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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.)

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.

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.)

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: 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.)

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., (© 2024. The Author(s).)

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III-VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena . This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK) / extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Post-acne hyperpigmentation (PAH) occurs secondary to acne vulgaris and may cause significant adverse effects. Although may occur in any skin types, PAH has been found to be more common and severe in people with colored skin. This study aimed to assess the effectiveness of combination serum containing galactomyces ferment filtrate (GFF), dexpanthenol, and Centella asiatica for treating PAH. This randomized controlled clinical trial involved Fitzpatrick skin type (FST) IV and V patients with PAH. Subjects were equally divided into treatment group, who received three drops of combination serum twice daily for 8 weeks, and placebo group. The melanin index (MI) and Lightness (L*) score were assessed every 2 weeks. Out of 51 subjects, the L* score of the treatment group in subjects with FST V was significantly higher on the 4th and 6th week compared to the placebo group ( P ˂ 0.05). The MI of subjects with FST IV was significantly lower compared to the placebo group after 8 weeks ( P ˂ 0.05). The treatment group showed consistent increasing and decreasing trend in L* score and MI, respectively ( r ˃ 0.9, P ˂ 0.05). Combination serum containing GFF, dexpanthenol, and C. asiatica may be effective in treating PAH in subjects with colored skin by accelerating lessening of PAH.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Melanin is synthesized in melanocytes and transferred to keratinocytes through dendrites. Endogenous pyruvate is a key metabolite for ATP production in glycolysis, and the tricarboxylic acid (TCA) cycle and exogenous pyruvate provide protection against oxidative stress and acidosis in the intercellular space. The function of pyruvate in the regulation of dendrite outgrowth remains to be elucidated., Objective: We examined the effect of pyruvate on dendritic elongation and skin pigmentation METHODS: Murine B16F10 melanoma cells and human primary melanocytes were used for in vitro analysis. Melanin quantitation and histochemical staining were performed in a 3D pigmented human skin model., Results: We demonstrated the participation of monocarboxylate transporters (MCTs) responsible for the membrane transport of pyruvate in B16F10 melanoma cells. The accumulation of pyruvate occurred in a pH-dependent manner, which was highly sensitive to a specific MCT inhibitor (α-cyano-4-hydroxycinnamic acid). α-MSH-induced morphological changes, including dendrite elongation and growth-cone-like structure, were diminished in B16F10 cells upon treatment with pyruvate. In addition, the number of dendrite branches was reduced in normal human epidermal melanocytes. As the Rho-subfamily of monomeric GTP-binding proteins modulates dendrite formation, we subsequently examined the suppression of Rac1 activation by pyruvate, but not RhoA and Cdc42. Furthermore, pyruvate showed anti-melanogenic effects against UV-induced pigmentation in reconstructed pigmented epidermis, established by co-seeding autologous melanocytes and keratinocytes, which act similar to in vivo skin tissue., Conclusion: These results suggest that pyruvate treatment may be an alternative or additive therapeutic strategy to prevent hyperpigmentation., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Objective: Sclerotherapy for the treatment of varicose veins is one of the most common medical procedures performed in the Western world, and hyperpigmentation is one of the most frequent, dreaded, minor adverse events. There has recently been some interest in investigating the inflammatory response of the local endothelium after sclerotherapy and the possible benefits of venoactive drugs because of their pleiotropic properties. The aim of this study was to evaluate whether adding a venoactive drug (sulodexide) to the standard sclerotherapy treatment protocol for patients with varicose veins can reduce the occurrence of postsclerotherapy hyperpigmentation., Methods: We carried out a prospective, multicenter, randomized controlled trial with a parallel group design. It included 720 patients with telangiectasia, reticular veins, or varicose veins who were candidates for sclerotherapy. Patients with reflux in deep system or saphenous veins were excluded. Group A consisted of 354 patients who received an oral dose of sulodexide twice a day for 7 days before scheduled sclerotherapy; the treatment then continued for 3 months. Group B consisted of 366 patients who received the standard sclerotherapy protocol. Polidocanol was used as the sclerosing agent, and 20 to 30 mm Hg compression stockings were used in both groups for 7 days. Control photographs were taken, and a follow-up examination took place after 1 month and 3 months. Computer software was used to analyze the treated area for incidence of hyperpigmentation, total area of hyperpigmentation, skin tone increase in the hyperpigmented area, vein disappearance, and incidence of major bleeding. The sample size was calculated to give a statistical power of 80%. Student t-test and the χ 2 test were used for comparative analyses, as appropriate. The level of significance was set at P < .05., Results: A total of 609 patients completed the 3-month follow-up: 312 in group A and 297 in group B. After 1 month, the incidence of hyperpigmentation was 8.7% in group A and 14.8% in group B (P = .01). Group A developed an average area of hyperpigmentation of 10.7% compared with 18.2% in group B (P = .01), and the skin tone of the hyperpigmented area was lower in group A than in group B (P = .02). However, the latter difference was not significant after 3 months. The overall vein disappearance rate was similar in both groups., Conclusions: Our analysis shows that by adding a venoactive drug (sulodexide) to the standard sclerotherapy protocol, the occurrence of hyperpigmentation is reduced without affecting the desired therapeutic vein elimination response., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Postinflammatory hyperpigmentation (PIH) occurs following cutaneous injury and is common following resolution of acne especially in patients with skin of color. The objective of this study was to further validate a trichloroacetic acid (TCA)-induced PIH model and compare it to acne-induced PIH using topical bakuchiol, a botanical extract that has been shown to have antimicrobial, anti-inflammatory, antioxidant, and antiacne properties. A prospective, non-randomized clinical trial was conducted on subjects with skin phototypes IV-VI with a history of acne-induced PIH. Subjects applied bakuchiol or vehicle cream twice daily to 2 acne-induced and 2 TCA-induced PIH lesions for 28 days with a third lesion serving as a control in each group. Degree of improvement was defined as the change in the Investigator Global Assessment (IGA) score over 28 days of treatment. Twenty subjects (6 males, 14 females) completed the study. For TCA-induced PIH sites, there was a statistically significant (p < 0.05) degree of improvement with bakuchiol treatment (- 0.50 ± 0.18) compared to vehicle (0.05 ± 0.15) and control (- 0.06 ± 0.17). For acne-induced PIH, there was a greater degree of improvement for bakuchiol (- 1.06 ± 0.23) when compared to vehicle (- 0.56 ± 0.16) and control (- 0.69 ± 0.18); however, statistical significance was not reached (p > 0.05). TCA-induced PIH sites were uniform in size and pigment intensity thereby allowing better comparison among sites. This emphasizes the relevance of using this model for PIH which may help reduce the barriers in clinical trials and help improve access to treatments for patients who suffer from PIH. The results suggest that topical bakuchiol may decrease the severity of PIH.

Rationale: Many external factors can induce the melanogenesis and inflammation of the skin. Salidroside (SAL) is the main active ingredient of Rhodiola , which is a perennial grass plant of the Family Crassulaceae. This study evaluated the effect and molecular mechanism of SAL on skin inflammation and melanin production. It then explored the molecular mechanism of melanin production under ultraviolet (UV) and inflammatory stimulation. Methods: VISIA skin analysis imaging system and DermaLab instruments were used to detect the melanin reduction and skin brightness improvement rate of the volunteers. UV-treated Kunming mice were used to detect the effect of SAL on skin inflammation and melanin production. Molecular docking and Biacore were used to verify the target of SAL. Immunofluorescence, luciferase reporter assay, CO-IP, pull-down, Western blot, proximity ligation assay (PLA), and qPCR were used to investigate the molecular mechanism by which SAL regulates skin inflammation and melanin production. Results: SAL can inhibit the inflammation and melanin production of the volunteers. SAL also exerted a protective effect on the UV-treated Kunming mice. SAL can inhibit the tyrosinase (TYR) activity and TYR mRNA expression in A375 cells. SAL can also regulate the ubiquitination degradation of interferon regulatory factor 1 (IRF1) by targeting prolyl 4-hydroxylase beta polypeptide (P4HB) to mediate inflammation and melanin production. This study also revealed that IRF1 and upstream stimulatory factor 1 (USF1) can form a transcription complex to regulate TYR mRNA expression. IRF1 also mediated inflammatory reaction and TYR expression under UV- and lipopolysaccharide-induced conditions. Moreover, SAL derivative SAL-plus (1-(3,5-dihydroxyphenyl) ethyl-β-d-glucoside) showed better effect on inflammation and melanin production than SAL. Conclusion: SAL can inhibit the inflammation and melanogenesis of the skin by targeting P4HB and regulating the formation of the IRF1/USF1 transcription complex. In addition, SAL-plus may be a new melanin production and inflammatory inhibitor., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Retinol influences the process of keratinization of the epidermis, which improves stratum corneum structure and reduces transepidermal water loss. It also significantly enhances mature skin by brightening hyperpigmentation and reducing the signs of photoageing. Cosmeceuticals are intended to both provide aesthetic effects for the skin and allow dermatological treatment. The aim of the study was to assess the rejuvenating effect of retinol serum on facial skin at concentrations of 0.3 and 0.5%, as well as any improvements in skin brightening and elasticity., Materials and Methods: Thirty-seven volunteers were included in the study, after confirming tolerance. The novel formula was applied once daily to the face for a period of 12 weeks: one retinol concentration on the left side and the other on the right. The initial study with liquid crystal formula (study vehicle) was carried out for 8 weeks on 28 volunteers. Treatment efficiency was evaluated at baseline, and 56 and 84 days following treatment using the multi probe adapter and Fotomedicus imaging system. PRIMOS was used to measure skin surface roughness. The visual analogue scale method enabled the results to be determined by 3 independent specialists., Results: Skin hyperpigmentation, unevenness, and wrinkles gradually decreased over the course of treatment, both on the left and right parts of the face. Adverse events were predominantly mild or moderate skin irritation. More frequent and more intense symptoms were observed on the left side (0.5%)., Conclusion: Retinol in liquid crystal formulation is safe and provides significant clinical benefits associated with unification of skin colour, overall skin tone, skin elasticity, and moisture. Regular use of retinol typically results in brightening of the skin and reduced signs of ageing. The objective findings confirmed the effectiveness of the procedures., (© 2020 S. Karger AG, Basel.)

Introduction: Latanoprost is a prostaglandin F2α analogue, which has been used as a first-line drug for open-angle glaucoma. Common side effects of latanoprost include hyperpigmentation. While it usually occurs on irides or periocular skin, diffuse facial hyperpigmentation is rarely reported., Case Presentation: A 71-year-old woman was presented with diffuse gray-brown colored maculopatches on her face. The symptom appeared 1 week after she started to use latanoprost eye drops for glaucoma. Biopsy specimen revealed vacuolar degeneration of dermo-epidermal junction and pigment incontinence in dermis., Objective: The aim of this paper is to introduce a rare adverse effect of latanoprost and effective way of treatment., Methods: We stopped her from using latanoprost. She was also treated with 532-nm potassium titanyl phosphate laser and low-fluence 1064-nm Q-switched Nd:YAG laser, while using topical agents., Result: After 10 weeks, we observed hyperpigmentation of her face was effectively and safely treated. The patient was satisfied with the result., Conclusion: Diffuse facial pigmentation could be one of the latanoprost-induced adverse effects and the laser treatments with topical agents we used can make it improve faster., (© 2019 Wiley Periodicals, Inc.)

BACKGROUND: Visible light (VL) has multiple effects on the skin that currently available sunscreens do not protect against. Polypodium leucotomos extract (PLE) has properties that may offer protection against VL. OBJECTIVES: To determine the effectiveness of PLE in preventing VL-induced effects. METHODS: Twenty-two subjects with Fitzpatrick skin phototype IV-VI were enrolled. On day 0, subjects were irradiated with VL. Clinical Investigator’s Global Assessment (IGA) scoring and spectroscopic evaluations were performed immediately, 24 hours, and 7 days after irradiation. Subjects then received a 28-day supply of PLE (480 mg daily). Irradiation and evaluation were repeated. Three 4-mm punch biopsies were obtained for immunohistochemistry analysis: one from normal unirradiated skin and the other two twenty-four hours after irradiation, pre- and post-PLE, from sites irradiated with highest dose of VL. RESULTS: All subjects had immediate pigment darkening, persistent pigment darkening, and delayed tanning both pre- and post-PLE. For the highest VL dose (480 J/cm²) spectroscopic assessments demonstrated a statistically significant decrease in persistent pigment darkening and delayed tanning post-PLE. In addition, there was a significant decrease in cyclooxygenase-2, and a trend towards decreases in the markers for cellular damage post-PLE. While there was a trend towards lower IGA scores post-PLE, statistical significance was not reached possibly due to lack of sensitivity of the visual IGA scoring system in detecting small changes. CONCLUSIONS: Spectroscopic data and immunohistochemistry indicate an effect of PLE on visible light induced effects. As such, PLE may be used as an adjuvant to traditional means of photoprotection to protect against the effects of VL. Clinical trial registration number: NCT02904798. J Drugs Dermatol. 2019;18(12):1198-1203.

Melasma and postinflammatory hyperpigmentation (PIH) are the most common forms of dyschromia in patients with skin of color. Both are associated with a high psychological burden of disease. To exacerbate this burden, the need for treatment is chronic, and the results are often suboptimal in the eyes of the patient. Successful treatment is therefore contingent upon a correct diagnosis, patient education, and a carefully considered therapeutic approach. The latter is often multimodal in its design, incorporating sun protection, topical and systemic medications, and in some cases, procedural intervention. Although topical hydroquinone is a mainstay of treatment for melasma and PIH, there are alternatives that have emerged as of late that have shown varying degrees of promise, both in terms of safety and efficacy. In this article, we review the epidemiological, clinical, and histologic features of melasma and postinflammatory hyperpigmentation, and discuss important considerations for both established and emerging treatments for these vexingly common and difficult to treat conditions.

Background: Hyperpigmentation following ultraviolet irradiation has cosmetic concerns. Botulinum toxin type A can favorably affect skin pigmentation. However, the mechanism of skin pigmentation is unclear., Methods: In vitro, human epidermal melanocytes were co-cultured with human keratinocytes. After cells were treated with botulinum toxin type A, cell morphology, proliferation, and dendricity were analyzed, and immunofluorescence, tyrosinase activity, and melanin contents were determined. To evaluate the effect of botulinum toxin type A on ultraviolet B-irradiated mouse skin, ultraviolet B alone was applied to one side of the back of each mouse as a control, whereas ultraviolet B plus injection of botulinum toxin type A was applied to the contralateral side. Skin pigmentation, histology, and the number of dihydroxyphenylalanine-positive melanocytes were evaluated. The L* colorimeter value was measured. Enzyme-linked immunosorbent assay determinations of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 were performed., Results: Immunohistochemical staining revealed botulinum toxin type A in the cytoplasm of melanocytes and in the positive control. In vitro, melanocyte dendricity and melanin contents were decreased slightly but significantly (p < 0.05) after botulinum toxin type A treatment. In vivo, botulinum toxin type A suppressed skin pigmentation. The number of dihydroxyphenylalanine-positive melanocytes was also significantly lower than in the control side. Tyrosinase activity and melanin content were also significantly reduced (p < 0.05). Botulinum toxin type A also significantly reduced the amounts of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 (all p < 0.05)., Conclusion: Botulinum toxin type A can suppress epidermal melanogenesis through both direct and indirect mechanisms.

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.

Background: Hyperpigmentation is a common dermatologic problem that may have substantial impact on the patient, since it affects the appearance and quality of life, and may influence treatment adherence. There are few studies of drug-induced hyperpigmentation., Methods: We studied drug-induced hyperpigmentation in patients attending an outpatient dermatology clinic in the Western Area of Valladolid (Spain) from August 1, 2017 to April 20, 2018., Results: The incidence of drug-induced hyperpigmentation was 1.31% in patients attending a first dermatology consultation in the study period. Of the 16 patients, 8 were taking more than 1 drug. The most frequent drugs identified were nonsteroidal anti-inflammatory agents (25%), antihypertensive agents (18.75%), antimalarials (12.5%), antibiotics, antineoplastic agents, psychoactive agents, simvastatin, allopurinol, amiodarone and mucolytic (6.25% each). Hyperpigmentation was found in the mucosa in 25% of patients and in photograph-exposed areas in 37.5%., Discussion: Diagnosing drug-induced hyperpigmentation is a dermatologic challenge. A differential diagnosis with hyperpigmentation caused by endocrine and metabolic disorders, the most closely-related disorders to drug-induced hyperpigmentation, and with hyperpigmentation of idiopathic origin, should be conducted. Drug-induced hyperpigmentation is a relatively frequent reason for consultation, especially in polypharmacy patients. The sample may have been biased as many patients receiving treatments frequently associated with drug-induced hyperpigmentation, such as antineoplastic drugs, are diagnosed and treated by other specialties, such as oncologists., Conclusion: Family physicians and specialists should consider drugs as a cause of hyperpigmentation to facilitate the correct diagnosis and treatment., Competing Interests: Conflict of interest: none declared., (© Copyright 2019 by the American Board of Family Medicine.)

Human skin pigmentation is a result of constitutive and facultative pigmentation. Facultative pigmentation is frequently stimulated by UV radiation, pharmacologic drugs, and hormones whereby leads to the development of abnormal skin hyperpigmentation. To date, many state-of-art depigmenting compounds have been studied using in vitro model to treat hyperpigmentation problems for cosmetic dermatological applications; little attention has been made to compare the effectiveness of these depigmenting compounds and their mode of actions. In this present article, new and recent depigmenting compounds, their melanogenic pathway targets, and modes of action are reviewed. This article compares the effectiveness of these new depigmenting compounds to modulate several melanogenesis-regulatory enzymes and proteins such as tyrosinase (TYR), TYR-related protein-1 (TRP1), TYR-related protein-2 (TRP2), microphthalmia-associated transcription factor (MITF), extracellular signal-regulated kinase (ERK) and N-terminal kinases (JNK) and mitogen-activated protein kinase p38 (p38 MAPK). Other evidences from in vitro assays such as inhibition on melanosomal transfer, proteasomes, nitric oxide, and inflammation-induced melanogenesis are also highlighted. This article also reviews analytical techniques in different assays performed using in vitro model as well as their advantages and limitations. This article also provides an insight on recent finding and re-examination of some protocols as well as their effectiveness and reliability in the evaluation of depigmenting compounds. Evidence and support from related patents are also incorporated in this present article to give an overview on current patented technology, latest trends, and intellectual values of some depigmenting compounds and protocols, which are rarely highlighted in the literatures., (© 2019 Wiley Periodicals, Inc.)

Ashy dermatosis is a rare cutaneous disorder of unknown etiology. We describe a case of adult ashy dermatosis developing in a patient with squamous cell carcinoma of the lung, which was resolved by the administration of pembrolizumab in parallel with multiple vitiligo. Interestingly, immunohistochemical staining revealed that lesional skin of the ashy dermatosis contained cytotoxic T cells and programmed death ligand 1 expressing cells. To our knowledge, this is the first case of adult ashy dermatosis resolved by pembrolizumab., (© 2019 Japanese Dermatological Association.)

Drug-induced pigmentation accounts for up to 20% of all cases of acquired pigmentation. A thorough review of medical history and previous and ongoing medications as well as a complete skin examination can guide diagnosis. Implicated agents include alkylating/cytotoxic agents, analgesics, antiarrhythmics, anticoagulants, antiepileptics, antimalarials, antimicrobials, antiretrovirals, metals, prostaglandin analogs, and psychotropic agents, among others. Confirming true drug associations can be challenging, especially in the setting of delayed onset of pigmentation and coexisting polypharmacy.

Skin color disorders can be caused by various factors, such as excessive exposure to sunlight, aging and hormonal imbalance during pregnancy, or taking some medications. Kojic acid (KA) is a natural metabolite produced by fungi that has the ability to inhibit tyrosinase activity in synthesis of melanin. The major applications of KA and its derivatives in medicine are based on their biocompatibility, antimicrobial and antiviral, antitumor, antidiabetic, anticancer, anti-speck, anti-parasitic, and pesticidal and insecticidal properties. In addition, KA and its derivatives are used as anti-oxidant, anti-proliferative, anti-inflammatory, radio protective and skin-lightening agent in skin creams, lotions, soaps, and dental care products. KA has the ability to act as a UV protector, suppressor of hyperpigmentation in human and restrainer of melanin formation, due to its tyrosinase inhibitory activity. Also, KA could be developed as a chemo sensitizer to enhance efficacy of commercial antifungal drugs or fungicides. In general, KA and its derivatives have wide applications in cosmetics and pharmaceutical industries., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cutaneous pigmentation plays critical role in determining the color of skin along with photo protection of skin from dreadful effects of ultraviolet radiations. Conversely, abnormal accumulation of melanin is responsible for hyper pigmentary disorders such as melasma, senile lentigines and freckles. Because of the visible nature of dermatologic diseases, they have a considerable psychosomatic effect on affected patients. Tyrosinase inhibitors are molecules that interrelate in some way with the enzyme to prevent it from working in the normal manner. Past many decades witnessed the quest for the development of natural tyrosinase inhibitors due to imperative role played by tyrosinase in the process of melanogenesis and fungi or fruit enzymatic browning. Mechanism of pigmentation is characterized by the intact process of the synthesis of specialized black pigment within melanosomes. Melanin is synthesized by a cascade of enzymatic and chemical reactions. For this reason, melanin production is mainly controlled by the expression and activation of tyrosinase. In the current article, we discussed tyrosinase inhibitors from the natural sources, which can be an essential constituent of cosmetics products and depigmenting agents for the treatment of hyperpigmentory disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Skin hyperpigmentation is the darkening of skin due to the increased production of melanin in the body., Objectives: To evaluate the efficacy and safety of a botanical-based Rosa E pigmentation serum in healthy fair skin female volunteers with wrinkles, skin tone, and pigmentation., Methods: This was a single-arm, open label study conducted in healthy Indian females; 18 subjects aged 30-55, having fair Caucasian-like skin with at least 2 dark skin pigments with facial wrinkles diagnosed by dermatologist were selected. Rosa E pigmentation serum was applied twice a day for 84 days. Effect was evaluated by (i) instrumental technique (spectrophotometer ® 2600D), (ii) clinically by dermatologist regarding product efficacy (skin tone, antiwrinkle, pigmentation), and (iii) volunteers self-evaluation., Results: The L* value of spectrophotometer reading represents lightness in the skin pigment. Reduction in the pigment was reported from day 14, with significant reductions observed till day 84 compared with baseline. Significant (P < .0001) skin pigmentation lightening was seen on day 14 (1.11) vastly improving on day 84 (1.94) based on photographic assessments. The significant reduction in skin pigment was 76.85%, Felix von Luschan skin color score was 30.24% (P < .0001) with a 7.38-fold reduction in skin tone and 57% reduction in facial wrinkles at day 84 from baseline., Conclusions: Rosa E pigmentation serum was found safe and effective in significant reduction in skin pigments, improvement of skin tone, and antiwrinkle properties instrumentally, clinically, and self-evaluation by volunteers. In these evaluations, best results were seen the longer the Rosa E was used., (© 2017 Wiley Periodicals, Inc.)

Introduction: Cutaneous hyperchromias are disorders of skin pigmentation involving increased melanin production and its irregular accumulation in skin cells. The use of sunscreens is fundamental for the control of hyperchromias by reducing the stimulation of pigmentation, as melanin synthesis is mainly stimulated by solar radiation. Many studies have demonstrated that visible light can induce significant skin damage. Considering the effects of visible light, effective photoprotection should not be limited only to UV protection but should also involve visible and infrared protection., Objective: The aim of this study was to evaluate the efficacy of UV-VIS sunscreens in protecting skin against damages caused by solar radiation and the influence of visible light on the appearance of cutaneous hyperchromias., Methods: Forty volunteers aged 18 to 39 years with skin hyperpigmentation participated in the study. To evaluate the efficacy of the formulations developed, the percentage of hyperpigmented area was evaluated using high-resolution images-Visioface ® Quick (Courage-Khazaka, Germany) and the analysis of epidermal pigmentation was performed by RCM-Vivascope ® 1500 (Lucid, USA). Also, the melanin index was determined using the Mexameter ® M X16 colorimeter (Courage-Khazaka, Germany)., Results: The developed formulations were effective in the reduction in melanin index, epidermal pigmentation, and percentage of hyperpigmented area., Conclusion: Finally, this study discusses how the combination of UV filters and pigments can protect the skin from solar radiation and reduces skin hyperpigmentations., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We have previously found that mycelia culture broth of eight kinds of traditional herbal extracts fermented with Phellinus linteus (previously named as 8-HsPLCB) not only inhibited melanin and tyrosinase activity, but also reduced the contents of melanogenesis-related proteins, including tyrosinase and microphthalmia-associated transcription factor, in 3-isobutyl-1-methylxanthine-stimulated B16F0 melanoma cells. For a further study, the effect of 8-HsPLCB against skin pigmentation in brown guinea pigs with ultraviolet B (UVB)-induced hyperpigmentation was investigated. 8-HsPLCB (3%) and arbutin (2%) as positive controls were applied topically twice daily for 4 weeks to the hyperpigmented areas. 8-HsPLCB showed skin-lightening effect as effective as arbutin, one of the most widely used in whitening cosmetics. Melanin index values as the degree of pigmentation showed a significant reduction week by week post 8-HsPLCB treatment and then substantially reduced by 4 weeks. The degree of depigmentation after 4 weeks of topical application with 8-HsPLCB was 32.2% as compared with before treatment (0 week). Moreover, using Fontana-Masson staining and hematoxylin-eosin staining, 8-HsPLCB reduced melanin pigmentation in the basal layer of the epidermis and epidermal thickness changes exposed to the UV-B irradiation as compared with non-treatment and vehicle treatment. The intensity of the skin-lightening effect of 8-HsPLCB was similar to arbutin. These results suggest that the skin-lightening effect of 8-HsPLCB might be resulted from inhibition of melanin synthesis by tyrosinase in melanocytes. To conclude, 8-HsPLCB treatment showed reduction of the melanin pigment and histological changes induced by UV irradiation in brown guinea pigs.

Dyschromia is one of the primary complaints for patients with skin of color. Treatments need to achieve a balance between tolerability and efficacy to address existing hyperpigmentation without causing additional damage that could trigger post-inflammatory hyperpigmentation (PIH). An open-label, single-center study was conducted to assess the efficacy of a novel comprehensive pigmentation control serum (LYT2) combined with a series of three very superficial chemical peels (VP) in skin of color subjects. Seventeen female and male subjects aged 36 to 69 years with Fitzpatrick Skin Types III-VI and moderate to severe facial hyperpigmentation were enrolled in the 12-week clinical study. Subjects identified as Asian, Hispanic, African American, or Caucasian ethnicities. Subjects received a series of 3 VP treatments every 4 weeks. LYT2 was applied twice-daily in between VP treatments. Investigator assessments for overall hyperpigmentation, overall photodamage, and skin tone unevenness, as well as standardized digital photography and subject self-assessment questionnaires were conducted at all visits (baseline and weeks 4, 8, and 12). In vivo reflectance confocal microscopy (RCM) of a target lesion was conducted (in a subset of subjects) at baseline and week 12. Fourteen subjects completed the study. The treatment regimen provided statistically significant improvements in all efficacy parameters at weeks 8 and 12 (all P less than equal to 0.03, student's t-test). Standardized digital photography and RCM images support the improvements in overall hyperpigmentation observed by the investigator. At the end of treatment, the regimen was highly rated by subjects with 100% of subjects (strongly agree/agree) that the combination "decreased the appearance of uneven skin tone and discolorations" and "reduced the appearance of sun damage." In addition to this clinical study, independent case studies with this combination treatment regimen at a separate study site were also conducted with results that corroborate the formal clinical study findings. The comprehensive results from these studies suggest that the combination of a comprehensive pigmentation control serum with a series of 3 very superficial chemical peels may provide an effective treatment approach for hyperpigmentation in skin of color patients.

J Drugs Dermatol. 2017;16(4):301-306.

Purpose: To present a case of minocycline-induced blue scleral pigmentation and discuss the pathophysiology and differential diagnoses. The uses, mechanisms, and other adverse effects of minocycline will also be highlighted., Case Report: An elderly Caucasian male patient presented for routine ocular examination complaining of blue discoloration to the whites of his eyes. He was found to have bilateral blue scleral pigmentation and blue discoloration to various other dermal areas of his body. The blue pigmentation was also visible in the posterior segment within a scleral crescent around his right optic nerve. This pigmentation was determined to be caused by long-term use of oral minocycline., Conclusions: Long-term minocycline use may induce scleral, dermal, and organ hyperpigmentation, typically blue or black in coloration. The pigmentation may reverse with discontinuation of the medication, but can also be permanent. The exact mechanism of pigment deposition remains uncertain, but several theories have been proposed. While the cosmetic appearance may be dramatic, this side effect is not known to cause any systemic or ocular morbidity.

In European folk medicine, the fruits of Juniperus communis are used in the treatment of skin-related disorders such as skin infection, itching, and psoriasis. Previously, we reported that the EtOAc fraction of J. communis (EAJC) contained tyrosinase inhibition properties in vitro non-cellular experiment. The aim of this study was to evaluate anti-melanogenic effect of standardized EAJC on a hyperpigmentation animal model. Therapeutic effects of EAJC toward skin hyperpigmentation were confirmed by both in vivo experiment and in vitro cell-based assay. Skin depigmenting effect was detected by topical treatment of EAJC for 11 d to HRM-2 melanin-possessing hairless mice. Histologic findings including significantly decreased melanin depositions could be observed in dorsal skin samples of EAJC-treated group. In addition, the EAJC (50 µg/mL) attenuated melanin production through down-regulation of tyrosinase activity and protein expression in B16 murine melanoma cells. According to the phytochemical analysis, EAJC was found to contain hypolaetin-7-O-β-D-xylopyranoside and isoscutellarein-7-O-β-D-xylopyranoside as main components. Hypolaetin-7-O-β-D-xylopyranoside was responsible for the skin-lightening effect of EAJC by reducing the number of melanocytes in dorsal skins of HRM-2 mice. The present study provided direct experimental evidence for skin-lightening effect of EAJC in UV-irradiated hairless mouse model. Therapeutic attempts with the J. communis might be useful in the management of skin pigmentation-related diseases.

Post-inflammatory hyperpigmentation (PIH) is a hyperpigmentation of the skin occurring after and sometimes during an inflammatory process. Although more frequent in dark skinned individuals, PIH can be observed in any type of skin and at all ages. In most case a strong impact on the quality of life of affected individuals is observed. The pathophysiology of PIH remains largely unknown. The activation of the melanocytes occurs in the first week following the inflammation emphasizing the crucial role of early preventive measures. Photoprotection with balanced UVA and UVB protection is required. Visible light could also play a role in PIH but this remains to be demonstrated. Healing topics with anti-inflammatory properties are of interest after a skin procedure. When the risk of PIH is high or when PIH occurs, topical steroids remains the gold standard approach., (© 2016 Elsevier Masson SAS. Tous droits réservés.)

Glutathione is a low molecular weight thiol-tripeptide that plays a prominent role in maintaining intracellular redox balance. In addition to its remarkable antioxidant properties, the discovery of its antimelanogenic properties has led to its promotion as a skin-lightening agent. It is widely used for this indication in some ethnic populations. However, there is a dichotomy between evidence to support its efficacy and safety. The hype around its depigmentary properties may be a marketing gimmick of pharma-cosmeceutical companies. This review focuses on the various aspects of glutathione: its metabolism, mechanism of action and the scientific evidence to evaluate its efficacy as a systemic skin-lightening agent. Glutathione is present intracellularly in its reduced form and plays an important role in various physiological functions. Its skin-lightening effects result from direct as well as indirect inhibition of the tyrosinase enzyme and switching from eumelanin to phaeomelanin production. It is available in oral, parenteral and topical forms. Although the use of intravenous glutathione injections is popular, there is no evidence to prove its efficacy. In fact, the adverse effects caused by intravenous glutathione have led the Food and Drug Administration of Philippines to issue a public warning condemning its use for off-label indications such as skin lightening. Currently, there are three randomized controlled trials that support the skin-lightening effect and good safety profile of topical and oral glutathione. However, key questions such as the duration of treatment, longevity of skin-lightening effect and maintenance protocols remain unanswered. More randomized, double-blind, placebo-controlled trials with larger sample size, long-term follow-up and well-defined efficacy outcomes are warranted to establish the relevance of this molecule in disorders of hyperpigmentation and skin lightening.

Objectives: Pharmacological studies of Aster spathulifolius Maxim(AS) have demonstrated its anti-allergy, anti-viral and anti-obesity effects, however, its anti-melanogenic effects is still unclear. In this study, the effects of AS extract (ASE) on the inhibition of melanin synthesis were investigated in vitro and in vivo., Methods: To perform this study, the contents of melanin and tyrosinase activity were analysed in B16F10 melanoma cells. Western blotting was carried out to determine the underlyling mechanism. Additionally, we investigated the effect of this extract on hyperpigmentation in C57bL/6J mice induced by 3, 6 and 9 weeks of UVB irradiation., Key Findings: AS extract led to reduced melanin synthesis through the regulation of MITF and its downstream signals. Furthermore, ASE increased the phosphorylation of MAPK/ERK and Akt/GSK3β signalling pathway components. In vivo study, hypopigmentation effects were also observed. The melanocyte activity and the distribution of melanin granules were decreased in UVB-irradiated mice treated with ASE., Conclusions: These results suggest that the ASE may be promising as an active anti-melanogenic component, and further investigations should be performed regarding its potential as a whitening agent in the field of cosmetics., (© 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.)

Postinflammatory hyperpigmentation (PIH) has posed a substantial challenge for patients with higher Fitzpatrick skin types, specifically types III to VI. Treatment modalities pose a number of limitations due to the number of treatments required, potential side effects, and overall efficacy. Fortunately, multiple therapies have been delineated that can be moderately to highly efficacious in treating PIH in patients with skin of color. This article will review some of these modalities and procedures for this common patient concern.

Postinflammatory hyperpigmentation (PIH) is the most common adverse effect of laser treatment in dark-skinned individuals. Little is known whether PIH can be prevented or minimised. The objective of this study was to investigate the effect of short-term application of topical corticosteroids on the incidence of PIH after ablative fractional resurfacing in Asians. Forty subjects with skin phototype IV and atrophic acne scars were treated with a fractional CO2 laser on both sides of the face. Post-operatively, clobetasol propionate 0.05% ointment was applied to one randomly selected side of the face for the first 2 days, followed by an application of petrolatum jelly for the rest of the week (petrolatum was applied to the other side for 7 days). Assessments on the clinical outcome, the wound healing process and the occurrence of PIH were obtained once weekly for the first month and at 2 and 3 months post-treatment. The side of the face treated with petrolatum alone had significantly (p < 0.001) higher incidence of PIH (75%) after laser irradiation than the side of the face treated with topical corticosteroids and petrolatum (40%). The PIH occurring on the petrolatum-treated sides had significantly higher intensity (p < 0.001) and was spread over a significantly larger area (p < 0.001), compared with the corticosteroid- and petrolatum-treated sides. In conclusion, a short-term application of topical corticosteroids postoperatively is associated with a decreased risk of PIH after ablative fractional resurfacing.

Purpose: To report periocular skin hyperpigmentation related to prostaglandin analogue (PGA) use in children with glaucoma., Methods: This cross-sectional study examined children treated with PGA for at least 6 months between June 2013 and December 2013. The pigmentation scores of the upper eyelids, lower eyelids and cheek were recorded with a chromameter. Hyperpigmentation was defined as a positive difference in scores between the cheek and the upper/lower eyelid. The influence of age, baseline skin pigmentation, duration of PGA, type of PGA and mono- or multitherapy on hyperpigmentation were evaluated. Subjective grading of pigmentation on standardized face photographs and the parent's perception of hyperpigmentation were also recorded. A P value of <0.05 was considered significant., Result: A total of 55 patients were included. Hyperpigmentation of the upper and lower eyelids occurred in all eyes. Subjectively, 26 (47%) eyes had mild and 14 (26%) moderate hyperpigmentation. The upper eyelid showed significantly greater hyperpigmentation than the lower eyelid (P = 0.00004). Chromameter measurements overlapped with pigmentation grading on photographs. The type of and duration of PGA use, PGA mono- or multidrug therapy or baseline skin pigmentation had no effect on the grade of hyperpigmentation., Conclusions: PGA use for more than 6 months was associated with periocular skin hyperpigmentation that was greater in the upper eyelid versus lower eyelid. All variables examined failed to show a relationship with the grade of hyperpigmentation., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Adverse cutaneous reactions are frequently reported to occur with the use of psychotropic medications, which may lead to poor drug compliance. As compared to other groups of psychotropic medication, antipsychotics, both typical and atypical, are less likely to cause adverse cutaneous reactions. The most frequent cutaneous adverse reactions associated with antipsychotics include fixed drug eruptions, exanthematous eruptions, photosensitivity reactions and altered skin pigmentation. Most of these commonly seen cutaneous adverse reactions are benign and easily treatable. Rarely, severe cutaneous adverse reactions such as erythema multiforme, Steven-Johnson syndrome are toxic epidermal necrolysis and have also been associated with antipsychotics. Olanzapine is one of the most commonly prescribed atypical antipsychotic with metabolic complications as most common adverse effects. Dermatological reactions are rarely observed with olanzapine. We report occurrence of pellagroid skin lesions over exposed areas of upper limbs with olanzapine that resolved completely after its discontinuation.

Background: Lignin peroxidase is a cosmetic skin-lightening alternative that breaks down plant cell walls and melanin., Objective: This research examined the topical efficacy of lignin peroxidase in pigment lightening., Methods: Sixty women aged 18 to 65 years with mild to moderate facial dyspigmentation were enrolled for 12 weeks in 2 cohorts. Cohort 1 applied lignin peroxidase to 1 randomized side of the face and nothing to the opposite side. Cohort 2 applied lignin peroxidase to 1 facial side and generic hydroquinone to the other. Investigator, subject, and dermospectrophotometer measurements were obtained., Results: In cohort 1, improved skin texture (P < .001), roughness (P < .001), and overall appearance (P = .002) was noted at week 2 with lignin peroxidase versus no treatment. By week 12, there was a decrease in spot size with lignin peroxidase versus no treatment (P = .014). This was confirmed by a statistically significant reduction in melanin scores with the dermospectrophotometer on lignin peroxidase-treated side at weeks 4, 8, and 12 (P = .003) and a similar reduction in Melasma Area Severity Index score. Cohort 2 demonstrated parity between lignin peroxidase and hydroquinone, but lignin peroxidase was statistically superior in skin texture and roughness., Limitations: The sample size was limited., Conclusions: Lignin peroxidase might be an over-the-counter skin-lightening preparation with efficacy parity to hydroquinone., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Hyperpigmentation disorders are of social and cosmetic concerns to many individuals due to their prevalent locations on highly visible parts of the body. Topical formulation containing hydroquinone is the most widely used remedy for the treatment of hyperpigmentation disorders. However, reports of side effects in long-term usage have raised concerns for its use in cosmetic products. Thus, it is highly desirable to develop a safe and effective alternative to treat hyperpigmentation disorders. The objective of the current study is to investigate the de-pigmenting efficacy of 4-hexyl-1,3-phenylenediol in various in vitro models and in a randomized controlled clinical study. We showed that 4-hexyl-1,3-phenylenediol significantly reduced melanogenesis in primary human melanocytes, murine melanoma cells, and pigmented human epidermal equivalents. It was determined that the reduction in melanogenesis is mediated through inhibition of tyrosinase enzyme activity and protein expression. Further investigation revealed that the inhibition of melanogenesis is reversible and is not associated with cellular toxicity in melanocytes. In addition, significant improvements in key clinical parameters such as overall skin lightening, appearance of spots on the cheeks, overall contrast between spots and surrounding skin, and overall pigmentation size were detected in a double-blinded, randomized controlled clinical study. In conclusion, our findings clearly demonstrated the potency of 4-hexyl-1,3-phenylenediol in modulating skin pigmentation, and it is safe and well tolerated after 12-week topical application.