The impact of methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) UVA1 filter on pigmentary and ageing signs: An outdoor prospective 8-week randomized, intra-individual comparative study in two populations of different genetic background.

BACKGROUND: Of all ultraviolet (UV) radiations reaching the earth, UVA1 rays have a higher potential of penetrating and producing clinically harmful consequences. While UV radiations up to 370 nm are well-blocked by current sunscreens, a photoprotection gap remains for the UVA1 wavelengths between 370 and 400 nm. OBJECTIVE: This study was to assess under outdoor summer conditions the impact on pigmentation and skin ageing signs of a protection against UVA1 using methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) filter added to a reference SPF50 sunscreen, in comparison with the same sunscreen without the MCE filter. MATERIALS AND METHODS: This prospective randomized comparative intra-individual study was conducted in 113 women in Brazil and China. Subjects had their face and two forearms exposed twice-daily to a 1-h outdoor sunlight exposure over 8 weeks. Before exposure, the SPF50 sunscreen containing 3% MCE was applied on one half-face and one forearm and the same reference product without MCE on the other half-face and forearm. Primary study endpoint was skin colour changes (chromametry). Other endpoints included expert panel grading of pigmentation and facial skin ageing, and naïve panel assessment of facial skin radiance and homogeneity. RESULTS: After 8 weeks, the skin was darker on both forearms but the increase in sun-induced pigmentation was smaller with the SPF50/MCE sunscreen. Expert panel evaluations showed no change in severity scores for pigmentation and a decreased severity scores for facial skin ageing in areas protected with the SPF50/MCE product: severity scores in areas protected with the SPF50 alone were either increased (pigmentation) or unchanged (skin ageing). Naïve panel evaluations of skin radiance and homogeneity showed statistically significant superiority of the SPF50/MCE product. CONCLUSION: Overall, this study demonstrates that a protection with the SPF50/MCE sunscreen significantly reduces pigmentation and ageing signs compared to the same SPF50 sunscreen.

Impact on facial skin aging signs of a 1-year standardized photoprotection over a classical skin care routine in skin phototypes II-VI individuals: A prospective randomized trial.

BACKGROUND: Data reflecting the impact of photoprotection on cutaneous aging are scarce and mostly limited to fair skin. OBJECTIVE: To assess the effectiveness of a photoprotective product in counteracting the photoaging process in different skin phototypes over 1 year compared against a classical routine. MATERIALS AND METHODS: Two hundred and ninety Brazilian women aged 30-65 years, with skin phototype II-VI were equally randomized in two groups. Group 1 kept on their routine whereas Group 2 applied, twice daily, a photoprotective product (SPF 60, PPD = 24.1) replacing the one they routinely used. Volunteers reported the duration of their daily sun-exposure. Standardized photographs taken at D0 and D365 were analysed by 15 dermatologists to assess eight wrinkles and pigmentation signs. RESULTS: A global increase in severity was reported which was significant for Group 1. This increase was lower in Group 2 where only half the signs showed significant worsening. In Group 2 versus Group 1, the increase in forehead wrinkles, marionette lines, wrinkles created by ptosis and size of dark spot was significantly (p < 0.05) decreased by 30%-50%. CONCLUSION: Daily application of a high photoprotective product significantly decreases the progression of skin aging signs after 1 year in skin phototypes II-VI.

A new in vitro method to predict in vivo photoprotection of skin hyperpigmentation induced by visible light.

BACKGROUND: Ultraviolet radiation is the main cause of skin pigmentation, but more recently visible light has been shown to be an important contributor especially in melano-competent subjects. Photoprotection from visible light can improve several hyperpigmentation disorders. Recently, a visible light photoprotection assessment method has been proposed based on in vivo pigmentation; the visible light photoprotection factor (VL-PF) is determined by assessment of the change in colorimetry parameter ITA over several days measured using a chromameter. Although in vivo methods remain the most representative of real life, in vitro methods are more suited to screening sunscreen formulations. OBJECTIVE: The aim of this study was to evaluate the correlation between in vivo and in vitro methods in assessing protection against visible light induced pigmentation. METHODS: We first analysed the in vitro protective properties of the 10 commercially available sunscreens using transmission measurements in the visible spectrum. Then, we performed a monocentric, double-blind, randomized controlled study with intra-individual comparisons in 20 healthy subjects and measure the VL-PF in vivo of those sunscreens. The correlation between the VL-PF and the percentage of blocked light was evaluated using the coefficient of determination R2 . RESULTS: A strong significant correlation was demonstrated between in vivo visible light protection factor and in vitro transmittance measurements, with the highest correlation factor at 420 nm and in the spectrum covering from 400 to 469 nm. CONCLUSION: Transmittance measurements were found to be a good predictive tool to evaluate sunscreen visible light photoprotection efficacy and could be used to select formulations for final in vivo testing.

Artificial Intelligence analysis of over half a million European and Chinese women reveals striking differences in the facial skin ageing process.

BACKGROUND: Artificial Intelligence (A.I) and deep learning-based algorithms are increasingly being used in dermatology following the emergence of powerful smartphones with high-resolution cameras. OBJECTIVES: To use an A.I-based algorithm, validated by dermatologists, to compare the evolution of the skin ageing process among Chinese and European women. METHODS: Selfie images were taken by 465 587 European and 79 016 Chinese women ranging from 18 to 85 and 18 to 69 years old, respectively, without facial skin diseases and who had access to a smartphone with a high-resolution camera (≥4 Megapixels). The selfies were analysed by facial skin diagnostic using a smartphone application to grade the severity of 9 facial signs (including wrinkles, sagging, vascular, pigmentation signs, pores). RESULTS: Wrinkles/texture, ptosis and sagging increased linearly with age in European women compared to lower scores and more gradual increase in the younger age-classes in Chinese women. In Chinese women, pigmentation signs increased regularly between 18 and 40 years, plateaued between 40 and 60 years, then increased in the over 60s compared to lower scores and a slower more regular increase with age in European women. Vascularization signs increased steadily with age in European women compared to no significant change in Chinese women. CONCLUSIONS: Marked differences were observed in the skin ageing process between European and Chinese populations, both in the prevalence of each facial ageing sign and their kinetics. Automatic grading performed on selfies and analysed by A.I is a fast and confidential method for quantifying signs of facial ageing and identifying the main issues for each population and age-class, which is of practical interest, as it will allow the development of tailored prevention and therapeutic measures.

The use of lasers in vitiligo, an overview.

Various types of lasers have been demonstrated to be effective in the treatment of vitiligo. The mode of action of these lasers is just as varied as the purpose of intervention. Many clinicians are not aware of the unique opportunity these lasers offer to improve the outcomes of vitiligo treatment. To date, no clear overview exists of the use of lasers in vitiligo treatment. Thus, the aim of this review is to discuss the various types of lasers and provide an overview of the evidence for their efficacy. We found good evidence from a systematic review that the excimer laser is effective, induces repigmentation rates comparable to NB-UVB and has improved outcomes when combined with calcineurin inhibitors. Ablative lasers are commonly used for tissue graft or melanocyte-keratinocyte cell graft transplantation. They provide safe, fast and uniform denudation of the epidermis with propitious repigmentation outcomes. We found conflicting evidence from two systematic reviews regarding the efficacy of fractional ablative lasers for improving outcomes of NB-UVB therapy, a systematic review including only fractional ablative lasers provided evidence for efficacy. Q-switched nanosecond lasers have shown to be safe and effective for inducing depigmentation, although recurrence is common, and most studies were small and retrospective. Despite proven efficacy and safety, laser treatments are relatively expensive and suited for limited body surface areas and selected cases. Each type of laser has benefits and risks associated and should, therefore, be individually chosen based on location, extent, activity and type of vitiligo.

Male genital vitiligo.

Vitiligo is a polygenetic multifactorial disease leading to melanocytic loss in skin and sometimes in hair. Genital areas may be involved and represent a specific therapeutic challenge. Surprisingly, data on male genital vitiligo remain scarce. This review aims to collate current knowledge on male genital vitiligo and to discuss the risks and benefits of the various therapeutic approaches. Male genital vitiligo is relatively frequent and often induces marked impairment of quality of life, with a specific impact on sex life. Prompt recognition of activity remains mandatory to halt disease progression, as repigmentation remains difficult to achieve in most cases. Thanks to progress in understanding of the pathophysiology of vitiligo, new therapeutic approaches are under development. Topical ruxolitinib, a JAK pathway inhibitor, is currently the product in the most advanced stage of development, with a very encouraging repigmentation rate on the face, although specific efficacy in genital area remains to be assessed. The next generation of treatments, such as topical WNT agonists, could be of great interest in genital vitiligo as they will not require combination with UV therapy and they may be able to enhance the differentiation and proliferation of melanocyte stem cells in this difficult-to-treat area.

Development of a shared decision-making tool in vitiligo: an international study.

BACKGROUND: Shared decision-making tools (SDMt) are visual tools developed to promote joint medical decisions between physicians and patients. There is a paucity of such tools in dermatology. OBJECTIVES: To develop and validate a SDMt for use in specialized consultation for vitiligo. METHODS: A prospective cross-sectional study was carried out from March 2019 to March 2020. We first conducted a qualitative study of topics discussed by patients and clinicians during therapeutic decision-making in the setting of a specialized consultation for vitiligo using an anchored-theory method, which allowed conceptualization of the SDMt. The usefulness of the SDMt was evaluated by a working group of multidisciplinary health workers and patients with vitiligo. Consensus on the final tool was obtained through an e-Delphi method. RESULTS: We recruited 30 patients with vitiligo for the qualitative study, which identified 91 topics related to therapeutic decision-making. Hierarchical clustering analysis confirmed the distribution of these topics in two subgroups (general treatment goals and priorities, and topics specific to each treatment). The consensus of a multidisciplinary group was used to develop the SDMt. The tool was comprised of eight A5 cards, which addressed face repigmentation; body repigmentation (limited area); body repigmentation (extended area); partial or complete depigmentation; coping with the disease; stabilization of disease; maintaining repigmentation; and disease information. Cognitive interviews confirmed the satisfaction, readability and usefulness of the SDMt. The SDMt was then translated and culturally validated in English. CONCLUSIONS: We developed a tool for shared decision-making in nonsegmental vitiligo, which we translated and cross-culturally validated in a US patient population with vitiligo to ensure its generalizability.

Oral gliadin-protected superoxide dismutase in addition to phototherapy for treating non-segmental vitiligo: A 24-week prospective randomized placebo-controlled study.

BACKGROUND: Despite a solid rationale, the usefulness of antioxidants in treating vitiligo has not been clearly demonstrated. Combining superoxide dismutase (SOD) with a wheat gliadin biopolymer protects it during the passage through the gastrointestinal tract. OBJECTIVE: To evaluate the efficacy of gliadin-protected SOD (GP-SOD), associated with narrowband ultraviolet B(NB-UVB), for treating vitiligo. METHODS: We conducted a 24-week monocentric interventional prospective randomized placebo-controlled trial in the tertiary center for vitiligo care in the department of Dermatology of Nice University hospital, Nice, France. Subjects with non-segmental vitiligo affecting more than 5% of the total body surface were included. The subjects received gliadin-protected SOD (GP-SOD; 1 g/day for 12 weeks followed by 0.5 g/day for 12 weeks) or placebo in combination with twice-weekly sessions of NB-UVB. The primary endpoint was the total repigmentation rate at 24 weeks, compared with baseline, as assessed by investigator-assessed Vitiligo Extent Score (VES) on standardized pictures. RESULTS: A total of 50 patients were included. After 24 weeks, a greater improvement in VES was observed in the GP-SOD group (19.85%; SE 4.63, P < 0.0001) compared with the placebo group (8.83%; SE 4.72, P = 0.0676). Tolerance was good in both groups. No related side-effect was reported. CONCLUSIONS: The use of GP-SOD appears to be a useful add-on to phototherapy in the treatment of vitiligo patients.

Photoprotection according to skin phototype and dermatoses: practical recommendations from an expert panel.

Increasing evidence on the impact of the different wavelengths of sunlight on the skin demonstrates the need for tailored recommendations of sunscreen according to skin phototype and dermatoses, which is now possible due to advances in the filters and formulations of sunscreens. A selective literature search was performed by an international expert panel, focusing on the type of sunscreen to recommend for photoaging, skin cancers, photodermatoses, pigmentary disorders and skin inflammatory disorders. Protection against ultraviolet (UV)B is especially important for light skin as there is a high risk of sunburn, DNA damage and skin cancers. Darker skin may be naturally better protected against UVB but is more prone to hyperpigmentation induced by visible light (VL) and UVA. Protection against UVA, VL and infrared A can be helpful for all skin phototypes as they penetrate deeply and cause photoaging. Long-wave UVA1 plays a critical role in pigmentation, photoaging, skin cancer, DNA damage and photodermatoses. Adapting the formulation and texture of the sunscreen to the type of skin and dermatoses is also essential. Practical recommendations on the type of sunscreen to prescribe are provided to support the clinician in daily practice.

Adult skin acute stress responses to short-term environmental and internal aggression from exposome factors.

Exposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short-term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine-immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell-mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.

Reliability and validity of the Vitiligo Signs of Activity Score (VSAS).

BACKGROUND: The associations between disease activity and several clinical signs in vitiligo have been described, but a widely accepted and validated scoring system is lacking. OBJECTIVES: To validate the Vitiligo Signs of Activity Score (VSAS) for physicians. METHODS: Three visible clinical signs were scored on 15 body locations: confetti-like depigmentation (c), Koebner phenomenon (k) and hypochromic areas/borders (h). The inter- and intrarater reliability of the global VSAS and VSAS subscores (c-VSAS, k-VSAS and h-VSAS) were tested by four and three raters (physicians), respectively. Construct validity and feasibility were evaluated. RESULTS: The VSAS demonstrated good inter-rater reliability, with an intraclass correlation coefficient (ICC) of 0·87 in the first round and 0·90 in the second round. The intrarater reliability ICCs were all ≥ 0·86. The inter-rater reliabilities of the subscores were excellent for c-VSAS and fair for k-VSAS and h-VSAS (ICC 0·83, 0·51 and 0·53, respectively, in the first round). Evidence for construct validity was provided. The completion time by the raters (median 2·18 min per patient) improved during the second round (median 1·33 min per patient). A limitation of the study is the low number of patients, mainly of skin phototypes II-III, from a single tertiary centre. CONCLUSIONS: The VSAS appears to be a valid and reliable instrument to score visible clinical signs linked to disease activity in a standardized way. What is already known about this topic? Evidence exists for a possible link between several visible clinical signs in vitiligo and disease activity. A widely accepted and validated scoring system to quantify these clinical signs is lacking. What does this study add? The Vitiligo Signs of Activity Score (VSAS) underwent preliminary validation and may assist quantification of visible clinical signs linked to disease activity in a standardized way in clinical practice and trials. What are the clinical implications of this work? VSAS may be used for future trials that aim to establish the clinical significance of the specific visible clinical signs in vitiligo in a more controlled setting. Linked Comment: Eleftheriadou. Br J Dermatol 2020; 183:801-802.

Clinical and biological impact of the exposome on the skin.

The skin exposome is defined as the totality of environmental exposures over the life course that can induce or modify various skin conditions. Here, we review the impact on the skin of solar exposure, air pollution, hormones, nutrition and psychological factors. Photoageing, photocarcinogenesis and pigmentary changes are well-established consequences of chronic exposure of the skin to solar radiation. Exposure to traffic-related air pollution contributes to skin ageing. Particulate matter and nitrogen dioxide cause skin pigmentation/lentigines, while ozone causes wrinkles and has an impact on atopic eczema. Human skin is a major target of hormones, and they exhibit a wide range of biological activities on the skin. Hormones decline with advancing age influencing skin ageing. Nutrition has an impact on numerous biochemical processes, including oxidation, inflammation and glycation, which may result in clinical effects, including modification of the course of skin ageing and photoageing. Stress and lack of sleep are known to contribute to a pro-inflammatory state, which, in turn, affects the integrity of extracellular matrix proteins, in particular collagen. Hormone dysregulation, malnutrition and stress may contribute to inflammatory skin disorders, such as atopic dermatitis, psoriasis, acne and rosacea.

Efficacy and tolerability on melasma of a topical cosmetic product acting on melanocytes, fibroblasts and endothelial cells: a randomized comparative trial against 4% hydroquinone.

BACKGROUND: Recent data demonstrated that an altered basal membrane, activated melanocytes and secreted factors from keratinocytes but also fibroblasts and endothelial cells are involved in the pathophysiology of melasma. OBJECTIVES: To evaluate the efficacy and tolerability on melasma of a new topical skin-lightening cosmetic product combination (CCP) targeting several factors identified to be involved in melasma pathogenesis compared to 4% hydroquinone (HQ). METHODS: Forty-three women with melasma were enrolled in a 12-week double-blind, randomized, parallel-group trial and treated with CCP or 4% HQ cream. Efficacy was evaluated with the modified Melasma Area Severity Index (mMASI) score and colorimetric change. Cutaneous tolerability and patient satisfaction were also investigated. RESULTS: The mMASI score decreased for both products from baseline and over the study period. At week 12, 90% of the subjects who received the combination products had an improvement in pigmentation vs. 79% with HQ. Similarly, both products significantly increased Individual Typological Angle parameters. For both measures, no statistically significant difference was observed between CCP and HQ in terms of change from baseline. CPP was very well tolerated. CONCLUSIONS: Cosmetic product combination is as effective as HQ in the management of facial dyspigmentation and represents a safe alternative.

Photoprotection of the future: challenges and opportunities.

The use of sunscreens is an important and essential component of photoprotection. Since their introduction during the first half of the last century, sunscreens have benefited enormously from major technological advances such as the development of novel UV filters; as a result, their efficacy in preventing UV-induced erythema is unequivocal. More recently, however, new challenges have appeared, which have prompted a robust discussion about the safety of sunscreens. These include topics directly related to photoprotection of human skin such as improved/alternative methods for standardization of assessment of the efficacy of sunscreens, but also many others such as photoprotection beyond UV, concerns about human toxicity and ecological safety, the potential of oral photoprotective measures, consequences of innovative galenic formulations. On a first glance, some of these might raise questions and doubts among dermatologists, physicians and the general public about the use sunscreens as a means of photoprotection. This situation has prompted us to critically review such challenges, but also opportunities, based on existing scientific evidence. We conclude by providing our vision about how such challenges can be met best in the future in an attempt to create the ideal sunscreen, which should provide adequate and balanced protection and be easy and safe to use.

Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double-blind, controlled study.

BACKGROUND: Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series. OBJECTIVES: To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial. METHODS: Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase® or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events. RESULTS: During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis). CONCLUSION: Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.

A systematic review of outcome reporting in laser treatments for dermatological diseases.

The standardization of outcome reporting is crucial for interpretation and comparison of studies related to laser treatment of skin disorders. In collaboration with the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN), a procedure has been proposed to find consensus on the most important generic outcome domains (what to measure) for implementation in the international Laser TrEAtment in Dermatology (LEAD) registry. As the first step in the development of a generic outcome set for the LEAD registry, we undertook a systematic review to identify outcomes, outcome measurement instruments, methods and definitions reported in recently published literature of laser treatments for skin disorders. A systematic search was conducted and generated a total of 707 papers. We assessed 150 studies including all types of studies involving laser treatments for the skin. Two researchers independently extracted the type, definition and frequency of all outcomes and used outcome measurement instruments. We identified 105 verbatim outcomes that were categorized into eight domains recommended by the COMET framework: appearance, long-term effects, physician and patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning and adverse events. Heterogeneity in outcome reporting (e.g. categories and outcome measurement instruments) was high, and definitions were insufficiently reported. There was a clear under representation of life impact domains, including satisfaction (23%) quality of life (3%) and psychological functioning (1%). Outcome reporting concerning laser treatments for the skin is heterogeneous. Standardized outcomes are needed for improving evidence synthesis. Results of this review will be used in the next step to reach consensus between stakeholders on the outcome domains to be implemented in the LEAD registry.

Association of combined PD-L1 expression and tumour-infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma.

BACKGROUND: Recent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD-L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas. OBJECTIVES: We investigated whether the presence and the features of pretreatment CD8+ tumour-infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma. METHODS: In this retrospective study, we evaluated the association of PD-L1 expression ≥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non-ICIs). RESULTS: PD-L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (κ = 0.283). No significant association was noted between PD-L1 expression and CD8+ TIL profile analysed as single markers and OS or response to immunotherapy. Instead, their combined analysis in primary melanoma samples showed that the PD-L1-/CD8+ status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non-ICIs (P = 0.009). Conversely, the PD-L1+/CD8+ status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non-ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8+ TIL+/PD-L1- (P = 0.02). CONCLUSIONS: The pretreatment combination of PD-L1 expression with the level of CD8+ TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens.

Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment.

BACKGROUND: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: To assess the inflammation in the skin of patients with EBS-gen sev. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. CONCLUSIONS: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.

Sunscreen photoprotection and vitamin D status.

BACKGROUND: Global concern about vitamin D deficiency has fuelled debates on photoprotection and the importance of solar exposure to meet vitamin D requirements. OBJECTIVES: To review the published evidence to reach a consensus on the influence of photoprotection by sunscreens on vitamin D status, considering other relevant factors. METHODS: An international panel of 13 experts in endocrinology, dermatology, photobiology, epidemiology and biological anthropology reviewed the literature prior to a 1-day meeting in June 2017, during which the evidence was discussed. Methods of assessment and determining factors of vitamin D status, and public health perspectives were examined and consequences of sun exposure and the effects of photoprotection were assessed. RESULTS: A serum level of ≥ 50 nmol L-1 25(OH)D is a target for all individuals. Broad-spectrum sunscreens that prevent erythema are unlikely to compromise vitamin D status in healthy populations. Vitamin D screening should be restricted to those at risk of hypovitaminosis, such as patients with photosensitivity disorders, who require rigorous photoprotection. Screening and supplementation are advised for this group. CONCLUSIONS: Sunscreen use for daily and recreational photoprotection does not compromise vitamin D synthesis, even when applied under optimal conditions. What's already known about this topic? Knowledge of the relationship between solar exposure behaviour, sunscreen use and vitamin D is important for public health but there is confusion about optimal vitamin D status and the safest way to achieve this. Practical recommendations on the potential impact of daily and/or recreational sunscreens on vitamin D status are lacking for healthy people. What does this study add? Judicious use of daily broad-spectrum sunscreens with high ultraviolet (UV) A protection will not compromise vitamin D status in healthy people. However, photoprotection strategies for patients with photosensitivity disorders that include high sun-protection factor sunscreens with high UVA protection, along with protective clothing and shade-seeking behaviour are likely to compromise vitamin D status. Screening for vitamin D status and supplementation are recommended in patients with photosensitivity disorders.