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4-n-butylresorcinol (4-nBR) is a valuable ingredient to lighten skin and reduce pigmentation, contributing to an even skin tone and a more youthful appearance. However, its poor solubility, low stability, and strong irritation to the skin limit its application. In this study, 4-nBR was prepared into 4-n-butylresorcinol nanoemulsion (4-nBR-NE) for the first time, enhancing the solubility and stability of 4-nBR while greatly reducing its skin irritation. The relationship between the viscosity of nanoemulsion and the formulation process, as well as the impact of surfactant ratio on the formability of 4-nBR-NE were further studied. This led to the successful development of a nanoemulsion with adjustable viscosity (AV-NE) and with a low surfactant content. The particle size of 4-nBR-NE was 13.34 ± 0.16 nm with a PDI of 0.0853 ± 0.0191, indicating a uniform particle size distribution. The encapsulation rate of 4-nBR-NE was determined to be 80.05 ± 0.75 % via UV-Vis spectrophotometry. In addition, 4-nBR-NE demonstrated excellent stability over several months, with negligible changes in particle size. Cellular and transdermal evaluations confirmed that the preparation of 4-nBR-NE effectively reduced the original irritation cause by 4-nBR on cells and skin. Then, 4-nBR-NE was incorporated into an essence. This advancement enhances the applicability of 4-nBR in treating pigmentation disorders such as melasma and freckles, thereby increasing its applicability in pharmaceutical and cosmetic industries., Competing Interests: Declaration of Competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier Masson SAS.)

Phototoxic reactions are among the most common skin-related adverse effects induced by drugs. It is believed that the binding of chemicals to melanin biopolymers is a significant factor influencing skin toxicity. The formation of drug-melanin complexes can lead to the accumulation of drugs or their photodegradation products in pigmented cells, potentially affecting phototoxic reactions. Current procedures for assessing the phototoxic potential of drugs are based on tests using immortalized mouse fibroblasts. This study aimed to assess the phototoxic potential of selected drugs that form complexes with melanin (chloroquine, chlorpromazine, doxycycline) using human melanocytes with varying degrees of pigmentation. Parallel research was conducted on human dermal fibroblasts. To induce phototoxicity, cell cultures were irradiated using a sunlight simulator (5 J/cm 2 for UVA spectrum). To account for the process of drug accumulation, two experimental models with different incubation times of cells with drugs before irradiation were used. The photo-irritation factor (PIF) was calculated based on NRU and WST-1 screening tests. Additionally, cell viability was examined cytometrically, and analyses of the cell cycle and reduced glutathione levels were conducted. The results indicated that drugs binding with melanin exhibited different levels of cytotoxicity and phototoxicity towards fibroblasts and melanocytes. These observed differences impact the values of PIF, potentially complicating the interpretation of the studies. Additional analyses, such as examining cell subpopulations in the sub-G1 phase and determining the level of reduced glutathione, can enhance the assessment of the phototoxicity of drugs on pigmented cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Retinoids are derivatives of vitamin A prominently used in cosmeceuticals to reverse signs of photoaging. Retinaldehyde (retinal) is 10x more bioavailable than retinol and is gaining traction in the skincare industry for being the strongest over-the-counter retinoid. This study evaluated the efficacy and tolerability of a novel retinal formulation including peptides, ceramides, and lipids, designed to sustain the potency of the retinal and enhance delivery to reverse clinical signs of photoaging. This study was a trial of the test product (Retinal Night Advanced 0.1% Retinal Firming Treatment, Dr. Whitney Bowe Beauty, Greenwich, CT) in which 32 female subjects were enrolled. 47% of subjects had skin of color (Fitzpatrick Skin Type III-VI) and 57% had sensitive skin. Subjects applied the test product 3 nights weekly to the face, neck, and chest for 8 weeks. Fine lines of the face had 12% visible change by week 8 (P<0.0001). Fine lines on the chest showed progressive visible improvement of 11% at week 2 (P=0.0005) and 19% at week 8 (P<0.0001). There was a 19% improvement in visible hyperpigmentation of the face by the 8-week mark (P<0.0001). Visible texture of the face improved by 5% (P=0.0078) and pores improved by 20% at week 8 (P<0.0001). Patch testing revealed no signs of sensitization or irritation. This clinical study demonstrates that this retinal formulation is safe, well-tolerated, and effective in improving the appearance of fine lines, hyperpigmentation, texture, and pores. J Drugs Dermatol. 2024;23(11):992-997. doi:10.36849/JDD.8058R1&nbsp.

Skin cancer most commonly affects fair-skinned individuals1; however, it can appear in individuals of all skin tones. Photoprotective behaviors such as applying sunscreen should be practiced by all individuals regardless of skin tone. Herein, the authors discuss the cost and protection of popular sunscreens targeted towards patients with darker skin or skin of color (SOC), and suggest important considerations providers should take into account when advising about sunscreen recommendations for patients with skin of color. J Drugs Dermatol. 2024;23(11):e181-e182. doi:10.36849/JDD.8710e.

The potential therapeutic effects of carnosic acid (CA) on postinflammatory hyperpigmentation (PIH) were evaluated, including its effects on melanin deposition in zebrafish, melanogenesis and melanosome transfer in skin cells and skin wound healing in mice. Our results demonstrated that CA dose-dependently decreased melanin deposition in the skin of juvenile zebrafishes. It also inhibited melanogenesis in melanoma cells and melanosome transfer to keratinocytes. Next, CA was loaded in a liposome-hydrogel system (LP-GEL) to treat skin wounds in mice. The results showed that CA-LP-GEL, as well as LP-GEL, could accelerate skin wound healing and repair the structure of healing skins in mice. Comparatively, the levels of inflammatory factors (IL-1β and TNF-a) in healing skins were significantly increased by LP-GEL, but reduced by CA-LP-GEL. In addition, Fontana-Masson staining analysis of healing skin showed that the melanoma cells were restored by the treatment of LP-GEL and CA-LP-GEL, while the melanin content was significantly increased only by LP-GEL. Real-time PCR data showed that CA decreased the gene expression related with melanogenesis (MITF, TYR and TRP-1), melanosome transfer (MLPH, Myova and Rab27a) and inflammatory cytokines (IL-1β and TNF-α) in vitro and in vivo. In conclusion, CA could reduce melanin deposition in the skin by inhibiting melanogenesis and melanosome transfer. CA-LP-GEL was found to accelerate skin wound healing and suppress inflammation and hyperpigmentation in mice. These results suggest that CA has a big developing potentiality for PIH treatment., Competing Interests: Declaration of Competing Interest The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors read and approved the final manuscript., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The treatment of vitiligo is a persistent challenge in dermatology. New treatments are being offered and studied in this field for those resistant to or intolerant of classical therapies., Aims: In this systematic review, we study the use of prostaglandin analogues (PGAs) and phosphodiesterase inhibitors (PDEIs) in the treatment of vitiligo, as they are known for their pigmentation inducing effects through activating melanocytes., Methods: We searched four main online databases with the keywords "Vitiligo", "Prostaglandin analogue" and "Phosphodiesterase inhibitor"., Results: A total of 42 articles were included, with 1027 cases, studying drugs like bimatoprost, latanoprost, travoprost, dinoprostone, apremilast, crisaborole, etc. Among the included studies, the treatment regimens are commonly once or twice daily for 12-48 weeks, with a mean of 20.61 weeks, and the routes of administration are mainly topical gels or ophthalmic solutions and oral tablets. Side effects are mild and tolerable, namely erythema, itching or burning sensations at application site for topicals, or gastrointestinal problems with apremilast. Repigmentation results are significant in both adult and pediatric patients and progressive or stable vitiligo. PGAs and PDEIs outperform many classical therapies, for example, narrowband ultraviolet B phototherapy (NB-UVB), tacrolimus, mometasone or methylprednisolone mini-pulse. PGAs or PDEIs are usually used in combination therapies to either cause synergism or increase drug delivery, and almost always enhance repigmentation, for example, with NB-UVB, fractional CO 2 laser, microneedling, and mometasone., Conclusion: Monotherapy or add-on PGAs and PDEIs can be considered effective treatments for vitiligo and promising last resorts for those resistant to other therapies., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Natural herbs have been widely considered a reservoir for skin-lightening ingredients, but discovery of the effective ingredients from herbs remains a large challenge., Aim: This research aimed to rapidly identify compounds with skin-lightening activity in Chinese herbs., Methods: The structure information of herbal compounds was collected and selected from the open-source data. High throughput virtual screening (HTVS) and Extra precision (XP) docking modes were used to screen for compounds that could bind to the mushroom tyrosinase involved in melanin synthesis. Furthermore, molecular dynamics (MD) simulations were introduced to assess the binding stability of those compounds with the key target protein. The candidate compounds found by this kind of multidimensional molecular screening were finally tested for their ability to inhibit pigmentation and potential toxicity using an in vivo zebrafish animal model., Results: A Natural Compounds Database was established with 5616 natural compounds. Fourteen compounds with favorable binding capability were screened by the XP docking mode with mushroom tyrosinase and five compounds among them were found to have superior dynamic binding performance through MD simulations. Then the Zebrafish animal experiments revealed that two components, sennoside B (SB) and sennoside C (SC), could significantly inhibit melanogenesis rather than the other three compounds. Meanwhile, there were no obvious side effects observed in SB and SC about the morphology, heart rate, or body length of zebrafish., Conclusion: A strategy for rapid screening of compounds with whitening activity has been established, and two potent skin-lightening compounds, SB and SC, have been identified from a vast library of herbal compounds. This study revealed that SB and SC have potential for topical use in skin lightening for the first time. The findings of this study would provide an important theoretical basis for the application of these two compounds in the cosmetic field in the future., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Poly-D,L-lactic acid (PDLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. PDLLA filler also increases M2 macrophages and IL-10. Ultraviolet (UV) radiation induces dermal hyperpigmentation by disrupting the basement membrane (BM), allowing melanin to move into the dermis. Therefore, using UV-irradiated macrophages and animal skin, we determined whether PDLLA filler decreased M1 macrophages and skin inflammation, thereby reducing BM destruction and dermal hyperpigmentation. UV radiation increased the M1 macrophage marker CD86 and TNF-α expression, which was inhibited by the treatment of macrophages with PDLLA. In fibroblasts treated with conditioned medium from UV-irradiated macrophages, NF-κB activity, NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1), IL-18, MMP2, and MMP9 increased, but all decreased after PDLLA treatment. Similar to the in vitro study, UV-irradiated mouse skin showed increased CD86, NLRP3, ASC, pro-caspase-1, MMP2, and MMP9, which decreased after PDLLA injection. Disruption of the lamina densa of the BM and dermal pigmentation increased after UV irradiation and decreased after PDLLA injection. In conclusion, PDLLA reduced dermal pigmentation by decreasing BM destruction in UV-irradiated skin. PDLLA has the potential to reduce dermal pigmentation by regenerating the BM.

The oculocutaneous albinism II ( OCA2 ) gene encodes a melanosomal transmembrane protein involved in melanogenesis. Recent genome-wide association studies have identified several single nucleotide polymorphisms within OCA2 genes that are involved in skin pigmentation. Nevertheless, there have been no attempts to modulate this gene to improve skin discoloration. Accordingly, our aim was to identify compounds that can reduce OCA2 expression and to develop a formula that can improve skin brightness and reduce hyperpigmented spots. In this study, we investigated the effects of OCA2 expression reduction on melanin levels, melanosome pH, and autophagy induction through siRNA knockdown. Additionally, we identified several bioactives that effectively reduce OCA2 expression. Ultimately, in a clinical trial, we demonstrated that topical application of those compounds significantly improved skin tone and dark spots compared to vitamin C, a typical brightening agent. These findings demonstrate that OCA2 is a promising target for the development of efficacious cosmetics and therapeutics designed to treat hyperpigmentation.

Persistent racial disparities in health outcomes have catalyzed legislative reforms and heightened scientific focus recently. However, despite the well-documented properties of skin pigments in binding drug compounds, their impact on therapeutic efficacy and adverse drug responses remains insufficiently explored. This perspective examines the intricate relationships between variation in melanin-based skin pigmentation and pharmacokinetics and -dynamics, highlighting the need for considering diversity in skin pigmentation as a variable to advance the equitability of pharmacological interventions. The article provides guidelines on the selection of New Approach Methods (NAMs) to foster inclusive study designs in preclinical drug development pipelines, leading to an improved level of translatability to the clinic., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Tokishakuyakusan (TSS), a traditional Kampo medicine, can effectively alleviate symptoms unique to women, such as menstrual pain and menopausal symptoms, and this effect is believed to be related to its ability to increase the secretion of female hormones. TSS is also believed to be effective against skin pigmentation. However, no studies have examined the effect of TSS on pigmentation., Aim of the Study: In this study, we conducted basic research to determine the effects of TSS on pigmentation., Materials and Methods: Female HRM-2 mice were given free access to a normal diet or a TSS-containing diet for 7 weeks. For 3 weeks starting from the 4th week of treatment, the back of the skin was irradiated with ultraviolet (UV) light, and the melanin level was measured. The expression levels of melanogenesis-related genes and inflammatory markers in the skin were analyzed., Results: The melanin level in the skin of the mice exposed to UV radiation was approximately three times greater than that in the skin of the mice in the non-UV-irradiated group, confirming pigmentation due to UV irradiation. The protein expression levels of tyrosinase (Tyr), tyrosinase-related protein-1 (Tyrp1), and dopachrome tautomerase (Dct), which are important for melanin production, were significantly greater in the UV irradiation group than in the non-UV irradiation group. In contrast, the amount of skin melanin in the mice treated with TSS was significantly lower than that in the UV-irradiated group, and the expression levels of melanogenesis-related enzymes were also lower. Furthermore, TSS significantly decreased the expression of microphthalmia transcription factor (Mitf), a transcription factor for melanogenesis-related enzymes, and the inflammatory cytokines interleukin-1β and interleukin-6., Conclusions: TSS inhibits melanin production in melanocytes by suppressing the increase in the expression of melanogenesis-related enzymes caused by UV irradiation. These findings suggested that this effect of TSS is exerted through the combined regulation of MITF expression and anti-inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Vitiligo remains a challenging condition to treat. Fire needle therapy, a traditional Chinese medicine technique, has potential as an alternative therapeutic strategy. However, rigorous evidence on its efficacy is lacking., Objective: We aimed to evaluate the efficacy and safety of fire needle therapy, alone and combined with topical tacrolimus ointment, for non-segmental stable vitiligo., Methods: In this 6-month randomized self-controlled trial, 35 vitiligo patients were enrolled, providing three similar lesions each. Lesions were randomly allocated to receive fire needle monotherapy, 0.1% tacrolimus ointment monotherapy, or combined fire needle and tacrolimus ointment therapy. The main outcome was change in vitiligo surface area., Results: In total, 29 patients completed the 6-month follow-up. The combination therapy group showed significantly greater reductions in vitiligo surface area compared to monotherapy groups starting at months 4 and 5. By the end of the study, combination therapy resulted in remarkably higher repigmentation responses, with 89.7% of lesions showing at least mild (≥25%) repigmentation and 51.7% showing good (≥50%) repigmentation. This significantly exceeded the outcomes with topical tacrolimus ointment alone, which only achieved 6.9% mild response and 6.9% good response. Fire needle monotherapy also demonstrated steady repigmentation over time, with 69% of lesions attaining a mild response by month 6. Importantly, no major adverse events occurred., Conclusion: This study provides promising preliminary evidence supporting the use of fire needle therapy, alone or in combination with topical tacrolimus ointment, for inducing repigmentation in non-segmental stable vitiligo. As a non-pharmacological approach, fire needle therapy warrants further study as an alternative vitiligo treatment., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.

The oral administration of antioxidants may suppress UV-B-induced skin damage. HITHION YH-15, the extract of Torula yeast (Cyberlindnera jadinii), is rich in cysteine-containing peptides such as reduced and oxidized glutathione (GSH and GSSG), γ-glutamylcysteine (γ-Glu-Cys), and cysteinylglycine (Cys-Gly). These four constituents are termed cysteine peptides. In this study, we investigated the protective effects of cysteine peptides against UV-B in a randomized, placebo-controlled, double-blind, parallel-group study. A total of 90 healthy males and females aged 30-59 years were enrolled and randomized into two groups of 45 individuals each (cysteine peptides (48 mg/day) and placebo). Changes in UV-B-induced erythema and pigmentation were compared between groups after 5 weeks of test food intake. The minimal erythema dose (MED) significantly increased (*p = 0.019) in the cysteine peptides group compared to that in the placebo group, indicating suppression of UV-B-induced erythema. ΔL* value significantly increased (***p < 0.0001) in the cysteine peptides group compared to that in the placebo, indicating pigmentation suppression. We demonstrated that oral administration of cysteine peptides suppresses UV-B-induced erythema and pigmentation through multiple mechanisms. Thus, cysteine peptides may find use as nutricosmetics for maintaining skin health and well-being.UMIN Clinical Trials Registry ID: UMIN 000050157., (© 2024. The Author(s).)

Background: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations., Objectives: We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011-2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting., Methods: The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors., Results: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT., Conclusions: ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Efficacy and safety of ritlecitinib (an oral JAK3/TEC family kinase inhibitor) were evaluated in patients with nonsegmental vitiligo (NSV) across Fitzpatrick skin types (FSTs). Patients with FST I-III ('light skin'; n = 247) and FST IV-VI ('dark skin'; n = 117) received once-daily ritlecitinib 50 mg (with/without 4-week loading dose), low-dose ritlecitinib or placebo for 24 weeks. At baseline, patients with light skin displayed higher CLM-1 and NCR1 serum levels than patients with dark skin (p < 0.05). At 24 weeks, ritlecitinib 50 mg improved the extent of depigmentation measured by percent change from baseline in facial-vitiligo area scoring index (placebo-adjusted mean difference [90% CI]) in patients with light (-15.2 [-24.7, -5.8]; p = 0.004) and dark (-37.4 [-50.3, -24.4]; p < 0.0001) skin, with continuous re-pigmentation through week 48. Treatment-emergent adverse events were similar across FSTs. At weeks 4 and 24, ritlecitinib 50 mg reduced CXCL11 serum levels (p < 0.001) in patients with light skin, whereas patients with dark skin had increased levels at week 4 (p = 0.05) and no significant change at week 24. Ritlecitinib 50 mg decreased IL-9 and IL-22 expression levels in dark skin compared with light skin (qPCR; p < 0.05). These differences in immune dysregulations may explain why NSV patients with dark skin respond to therapy earlier than patients with light skin., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acne can cause disfiguring sequelae, such as scarring, post-inflammatory erythema (PIE), and post-inflammatory hyperpigmentation (PIH). These post-inflammatory dyschromias pose a significant psychological burden on patients. This burden disproportionately affects skin of color (SOC) patients and can be the most distressing aspect of acne in SOC patients with skin types IV to VI. Multiple non-ablative lasers are used in the treatment of acne-related PIE and PIH. Combination therapies have shown promise in conditions such as rosacea, acne, and post-inflammatory dyschromia. Addressing both the inflammatory and scarring components of acne is key. Given the role of oxidation in the inflammatory cascade, including antioxidants could be an efficacious adjuvant with non-ablative lasers. This is a single-site, randomized, controlled clinical study of 25 subjects with skin types I to VI with facial PIE and/or PIH from acne. The primary objective was to investigate the clinical efficacy of non-ablative laser therapy followed by the topical application of Silymarin/Salicylic Acid/L-Ascorbic Acid/Ferulic Acid (SSAF) or control in the improvement in oily skin patients with facial PIE and PIH due to acne lesions. There was a statistically significant decrease in PIH and intralesional melanin in patients treated with a combination SSAF and non-ablative laser therapy. Improvement of both PIE and PIH was augmented in combination with SSAF and laser-treated patients compared with the laser-only group, with a concomitant increase in collagen density. This was even more strikingly marked in the SOC subjects, potentially providing an energy-based device (EBD)-based therapy in this population. Limitations of this study include small sample size and length of post-treatment follow-up. J Drugs Dermatol. 2024;23(9):769-773. doi:10.36849/JDD.8309.

Background: As the racial/ethnic diversity of the US population grows, it is imperative for dermatologists to recognize the nuances in the aesthetic treatment of diverse populations., Objective: This comprehensive review explores the safety and efficacy of botulinum toxin A (BTX-A) in skin of color (SOC) populations and highlights variations in aging patterns, skin properties, and aesthetic concerns in SOC populations., Materials and Methods: A review of PubMed/MEDLINE databases from 2004 to 2024 was performed using combinations of the terms botulinum toxin, SOC, Fitzpatrick, race/ethnicity, and Asian, Latin American, Caribbean, Middle Eastern, African, and Pacific countries., Results: Twenty-three articles examining the use of BTX-A in SOC populations were identified. Twelve studies were from East Asia, 5 from the United States and/or Canada, 3 from South Asia/Southeast Asia, 2 from South America, and 1 from the Middle East. Available data suggest that BTX-A is efficacious and well tolerated in SOC populations., Conclusion: Increased SOC representation in clinical trials may guide the development of tailored treatment approaches to optimize aesthetic outcomes for patients with SOC. A comprehensive knowledge of the variations in aging patterns, skin properties, and aesthetic concerns across SOC populations is essential for providing culturally sensitive cosmetic dermatologic care for diverse populations., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Drug-induced pigmentation (DIP) is estimated to account for 20% of all cases of acquired hyperpigmentation. Over 50 agents have been implicated, including antibiotics, antimalarials, antiretrovirals, antipsychotics, prostaglandin analogs, heavy metals, and chemotherapeutic agents. The skin, mucosal surfaces, nails, and hair can all be affected, with the color, distribution, onset, and duration of pigmentation varying between offending agents. Both a thorough physical examination and medication history are necessary to determine the offending agent. In terms of mechanism, DIP occurs most frequently through the accumulation of melanin within the dermis but also by drug accumulation, pigment synthesis, and iron deposition. Photoprotection, including applying a broad-spectrum sunscreen, wearing photoprotective clothing, and seeking shade, plays an important role in the prevention of exacerbation of DIP. Multiple lasers, including the picosecond alexandrite, Q-switched Nd:YAG, Q-switched alexandrite, and Q-switched ruby lasers, have been successful in obtaining clearance of DIP. In this review, we examine the unique characteristics of each of the inciting agents in terms of incidence, clinical presentation, time to onset and resolution, and pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The physiological role of α-melanocyte stimulating hormone in regulating integumental pigmentation of many vertebrate species has been recognized since the 1960's. However, its physiological significance for human pigmentation remained enigmatic until the 1990's. α-Melanocyte stimulating hormone and related melanocortins are synthesized locally in the skin, primarily by keratinocytes, in addition to the pituitary gland, and therefore act as paracrine factors for melanocytes. Human melanocytes express the melanocortin 1 receptor, which recognizes α-melanocyte stimulating hormone and the related adrenocorticotropic hormone as agonists. This review summarizes the current knowledge of the pleotropic effects of the activated melanocortin 1 receptor that maintain human melanocyte homeostasis by regulating melanogenesis and the response to environmental stressors, mainly solar radiation. Certain allelic variants of the melanocortin 1 receptor gene are associated with specific pigmentary phenotypes in various human populations. Variants associated with red hair phenotype compromise the function of the encoded receptor. Activation of the human melanocortin 1 receptor regulates eumelanin synthesis and enhances DNA damage response of melanocytes to solar radiation and oxidative stressors. We describe how synthetic selective melanocortin 1 receptor agonists can be efficacious as sunless tanning agents, for treatment of vitiligo and photosensitivity disorders, and for prevention of skin cancer, including melanoma., (© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo., (© 2024 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

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., (© 2024 Wiley Periodicals LLC.)

The skin is vulnerable to damage from ultraviolet rays and oxidative stress, which can lead to aging and pigmentation issues. This study investigates the antioxidant and whitening efficacy of a decapeptide (DP, KGYSSYICDK) derived from marine fish by-products and evaluates its potential as a new skin-whitening agent. DP demonstrated high antioxidant activity, showing comparable or superior performance to Vitamin C (Vit. C) in ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. In hydrogen peroxide (H 2 O 2 )-treated HaCaT cells, DP increased cell viability and reduced reactive oxygen species (ROS) generation. Furthermore, DP inhibited tyrosinase activity and decreased melanin production in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells in a dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that DP reduces the mRNA expression of MITF , tyrosinase , and MC1R , thus suppressing melanin production. DP exhibits strong binding interactions with multiple amino acid residues of tyrosinase, indicating potent inhibitory effects on the enzyme. These results suggest that DP possesses significant antioxidant and whitening properties, highlighting its potential as a skin-whitening agent. Future research should focus on optimizing DP's structure and exploring structure-activity relationships.

Background: There is a paucity of data on the treatment of psoriasis in patients with skin of color &ndash; 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 &ge; 18, BSA &ge;10%, PASI Score &ge; 12, IGA &ge; 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.

Introduction: Burns to the face and neck are a source of considerable distress and a challenge to manage with dressings. Further, these often superficial injuries pose a risk of scarring and altered pigmentation. Silicone gels have emerged as a potential solution to the challenges of conservative management for face and neck burn injuries. The aims of this study were to explore the effect of topical silicone compared to routine treatment of conservatively managed burns to the face and neck., Methods: This single-blind, randomised, controlled trial compared topical silicone film-forming dressing to standard of care for superficial partial thickness burns to the face and neck. Time to healing was the primary outcome and secondary outcomes included: 1) scar assessments (modified Vancouver Scar Scale, Dermalab Combo and Patient and Observer Scar Assessment Scale) at six weeks and three months; and 2) pain intensity scale at wound review appointments., Results: Of the 55 participants in the face/neck study, 34 were male and 21 were female. Median age was 36 years (range from 25 to 47 years). The median time to healing for the silicone group was 9 days (CI 7.6 -10.4) and the control group was 7 days (CI 5.3- 8.7), p = 0.056. Analysis demonstrated significantly reduced pigmentation at six weeks in mVSS scores for the silicone group (Md = 0, IQR = 0) compared to the control group (Md = 0, IQR = 0 - 3), p = 0.043. We found no evidence of differences in reported pain between the groups (Silicone - Md = 1.15, IQR 0.3 - 4.5 vs control group - Md = 1.5, IQR 0.6 - 3.8, z = -0.63, p = 0.53). No other differences were observed, and no adverse events were associated with the topical silicone in the study whereas an infection and a reaction were experienced in the control group., Conclusion: Film-forming silicone gel had comparable effects to standard of care emollient on wound healing of superficial partial thickness burns of the face and neck. Silicone treated wounds were associated with a significant improvement in scar pigmentation outcome at six weeks post-burn., Competing Interests: Declaration of Competing Interest All authors warrant that they have no competing interests to declare with respect to this study and the findings stated herein with integrity. Ms Poelchow’s involvement in the study was funded at arm’s length by Stratpharma AG and was in partial fulfilment of requirements for her Masters of Philosophy award (conferred 2023, The University of Notre Dame Australia). Stratpharma AG scientific advisors and representatives were consulted during the design of the study; were not involved in the conduct of the study or collection of data and outcomes; and, did not have access to raw data. Stratpharma AG representatives and advisors were given opportunity to review the manuscript and provide their feedback on the wording of the report text only after independent interpretation. The interpretation of raw data and results was conducted solely by the clinicians and academic supervisors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Skin photoaging and uneven pigmentation are common dermatological concerns. Tetrahexyldecyl ascorbate (THDA) and acetyl zingerone (AZ) are potent antioxidants that have been shown to have anti-photoaging and anti-pigmentation effects. THDA is a more stable and penetrable form of vitamin C. AZ is an antioxidant derived from ginger which has clinical evidence for improving photoaging. However, no studies have assessed how they may synergistically act on the skin., Aims: This study aims to assess whether a serum containing both THDA and AZ can improve photoaging and the appearance of uneven facial pigmentation., Patients/methods: This open-label study was conducted on 35 healthy individuals aged 21-55. All subjects were instructed to use three to five drops of the topical serum (Power-C Serum, Image Skincare, Lantana, FL) daily for 12 weeks. Videomicroscopy and high-resolution photography and various skin biophysical measurements were taken at baseline, 1, 4, and 12 weeks. Outcomes included skin tone and pigmentation, transepidermal water loss (TEWL), skin smoothness, firmness, and elasticity., Results: Compared to baseline, the results at 12 weeks revealed significant decreases in skin pigmentation (p < 0.0001), decreased fine lines and wrinkles (p < 0.0001), and increased smoothness (p < 0.0001), firmness (p < 0.0001), and elasticity (p < 0.0001). Additionally, transepidermal water loss was significantly decreased at 4 weeks compared to baseline (p = 0.01), indicating an increased epidermal barrier integrity., Conclusions: Overall, these findings provide evidence for the combined use of THDA and AZ to address skin photoaging and dyspigmentation changes., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: Hyperpigmentation disorders are very frequent, affect the quality of life and may become a psychological burden for afflicted patients. Many anti-pigmenting or depigmenting agents are available with various efficacy and almost no comparative data. 2-mercaptonicotinoyl glycine (2-MNG) was recently proposed as a viable candidate showing safe and effective results on hyperpigmentation control in vitro and in vivo., Objectives: A Bayesian network meta-analysis (BNMA) was conducted to map and rank the anti-pigmenting and depigmenting efficacy of 2-MNG 0.5% on UV daylight (UVDL)-induced pigmentation together with 13 other reference molecules. A comparison in the kinetics of 2-MNG 0.5% was also performed., Methodology: Fourteen studies were conducted, for each, on 15-30 women of skin phototype III in Shanghai, China and Paris, France. The products were applied on mini zone, in randomized and blinded protocol, on the back, 5 days a week during 6 weeks, at a dose of 4 mg/cm 2 . During the second week, volunteers were exposed under to varying minimum erythemal dose of UVDL during 4 consecutive days-adapted to obtain a similar induction of skin pigmentation regardless of the population. Assessments were performed instrumentally using Chromameter®. Ascorbic acid 7% was used as a positive control for all experiments. A Bayesian network meta-analysis was then established to map and follow the kinetics of 2-MNG 0.5% performance with 13 reference molecules (glutathione 2%, kojic acid 1%, hydroquinone 4%, ascorbyl glucoside 2%, niacinamide 4%, etc.)., Results: 2-MNG 0.5% dominated the ranking at all time points with a significant high probability of strong efficacy against UVDL-induced pigmentation. Ascorbic acid 7% ranks second after 4 days of irradiations (D 12 ) whereas hydroquinone 4% ranks second 1 month after irradiations (D 40 ). In the kinetics, 2-MNG at 0.5% was effective as from the end of irradiations (D 12 ) to the study endpoint (D 40 ). This suggested an immediate and persistent efficacy across all timepoints evaluated., Conclusion: The BNMA revealed a rapid and lasting efficacy of 2-MNG 0.5% on the anti-pigmenting and depigmenting phases of the clinical protocol. 2-MNG 0.5% ranked first, with immediate and lasting effect compared to 13 other references. This study is the first allowing comparison between reference anti-pigmenting and depigmenting agents and will help clinicians for proposing the most effective approach for their patients., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: In Eastern culture, a fair complexion is the standard of beauty, leading to appearance-related distress among women with darker skin or facial pigmentation. Women seek whitening cosmetics to enhance their skin tone or correct their pigmentation, but their safety and effectiveness are paramount factors to consider. In this study, we evaluated the safety and whitening effects of a compound formula denoted as TEST comprising astaxanthin, nicotinamide, arbutin, and tranexamic acid., Methods: Primary skin irritation and skin-whitening efficacy were examined. Three qualified melanization areas were treated with TEST, 7% ascorbic acid, or a blank. Skin color, the individual type angle (ITA°), and the melanin index (MI) were compared among treatment areas., Results: TEST did not induce a skin response and exhibited a significantly higher ITA° than the blank, while no significant difference was observed with that of 7% ascorbic acid. Furthermore, the MI of TEST was significantly reduced posttreatment., Conclusions: TEST could be integrated into spot-fading and skin-whitening cosmeceuticals or functional cosmetics., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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., (© 2024. The Author(s).)

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.

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 IC 50 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).

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.

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.&nbsp; 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.&nbsp; 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.&nbsp; 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.&nbsp;J Drugs Dermatol. 2024;23(7):538-544.&nbsp; doi:10.36849/JDD.8082.

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&nbsp;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.&nbsp; doi:10.36849/JDD.8223.

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., (© 2024 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Background: Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging., Aims: To examine the effects of THDA and AZ (THDA-AZ) on skin photoaging compared to THDA alone., Patients/methods: In this double-blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA-AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self-perception of skin and tolerability were assessed through questionnaires., Results: Average wrinkle severity was significantly decreased in the THDA-AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA-AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA-AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema., Conclusions: Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis., Competing Interests: Declaration of Competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previous studies have shown that all kinin system is constitutively expressed in the normal and inflamed skin, with a potential role in both physiological and pathological processes. However, the understanding regarding the involvement of the kinin system in skin pigmentation and pigmentation disorders remains incomplete. In this context, the present study was designed to determine the role of kinins in the Monobenzone (MBZ)-induced vitiligo-like model. Our findings showed that MBZ induces higher local skin depigmentation in kinin receptors knockout mice (KOB1R, KOB2R and KOB1B2R) than in wild type (WT). Remarkably, lower levels of melanin content and reduced ROS generation were detected in KOB1R and KOB2R mice treated with MBZ. In addition, both KOB1R and KOB2R show increased dermal cell infiltrate in vitiligo-like skin, when compared to WT-MBZ. Additionally, lack of B1R was associated with greater skin accumulation of IL-4, IL-6, and IL-17 by MBZ, while KOB1B2R presented lower levels of TNF and IL-1. Of note, the absence of both kinin B1 and B2 receptors demonstrates a protective effect by preventing the increase in polymorphonuclear and mononuclear cell infiltrations, as well as inflammatory cytokine levels induced by MBZ. In addition, in vitro assays confirm that B1R and B2R agonists increase intracellular melanin synthesis, while bradykinin significantly enhanced extracellular melanin levels and proliferation of B16F10 cells. Our findings highlight that the lack of kinin receptors caused more severe depigmentation in the skin, as well as genetic deletion of both B1/B2 receptors seems to be linked with changes in levels of constitutive melanin levels, suggesting the involvement of kinin system in crucial skin pigmentation pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

Objective: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach., Methods: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18., Results: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream., Conclusion: ZER demonstrated significant potential as a skin-lightening agent., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.

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., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Acne-induced hyperpigmentation (AIH) may accompany acne vulgaris (AV) inflammation in all skin phototypes. Trifarotene has shown depigmenting properties in vivo. This study evaluated trifarotene plus skincare because it is increasingly recognized that holistic AV management should include skincare and treatments., Methods: This is a phase IV double-blind, parallel-group study of patients (13-35 years) with moderate AV and AIH treated with trifarotene (N = 60) or vehicle (N = 63) plus skincare regimen (moisturizer, cleanser, and sunscreen) for 24 weeks. Assessments included the AIH overall disease severity (ODS) score, post-AV hyperpigmentation index (PAHPI), exit interviews, photography, and acne assessments. Standard safety assessments were included., Results: Trifarotene 50 μg/g cream improved significantly from baseline in ODS score versus vehicle (-1.6 vs. -1.1, P = 0.03) at Week 12, but scores were comparable between groups at Week 24 (primary endpoint). Trifarotene had a better reduction in PAHPI score at Week 24 (-18.9% vs. -11.3% vehicle, P < 0.01). Lesion count reductions were higher with trifarotene at Week 12 versus vehicle (P < 0.001) and at Week 24 (P < 0.05), as were IGA success rates versus vehicle at Weeks 12 (P < 0.05) and 24 (P < 0.05). Patients agreed that the skincare regimen contributed to less irritation, making treatment adherence easier. Photography showed improvements in pigmentation and erythema across all skin types. AEs were more common in the vehicle group versus trifarotene (30.2 vs. 16.7%, respectively)., Conclusions: In all skin phototypes, there was more rapid improvement in the ODS and PAHPI scores with trifarotene by Weeks 12 and 24, respectively. The combination of trifarotene and skincare correlated with high patient satisfaction and adherence to the treatment protocol., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use., Aims: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically., Methods: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112., Results: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability., Conclusion: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort., (© 2024 ISDIN SA. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: Vitiligo is a skin pigmentation disorder caused by the selective degradation of melanocytes. This study investigates the therapeutic effects of microneedling with and without N-acetylcysteine (NAC) in patients with persistent and limited vitiligo., Method: This research employed a clinical trial design with double-blind randomization. Individuals affected by vitiligo and seeking treatment at Rasool Akram Medical Complex were divided into two separate treatment groups. In the intervention group, 24 affected areas underwent meso-microneedling using 5% NAC ampoules over six sessions, in addition to the application of 4.7% NAC cream once daily on the specified area. Conversely, the control group, consisting of 22 lesions, underwent microneedling using distilled water during six sessions. The severity of lesions and the extent of repigmentation were gauged using the Modified VETI Score. Assessment of treatment efficacy was determined through both physician evaluations and patient feedback., Results: Twenty patients with a mean age of 36.4 years were recruited. The mean percentage of lesions and their intensity were significantly improved 2 weeks after the third session and 1 month after the end of the treatment (p < 0.01). There was no statistically significant difference between the intervention and control groups. Gender, age, family history, duration of disease, duration of disease stability, and history of hypothyroidism had no statistically significant relationship with patients' treatment outcomes (p > 0.05)., Conclusion: Microneedling with or without the application of NAC appears to be an effective treatment option for persistent vitiligo lesions. However, despite the higher improvement rate with the application of NAC, the difference was not significant., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)