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Background: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines., Methods: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale., Results: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51-71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands ( p < .01). No adverse events were noted., Conclusion: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery, Inc.)

Background: During aging, human skin is facing hyperpigmentation disorders: senile lentigo (chronobiologic aging) leads to loss of melanogenesis' control while solar lentigo (UV exposure) promotes an increase of oxidized proteins, melanogenesis, and lipofuscin., Aims: Stromal-cell-derived-factor-1 (SDF-1) was identified as key regulator of hyperpigmentation and its expression is reduced in senescent fibroblasts, highlighting this protein as new target for skin hyperpigmentation., Materials: We developed two skin explant models mimicking of senile and solar lentigo, based on H 2 O 2 systemic treatment and UV irradiation, respectively. We evaluated Himanthalia elongata extract (HEX) on these models after 5 days of treatment and analyzed SDF-1 expression and skin pigmentation. For solar lentigo, we also analyzed oxidized proteins and lipofuscin accumulation. Finally, we evaluated HEX in vivo on nearly 100 multi ethnicities' volunteers., Results: SDF-1 expression decreased in senile lentigo model, associated with hyperpigmentation. HEX application restored SDF-1 expression, leading to skin pigmentation decrease. For solar lentigo, we showed an impact of UVs on SDF-1 expression linked to hyperpigmentation, while the application of HEX restored SDF-1 expression and reduced skin pigmentation. On same model, HEX reduced oxidized proteins quantity and lipofuscin which increased after UV exposure. Clinically, HEX reduced dark spot pigmentation on Caucasian volunteers' hands and on Asian and African volunteers' face after 28 days., Discussion: We have developed ex vivo models mimetic of senile and solar lentigo and showed for a very first time that SDF-1 can be also a key regulator for UV-induced hyperpigmentation., Conclusion: Our ex vivo and clinical studies highlighted the power of HEX with strong reduction of dark spots regardless of volunteers' ethnicities., (© 2022 Givaudan France. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Purpose of Review: Acquired postinflammatory lentiginosis is a phenomenon that has been previously termed 'induction of lentiginosis in assorted dermatoses' or the ILIAD phenomenon., Recent Findings: Although some cases have been described as arising exclusively in those who applied topical calcineurin inhibitors (TCIs), other patients have presented with similar findings in other nonatopic disorders (contact dermatitis, psoriasis, lichen planus, focal dermal hypoplasia), and without antecedent use of TCIs., Summary: Inflammatory skin disorders can produce localized areas of cutaneous lentiginosis, particularly as the inflammation retreats in response to treatment. This post-inflammatory lentiginosis or ILIAD phenomenon may be potentiated by use of topical and systemic anti-inflammatory medications, including TCIs, topical corticosteroids, methotrexate, and systemic biologic agents. Although this phenomenon has not been associated with melanocytic neoplasia, ongoing periodic monitoring for dysplastic changes is reasonable., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Photoaging is premature skin aging resulting from oxidative stress generated by exposure to solar radiation. A key clinical feature is solar lentigines, areas of hyperpigmentation on sun-exposed skin. Skin pigmentation is determined by cross-talk between keratinocytes and melanocytes, which is exquisitely sensitive to oxidative stress. Toll-like receptor (TLR) signaling and NF-E2-related factor 2 (NRF2) signaling, an endogenous antioxidant system, serve as a bridge between the oxidative stress response and immune regulation. Moreover, TLR-mediated induction of IL-6 production has been shown to prevent ultraviolet (UV)-induced hyperpigmentation., Methods: Shave biopsies of solar lentigines were obtained from 14 individuals. An additional 7 subjects applied broccoli sprout extract (BSE) containing sulforaphane daily or vehicle on photodamaged skin. Immunofluorescence staining was used to determine total and phosphorylated NRF2 in the lentiginous skin. Dermoscopy and Fontana & Masson staining were used to assess the effect of topical BSE on UV-induced pigmentation. Similar topical treatments were performed in a mouse model of UVB-induced hyperpigmentation utilizing WT, Nrf2-/-, or K14-Cre-ERT2IL-6Rαfl/fl C57BL/6 mice., Results: NRF2 expression is altered in solar lentigines, and UV-induced skin pigmentation in humans could be ameliorated with topical BSE. Corresponding mouse models replicated the authors' clinical findings and identified a potential mechanistic link to IL-6Rα signaling in keratinocytes., Conclusion: The authors' findings suggest that dysregulation of NRF2 signaling is involved in the pathogenesis of UV-induced skin pigmentation and pharmacological activation of NRF2 may represent a potential therapeutic target in photoaging., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background and Objective : Little is known about the anti-pigmentation effects of whitening agents on solar lentigines. Epidermal growth factor (EGF) has been used as a booster for wound healing in the skin, and it has been suggested to have anti-pigmentation effects. This study aimed to evaluate the effect and safety of EGF-containing ointment for treating solar lentigines with a Q-switched (QS) 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (Bluecore company, Seoul, Republic of Korea). Materials and Methods : Subjects who underwent QS 532 nm Nd:YAG laser treatment of solar lentigines were randomly assigned to treatment with an EGF ointment or petrolatum. After the laser procedure, the subjects were administered the test ointment twice a day for 4 weeks. The physician's assessment of the degree of pigment clearance and patient's satisfaction were assessed after 4 and 8 weeks. Additionally, the melanin index (MI), erythema index (EI), transepidermal water loss (TEWL), and post-inflammatory hyperpigmentation (PIH) were evaluated. This trial was registered with ClinicalTrials.gov (NCT04704245). Results : The blinded physician's assessment using 5-grade percentage improvement scale and patient's satisfaction were significantly higher in the study group than in the control group at the 4th and 8th weeks. The MI was significantly higher in the control group than in the study group at the 4th and 8th weeks. The EI and TEWL did not differ significantly between the two groups at either time point. The incidence of PIH was higher in the control group (37.5%) than in the EGF group (7.14%) at the 8th week. Conclusions : The application of EGF-containing ointment on facial solar lentigines with a QS 532 nm Nd:YAG laser showed efficient and safe therapeutic effects, with less PIH. Thus, EGF-containing ointment could be suggested as the promising adjuvant treatment strategy with a QS laser for solar lentigines.

Solar lentigo, benign lesions which mostly appear on chronically, sun-exposed surfaces, are associated with ageing. Patients are increasingly requesting a more uniform skin texture, especially for hands. Treatment options include dermoabrasion, intense pulsed light, cryotherapy, peelings, and laser therapy. Topical compounds can be employed, in alternative or associated with dermatologic procedures. The current study was designed to evaluate solar lentigo hyperpigmentation, skin architecture and clinician and patient assessments comparing a dermocosmetic lightening product (active) with a moisturizing product (control) according to clinical, digital and subjective analyses in 72 lesions over 12-month follow up period. Statistically significant differences were observed between the lesions treated with the active compared to the control in terms of papillary brightness (p = 0.03) and contrast (p = 0.03), and in the limitation of dermal-epidermal junction destructuring (p = 0.03) according to dermal-epidermal junction destructuring score at Reflectance Confocal Microscopy. Luminance (p = 0.04) and redness (p = 0.03) were improved at color analysis, and physician and patient evaluations favored the active in efficacy and patient satisfaction investigations. The dermocosmetic lightening product utilized in the current study proved to be more effective, according to clinical, digital and subjective analyses in reducing lesion hyperpigmentation, stabilizing the lesion skin architecture and increasing patient satisfaction compared to the control in a cohort of 36 subjects, over a 12-month period. Beside demonstrating the efficacy of this topical lightening product, we propose a "destructuring score", which improves the robustness of solar lentigo's evaluation, and can be used in future studies to standardize the quantitative comparisons of different treatment options., Competing Interests: Author Ana Beatris Rossi was a full time employee of Pierre Fabre Dermocosmetics when the study was designed, conducted and analyzed. Authors Gwendal Josse, Jimmy Le Digabel, Emmanuel Questel are full time employee of Pierre Fabre dermocosmetics. Pierre Fabre Dermocosmetics provided funding for the study. Authors Gwendal Josse, Ana Beatris Rossi, Jimmy Le Digabel, Emmanuel Questel received support in the form of salary from this funder. Pierre Fabre Dermocosmetics had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We confirm that the declared competing interests does not alter our adherence to PLOS ONE policies on sharing data and materials.

Little is known about the anti-pigmenting effects of whitening agents on solar lentigos (SLs), which comprise ~ 60% of hyperpigmented facial lesions of Asian subjects. Lotions with or without 6% L-ascorbate-2-phosphate trisodium salt (APS) [test lotion (TL) and placebo lotion (PL), respectively] were applied twice daily for 24 weeks in a double-blind half-face study of 27 Japanese females with SLs on both sides of their faces. Pigmentation scores were evaluated using a photo-scale and the skin colors were assessed using a color difference meter and a mexameter for SLs and the non-lesional surrounding skin (NLS). Although the pigmentation scores were not significantly different between the TL and PL-treated SLs after 24 weeks, the L values of TL-treated SLs and NLS increased significantly with a significantly higher △L value in SLs than in NLS. In contrast, the L values of PL-treated SLs and NLS remained unchanged after the treatment. The number of subjects with > 2.0 △L was 7 of 27 (TL) and 0 of 27 (PL) in SLs and 3 of 27 (TL) and 0 of 27 (PS) in NLS. In contrast, the melanin index in TL-treated SLs and NLS significantly decreased with a significantly higher △melanin index in SLs than in NLS. Similarly, the melanin index of PL-treated SLs and NLS were significantly decreased with a significantly higher △melanin index in SLs than in NLS. These findings strongly indicate that APS has a weak but significant anti-pigmenting effect on SLs and a significant whitening effect even on normally pigmented healthy skin.

Background/purpose: The aim of this study was to measure lentigines' pigmentation over a long period of time and evaluate if summer over-pigmentation can be avoided by the use a SPF30 day skin cream., Methods: Seventeen healthy female volunteers aged 50 and over and presenting lentigines participated in the study from spring to summer. Throughout the study, all subjects applied a SPF30 daily skin cream to only one hand. Color measurements of the target lesions were performed with a chromameter and with a color-calibrated camera. Target lesions were also imaged with in vivo reflectance confocal microscopy (RCM). A specific procedure for re-registering the images was developed to ensure that the same papillae were measured over time., Results: Both color measurement methods, chromametry and color-calibrated camera, showed that lentigines treated over time with the SPF30 day skin cream were significantly lighter than the non-treated lentigines. The RCM images showed a decrease in the papillary contrast for the treated lentigines., Conclusion: This study shows that this over-pigmentation can be avoided using a SPF30 day skin cream. Moreover, we have demonstrated that very fine re-registration of the RCM images is possible and ensures a more robust analysis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c-kit (most commonly), platelet-derived growth factor receptor A, neurofibromatosis-1, and succinate dehydrogenase genes., Materials and Methods: We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and café-au-lait macules were present along with multifocal GIST. Immuhistochemical analysis of CD34 and CD117 was performed on GIST biopsy samples from both siblings, while c-kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin-embedded gastric biopsy specimens of affected siblings., Results: Histopathology revealed positive expression of CD117 and CD34. Mutational analysis showed the germline c.1676T>C mutation in c-kit exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T>A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them., Conclusions: A c-kit mutational test in familial GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment., (© 2017 The International Society of Dermatology.)

Aims: Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people>50years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all-trans retinoic acid (ATRA) is an attractive option for self-treatment at home. We have developed an ATRA-loaded microneedle patch (ATRA-MN) and confirmed the pharmacological effects of ATRA-MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA-MN in subjects with seborrheic keratosis or senile lentigo., Main Methods: ATRA-MN was applied to the lesion site of each subject for 6h once per week for 4weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA-MN, the desquamation and whitening ability of the investigational skin was observed., Key Findings: Desquamation of the stratum corneum was observed following four ATRA-MN applications at 1-week intervals, but ATRA-MN applications did not induce severe local or systemic adverse effects., Significance: These results showed that ATRA-MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Solar lentigo (SL) is a representative photoaging skin disorder. Alteration of the main epidermal constituent cells-keratinocytes and melanocytes-in relation to the photoaged dermal environment or chemokine/cytokine network is suggested as its pathogenesis. Among these, we focused on monocyte chemoattractant protein-1 (MCP-1), as it is known to be associated with tissue aging. For the first time, we report that the MCP-1 receptor, CCR2, is expressed in normal human melanocytes. In SL tissue, there was an increase of CCR2+Melan A+ melanocytes with positivity to Rb protein compared to peri-lesional normal skin. MCP-1 induced the proliferation of normal human melanocytes without a significant change in the melanin content. MCP-1 treatment in normal human keratinocytes showed an increase in senescence-associated β-galactosidase staining and p53 and p21 protein expressions. In summary, MCP-1 may participate in the development of SL by affecting epidermal constituent cells, for example, by inducing melanocyte proliferation and keratinocyte senescence.

Background: For effective skin depigmentation, the skin depigmentation agent must be delivered to melanocytes, where melanin is synthesized. Although dissolving microneedle (DMN) is one of the best transdermal drug delivery systems to deliver the active compound, no clinical trial has been conducted in terms of safety and efficacy., Objectives: To assess the clinical efficacy and safety of a DMN patch that contained 4-n-butylresorcinol, a skin depigmentation agent., Methods: In the safety assessment, 31 subjects were selected for primary skin irritation test using Frosch & Kligman's method and 50 women for the cumulative irritation test and sensitization potential test using a modification of the Shelanski-Shelanski method. In the efficacy assessment, the 4-n-butylresorcinol DMN patch was compared with a control (DMN without 4-n-butylresorcinol) in our double-blind, placebo-controlled study with 45 subjects by measuring two parameters, the melanin index and individual typology angle value, during 8 weeks of administration., Results: The 4-n-butylresorcinol DMN patch was shown to be safe based on the results of the safety assessment and was more than two times effective than the control patch., Conclusion: The 4-n-butylresorcinol DMN patch was effective and safe for skin depigmentation through targeting melanocytes and could be a useful functional cosmetic product., (© 2015 Wiley Periodicals, Inc.)

Introduction: Topical photodynamic therapy (PDT) is acknowledged to be a safe and efficient therapeutic option for the selective destruction of actinic keratosis and superficial carcinomas. Over the past 15 years, topical PDT has also been shown to be a possible method for "photorejuvenation.", Materials and Methods: An extensive review was performed of in vitro and in vivo (animals, organ transplant recipients, or immunocompetent patients) studies., Results: The studies point to a high level of efficacy. Tone, lentigos, skin roughness, and moreover texture and fine wrinkles because of the effects of dermal remodeling are improved. Adverse effects are generally described as mild to moderate, without scarring, along with a fast recovery time. Patients with fair phototypes and a history of sun exposure and actinic damage of varying severity are the best candidates for this technique. Photodynamic photorejuvenation sessions can both rejuvenate their skins and also treat their visible or incipient UV-induced lesions. New protocols either with daylight use and/or previous intensification by laser or microneedling seem promising., Conclusion: The photodynamic rejuvenation technique seems to show excellent short-term efficacy and tolerability.

Background: Arbutin is one of the most effective lightening substances. Serratula quinquefolia is a new source of its β-anomer. The HPLC method showed that the solid content of this compound in the dried plant raw material accounts for 6.86%. The leaves of Serratula quinquefolia do not contain hydroquinone., Aims: To assess the efficacy of the aqueous extract from' leaf of five-leaf serratula as a skin-lightening agent., Patients/methods: We did a randomized, placebo-controlled, double-blind trial. The study involved 102 women aged 26-55, with two kinds of hyperpigmentary diseases: melasma and lentigo solaris. Patients were randomly assigned to one of the treatment groups: a study group (N = 54) or a control group (N = 48). The study group applied the cream with the aqueous extract from leaf of five-leaf serratula containing 2.51% of arbutin. The cream was applied twice a day on the discolored side for 8 weeks., Results: The experimental data showed that the cream with the extract causes decreased level of melanin in the skin pigmentation spot. Clinical effect in the form of lightening and evening skin tone on the discolored side was observed in 75.86% of the female patients with melasma and 56.00 % of the female patients with lentigo solaris., Conclusions: The cream with the aqueous extract from leaf of five-leaf serratula proved to be an effective and safe preparation for lightening skin discolorations (66.67 % of the female patients in the study group)., (© 2015 Wiley Periodicals, Inc.)

Background and Objective: To assess an objective method evaluating the effects of a retinaldehyde-based cream (RA-cream) on solar lentigines; 29 women randomly applied RA-cream on lentigines of one hand and a control cream on the other, once daily for 3 months., Methods: A specific method enabling a reliable visualisation of the lesions was proposed, using high-magnification colour-calibrated camera imaging. Assessment was performed using clinical evaluation by Physician Global Assessment score and image analysis. Luminance determination on the numeric images was performed either on the basis of 5 independent expert's consensus borders or probability map analysis via an algorithm automatically detecting the pigmented area., Results: Both image analysis methods showed a similar lightening of ΔL* = 2 after a 3-month treatment by RA-cream, in agreement with single-blind clinical evaluation., Conclusion: High-magnification colour-calibrated camera imaging combined with probability map analysis is a fast and precise method to follow lentigo depigmentation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hyperpigmentation is a common concern and has many causes including lentigines and melasma. Currently available topical products for hyperpigmentation are limited by their potential for irritation, lack of demonstrated efficacy or regulatory concerns., Objective: To compare the efficacy of a new skin lightening product with and without iontophoresis to a known effective product (tretinoin) and placebo on hyperpigmentation caused by lentigines and/or melasma. Secondary objectives included an assessment of the product's effects on the appearance of rhytides and roughness., Methods and Materials: Eighty subjects were randomized into one of four treatment groups: proprietary lightening product, proprietary lightening product with iontophoresis, tretinoin 0.05% cream, or vehicle control. Seventy-four subjects completed all study visits. Blinded assessments of subjects were performed at each visit under ambient and Wood's light., Results: The proprietary skin lightening product improved facial hyperpigmentation versus placebo under ambient light (P= 0.05) and Wood's lamp (P= 0.01) examination. Tretinoin also improved facial hyperpigmentation versus placebo under Wood's lamp (P= 0.01). The proprietary product was better tolerated than tretinoin, with fewer subject reported side effects., Conclusion: The investigational product was effective and may be better tolerated than tretinoin cream.

Background: Solar lentigines are common benign macular hyperpigmented lesions localized on sun-exposed areas., Objective: To evaluate the efficacy and safety of a new depigmenting agent containing a retinoid (retinaldehyde), a new phenolic agent (4-(1-phenylethyl)-resorcinol) and a reducing agent (δ-tocopheryl-β-D-glucopyranoside) in the topical treatment of solar lentigines., Patients and Methods: Twenty patients with solar lentigines of the face and hands applied the depigmenting agent on each lentigo once daily for 12 weeks. The outcome was evaluated at 45 days (T1) and 3 months (T2) after the end of treatment compared to baseline (T0) by means of clinical evaluation, Mexameter® and Visioface devices for digital and ultraviolet computerized image analysis of skin color as well as in vivo reflectance confocal microscopy., Results: Image analysis and confocal laser reflectance microscopy showed that hyperpigmentation was significantly reduced at T2 compared to baseline and to controls., Conclusion: The study treatment was well tolerated and showed significant improvement in the depigmentation of solar lentigines.

Background: Although bleaching treatment using all-trans retinoic acid (RA) and hydroquinone (HQ) improves epidermal melanosis, the application of two medications and the irritant dermatitis induced by RA inconvenience patients. To overcome these problems, we developed a silicone sheet containing RA and HQ., Objective: To compare the efficacy of a silicone sheet containing RA and HQ with that of conventional bleaching treatment., Method: Silicone sheets containing 1% RA and 5% HQ were applied at night during the bleaching phase of 4 weeks, followed by application of sheets containing 5% HQ during the healing phase of 4 weeks. Hemifacial epidermal melanosis, for which the sheets were applied, was compared with a contralateral face which was treated conventionally using RA and HQ. Twenty-four Japanese women who were enrolled in this study and followed up for more than 6 months were analyzed., Results: RA/HQ sheets improved epidermal melanosis, as did the conventional bleaching method, but irritant dermatitis occurred less in patients treated using silicone sheets., Conclusion: RA/HQ sheets, which are easily applied to face skin, can improve epidermal melanosis to the same extent as conventional bleaching., (© 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.)

Background: Hyperpigmentation and solar damage remains a difficult problem to treat with topical agents., Aims: To evaluate a novel skin-lightening complex (SLC) comprising four actives targeting melanin formation at multiple levels, namely disodium glycerophosphate, L-leucine, phenylethyl resorcinol, and undecylenoyl phenylalanine, in an oil-in-water emulsion cream., Patients/methods: Skin-lightening complex was evaluated in 80 female subjects of skin types I-III with at least moderate mottled hyperpigmentation. After a wash-out period of 1 month with a sunscreen, the subjects added a cream containing the SLC for 12 weeks twice daily to entire face and continued the sunscreen use., Results: Whereas there was no significant change during the wash-out period, the primary endpoint mottled hyperpigmentation decreased by 32% after the 12-week treatment period with the SLC cream. Secondary endpoints such as severity and number of lentigines, skin tone, and skin brightness also improved. In all, 57% of the subjects showed at least a moderate response, 17% did not improve, and 3% got worse after the treatment., Conclusions: The SLC cream was well tolerated, in particular when comparing with exfoliating or peeling agent containing skin-lightening products. When used with a daily sunscreen, this study confirms that the SLC represents an alternative to hydroquinone, retinoids, and many other skin-lightening actives., (© 2013 Wiley Periodicals, Inc.)

Hyperpigmentations are very frequent situations that can have considerable impact on the quality of life of affected individuals. However, even if the esthetic prejudice they generate is undeniable, lentigo and melasma are benign conditions that require above all a risk-free management. In addition to the dermatological procedures (peeling, laser, etc.) and the topical drugs available to the dermatologist, there remains significant room for depigmenting dermocosmetic products. These products succeeded to transpose features of the classic pharmaceutical formula invented by Kligman from which they were inspired to the field of dermocosmetics. They comprise activators of epidermal turn-over, skin exfoliants, and active ingredients that interfere with the different stages of melanogenesis, without having the side effects of hydro quinone whose usage remains limited to the field of prescription drugs. Antioxidants are a particularly interesting addition because they participate in reducing cutaneous inflammation and efficiently complete the action of the other components of a depigmenting formula. It is important to remind the aggravating role that sun exposure has on hyperpigmentations. Therefore, measures of rigorous photoprotection are mandatory. Medical makeup, transitory or definite, is an interesting option for the management of hyperpigmentations. Consequently, depigmenting dermocosmetics, used in monotherapy but-most frequently- in combination with dermatological procedures, can be used in literally all types of hyperpigmentations with an efficacy that is dependent on the specific etiology. They are suited to be part of a treatment program that has to be adapted on a case-by-case basis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Lentigines are a common pigmentary disorder in adults and in patients treated by psoralen and ultraviolet A (PUVA) radiation. Their appearance following treatment with narrow-band ultraviolet B (NB-UVB) radiation has been reported in only two patients., Objective: To describe the clinical and histological features of NB-UVB-induced lentigines their relation to dosimetry and the course of the eruption in patients with mycosis fungoides (MF)., Methods: The files of all patients with MF treated in our department in 2003-2010 were searched to identify those in whom lentigines appeared following monotherapy with NB-UVB radiation., Results: Of the 73 patients with early stage MF identified, 10 met the study criteria. Lentigines were detected in skin previously involved by MF in seven patients, and in both involved and uninvolved skin in three patients. They appeared during therapy in three patients, after a mean of 56 exposures (range 50-61), and several months (mean 7.8) following completion of treatment in seven patients, after a mean of 69 exposures (range 32-157). Histopathological study of lesions from five patients revealed basal hyperpigmentation relative to adjacent normal-looking skin. Two lesions had a slight increased number of normal-looking melanocytes on immunohistochemical staining with melanoma cocktail. One lesion had elongated rete ridges. The lesions persisted throughout follow-up (mean 26.7 months) in 8 patients., Conclusions: Patients with MF treated with NB-UVB may acquire lentigines. As opposed to PUVA-induced lentigines which are a known common side-effect of long-term treatment, NB-UVB-induced lentigines are uncommon but appear earlier, even after a few months of treatment., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Background: Solar lentigines (SL) are benign signs of sun damage that many people find distressing., Aim: To assess the efficacy and safety of L-ascorbic acid 10% + phytic acid 2% for treating SL., Patients/methods: A double-blind, vehicle-controlled trial in 30 healthy subjects with ≥2 SL. Subjects were randomly assigned to apply product to one side of the body and vehicle to the other twice daily for 3 months with follow-up of 2 months., Results:   The pigmentation index for product-treated SL was reduced (maximum reduction 1.3 at 3 months [M3]), while that for vehicle-treated lesions remained stable. These differences were statistically significant for M1-M4 (P ≤ 0.003). Dermoscopy detected significant intergroup differences in pigmentation at M5 (P=0.011). Colorimetry results indicated a statistically significant improvement in brightness (L*) between study drug and vehicle at M5. Fifteen subjects experienced 23 adverse events; six (mostly halo depigmentation) were judged possibly related to the study drug. There were six instances of mild-to-moderate intolerance in the study drug group and five in the vehicle-treated group., Conclusions: Study treatment was significantly more efficacious than vehicle in many respects and was well tolerated. Future, larger studies are needed to confirm these results and to compare the product with gold standard treatments., (© 2011 Wiley Periodicals, Inc.)

Background: Actinic (solar) lentigines are melanotic tumors frequently developed during photoaging on the dorsum of the hands. Bleaching (whitening) agents are commonly offered to fade their darker aspect. In general, regular colorimetric methods show poor sensitivity to disclose any bleaching effect., Method: The present randomized controlled study on 24 women was designed to objectively assess the clinical efficacy of a combination of bleaching agents on actinic lentigines. In the endeavor of improving sensitivity, the ultraviolet light-enhanced visualization (ULEV) method was used to derive analytical measurements of lentigo areas and darkness. The test product was a commercially available formulation associating glycolic acid, kojic acid, lipohydroxyacid, and a Vitreoscilla extract. The Analysis® Olympus and Adobe Photoshop® quantitative methods were applied to the ULEV pictures., Results: Data indicated a rapid bleaching effect arising as early as after 1 month of daily applications. The effect progressively increased over 3 months of therapy., Conclusion: The presently described analytical method appears to be sensitive to document some bleaching effects on actinic lentigines., (© 2011 Wiley Periodicals, Inc.)

Background: Jasmonates are plant stress hormones. These small hydrophobic compounds exhibit anti-cancer activities, in vitro and in vivo, against cancer cells of various histological origins. Moreover, they show a selective activity against transformed cells and affect drug-resistant cells as well., Aim: The aim of this study was to evaluate the activity of a powerful jasmonate derivative, that is methyl jasmonate., Material and Methods: Methyl jasmonate was applied topically on cancerous and pre-cancerous skin lesions from eight patients., Results: Methyl jasmonate did not cause any meaningful local or systemic side effects. Three patients exhibited positive responses. Two patients had complete recovery and one had a recurrence of the lesion three months post treatment., Conclusions: Methyl jasmonate is a potentially promising novel topical treatment for prcancerous and cancerous skin lesions. Methyl jasmonate should be evaluated in a larger series of patients.

Background: Solar lentigines are common, benign, cosmetically disfiguring lesions. Available physical treatments are effective, but they are costly and carry risks of side-effects., Objective: To evaluate the efficacy and safety of a preparation containing undecylenoyl phenylalanine 2% in the topical treatment of solar lentigines., Methods: In total, 36 patients with solar lentigines of the hands were randomly assigned to apply the active preparation on one side and the vehicle alone on the other side, twice daily for 12 weeks. Patients were evaluated monthly for efficacy and safety., Results: In all, 30 patients (28 women and 2 men; age range 47-75 years) completed the study. The duration of lesions ranged from 8 months to > 10 years. All patients responded partially on the side of the active treatment. Of the partial responders, 19 (63.3%) had moderate improvement and 11 (36.6%) had marked improvement. Improvement was evident from the first follow-up visit. On the side of the vehicle, 26 remained stable (86.6%) and 4 (13.3%) had partial improvement. There was a significant difference (P < 0.01) in efficacy of the active preparation vs. the vehicle. Using patient assessment ratings, 80% were 'much more satisfied/more satisfied' with the result. The reported side-effects were minor and included erythema and itching or burning on the side of active treatment., Conclusions: Undecylenoyl phenylalanine 2% is a novel depigmenting agent, which possibly acts as an alpha-melanocyte-stimulating hormone antagonist, thus inhibiting melaninogenesis. It achieved a significant lightening of the lesions with minimal side-effects. Most patients were satisfied with the improvement. Undecylenoyl phenylalanine 2% may represent a safe, effective and inexpensive therapeutic alternative for solar lentigines.

The purpose of this study was to assess the in vivo efficacy of a cosmetic formulation containing plant extracts including orchid extracts, compared to 3% vitamin C derivative formulated with the same excipient, in Japanese female adult volunteers with melasma and/or lentigo senilis. The ethics committee of Osaka National Hospital approved the protocol of the study. Before recruitment, selection and inclusion of a volunteer in this study, signed informed consent was obtained from each volunteer after she was given clear and precise information on the study, enabling her to appreciate the aim of the study and the consequences of her consent. Forty-eight female volunteers aged 30-60 years applied the plant extracts and vitamin C derivative to one side of the face. After repeated application for 8 weeks, efficacy was evaluated clinically by colorimetric measurements and subjectively using a questionnaire. After 8 weeks of treatment, both the clinical evaluations by a dermatologist and the questionnaire surveys by volunteers indicated that the cosmetic formulation containing plant extracts was significantly effective in improving the size, brightness, color intensity, clarity, visibility and global appearance of the pigmented spots, and also the luminosity complexion and skin clarity of the face. The good agreement between the results of clinical evaluations and those of questionnaire surveys showed that the orchid-rich plant extracts possess efficacy similar to vitamin C derivative in whitening the skin as well as melasma and lentigo senilis on the face of Japanese women.

Background: Gastrointestinal stromal tumors (GISTs) harbor gain-of-function mutations of the c-kit tyrosine kinase receptor. Imatinib mesylate is an inhibitor of c-kit and is indicated in the treatment of chronic myeloid leukemia and GISTs. Reported adverse effects of imatinib include hypopigmentation, depigmentation, and hyperpigmentation. Although the exact mechanism by which these occur is unclear, it is likely that inhibition of c-kit leads to downstream inhibition of the tyrosinase gene promoter and thus to inhibition of pigment production., Observations: A 45-year-old woman with a history of multiple dysplastic nevi and lentigines was diagnosed as having familial GIST syndrome. Treatment with imatinib mesylate was started in an attempt to decrease the tumor load. Three months after treatment initiation, the patient noted a decrease in the number of pigmented lesions, lightening of the skin in her genital area, and graying of her terminal hair., Conclusions: The potential association between a specific genetic mutation and pigmentation changes secondary to imatinib therapy may account for the variety in presentation of this potential side effect. Further genetic studies paired with melanocyte-specific or c-kit-specific stains of affected tissue are warranted to better understand the relationship between the genetic mutation and the effect of imatinib on pigmentation.

Background: Solar lentigines represent a common feature of photoaging, particularly on the back of the hands. Bleaching agents are usually proposed to lighten the shade of the lesions., Methods: The study was randomized and designed to assess the effect of a bleaching solution containing 2% mequinol (4-hydroxyanisole, 4HA) and 0.01% tretinoin (Solagé). The formulation was applied twice daily for 3 months on solar lentigines present on the back of one hand. The lesions on the other hand were treated with the ethyl alcohol vehicle which served as a control. Clinical diagnosis was confirmed using dermoscopy. In addition, objective measurements of the hypermelanosis were performed at 1-month intervals during and after treatment. Clinical assessments were used as well as narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light-enhanced visualization (ULEV method) and photodensitometry of the corneomelametry test., Results: The multipronged assessment of the lesional color demonstrated a significant lightening effect of the 4HA/tretinoin solution. This was demonstrated after 2 months of treatment and was maintained at least 2 months after stopping treatment., Conclusion: Both the visual ratings and the objective bioinstrumental methods indicate the rapid lightening effect of the 4HA/tretinoin formulation. After stopping treatment, the rate of repigmentation appeared to have slowed compared to the depigmentation phase.

Background: Solar lentigines are common sun-induced benign melanocytic proliferation that presents a significant cosmetic worrying for many middle-aged and elderly patients. Although the newer photoselective lasers have become the mainstay of treatment, cryotherapy and trichloroacetic acid (TCA) solution are inexpensive alternatives in the treatment of solar lentigines. The purpose of this study was to assess the efficacy of cryotherapy compared with TCA 33% on solar lentigines of the back of the hands (SLBH) in patients presenting to dermatologic clinic of our hospital., Methods: Each hand of 25 women with SLBH was treated randomly with either cryotherapy or TCA 33% solution. Photographs of the hands were taken prior to and 2 months following the treatment. The response and side- effect rate were compared., Results: Cryotherapy was more likely to produce substantial lightening of the solar lentigines than TCA 33% solution (P = 0.025) but more painful and took more time to heal. Post-inflammatory hyperpigmentation (PIH) was almost equal in two types of treatment (P > 0.05). Statistically, the better results were seen in fairer Fitzpatrick's skin types (P = 0.00)., Conclusion: Cryotherapy shows better results than TCA 33% solution in the treatment of SLBH particularly in lower Fitzpatrick skin types. PIH is the major complication of each type of treatments particularly in darker Fitzpatrick skin types. Generally, the major criterion for treatment of SLBH with cryotherapy or TCA is Fitzpatrick's skin type of patients.

While the efficacy and safety of topical 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% therapy has been established in Caucasian populations, those with skin types I-II, little research has focused on individuals with darker skin types. The purpose of this open-label study was to evaluate the efficacy and safety of mequinol 2%/tretinoin 0.01% solution in the treatment of solar lentigines in Asian, Latin/Hispanic, and African American ethnic groups with skin types II-V. Subjects were required to have >or= 10 solar lentigines on the dorsal forearms/hands and >or= 3 on the face. One lesion was designated the target lesion, however, all lesions were treated. Patients were treated with topical mequinol 2%/tretinoin 0.01% and clinically evaluated at 4, 8, 12, 16, 20, and 24 weeks as well as 4 weeks following treatment cessation. At each visit, lesions were evaluated using Target and Overall Lesion Pigmentation Index scores ranging from 0 (lightest) to 8 (darkest), where 4 indicated equal pigment with surrounding skin. Efficacy was determined based on pigmentation index scores, and safety was assessed using laboratory monitoring and adverse event (AE) reporting. Over 80% of the 259 subjects completing this study responded to mequinol 2%/tretinoin 0.01% therapy, with a majority of subjects maintaining clinical benefit at 4 weeks post-treatment. Most AEs reported were tolerable and overall mequinol 2%/tretinoin 0.01% therapy had a favorable benefit-to-risk ratio. This study therefore supports the theory that topical mequinol 2%/tretinoin 0.01% is an effective and safe treatment of solar lentigines in ethnic populations, and in those with dark skin types.

Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.

A new topical solution containing 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% (Solagé) was compared with its active components, its vehicle, and hydroquinone (HQ) 3% in the treatment of solar lentigines. In a randomized, parallel-group, double-masked study, 216 subjects applied the treatments twice daily for 16 weeks and were followed up for a further 24 weeks. A significantly higher proportion (P < or = .05) of subjects achieved clinical success with mequinol 2%/tretinoin 0.01% compared with HQ 3% as measured by both the lesional pigmentation on the forearm and the physician global assessment at the end of treatment. The proportion of subjects achieving clinical success on the face in the mequinol 2%/tretinoin 0.01% group was consistently higher than that in the HQ 3% group. Some treatment effects remained at the end of the treatment-free follow-up, with trends apparent on the face in favor of mequinol 2%/tretinoin 0.01% over HQ 3%. In all treatment groups, skin-related adverse events were mild or moderate and transient. In conclusion, the mequinol 2%/tretinoin 0.01% solution is a highly effective and well-tolerated treatment for solar lentigines and related hyperpigmented lesions, being superior to HQ 3% for lesions on the forearm and of similar efficacy for lesions on the face.

The objective of this open-label, noncontrolled study was to evaluate the safety of a combination solution containing 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% (Solagé) with a sunscreen in the treatment of solar lentigines. The study included a total of 406 subjects for a treatment period up to 24 weeks. Efficacy was evaluated clinically by grading the pigmentation level of the treated areas on the face and forearms. A total of 378 subjects were included in the safety population. Of the 173 subjects with skin-related and treatment-related adverse events, severity was reported as mild in 79 subjects, moderate in 71, and severe in 23. Hypopigmentation was observed in 4 subjects and had definitively resolved in 3 of these subjects at the end of the study or after treatment had been discontinued. Halo hypopigmentation was reported in 16 subjects. No allergic reactions were observed. Efficacy evaluation was based on data for 370 subjects. A total of 325 (88%) subjects had facial target lesions almost clear to clear, and a total of 298 (81%) subjects had forearm target lesions almost clear to clear. Our study shows that the mequinol 2%/tretinoin 0.01% solution is effective, convenient, and safe in the treatment of solar lentigines.

Background: The innate melanin pigmentation of skin is modulated during lifetime by a series of factors, including ageing and chronic ultraviolet light exposure. Actinic lentigines may be of particular concern from a cosmetic point of view. Conventional hypopigmenting agents are usually deceptive. Using cyclodextrins to form inclusion compounds with these agents might represent a more active drug delivery system., Objective: To assess sensitive and objective methods predicting the effects of a 2% hydroquinone-cyclodextrin formulation on solar lentigines., Study Design: Thirty Asian adults applied a 2% hydroquinone-cyclodextrin formulation once daily on solar lentigines of a forearm for 2 months. The other untreated forearm served as a control. Monthly assessments were performed using skin colorimetry and fluorescence video recording combined with image analysis. Corneomelametry following photodensitometry of cyanoacrylate skin surface strippings was performed after melanin staining of the samples., Results: The control untreated solar lentigines showed no significant variations in the biometrological parameters. By contrast, the test formulation induced lightening of the solar lentigines. Corneomelametry disclosed improvement after 1 months' treatment, whereas the other assessments only reached significance after 2 months., Conclusions: A 2% hydroquinone-cyclodextrin formulation proved to be effective in lightening actinic lentigines. Corneomelametry predicted the effects discernible at a later stage by in vivo colour assessments of the melanin content.

Background: Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied., Objective: We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines., Methods: In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months., Results: Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 +/- 0.9 (mean +/- SE) and 2.5 +/- 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 +/- 1.3 (P <.05). After 1 month of treatment, the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel (P <.05). After 9 months, 57% and 59% of the patients had lighter lesions in the adapalene 0.1% and 0.3% groups, respectively, in comparison with only 36% in the vehicle group (P <.05). Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene-, as compared with vehicle-treated group. The differences, however, were not statistically significant. A retrospective evaluation of paired clinical photographs (before and after 9-month treatment) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle., Conclusion: Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin.

Background: So-called darkened age spots encompass distinct pathological processes. The efficacy of topical depigmenting agents is difficult to objectivate., Objective: To assess the hypopigmenting effect of three cosmetic formulations using objective biometrological methods., Methods: 50 women of South-East Asian ancestry were enrolled in this pilot study. They had solar lentigines according to dermoscopic criteria. The lesions were treated by topical hypopigmenting formulations. Products were applied twice daily for 2 or 3 months. Assessments at 1-month intervals were made using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection and photodensitometry- and image-analysis-assisted corneomelametry., Results: A 20% azelaic acid formulation and another one containing 5% ascorbyl glucosamine, 1% kojic acid and alpha-hydroxyacid esters appeared inefficacious on solar lentigines. A stabilized soy extract showed a better although modest lightening effect when assessed by corneomelametry. The subclinical or faint mottled skin revealed by ultraviolet light examination better responded (p < 0.05) to treatments., Conclusion: Focal epidermal hyperpigmentation is better controlled by topical whitening agents when the increase in melanin content reflects a modest functional hyperactivity of melanocytes., (Copyright 2002 S. Karger AG, Basel)

Background: Solar lentigines are a chronic condition of the aging population resulting from years of cumulative sun exposure. A topical treatment that is both safe and effective would be welcome and useful. Combinations of therapeutic agents are often used and allow synergy of mechanisms with tolerability. A tyrosinase inhibitor in use in Europe, 4-hydroxyanisole (Mequinol), and the retinoid tretinoin have been used singly as depigmenting agents., Objective: The efficacy and safety of the combination product of 2% 4-hydroxyanisole (4HA [mequinol]) /0.01% tretinoin solution (tradename Solagé) were evaluated in two phase III, randomized, controlled, double-blind trials., Methods: Subjects were randomized to treatment with 4HA/tretinoin solution, one of the active components (4HA or tretinoin), or vehicle. Subjects applied the test solution with a wand applicator twice daily to all solar lentigines and related hyperpigmented lesions on the face, forearms, and backs of hands for up to 24 weeks. Trial 1 had a 24-week no-treatment regression phase and trial 2 had a 4-week no-treatment regression phase. Information collected included clinical assessments of Target Lesion Pigmentation, Physician's Global Assessment of Improvement/Worsening, an Assessment of Overall Cosmetic Effect, and a Subject's Self-Assessment Questionnaire., Results: The 4HA/tretinoin combination was clinically superior to each of its active components and to the vehicle in the treatment of solar lentigines. At the end of treatment, in trial 1 and trial 2, 4HA/tretinoin was statistically superior to each of its active components and vehicle on the forearms and face (P

Hydroquinone is a well known reagent used in the treatment of pigmentation disorders. The instability of the quinones and the required active concentration make topical treatment rather difficult. We tested the efficacy of an ascorbate-phytohydroquinone complex that inhibits the synthesis of melanin and promotes the degradation of the existing melanin. Lentigo senile lesions were evaluated before and after 1 month of treatment. Objective skin color evaluation was performed instrumentally. After one month of treatment, a clear depigmentation of the macules was measured. None of the volunteers reported any side effects from the prolonged treatment with the hydroquinone containing product.