, but this was mostly observed in pulmonary and hepatic fibrosis, and the involvement of EMT in a skin disease, morphea, has not been studied. Thus, we analyzed the involvement of EMT in skin fibrosis in morphea patients using pathological techniques. Skin lesions of six morphea patients were analyzed (five female and one male patient). As a control, non-light-exposed skin lesions of 11 healthy females were analyzed. Concretely, tissue samples were prepared from these subjects and subjected to immunostaining of transforming growth factor (TGF)-beta 1, alpha-smooth muscle actin (alpha-SMA) and fibronectin, which have been reported to be associated with fibrosis, and Snail1 and E-cadherin, which are considered to be involved in EMT, and expressions of these were analyzed. In morphea patients, dermal expression of TGF-beta 1, alpha-SMA and fibronectin, which are involved in fibrosis, was enhanced, and, at the same time, enhanced expression of Snail1 and reduced expression of E-cadherin, which are involved in EMT, were observed in the dermal eccrine glands. These findings suggested the progression of EMT in the dermal eccrine glands in morphea.

Backgroud: : More effective treatment strategies are needed for the chronic skin ulcers. Recently, it has been reported that clinical application of stem cells improve wound healing. Objective: We aimed to determine the dynamic time-course movement of epidermal stem cell markers especially p75 neurotrophin receptor (p75NTR) and Integrin beta-1 in wound healing process. Furthermore, we also investigated the presence of these markers in human. Methods: Epidermal Integrin beta-1(+) and p75NTR(+) cells were counted in wound healing process in mice. Both cells were also counted in human skin specimen obtained from chronic skin ulcers and healthy controls. Growth factor gene expression levels by purified mouse epidermal p75NTR. cells were also analyzed using real-time RT-PCR. Results: Integrin beta-1(+) and p75NTR(+) cells were proliferated from 3 days after wounding. Reepithelization was completed 7 days after wounding, and the numbers of cells were returned to the baseline levels by 14 days after wounding. Integrin beta-1(+) cells were proliferated in the basal layer, and p75NTR(+) cells were proliferated in the upper layer of epidermis. In human skin, Integrin beta-1(+) and p75NTR(+) cells were 81% +/- 12% and 36% +/- 15% of the basal cells, respectively. In patients with chronic skin ulcers, the percentage of Integrin beta-1(+) cells in the epidermis was identical to healthy controls. Surprisingly, p75NTR(+) cells were significantly decreased in chronic skin ulcer patients (1.2% +/- 2.6%; p < 0.0005) compared to healthy controls. Purified mouse epidermal p75NTR(+) cells expressed higher transforming growth factor-beta2 and vascular endothelial growth factor-alpha transcripts and lower epidermal growth factor transcripts than p75NTR(-) cells. Conclusion: These results suggest that Integrin beta-1(+) and p75NTR(+) cells play an important role in wound healing process, and that p75NTR may be a key molecule and a candidate for new therapeutic target besides preexisting molecules for chronic skin ulcer patients. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

61歳男性。NSAIDsとメトトレキサートの内服治療に抵抗性の関節症性乾癬に対してinfliximabを投与した。Infliximab投与により関節症状は劇的な改善を認めたが、2クール終了後にニューモシスチス肺炎(Pneumocystis pneumonia;以下PCP)を発症した。乾癬患者では、現在のところ生物学的製剤によるPCP発症のリスク評価とST合剤の予防投薬の明確なガイドラインがない。生物学的製剤の使用に際しては低頻度ではあるもののPCP発症の可能性について慎重に経過観察していく必要があると考えられる。(著者抄録)