A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial.

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.

Odyssey toward an understanding of acquired postinflammatory lentiginosis.

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.

A Randomized Controlled Trial on the Effectiveness of Epidermal Growth Factor-Containing Ointment on the Treatment of Solar Lentigines as Adjuvant Therapy.

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.

Protection against summer solar lentigo over-pigmentation with a SPF30 daily cream.

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.

Photodynamic Photorejuvenation: A Review.

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.

The Effect of MCP-1/CCR2 on the Proliferation and Senescence of Epidermal Constituent Cells in Solar Lentigo.

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 ß-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.

Clinical and instrumental evaluation of the efficacy of a new depigmenting agent containing a combination of a retinoid, a phenolic agent and an antioxidant for the treatment of solar lentigines.

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-ß-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.

Follow-up of solar lentigo depigmentation with a retinaldehyde-based cream by clinical evaluation and calibrated colour imaging.

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.

Single blind, randomized, controlled trial of a lightening product with and without iontophoresis versus tretinoin and vehicle for hyperpigmentation.

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.

Silicone sheet containing all-trans retinoic acid and hydroquinone for the treatment of epidermal melanosis.

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.

Targeting SDF-1 as an efficient strategy to resolve skin hyperpigmentation issues with Himanthalia elongata extract.

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 H2 O2 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.

NB-UVB (311-312 nm)-induced lentigines in patients with mycosis fungoides: a new adverse effect of phototherapy.

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.

Dermocosmetic management of hyperpigmentations.

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.

A preliminary study of the local treatment of preneoplastic and malignant skin lesions using methyl jasmonate.

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.

A Role for NRF2-Signaling in the Treatment and Prevention of Solar Lentigines.

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.

A randomized, double-blind, vehicle-controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of solar lentigines.

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.

Efficacy of D-pigment dermocosmetic lightening product for solar lentigo lesions of the hand: A randomized controlled trial.

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.

Whitening effect of L-ascorbate-2-phosphate trisodium salt on solar lentigos.

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.