RESUMEN
BACKGROUND: There is a paucity of data on the treatment of psoriasis in patients with skin of color – a diverse population among whom variations in clinical features and higher quality of life impact have been reported. This single-center, open-label clinical study evaluated the safety and efficacy of secukinumab in the treatment of moderate-to-severe plaque psoriasis in adults with Fitzpatrick skin types IV-VI. METHODS: A total of 20 male and female subjects (ages ≥ 18, BSA ≥10%, PASI Score ≥ 12, IGA ≥ 3) completed this study. The total study duration was 28 weeks. During the treatment period, subjects received secukinumab 300 mg subcutaneously at weeks 0, 1, 2, 3, and 4, then monthly through week 20. RESULTS: 73% of patients achieved at least 90% improvement in PASI score (PASI90) at week 16 compared to baseline (P=0.0592). There was a statistically significant proportion of patients achieving PASI75, IGA of clear or almost clear, and a change from baseline in DLQI total score at weeks 12, 16, and 24. A statistically significant reduction in IGAxBSA-75 score was achieved between week 16 and baseline. LIMITATIONS: The sample size was small and underpowered to detect statistically significant changes in some endpoints. Furthermore, the study period was interrupted by the COVID-19 pandemic, which contributed to numerous missing data points. CONCLUSION: Secukinumab 300 mg administered monthly was safe, well-tolerated, and efficacious in treating skin of color patients with psoriasis and improving health-related quality of life. Larger studies involving skin of color populations with psoriasis are warranted. J Drugs Dermatol. 2024;23(8):600-606. doi:10.36849/JDD.8128.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/diagnóstico , Masculino , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Pigmentación de la Piel/efectos de los fármacos , Inyecciones Subcutáneas , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Anciano , COVID-19RESUMEN
The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.
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Janus Quinasa 3 , Inhibidores de Proteínas Quinasas , Vitíligo , Humanos , Vitíligo/tratamiento farmacológico , Vitíligo/diagnóstico , Vitíligo/inmunología , Masculino , Femenino , Adulto , Janus Quinasa 3/antagonistas & inhibidores , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Resultado del Tratamiento , Quimiocina CXCL9/sangre , Quimiocina CCL5/sangre , Adulto Joven , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Antígeno B7-H1/sangre , Melanocitos/efectos de los fármacos , Método Doble Ciego , Pigmentación de la Piel/efectos de los fármacos , Administración Oral , Interferón gammaAsunto(s)
Compuestos Férricos , Maltosa , Humanos , Maltosa/análogos & derivados , Maltosa/administración & dosificación , Maltosa/efectos adversos , Compuestos Férricos/administración & dosificación , Compuestos Férricos/efectos adversos , Piel/patología , Piel/efectos de los fármacos , Hiperpigmentación/inducido químicamente , Hiperpigmentación/diagnóstico , Hiperpigmentación/patología , Femenino , Masculino , Administración Intravenosa , Persona de Mediana Edad , Pigmentación de la Piel/efectos de los fármacosRESUMEN
Strategies for successful aging, including the use of food supplements, are part of the approach to support skin youthfulness. To demonstrate the efficacy of fermented bilberry extract (FBE) against skin aging and uneven complexion, a clinical trial was carried out on 66 subjects with visible "crow's feet" wrinkles, mild-to-moderate skin slackness, and uneven skin tone. The wrinkle depth, skin smoothness (Ra) and roughness (Rz), skin firmness (R0) and elasticity (R2), skin coloration (ITA°), and skin antioxidant capacity were measured before and after 28 (D28), 56 (D56), and 84 (D84) days of product use (either FBE or a placebo). These parameters were also integrated with a clinical evaluation, carried out by a dermatologist, and a self-assessment questionnaire to align the measured efficacy with the visual or perceived efficacy. At D84, the wrinkle depth had decreased by 10.6%, Ra had improved by 7.9%, Rz had decreased by 7.3%, R0 had improved by 13.3%, R2 had improved by 12.4%, and skin antioxidant capacity had increased by 20.8%. ITA° increased by 20.8% and was accompanied by a decrease in the skin's redness component by 16.8% and an increase in the lightness component by 2.2%. The variation of all the above-mentioned parameters was statistically significant between the FBE and PL groups. Our findings demonstrate the efficacy of FBE in improving skin aging and complexion evenness.
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Antioxidantes , Extractos Vegetales , Envejecimiento de la Piel , Vaccinium myrtillus , Humanos , Envejecimiento de la Piel/efectos de los fármacos , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Femenino , Vaccinium myrtillus/química , Método Doble Ciego , Persona de Mediana Edad , Adulto , Masculino , Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de los fármacos , Fermentación , Suplementos Dietéticos , Anciano , AntocianinasRESUMEN
BACKGROUND: Visual casts and discoloration are common barriers to sunscreen use in melanin-rich populations. However, photoprotective measures are essential for individuals with all skin types, including darker skin. METHODS: Single-center, 7-day, open-label study of healthy adult females with Fitzpatrick Skin Types (FST) IV to VI and sensitive skin treated with once-daily daily facial moisturizer sun protection factor 35 (DFM SPF35). Subjects completed a cosmetic acceptability questionnaire at days 1 and 7. Photography using VISIA CR was performed at day 7. Adverse events were monitored throughout the study. RESULTS: Thirty-two (32) subjects participated; 31.3% had FST IV, 53.1% V, and 15.6% VI skin. DFM SPF35 was viewed as cosmetically elegant. At day 1, 96.7% of subjects agreed product was easy to apply; 90.0% reported soft skin after product use; 86.7% said it had a lightweight, non-greasy feel and hydrated the skin. At day 7, 93.7% reported no visible white residue on their skin and said the product applied easily/absorbed well. The majority (90.6%) would continue using and would recommend the product; and 87.5% reported the product blended seamlessly into their skin, which agreed with clinical photography. Responses were consistent among subjects with normal, oily, or combination skin. No adverse events were reported. CONCLUSIONS: DFM SPF35 blended well into the skin and was perceived favorably among subjects with SOC after 1 and 7 days of use. Subjects felt it had good cosmetic acceptability without unacceptable white residues or a greasy feeling. Dermatologists need to be versed in products that can be used on a variety of skin types.J Drugs Dermatol. 2024;23(7):515-518. doi:10.36849/JDD.8223.
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Fotograbar , Pigmentación de la Piel , Factor de Protección Solar , Protectores Solares , Humanos , Femenino , Protectores Solares/administración & dosificación , Protectores Solares/química , Protectores Solares/efectos adversos , Adulto , Persona de Mediana Edad , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiación , Adulto Joven , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/diagnóstico por imagen , Administración Cutánea , Encuestas y Cuestionarios , Crema para la Piel/administración & dosificación , Crema para la Piel/efectos adversos , Crema para la Piel/químicaRESUMEN
Variations in the epidemiology, clinical presentation, and disease course in atopic dermatitis (AD) patients with Skin of Color (SOC) compared with white counterparts have been reported. In this study, we evaluated the capability of a new imaging device (SkinCam) in quantifying skin texture changes in diverse patients, presenting with AD or xerosis, after using a prebiotic skincare routine over 10 weeks. A total of 39 subjects from diverse racial/ethnic backgrounds, aged 3 to 76 years old, with Fitzpatrick skin phototypes I to VI, presenting with mild AD and moderate to severe xerosis, were enrolled in the study. All subjects used a prebiotic cleanser on its own for 2 weeks, followed by a prebiotic moisturizer in conjunction for an additional 8 weeks. Standardized images of the subjects' legs were taken with SkinCam at several time points (baseline, week 2, and week 10), and analyzed for skin texture parameters. Our results demonstrate that both skin texture irregularity and skin color patterns significantly improve over time with a prebiotic skincare regimen in AD (n=12) and xerosis (n=24) subjects. Interestingly, image analyses showed more improvement over time in xerosis and AD SOC patients (n=18, Fitzpatrick IV-VI). Lastly, skin texture analyses from SkinCam imaging correlated with clinical assessments, showing significant improvement by prebiotic skincare regimen in all subjects by week 10. In summary, our results demonstrate that the SkinCam imaging device has the capability to effectively monitor skin texture parameters over time in both AD and xerosis patients with lightly and darkly pigmented skin. J Drugs Dermatol. 2024;23(7):557-563. doi:10.36849/JDD.8371.
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Dermatitis Atópica , Prebióticos , Cuidados de la Piel , Pigmentación de la Piel , Humanos , Dermatitis Atópica/diagnóstico , Adulto , Persona de Mediana Edad , Anciano , Femenino , Prebióticos/administración & dosificación , Masculino , Adulto Joven , Adolescente , Pigmentación de la Piel/efectos de los fármacos , Cuidados de la Piel/métodos , Niño , Preescolar , Etnicidad/estadística & datos numéricos , Resultado del Tratamiento , Crema para la Piel/administración & dosificaciónRESUMEN
BACKGROUND: All skin tones need to be protected from the damaging effects of solar radiation. Although mineral sunscreens offer protection, they can have a thick, greasy feel and leave a white cast, particularly on darker skin tones. Tints offset white cast and provide visible light protection; however, patients may prefer a sheer option. Therefore, a multifunctional, sheer, 100% mineral sunscreen moisturizer (MSM) with broad-spectrum SPF 50 was developed to have positive aesthetics and deliver anti-aging and skin health benefits to all skin tones. Methods: An IRB-approved, 12-week, open-label clinical study was conducted to investigate the efficacy and tolerability of the MSM. Thirty-nine (39) females aged 35 to 60 years with moderate-severe overall facial photodamage and representing all Fitzpatrick skin types (FST) were recruited. Participants applied the MSM to the face and neck in the morning and reapplied per US Food and Drug Administration requirements. Efficacy and tolerability grading, photography, ultrasound imaging, corneometer measurements, and questionnaires were completed at baseline and weeks 4, 8, and 12. Results: Statistically significant progressive improvements were demonstrated from baseline to week 12. At week 12, 23.4% and 26.5% mean improvements in overall photodamage were seen for FST I-III and FST IV-VI, respectively. Favorable tolerability was shown for both the face and neck. Photography corroborated clinical grading, and ultrasound imaging indicated a trend in skin density improvement. The MSM was well-perceived. Conclusion: The MSM is an efficacious and well-tolerated product for patients of all skin tones who desire a sheer, 100% mineral sunscreen moisturizer with anti-aging and skin health benefits. J Drugs Dermatol. 2024;23(7):538-544. doi:10.36849/JDD.8082.
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Envejecimiento de la Piel , Pigmentación de la Piel , Protectores Solares , Humanos , Femenino , Persona de Mediana Edad , Adulto , Protectores Solares/administración & dosificación , Protectores Solares/efectos adversos , Envejecimiento de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiación , Crema para la Piel/administración & dosificación , Crema para la Piel/efectos adversos , Cara , Resultado del Tratamiento , Administración Cutánea , Factor de Protección SolarRESUMEN
BACKGROUND: To understand the prevalence and types of publications addressing darker skin types within the existing evidence base for sunscreen use. Evidence Review: PubMed was searched from 1988, the time point at which the first skin of color (SOC) article was identified, through December 2022 using PubMed's Medical Subject Headings terms and keyword searches in title and abstract, with and without terms for SOC and ethnicity. Identified articles were reviewed for relevance, de-duplicated, and categorized; results are summarized. FINDINGS: Of the 5927 articles on sunscreen overall, only 314 (5.3%) articles addressed SOC, with the majority published since 2007 and representing only 4% to 7% of total publications annually except in 2022 when the proportion of SOC articles was 23.5%. Of the articles on SOC, many reported sunscreen knowledge and patient behaviors (29%), but very few reported clinical trials (5%). The 3 conditions most often discussed were melasma, post-inflammatory hyperpigmentation, and dyschromia. South Asian ethnicities (India, Pakistan, Bangladesh) had the highest representation within the literature, followed by Hispanics. CONCLUSIONS AND RELEVANCE: Although it was assumed there would be fewer papers discussing the use of sunscreen in darker skin types, the scale of the disparity revealed by this study is stark. The increase in a number of articles in 2022 suggests an increasing focus on SOC, but further discussion of the issues presented here will help the SOC community address gaps in the evidence base and better inform discussions on sunscreen and photoprotection between clinicians and patients.J Drugs Dermatol. 2024;23(7):575-577. doi:10.36849/JDD.8250.
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Pigmentación de la Piel , Protectores Solares , Humanos , Protectores Solares/administración & dosificación , Pigmentación de la Piel/efectos de los fármacos , Conocimientos, Actitudes y Práctica en Salud , Rayos Ultravioleta/efectos adversosRESUMEN
Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, p < 0.01).
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Monofenol Monooxigenasa , Fenilalanina , Envejecimiento de la Piel , Pigmentación de la Piel , Adulto , Femenino , Humanos , Persona de Mediana Edad , Agaricales/enzimología , Butiratos/química , Butiratos/farmacología , Método Doble Ciego , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Fenilalanina/química , Fenilalanina/análogos & derivados , Fenilalanina/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de los fármacosRESUMEN
Loss and absence of melanocytes due to a number of factors is responsible for vitiligo; known to be the commonest disorder of pigmentation. The aim of the current work was to compare the efficacy and safety of excimer light with topical tacrolimus ointment 0.1% versus excimer light with topical bimatoprost gel 0.01% in treatment of facial vitiligo. The study was carried out on 48 patients presented with facial vitiligo. The patients were divided randomly using sealed envelope method into two groups (24 patients each). Group 1 were treated with excimer light plus topical tacrolimus ointment 0.1% and group 2 treated with excimer light plus topical bimatoprost gel 0.01%. Clinical improvement based on the quartile grading scale at the end of treatment did not show any statistically significant difference between groups. The majority of subjects in both groups experienced good to excellent improvement. Only 20.9% of patients in group 1 and 33.3% of subjects in group 2 achieved less than 50% repigmentation (p = 0.889). Our study demonstrated that 0.01% topical bimatoprost gel in combination with excimer light is considered safe and effective as treatment of nonsegmental facial vitiligo with comparable results to 0.1% tacrolimus.
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Bimatoprost , Tacrolimus , Vitíligo , Humanos , Vitíligo/tratamiento farmacológico , Vitíligo/terapia , Vitíligo/diagnóstico , Tacrolimus/administración & dosificación , Bimatoprost/administración & dosificación , Femenino , Masculino , Adulto , Resultado del Tratamiento , Adulto Joven , Adolescente , Persona de Mediana Edad , Láseres de Excímeros/uso terapéutico , Administración Tópica , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiación , Cara , Administración Cutánea , Niño , Terapia Combinada/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéuticoRESUMEN
Nanotechnology is revolutionizing fields of high social and economic impact. such as human health preservation, energy conversion and storage, environmental decontamination, and art restoration. However, the possible global-scale application of nanomaterials is raising increasing concerns, mostly related to the possible toxicity of materials at the nanoscale. The possibility of using nanomaterials in cosmetics, and hence in products aimed to be applied directly to the human body, even just externally, is strongly debated. Preoccupation arises especially from the consideration that nanomaterials are mostly of synthetic origin, and hence are often seen as "artificial" and their effects as unpredictable. Melanin, in this framework, is a unique material since in nature it plays important roles that specific cosmetics are aimed to cover, such as photoprotection and hair and skin coloration. Moreover, melanin is mostly present in nature in the form of nanoparticles, as is clearly observable in the ink of some animals, like cuttlefish. Moreover, artificial melanin nanoparticles share the same high biocompatibility of the natural ones and the same unique chemical and photochemical properties. Melanin is hence a natural nanocosmetic agent, but its actual application in cosmetics is still under development, also because of regulatory issues. Here, we critically discuss the most recent examples of the application of natural and biomimetic melanin to cosmetics and highlight the requirements and future steps that would improve melanin-based cosmetics in the view of future applications in the everyday market.
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Color del Cabello , Melaninas , Melaninas/química , Melaninas/metabolismo , Humanos , Animales , Cosméticos/química , Nanopartículas/química , Pigmentación de la Piel/efectos de los fármacos , Nanoestructuras/química , Nanotecnología/métodosRESUMEN
BACKGROUND: The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV). MATERIALS AND METHODS: The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up. RESULTS: The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements. CONCLUSION: The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.
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Glucósidos , Paeonia , Terapia Ultravioleta , Vitíligo , Humanos , Vitíligo/terapia , Vitíligo/radioterapia , Vitíligo/tratamiento farmacológico , Femenino , Masculino , Adulto , Terapia Ultravioleta/métodos , Estudios Retrospectivos , Paeonia/química , Glucósidos/administración & dosificación , Glucósidos/uso terapéutico , Terapia Combinada/métodos , Persona de Mediana Edad , Adulto Joven , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Resultado del Tratamiento , Administración Oral , Extractos Vegetales/administración & dosificación , Adolescente , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiaciónRESUMEN
Skin yellowness is a hallmark of dull or unhealthy skin, particularly among Asians. Previous research has indicated a link between skin glycation and skin yellowness. However, the specific glycated chemicals contributing to yellowish skin appearance have not been identified yet. Using HPLC-PDA-HRMS coupled with native and artificially glycated human epidermal explant skin, we identified intensely yellow colored glycated chromophores "(1R, 8aR) and (1S, 8aR)-4-(2-furyl)-7-[(2-furyl)-methylidene]-2-hydroxy-2H,7H,8AH-pyrano-[2,3-B]-pyran-3-one" (abbreviated as AGEY) from human skin samples for the first time. The abundance of AGEY was strongly correlated with skin yellowness in the multiple skin explant tissues. We further confirmed the presence of AGEY in cultured human keratinocytes and 3D reconstructed human epidermal (RHE) models. Additionally, we demonstrated that a combination of four cosmetic compounds with anti-glycation properties can inhibit the formation of AGEY and reduce yellowness in the RHE models. In conclusion, we have identified specific advanced glycation end products with an intense yellow color, namely AGEY, in human skin tissues for the first time. The series of study results highlighted the significant contribution of AGEY to the yellow appearance of the skin. Furthermore, we have identified a potential cosmetic solution to mitigate AGEY formation, leading to a reduction in yellowness in the in vitro RHE models.
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Productos Finales de Glicación Avanzada , Queratinocitos , Piel , Humanos , Productos Finales de Glicación Avanzada/metabolismo , Piel/metabolismo , Queratinocitos/metabolismo , Queratinocitos/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Glicosilación , Epidermis/metabolismo , Cosméticos/química , Femenino , Adulto , Pigmentación de la Piel/efectos de los fármacosRESUMEN
INTRODUCTION: Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is challenging due to the chronic nature of the condition. Ruxolitinib cream 1.5% was recently approved by the Food and Drug Administration (FDA) as a Janus kinase 1 and 2 inhibitor for use in nonsegmental vitiligo for those 12 years and older. AREAS COVERED: The purpose of this review is to describe the role of ruxolitinib in treating nonsegmental vitiligo.We searched PubMed using search terms nonsegmental vitiligo, jak inhibitor, and ruxolitinib. Clinicaltrials.gov was used to identify clinical trial data including efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability. EXPERT OPINION: In both phase II and phase III (TRuE-V1 and TRuE-V2) trials, ruxolitinib cream 1.5% improved repigmentation with minimal adverse effects. Topical ruxolitinib is a much needed new vitiligo treatment option. Real life efficacy may not match that seen in clinical trials if the hurdle of poor adherence to topical treatment is not surmounted.
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Nitrilos , Pirazoles , Pirimidinas , Vitíligo , Humanos , Vitíligo/tratamiento farmacológico , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Pigmentación de la Piel/efectos de los fármacos , Janus Quinasa 1/antagonistas & inhibidores , Crema para la Piel/uso terapéutico , Janus Quinasa 2/antagonistas & inhibidores , Inhibidores de las Cinasas Janus/uso terapéuticoRESUMEN
The primary function of the skin is to form a mechanical, permeability, antimicrobial, and ultraviolet radiation barrier, which is essential for maintaining physiological homeostasis. Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti-ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low-concentration imiquimod. Results showed that topical application of low-concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low-concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low-concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next-generation sequencing result indicated that PKCη and Dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low-concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction.
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Imiquimod , Melaninas , Animales , Humanos , Ratones , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Hiperpigmentación/tratamiento farmacológico , Melaninas/metabolismo , Ratones Endogámicos C57BL , Monofenol Monooxigenasa/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Pigmentación de la Piel/efectos de los fármacos , Línea Celular , FemeninoAsunto(s)
Clofazimina , Humanos , Clofazimina/efectos adversos , Clofazimina/administración & dosificación , Femenino , Pigmentación de la Piel/efectos de los fármacos , Masculino , Hiperpigmentación/inducido químicamente , Leprostáticos/efectos adversos , Leprostáticos/administración & dosificación , Adulto , Persona de Mediana EdadRESUMEN
Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen® MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.
Asunto(s)
Epidermis , Melaninas , Melanocitos , Gases em Plasma , Humanos , Melaninas/metabolismo , Melaninas/biosíntesis , Melanocitos/metabolismo , Melanocitos/efectos de los fármacos , Gases em Plasma/farmacología , Epidermis/metabolismo , Epidermis/efectos de los fármacos , Epidermis/efectos de la radiación , Rayos Ultravioleta , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiación , Células Cultivadas , Especies Reactivas de Oxígeno/metabolismo , Biopsia , MelanogénesisRESUMEN
Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real-time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin-1 (ET-1) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co-culture, as evidenced by time-lapse live imaging and single-cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol-induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET-1 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR-TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management.
Asunto(s)
Receptores ErbB , Gefitinib , Hipopigmentación , Queratinocitos , Melaninas , Melanocitos , Inhibidores de Proteínas Quinasas , Receptores ErbB/metabolismo , Animales , Melaninas/metabolismo , Melaninas/biosíntesis , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Melanocitos/efectos de los fármacos , Melanocitos/metabolismo , Melanocitos/patología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/patología , Hipopigmentación/patología , Hipopigmentación/tratamiento farmacológico , Gefitinib/farmacología , Cobayas , Pigmentación de la Piel/efectos de los fármacos , Factor de Células Madre/metabolismo , Epidermis/efectos de los fármacos , Epidermis/patología , Epidermis/metabolismo , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Endotelina-1/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Factor de Crecimiento Epidérmico/farmacología , QuinazolinasRESUMEN
Dyschromia is a top diagnosis among African Americans (AA). Sunscreen is an essential part of its management, but AA have low sunscreen use. We sought to examine the perception of sunscreen utility in dyschromia and photoaging among patients who identify as AA or Black. This cross-sectional study recruited participants from the Case Western Reserve University Academic Dental Clinic. Participants completed an electronic survey that contained questions related to sunscreen use, knowledge of the sun's role in hyperpigmentation and photoaging, and whether sunscreen could be used for hyperpigmentation and photoaging. Of the 151 participants recruited, 63.6% (n = 96) were women and 36.4% (n = 57) were men. Consistent with previous reports, participants had lower sunscreen use (20.5%) than whites (43.5%). The majority of participants (80.1% and 58.3%, respectively) didn't attribute the sun to hyperpigmentation or photoaging. Participants with dark/brown spots were significantly more likely to not attribute the sun to hyperpigmentation than those without spots. (p = 0.003) Limitations for this study include its small sample size, recall and reporter bias, question misinterpretation, and lack of question neutrality. This study highlights the knowledge gap of a major contributing factor to dyschromia which in turn could be leading to their view of the decreased utility of sunscreen.
Asunto(s)
Negro o Afroamericano , Conocimientos, Actitudes y Práctica en Salud , Protectores Solares , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Negro o Afroamericano/estadística & datos numéricos , Negro o Afroamericano/psicología , Estudios Transversales , Hiperpigmentación/prevención & control , Envejecimiento de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de los fármacos , Luz Solar/efectos adversos , Protectores Solares/administración & dosificación , Encuestas y Cuestionarios/estadística & datos numéricosRESUMEN
Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.