Patch testing with the Japanese baseline series 2015: A 4-year experience.

BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.

Multicenter 1-month follow-up study of the patch-test reaction to the gold sodium thiosulfate of the TRUE Test and its association with piercings and dental metal history.

BACKGROUND: There is controversy over late and long-lasting reactions to gold sodium thiosulfate (GST). OBJECTIVES: To study the GST patch-test reaction by observing the application site after 1 month, and to clarify the relevance of GST sensitization by piercings and dental metals. PATIENTS: A retrospective analysis was performed on 746 patients (143 male; 603 female) who were patch tested using GST of the TRUE Test. We conducted a questionnaire on the presence of piercings or dental metals in these patients. RESULTS: The GST positive rate was 27.9% at day (D)3 and/or D7 and 40.3% up to the 1-month reading. The positive rate was significantly higher in female patients and increased with age. Sixty-two percent of cases with a positive reaction at D7 continued to show a positive reaction after 1 month. Eleven percent of cases with a negative reaction at D3 and D7 showed a late reaction. Both piercings and dental metals were related to gold sensitization. CONCLUSIONS: The GST of the TRUE Test had a high positive and low false-negative rate. The 1-month reading after the patch test was important for identifying late reactions. Piercing history and dental metal were associated with gold sensitization.

New solution of beauty problem by Staphylococcus hominis: Relevance between skin microbiome and skin condition in healthy subject.

BACKGROUND/AIMS: Recently, it was suggested that skin microbiome is related to some skin disease. The possibility of affecting the skin might be high, but there were few reports of the influence on the skin condition in healthy subjects. Our aim was to evaluate the relationship between skin condition and skin microbiome in healthy subjects. METHODS: Experiment 1: 293 Japanese healthy women were divided into two groups, good skin properties and poor skin properties by 14 skin physiology parameter values on the cheek using noninvasive method. Differences of abundance of bacterial species on the cheek between the two groups were evaluated. Experiment 2: 11 Japanese healthy women were applied Staphylococcus hominis (S. hominis) on half-side of cheek for eight times in 1 month. Difference of change of physiology parameter values comparing to placebo side was evaluated. RESULTS: Experiment 1: Multiple skin bacterial species were found to be significantly relevant in 14 physiology parameters. The abundance of S. hominis on the cheek with good skin properties group was significantly higher than poor skin properties group. Experiment 2: The application of S. hominis improved significantly the conspicuous pore number, melanin index, and the wrinkle count compared to placebo side. CONCLUSION: We found many skin bacterial species that might improve the skin condition in healthy women. In particular, S. hominis might have the potential to improve multiple skin beauty problems.

Positive reactions to gold sodium thiosulfate in patch test panels (TRUE Test) in Japan: A multicentre study.

BACKGROUND: The proportion of positive test results with gold sodium thiosulfate included in a patch test panel (P-GST) had been found to be greater than that with gold sodium thiosulfate 0.5% pet. by allergEAZE (A-GST). OBJECTIVES: To compare positive reactions to P-GST and A-GST, and to evaluate late reactions after the day (D) 7 reading. METHODS: A retrospective analysis was performed of 588 patients at participating departments (119 males; 469 females) who were patch tested with P-GST and A-GST in May 2015 to March 2016. RESULTS: Positive test reactions to P-GST and A-GST were observed in 15% and 6% of patients, respectively. Three patients reported a positive reaction occurring after the D7 reading. CONCLUSIONS: Gold sodium thiosulfate often gives a positive reaction after 2 to 3 weeks, and, in such cases, the positive reaction may be sustained, so it is recommended to assess the reaction for up to 1 month after application.

A multi-institutional joint study of contact dermatitis related to hair colouring and perming agents in Japan.

BACKGROUND: In Japan, allergic contact dermatitis caused by hair colouring agents is a considerable problem for those occupationally exposed and also for consumers. Over the last 20 years, p-phenylenediamine (PPD) has been a common allergen, with ∼7% positive patch test reactions. OBJECTIVES: To investigate which ingredients caused allergic contact dermatitis related to hair dye and perming solutions in Japan, to assess whether PPD is suitable for screening for hair dye allergy, and to propose allergens for a Japanese hairdresser series. METHODS: We selected 19 hair cosmetic allergens, including PPD, Bandrowski's base, cysteamine HCl, and ammonium thioglycolate. Altogether 203 patients (26 males and 177 females) with suspected contact allergy to hair colouring or perming solutions at 14 hospitals in Japan were included. RESULTS: The highest prevalence of positive reactions (35.1%) was for PPD. p-Methylaminophenol and o-aminophenol were often positive, both in the PPD-positive and in the PPD-negative patients. Moreover, cysteamine HCl often yielded positive test reactions. CONCLUSIONS: PPD is insufficient to diagnose contact allergy caused by to hair dyes. We recommend 13 allergens to be included in a Japanese hairdresser series.

Optimal patch application time in the evaluation of skin irritation.

We investigated the optimum application for evaluating skin irritation response by using samples of irritants commonly used as additives in cosmetics and other common household products. We studied 47 volunteers (16 men and 31 women). We selected three types of surfactant, one moisturizer, one anti-infective agent and one oil solution. Using Finn chambers on Scanpor tape, we performed the patch test. A total of 0.015 mL of each sample was applied to the Finn chamber. For liquids, circular filter paper was soaked in 0.015 mL of the sample. Samples were placed on the upper back of participants, and closed for 4, 24 or 48 h. A patch application time of 24 h is sufficient to detect primary skin irritation from irritants in cosmetics and other common household products. In addition, we found that skin irritation reactions were strongest at 24 h after patch removal and that the reaction tended to be weaker at 48 h after patch removal. Patch testing to evaluate irritants should be performed by means of a 24-h patch test with a follow-up reading at 24 h after patch removal. An application time of 24 h places less of a burden on patients than a 48-h patch test.

Use of Cutometer area parameters in evaluating age-related changes in the skin elasticity of the cheek.

BACKGROUND/AIM: The decrease of skin elasticity on the cheek is a major concern to woman. The Cutometer has been widely used to evaluate skin elasticity and its change with aging. Cutometer parameters derived from one suction have been traditionally used to evaluate skin elasticity, and few reports describe the use of multiple suctions to obtain parameters to assess the skin elasticity of the cheek. To find the most suitable Cutometer parameter that reflects age-related changes in the elasticity of cheek skin using multiple suctions. METHODS: The cheeks of 32 healthy Japanese women (mean age, 42.3 years) were assessed using the Cutometer MPA580 by measuring the skin mechanical parameters R0-R9, F2 and F3. Parameters F2 and F3 were obtained by the multiple suction method. The relationship between age and these parameters were then examined. RESULTS: Significant negative correlations were found between the age of subjects and R2, R3, R7, R8 and F3. Of these, the correlation coefficient was best between age and F3 (r = -0.641), followed R8 (r = -0.603). CONCLUSION: Although R parameters have been used to evaluate skin elasticity, our study showed that F3 parameters derived from multiple suctions appear to be suitable for evaluating the elasticity of cheek skin, since this parameter is less influenced by environmental factors compared with R parameters.

Quantitative evaluation of patch test reactions: a comparison between visual grading and erythema index image analysis.

BACKGROUND/AIMS: The interpretation of patch test reactions may vary between examiners. As test results are graded, an issue also arises when differing degrees of erythema are placed in the same grade. The purpose of this study was to quantitatively evaluate the degree of erythema in patch tests using image analysis and to study the usefulness of this method by comparing it with visual grading. METHODS: A total of 121 Japanese patients were patch tested with various materials. At 48 h, digital photographs of the patch test areas were taken, in addition to a visual evaluation by dermatologists. Digital images of the areas were converted to erythema index (EI) images using image processing and both EI and ΔEI (the difference between the patch test site and adjacent normal skin) values of the patch test sites were compared with the corresponding visual grades. RESULTS: An excellent linear correlation (r=0.95) was found between ΔEI and visual grades, although EI also significantly correlated with visual grades. There were significant differences (P<0.0001-0.05) between the mean ΔEI values of any two adjacent visual grades. CONCLUSION: ΔEI values derived from image processing appear to be suitable for the quantitative evaluation of erythema in patch tests. This method may be helpful in overcoming the subjectiveness of visual evaluation and for training non-experts in patch testing.

Relevance of the directionality of skin elasticity to aging and sagging of the face.

BACKGROUND: Forces acting in facial skin have been suggested to show directionality. Non-invasive methods of measuring this directionality may thus provide information related to aging processes. The Reviscometer(®) RVM600 device is capable of measuring directionality of forces on the skin. This device has not been used previously in a published study to evaluate changes in directionality of forces on facial skin with aging. AIM: The first objective of this pilot study was to investigate relationships between mechanical directionality using the Reviscometer(®) RVM600, the Cutometer(®) MPA580, and aging of the facial skin in a supine position. In addition, the study investigated relationships between mechanical directionality and 'skin sagging,' which may be caused by gravity. To validate this as a new measurement of mechanical directionality, we also performed double-blinded trials on two groups of subjects, with one group using a product containing an anti-aging substance and the other group using a placebo product without an anti-aging substance. METHODS: We examined 91 healthy Japanese women with a mean age of 48.5 years (range, 20-79 years) at the three sites on the face using the Reviscometer(®) RVM600 and the Cutometer(®) MPA580, and evaluation was performed for skin sagging in September and November 2008, and January 2009. The Reviscometer(®) RVM600 was used to measure resonance-running time (RRT) every 10° from 0° to 350°. Evaluation of skin sagging was undertaken by making marks on the face and using face photographs taken in both sitting and supine positions to calculate the sagging index. Usage testing was conducted on 38 healthy Japanese women in a double-blinded study with one group, using a preparation containing Yomogi AGEs Clearing (YAC) extract and another group using the same preparation without the YAC extract from October 2008 to April 2009. Mean age of these subjects was 44.0 years (range, 30-60 years). Measurements were taken at the three sites on the face using the Reviscometer(®) RVM600 and the Cutometer(®) MPA580 and sagging index. RESULTS: A significant correlation was identified between RRT parameters and subject age at all three measurement sites. Significant correlations between sagging index and RRT values were found for 110-170° and 290-350° only at the center of the cheek. Significant differences in RRT values were noted for 110-150° and 300-350° at this site between subjects with and without the use of YAC extract. A similar trend was found in sagging index for this site alone between subjects with and without YAC extract. CONCLUSION: The use of non-invasive procedures to measure skin mechanical parameters on the face in all directions may evaluate aging and effective preventive and restorative support.

Melanin and facial skin fluorescence as markers of yellowish discoloration with aging.

BACKGROUND: Although one clinical sign of aging and/or photoaging is a yellowish discoloration of the facial skin, little is known about the cause of this change. In addition to the increase in the epidermal melanin content, it has been suggested that advanced glycation end products (AGEs), which are known to accumulate in photoaged skin, may affect this discoloration. AIM: The objective of this pilot study was to non-invasively investigate the roles of melanin and AGEs in this yellowish discoloration of the facial skin. METHODS: We examined the spectral reflectance at the cheek in 40 healthy Japanese women of various ages (mean age, 38.1 years) using a reflectance spectrophotometer and a spectrofluorimeter. The degree of yellowish tint was evaluated in terms of b(*). The amount of melanin in the skin was evaluated by calculating the melanin index (MI) A(640)-A(670) [A(lambda): log(10) (1/reflectance) at a wavelength of lambda]. The amount of AGEs was roughly evaluated using the AGEs index, which is thought to linearly correlate with the amount of intrinsic fluorescence markers irrespective of the concentration of melanin and is defined as follows: AGEs index=I(5)/SQR (I(1)xI(2)). In this equation, the intensities of reflectance are I(1) at an excitation wavelength of 335 nm, I(2) at an emission wavelength of 390 nm and I(5) at 390 nm under an excitation wavelength of 335 nm. RESULTS: Both b(*) and the AGEs index were significantly correlated with subject age (r=0.34, P<0.05 and r=0.68, P<0.0001, respectively). Significant correlations were also observed between MI and b(*) (r=0.63, P<0.0001) and between the AGEs index and b(*) (r=0.53, P<0.0005). However, no significant correlations were seen between MI and the AGEs index. CONCLUSION: The AGEs index does not appear to be influenced by the amount of melanin and may be utilized as an indicator of the amount of AGEs in the skin. AGEs are likely to play a role in the yellowish discoloration of skin with aging.

Effects of vitamin C on dark circles of the lower eyelids: quantitative evaluation using image analysis and echogram.

BACKGROUND/AIMS: The pathogenesis of dark circles of the lower eyelid (DCLE) has been considered to involve stasis and hyperpigmentation of the eyelids. We have already reported that dermal thickness of lower eyelid skin may represent another factor that affects the appearance of DCLE. The aim of this study was to evaluate the efficacy of vitamin C, which is known to increase collagen, on DCLE through a clinical trial. METHODS: Fourteen subjects with DCLE applied either 10% sodium ascorbate (ANa) or ascorbic acid glucoside (AG) lotion in split-face fashion (opposite side: vehicle only) for 6 months. Melanin index (MI), erythema index (EI), thickness and echogenicity of the dermis at bilateral lower eyelids was measured during this trial. RESULTS: Change in EI was significantly smaller on the ANa-treated side than on the vehicle-treated side. Dermal thickness tended to be thicker for the ANa-treated side than for the vehicle-treated side, although no significant difference was seen. Both EI and dermal thickness tended to change in parallel manner. On the other hand, no significant differences in changes of EI, MI, and dermal thickness were found between AG- and vehicle-treated sides. CONCLUSION: ANa may improve DCLE by thickening the eyelid dermis and concealing dark coloration due to congested blood.

Adverse skin reactions due to pegylated interferon alpha 2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus.

Pegylated interferon (IFN)-alpha-2b with ribavirin has recently replaced "standard" IFN-alpha for the treatment of chronic hepatitis C. The most common side-effect of pegylated IFN-alpha-2b plus ribavirin combination therapy is localized inflammatory skin lesions at the site of injection. A 66-year-old female treated with once-weekly pegylated IFN-alpha-2b plus ribavirin for active chronic hepatitis C developed inflammatory skin lesions 2 months after starting antiviral treatment. The type of skin reactions observed were vesicle erythematous eruptions at the injection sites, and pruritic papular erythematous eruptions located on the face, neck, distal limbs, dorsa of the hands, trunk and buttocks away from the injection sites. Histological examination was performed on the pruritic papular erythematous eruption located on the left forearm, away from the injection sites. It showed epidermal spongiosis, a spongiotic microvesicle, and perivascular infiltration of the upper dermis with lymphocytes. The treatment was interrupted subsequently and the patient was rechallenged with pegylated IFN-alpha-2b plus ribavirin combination therapy, oral prednisolone with olopatadine hydrochloride and topical 0.1% diflucortolone valerate, which led to a significant improvement of skin lesions. Erythema with infiltration can occur at the injection sites of pegylated IFN-alpha-2b. However, the occurrence of vesicle erythematous eruptions away from the injection sites and autosensitization dermatitis apart from injection sites have not yet been frequently reported.

alpha-Melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes.

UV radiation is an important etiologic factor for skin cancer, including melanoma. Constitutive pigmentation and the ability to tan are considered the main photoprotective mechanism against sun-induced carcinogenesis. Pigmentation in the skin is conferred by epidermal melanocytes that synthesize and transfer melanin to keratinocytes. Therefore, insuring the survival and genomic stability of epidermal melanocytes is critical for inhibiting photocarcinogenesis, particularly melanoma, the most deadly form of skin cancer. The paracrine factors alpha-melanocortin and endothelin-1 are critical for the melanogenic response of cultured human melanocytes to UV radiation. We report that alpha-melanocortin and endothelin-1 rescued human melanocytes from UV radiation-induced apoptosis and reduced DNA photoproducts and oxidative stress. The survival effects of alpha-melanocortin and endothelin-1 were mediated by activation of the melanocortin 1 and endothelin receptors, respectively. Treatment of melanocytes with alpha-melanocortin and/or endothelin-1 before exposure to UV radiation activated the inositol triphosphate kinase-Akt pathway and increased the phosphorylation and expression of the microphthalmia-related transcription factor. Treatment with alpha-melanocortin and/or endothelin-1 enhanced the repair of cyclobutane pyrimidine dimers and reduced the levels of hydrogen peroxide induced by UV radiation. These effects are expected to reduce genomic instability and mutagenesis.

Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival.

The characterization of the melanocortin 1 receptor (MC1R) expressed on human melanocytes and the findings that certain mutations in the POMC gene or the MC1R gene result in red hair phenotype underscore the significance of melanocortins and MC1R in regulating human pigmentation. We demonstrated that human melanocytes respond to alpha-melanocortin (alpha-MSH) or ACTH with increased proliferation and melanogenesis, and to agouti signaling protein by abrogation of these effects. alpha-MSH and ACTH were equipotent and more potent than beta-MSH, and gamma-MSH was the least potent in activating the MC1R and stimulating melanogenesis and proliferation of human melanocytes. We characterized the MC1R genotype in a panel of human melanocyte cultures and identified three cultures that were homozygous for Arg160Trp, heterozygous for Arg151Cys and Asp294His, and heterozygous for Arg160Trp and Asp294His substitutions, respectively. Those cultures failed to respond to alpha-MSH with increase in cAMP levels, tyrosinase activity, or proliferation and had an exaggerated response to the cytotoxic effect of ultraviolet (UV) radiation. These loss-of-function mutations have been associated with red hair phenotype and increased risk for skin cancer. Melanocytes homozygous for Val29Met substitution in MC1R responded normally to alpha-MSH and UVB, suggesting that this variant is a polymorphism. We observed that alpha-MSH promotes human melanocyte survival by inhibiting the UV-induced apoptosis independently of melanin synthesis. This effect was absent in human melanocytes with loss of function MC1R mutations. We predict that the survival effect of alpha-MSH is caused by reduction of UV-induced DNA damage and contributes to the prevention of melanoma.