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We developed an artificial intelligence algorithm (AIA) for smartphones to determine the severity of facial acne using the GEA scale and to identify different types of acne lesion (comedonal, inflammatory) and postinflammatory hyperpigmentation (PIHP) or residual hyperpigmentation. Overall, 5972 images (face, right and left profiles) obtained with smartphones (IOS and/or Android) from 1072 acne patients were collected. Three trained dermatologists assessed the acne severity for each patient. One acne severity grade per patient (grade given by the majority of the three dermatologists from the two sets of three images) was used to train the algorithm. Acne lesion identification was performed from a subgroup of 348 images using a tagging tool; tagged images served to train the algorithm. The algorithm evolved and was adjusted for sensibility, specificity and correlation using new images. The correlation between the GEA grade and the quantification and qualification of acne lesions both by the AIA and the experts for each image were evaluated for all AIA versions. At final version 6, the GEA grading provided by AIA reached 68% and was similar to that provided by the dermatologists. Between version 4 and version 6, AIA improved precision results multiplied by 1.5 for inflammatory lesions, 2.5 for non‐inflammatory lesions and by 2 for PIHP; recall was improved by 2.6, 1.6 and 2.7. The weighted average of precision and recall or F1 score was 84% for inflammatory lesions, 61% for non‐inflammatory lesions and 72% for PIHP.

Background/Aims: There is increasing evidence that exposure to air pollutants, including particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2), might aggravate preexisting skin diseases such as eczema and urticaria. Here we investigated if a possible link exists between air pollution and acne vulgaris. We assessed the association between ambient air pollutant concentrations and the number of visits of patients for acne vulgaris to a dermatological outpatient clinic in Beijing, China, from April 1, 2012 to April 30, 2014. Methods: In this time period, 59,325 outpatient visits were recorded because of acne vulgaris. Daily air pollution parameters for PM10, PM2.5, SO2, and NO2 were obtained from the Beijing Municipal Environmental Monitoring Center. Results: Increased concentrations of ambient PM2.5, PM10, and NO2 were significantly associated with increased numbers of outpatient visits for acne vulgaris over the 2 years. These effects could be observed for NO2 in a single-pollutant model and for PM2.5, PM10, and NO2 in 2-pollutant models, which are closer to real-life exposure. Of note, these effects were specific because they were not observed for increased SO2 concentrations, which even showed negative correlations in all test models. Conclusion: This study provides indirect evidence for a link between acne vulgaris and air pollution.

The pigment responses of human skin to broadband UVA radiation (320-400 nm) occur in three distinct phases. The first phase includes immediate pigment darkening (IPD), the pigment that appears immediately after irradiation. The second phase involves an intermediate step, termed persistent pigment darkening (PPD), which leads to the third phase of neomelanogenesis or delayed tanning (DT). Since DT results from synthesis of new melanin, it persists beyond 5-7 days. We conducted studies on human subjects to investigate the dynamic responses of the IPD and PPD reactions to broadband UVA radiation at threshold and superthreshold doses. The threshold doses for IPD, PPD, and DT were found to be approximately 1, 11, and 18 J/cm2 , respectively. The colorimetry ΔL* value corresponding to minimal clinically perceptible pigmentation was found to be 0.8 ± 0.1. IPD appeared immediately and had an associated decay constant of approximately 1.4 minutes. At doses greater than PPD threshold, IPD reaction decayed while PPD developed indicating toward IPD being used as a substrate in the formation of PPD.

Diana Lüftner,1 Veronica Dell’Acqua,2 Frédéric Selle,3 Ahmed Khalil,3 Maria Cristina Leonardi,2 Alejandro De La Torre Tomás,4 George Shenouda,5 Jesus Romero Fernandez,4 Roberto Orecchia,2,6 Dominique Moyal,7 Sophie Seité7 1Department of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Campus Benjamin Franklin, Berlin, Germany; 2Department of Radiotherapy, IEO, European Institute of Oncology IRCCS, Milan, Italy; 3Tenon Hospital, Paris, France; 4Puerta de Hierro Hospital, Madrid, Spain; 5McGill Hospital, Montreal, Canada; 6Milan University, Milan, Italy; 7La Roche-Posay Dermatological Laboratory, Levallois-Perret, France Introduction: The purpose of this multicenter, prospective, observational, open-label study was to evaluate the use and tolerability of dermo-cosmetic products in preventing skin reactions associated with cancer treatments. Patients and methods: A 12-product kit was supplied to patients before chemotherapy began and was to be used throughout the treatment phase. Cutaneous adverse events were evaluated at each treatment session. Physicians evaluated skin reactions (edema, erythema, dryness, desquamation, pigmentation disorders, and cracks) and gave their opinion on the skin benefit for patients at the end of the study. Patients also evaluated the product benefit using the Patient Benefit Index (PBI) questionnaire. Results were analyzed by subgroups of casual and regular users, based on number and frequency of products used. Results: A total of 147 patients were enrolled in cancer services in Germany, France, Italy, Spain, and Canada. Mean age was 59 years with 71% being female. Product tolerance on whole body was rated good to excellent for at least 89% of the patients for each product. Aggravated skin reactions during the study were reported more frequently by casual users than regular users (39.5% versus 22%; p=0.029). Similarly, casual users reported more erythema aggravation (p=0.02) and desquamation (p=0.03) than regular users. PBI >1 was reported for 95.5% of patients and regular users had significantly higher scores than casual users (p=0.049). Discussion: Overall, the 12-product kit was very well tolerated, with regular users reporting benefits more frequently than casual users. Results support international recommendations to use appropriate skin care products to minimize the impact of cutaneous reactions associated with chemotherapy. Keywords: dermocosmetic, dermatological toxicity, skin side effect, skin reaction, palliative care

Purpose:As many as 50% of patients with cancer develop acute skin reactions to some degree with radiotherapy. Proactive skin care is often recommended to minimise these skin reactions and maintain the integrity of the epidermal barrier; nevertheless, no consensual guidelines are systematically used. This multicentre, observational, prospective study evaluated the tolerability and benefit of supportive and barrier protective skin care products in preventing radiotherapy-induced skin reactions in 253 women initiating radiotherapy (exclusive or adjuvant) for breast cancer.Methods:Patients received a kit of 5 commercially available skin care products before the first radiotherapy treatment. The following variables were assessed: cutaneous adverse events, investigator-assessed skin reactions (oedema, erythema, dryness, desquamation) before and after radiotherapy course, investigator, and patient opinion on products benefit. Results were analysed by frequency of product use (heavy versus low).Results:Average age was 60 years (range: 34-85). Over 92% of patients reported good to excellent tolerance on irradiated skin for each product. During the 6-week radiotherapy period, we observed that heavy product users had less skin reactions than the low users, particularly within 10 days of radiotherapy initiation (8% versus 18%; p = .031). Positive physician’s opinion on product use was more frequent for high (66.6%) versus low (32%) users. Patient-assessed patient benefit index was generally >1, indicating relevant treatment benefit, with a tendency for better benefit in high versus low users.Conclusions:These results support recommendations to use skin care products to minimise the impact of secondary cutaneous reactions with radiotherapy cancer treatment.

A review of the oxidization of squalene, a specific human compound produced by the sebaceous gland, is proposed. Such chemical transformation induces important consequences at various levels. Squalene by-products, mostly under peroxidized forms, lead to comedogenesis, contribute to the development of inflammatory acne and possibly modify the skin relief (wrinkling). Experimental conditions of oxidation and/or photo-oxidation mechanisms are exposed, suggesting that they could possibly be bio-markers of atmospheric pollution upon skin. Ozone, long UVA rays, cigarette smoke… are shown powerful oxidizing agents of squalene. Some in vitro, ex vivo and in vivo testings are proposed as examples, aiming at studying ingredients or products capable of boosting or counteracting such chemical changes that, globally, bring adverse effects to various cutaneous compartments.

Patients with photodermatoses or actinic keratosis benefit from very high ultraviolet B-ultraviolet A (UVB-UVA) photoprotection. However, poor compliance is an issue that jeopardizes adequate protection, leading to disease recurrence. This study evaluated the efficacy of a daily protective moisturizer with high UVB and UVA photoprotection applied 8 h before irradiation. A monocentric, open-label, prospective, control pilot study was performed including 10 patients. Patients were irradiated with UVB and UVA before and 8 h after topical application of the product. Reflectance confocal microscopy (RCM) assessment was performed 24 h later. Clinical assessment showed a statistically significant increase in minimal erythema dose (MED) after application of the product (p

In recent years, the critical role that inflammation may play in the development and progression of acne has become increasingly recognized. The prevalence of acne is similar between Asian and Caucasian women, but Asian women have a higher prevalence of inflammatory acne. They also report their symptoms exacerbate during periods of high air pollution. The objective of this study was to review the current evidence that links air pollution to worsening of acne symptoms. Firstly, a group of five Asian and three European scientists with expertise in Dermatology reviewed the current literature and described current acne treatment practices in their countries. During this activity, they identified the need for further epidemiological and clinical research. Secondly, additional studies ensued which provided evidence that acne symptoms might exacerbate in regions of high ambient air pollution. Based on these findings, the authors suggest that people with acne should protect the natural barrier function of their skin with emollients and ultraviolet (UV)A/UVB protection.

To date, facial acne flare-ups in adult women during the luteal phase of the menstrual cycle have been poorly investigated. To clinically characterize premenstrual acne flare-up in adult women and investigate the effect of a dermocosmetic treatment. This single-centre study included 32 young adult women with declared premenstrual acne flares and was composed of two phases: (1) an observational phase (two menstrual cycles) and (2) an interventional phase (one menstrual cycle) in a controlled, randomised, double-blind, intra-individual (half-face) setting in which a dermocosmetic (containing lipohydroxyacid, nicotinamide, and piroctone-olamine) and placebo were compared. Initially, during the first part of the study, we observed that premenstrual acne flare-ups in adult women were characterized by a significant increase in the number of papules (20.2 vs. 13.7; p = 0.0008) and to a lesser extent, closed comedones (25.6 vs. 22.7; p = 0.04). Secondly, during the interventional phase, the half-face treated with the dermocosmetic formulation showed a significantly lower number of inflammatory lesions (7.6 vs 9.4; p = 0.01) during the luteal phase compared to the half-face treated with the placebo. Tolerance of the dermocosmetic formulation was rated as good or excellent. Our data indicate a significant increase in the number of papules during premenstrual acne flare-ups in adult women and the use of a dermocosmetic may be of benefit in partially reducing this premenstrual inflammatory flare-up.

Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses. The patch contains functional layers of ultrathin stretchable electronics and a photosensitive patterned dye that reacts to UV radiation. Color changes in the photosensitive dyes correspond to UV radiation intensity and are analyzed with a smartphone camera. A software application has feature recognition, lighting condition correction, and quantification algorithms that detect and quantify changes in color. These color changes are then correlated with corresponding shifts in UV dose, and compared to existing UV dose risk levels. The soft mechanics of the UV patch allow for multi-day wear in the presence of sunscreen and water. Two evaluation studies serve to demonstrate the utility of the UV patch during daily activities with and without sunscreen application.

Skin exposure to acute or repetitive ultraviolet light induces risks which are now well identified. An efficient photoprotection is thus required for both UVB and UVA radiation. In particular, increasing evidence of the detrimental effects of UVA on skin has led to the development of a new generation of sunscreens that provide effective protection throughout the whole UV radiation spectrum. Many new UV filters have been introduced in the last decade, particularly UVA filters, with improved efficacy and safety. Sunscreen filters must be carefully combined to achieve esthetically pleasing products offering photostable and well-balanced photoprotection.

Summary The effects of acute or repeated suberythemal solar ultraviolet radiation (UVR) exposure on human skin have been insufficiently investigated. Such exposure almost certainly has important long-term consequences that include skin ageing and skin cancer. This review summarizes the published data on the biological effects of suberythemal exposure using a wide range of clinical, cellular and molecular endpoints, some of which may be considered as biomarkers for skin cancer and photoageing. We also include some recent unpublished results from our laboratories. The effects of UVA (320–400 nm), UVB (290–320 nm) and total solar UVR (290–400 nm) are compared. We demonstrate that avoiding sunburn does not prevent many indicators of cutaneous biological damage and that use of low sun protection factor (SPF) sunscreen can inhibit much of the damages induced by suberythemal exposure to UVR. However, even when applied correctly, sunscreen use will result in suberythemal exposure. The degree and spectral quality of such exposure will depend on the SPF and absorption spectrum of the sunscreen, but nonetheless it may contribute to cumulative photodamage. This review may help to determine the level of photoprotection required in sunscreens and daily use products, as well as the ideal ratio of UVB/UVA protection, to improve long-term photoprotection outcomes.

Synopsis The purpose of this study was to evaluate the impact of substrate roughness and of product spreading method on in vitro sun protection factor (SPF) measurement and to define the experimental conditions most appropriate to reach the best level of correlation to in vivo SPF. In vitro SPF assessment was carried out on 13 products (including different formulation types with SPF from 20 to 75) using various in vitro SPF protocols and comparing related predictive potential regarding in vivo SPF. In the first part, two spreading methods were compared on two types of PMMA (Polymethyl methacrylate plate with different roughness. The impact of a second spreading step after product drying was also evaluated. From the various investigated parameters, it was shown that (i) a higher roughness (Ra = 4, 5 μm) was preferred for O/W formulations (ii) using a defined sequence of light linear and circular strokes was more adequate than monitoring product spreading in terms of time and pressure (iii) both correlation to in vivo SPF and results variability were improved when a second spreading step was added. The altered protocol showed a good predictive potential regarding in vivo SPF values for O/W formulations (correlation coefficient 0.92, correlation curve slope 0.98) and coefficient of variation of in vitro results (14% of the mean SPF value) close to what is usually obtained in vivo. The repeatability of the protocol was also demonstrated. In the second part, we evaluated the impact of PMMA plate pre-treatment with paraffinum liquidum before spreading the product to get a better correlation between in vivo and in vitro SPF values for W/O formulations. This allowed us to define a protocol suitable for both O/W and W/O formulations. Resume L’objectif de cette etude etait d’evaluer l’impact sur les valeurs de SPF in vitro, d’une part de la rugosite des plaques de PMMA et d’autre part de la methode utilisee pour etaler les produits et de determiner les conditions operatoires offrant la meilleure correlation entre les valeurs de SPF in vitro et in vivo. A cette fin, le SPF in vitro de 13 produits solaires (couvrant differents niveaux de protection et differents types de formulation) a ete mesure avec les differents protocoles etudies et la predictivite du SPF in vitro par rapport aux valeurs in vivo a eteevaluee pour chaque protocole. Dans une premiere partie, deux methodes d’etalement des produits ont ete comparees sur deux types de plaques de PMMA presentant des rugosites differentes. L’apport d’une etape de re-etalement du film de produit apres sechage a egalement eteevalue. A partir de ces premiers resultats, nous avons pu montrer qu’il etait preferable d’utiliser des plaques de PMMA avec une rugosite plus importante (Ra de l’ordre de 4.5 μm) pour obtenir des valeurs de SPF in vitro mieux correlees au SPF in vivo et moins variables. Il est egalement ressorti qu’il etait plus approprie de definir la procedure d’etalement en terme de gestuelle qu’en termes de temps d’etalement et de pression. Enfin, il a ete demontre que le re-etalement du film residuel de produit apres sechage permettait d’ameliorer encore la correlation entre resultats in vitro et donnees in vivo et de reduire la variabilite des resultats in vitro. Le protocole de mesure du SPF in vitro ainsi defini offre une bonne predictivite des valeurs obtenues in vivo, pour les formulations H/E (coefficient de correlation egal a 0.92, courbe de correlation presentant une pente de 0.98) et la dispersion des resultats est proche de celle classiquement obtenue in vivo (coefficient de variation egal a 14% de la valeur moyenne du SPF in vitro). La repetabilite de ce protocole a eteegalement demontree. Dans une seconde partie, pour ameliorer la pertinence des SPF des formulations E/H mesures in vitro par rapport aux valeurs in vivo, l’effet d’un pre-traitement des plaques de PMMA avec de l’huile de vaseline a eteevalue. Il a ete montre que ce pre-traitement permettait d’atteindre une bonne concordance entre les resultats in vitro et in vivo non seulement pour ce type de formulation mais egalement pour tous les produits precedents. Ainsi, l’introduction d’un pre-traitement des plaques nous a permis d’obtenir un protocole de SPF in vitro adaptea la fois aux supports H/E et E/H.

Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones. Aim: To assess the efficacy of sunscreens containing a broad-spectrum UVA absorber the Mexoryl® SX or ecamsule and to compare formulations with and without it through a large number of clinical studies in human volunteers and patients. Methods: The following assessments were conducted: •Prevention of excessive pigmentation induced by UV exposure in Caucasian and Asian skins using a method that measures pigmentation protection factors (PPF). •Efficacy against DNA damage by measurement of pyrimidine dimer formation and p53 protein accumulation. •Protection of immune system using delayed type hypersensitivity (DTH) reactions to recall antigens, isomerization of urocanic acid (UCA), alteration of Langerhans cells (LC) density, morphology and function. •Reduction of epidermal and dermal alterations induced by repeated UVA or UV solar simulated radiation (SSR) using histology or immunohistology. •Prevention of the polymorphous light eruption (PMLE) in patients prone to develop this disease. Results: Mexoryl® SX-containing formulations showed a dose-dependent level of protection against pigmentation. For a same sun protection factor (SPF) the higher the UVA protection was, the higher was the PPF. Pyrimidine dimer formation and p53 accumulation were significantly reduced by formulations with Mexoryl® SX. In the studies looking at the suppression of DTH reactions to recall antigens by the different UV spectra, the LC alterations and the cis UCA formation, Mexoryl® SX formulations always showed a higher protective potency than sunscreen without it even when the protection against erythema was similar (products with same SPF). Mexoryl® SX formulations also prevented or significantly decreased to minimal, ferritin, tenascin and lysozyme expression induced by repeated UVA or SSR exposure. It also reduced the enhancement of collagenase 2 mRNA expression induced by SSR exposure. Finally PMLE study demonstrated that UVA protection was essential for the prevention of this photodermatose. Conclusion: Mexoryl® SX formulated in sunscreens or daily use products have been shown to be an effective UV absorber, leading to an increased efficacy of these products against a large number of biological damage induced by UVA, SSR or sun exposure.

The availability of new and highly potent UVA filters represents a major advance in the development of sunscreen products able to efficiently protect against a number of adverse effects induced by UVA radiation, including erythema, premature skin aging, photosensitivity disorders and some forms of skin cancer. Sunscreens are evaluated with sunburn as the end point using the sun-protection factor method. The action spectrum for sunburn is heavily weighed in the UVB range with a small contribution from the UVA (320–400 nm). It is recognized that the UVA protection effectiveness of sunscreens cannot be assessed with the sun-protection factor method. It has also been recognized that a need exists to develop a robust method to evaluate the effectiveness of UVA sunscreens. This review discusses the current in vivo and in vitro UVA test methods and the science behind them.

Background It is well established that ultraviolet (UV) radiation induces immunomodulatory effects that may be involved in skin cancer. Recent studies have shown that UVA (320-400 nm) and UVB (290-320 nm) radiation are immunosuppressive. As a result, sunscreens, which mainly absorb UVB, may be less effective in preventing UV radiation–induced immunosuppression than broad-spectrum products. Objective We sought to study the effects of UVA exposure on human delayed-type hypersensitivity (DTH) response and compare the efficacy of sunscreens having different levels of sun-protection factor (SPF) and UVA protection against both solar-simulated radiation and outdoor real-life sunlight exposure conditions. Methods DTH was assessed using a kit which includes 7 recall antigens that most of the participants encountered during childhood immunization. Evaluation of DTH test response was made 48 hours after test application before and after UV exposure with or without sunscreens. Results In unprotected participants, the response to DTH tests was significantly reduced irrespective of UV types of exposure (full-spectrum UVA, long UVA, solar-simulated radiation). A UVB sunscreen failed to protect from solar-simulated radiation-induced immunosuppression. In contrast, a broad-spectrum sunscreen with the same SPF but providing a high protection in the UVA range significantly reduced local UV-induced immunosuppression and prevented the distant effects. In the outdoor study, as compared with DTH responses obtained before sun exposure, no alteration of immune response was detected when the skin was protected by a broad-spectrum sunscreen having a high protection level in the UVA (SPF 25, UVA protection factor 14). Conversely a broad-spectrum sunscreen with lower protection against UVA (SPF 25, UVA protection factor 6) failed to prevent UV-impaired response. Limitations These results have been obtained after repeated exposure. Additional experiments obtained under acute exposure are in progress. Conclusion These findings clearly demonstrated the role of UVA in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire UV spectrum.

It is increasingly accepted that sunscreens should protect against ultraviolet radiation (UVR)-induced immunosuppression, with an index of protection that can be compared with the sun protection factor (SPF). Five groups of immunoprotection researchers met to discuss the status of immune protection factor (IPF) evaluation in human skin in vivo. Current methods rely on a suncreen's inhibition of UVR-induced local suppression of the contact hypersensitivity (CHS) response or the delayed-type hypersensitivity (DTH) response, using either the induction or the elicitation arms of these responses. The induction arm of the CHS response has the advantage of being sensitive to a single sub-erythemal exposure of solar-simulating radiation (SSR) that allows a direct comparison with the SPF. This approach, which necessitates sensitization, requires a large number of volunteers and is too labor intensive and time consuming to become a routine method. The elicitation arm of the CHS or DTH responses exploits prior sensitization to contact or recall antigens and has the advantage of being possible to apply on small groups of volunteers. Some current protocols, however, require repeat SSR exposures, which invalidates a direct comparison with SPF that is based on a single exposure. There is a need for a new simpler method of IPF that will have to be validated against existing models.

Sunscreens have been designed to protect against sunburn and their efficacy has, therefore, been labeled by the so-called sun protection factor (SPF). Although this value is well determined using a standardized protocol and it affords a good evaluation of the protection against erythema it may be inadequate to provide a relevant measurement of efficacy against other biologic damages. This is particularly true when action spectra and threshold dose are different from those of erythema. In the case of ultraviolet (UV)-induced immune suppression, the action spectrum is not known, so it cannot be asserted that SPF may accurately predict the level of protection against this endpoint. We addressed this issue by measuring in human volunteers the ability of two broad-spectrum SPF 15 sunscreens with different ultraviolet A (UVA) protection levels, to prevent the alteration of the efferent phase of the local delayed-type hypersensitivity (DTH) response to recall antigens (Multitest Pasteur/Merieux, Lyon, France) after acute solar-simulated UV exposure. We first determined the ultraviolet radiation (UVR) dose needed to induce a significant DTH inhibition in several groups of 15 volunteers. Two minimal erythemal doses (2 MED) were found to be the minimal immunosuppressive dose (MISD). As a result, the immune DTH response is reduced in average by 36%. The lower doses tested (0.5 and 1 MED) were ineffective. Sunscreen-treated groups were exposed to either 1 or 2 MED × SPF doses. As expected, no alteration in DTH response was observed in the groups exposed to 1 MED × SPF whatever the sunscreen applied. In contrast, after exposure to 2 MED × SPF, the DTH response remained unaltered in the group pretreated with the sunscreen product with the higher protection in the UVA range but was significantly suppressed by 55.7% in the group pretreated with sunscreen with a much lower protection in the UVA range. These data suggest that SPF may not be sufficient to predict the ability of sunscreens to protect from UV-induced immune suppression. Determining the level of UVA protection is particularly needed, as UVA seems to have a relatively low contribution to erythema but is highly involved in immunosuppression.

It is well established that ultraviolet radiation has immunomodulatory effects which may be involved in skin cancer. Recent studies have shown that UVA radiation (320-400 nm) as well as UVB (290-320 nm) is immunosuppressive. This means that sunscreens which mainly absorb UVB (protection against erythema) may be less effective in preventing UVR-induced immunosuppression than broad-spectrum products. We have studied the effects of UVA exposure on the human delayed-type hypersensitivity response (DTH) and compared the efficacy of sunscreens having different levels of UVA protection under both solar-simulated radiation (SSR) chronic exposures or acute exposure and outdoor real-life solar exposure conditions. DTH was assessed using recall antigens. Our studies clearly demonstrate the role of UVA in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire UV spectrum. These data suggest that sun protection factor may not be sufficient to predict the ability of sunscreens for protection from UV-induced immune suppression. Determining the level of UVA protection is particularly necessary, because UVA seems to have a relatively low contribution to erythema but is highly involved in immunosuppression.

Background/Aim: The issue of the photostability of sunscreens has been frequently raised because of the possible loss of photoprotection, mainly in the UVA range, during sun exposure. Up to now, in vitro techniques have been mainly proposed to evaluate photostability. These techniques have generated controversial debates concerning the predictive value of these in vitro observations in relation to the in vivo reality during sun exposure. Methods: Diffuse reflectance spectroscopy (DRS) is a recently developed technique that allows measurement of the UVA efficacy of sunscreen products in vivo on human volunteers. The absorption spectrum of the product is obtained by measuring the change in reflection of the skin with and without product. From this absorption spectrum, the UVA protective efficacy of the test product can be calculated for an appropriate source and a given biological action spectrum. We have used the DRS technique in vivo to determine the photostability of sunscreen products by measuring reflection spectra in the UVA range (320–400 nm) before and after product application and before and after UV exposure of the test products. Comparison between these spectra or between the corresponding calculated UVA protection factors has made it possible to determine the remaining level of protection in the UVA range after exposure. This study was designed to compare in vivo the protective efficiency and the photostability of three marketed sunscreen products (SPF 23–30) after solar-simulated exposure for SPF testing or after actual sun exposure. These in vivo data were then compared to in vitro photoinstability results. Results: According to the in vitro measurements, one sunscreen product was found photostable and two products photo-unstable. After UVe exposure for in vivo SPF determination, a decrease in UVA absorption and UVA-PF was observed for the two photo-unstable products, while the photostable product did not present any decrease in UVA absorption. These results were confirmed through exposure to actual sun. Conclusion: Our study confirms the prediction of the in vitro methods previously used to assess the photostability of sunscreen products. In addition, DRS provides a powerful new tool for the in vivo simultaneous evaluation of photostability and estimation of the UVA protection factor of sunscreen products performed during the test for SPF determination.

Background/Aims: The accuracy and reliability of any method to assess the UVA protection effectiveness of sunscreens needs to be demonstrated. The aim of the present study was to calibrate the effectiveness of a biological end point (Persistent Pigment Darkening, PPD) to assess UVA photoprotection. Methods: Persistent Pigment Darkening was selected as the end point because its action spectrum extends across the UVA. A broad UVA source was chosen to challenge all UVA wavelengths. Attenuation of UVA was performed with neutral density filters (equally absorbing at all wavelengths). Human subjects were tested with a series of UVA beams attenuated by the neutral density filters. The UVA protection effectiveness of a standard sunscreen was also tested with four panels of volunteers to assess the reproducibility of the method. Results: The attenuation factors of the neutral density filters were found to correspond to the UVA protection factors arrived at with PPD as the end point. The repetitive tests showed a good internal consistency of the method. Conclusions: The calibration procedure proposed shows threshold PPD, used as an end point in a UVA-PF test method, to be a reliable endogenous dosimeter for UVA radiation that enters the skin.

Nuclear p53 expression is a sensitive parameter for the detection of ultraviolet (UV)-induced skin damage, and it has been used as an endpoint to evaluate the effectiveness of sunscreens. In this study, we compared the protection provided by two sunscreens having identical sun protection factors (SPF) but different UVA protection factors (UVA-PF) measured by the persistent pigment darkening method (PPD). The SPF of the sunscreens was 7 and the UVA-PF were respectively 7 and 3. Nuclear p53 protein was quantified in human skin biopsies treated with sunscreens and exposed 8 times to 5 MED of solar simulated radiation (SSR). The results showed that both sunscreens offered only partial protection against the increased expression of nuclear p53 protein induced by repetitive SSR exposures. However, a significantly lower level of p53-positive cells was found in areas protected with the sunscreen having the higher UVA-PF compared to the other sunscreen protected areas. In order to verify whether the difference in efficacy of these products was due to the difference in UVA absorption capacity, we quantified epidermal p53 protein accumulation after 8 exposures to either UVA (320-400 nm) or UVA1 (340-400 nm). We showed that as with SSR, repetitive exposures to 12.5 and 25 J/cm2 of UVA or UVA1 induced a significant increase in p53-positive cells in the human epidermis. These results confirmed that SPF determined on the basis of an acute erythemal reaction does not predict the level of protection against cumulative damage. They also showed that the protection provided by two sunscreens with different UVA protection factors is different (based on nuclear p53 protein accumulation), and that the PPD method can distinguish varying levels of sunscreen efficacy against UVA-induced cell damage.

There is now considerable evidence that chronic UVA exposure induces damage in animal and human skin; however, little is known about UVA protection of human skin. The aim of this study is to evaluate the efficacy of Mexoryl® SX, a broad UVA absorber (λ max = 345 nm) against UVA-induced changes in human skin. The regimen of UVA exposure (13 weeks with increasing suberythemal doses) induces intense pigmentation with no erythema. Skin hydration and elasticity decrease, whereas total skin thickness, assessed by echography, remains unchanged. Irradiated epidermis reveals a significant thickening of the stratum corneum, an absence of hyperplasia and an increase in the expression of the protective iron-storage protein ferritin. No significant alterations are seen using antisera against type IV collagen or laminin, suggesting that the dermal-epidermal junction (DEJ) is mainly preserved. In dermis, enhanced expression of tenascin is seen just below the DEJ but type I procollagen, which is localized at the same site, is unaltered. Although we are unable to visualize any changes in elastic network organization using Luna staining or specific antiserum directed against human elastin, we notice an increased deposition of lysozyme or alpha-1 antitrypsin on elastin fibres. Mexoryl® SX (5%) efficiently prevents these alterations. Thus, these results suggest that UVA photoprotection can prevent early putative alterations leading to photoageing. © 1998 Elsevier Science S.A. All rights reserved.

Synopsis A multicentred study derived from the COLIPA in vitro UVA method was performed to assess the influence of test conditions on UVA protection factor (UVAPF) values in terms of amplitude, reproducibility between laboratories and correlation with in vivo UVA results. Eight products with a range of in vivo UVAPF from three to 29 were used. Two different types of plates, namely high-roughness (5 μm) and low-roughness (2 μm) plates, were used with a different application rate for each (1.3 mg cm−2 and 0.75 mg cm−2 respectively). The UVR dose applied to both plate types followed the same principle as the original test (1.2 J. cm−2 × UVAPF0). Strong, significant correlations between in vitro and in vivo UVAPF values were observed for both plate types (Pearson correlation > 0.9, P ≤ 0.01). The correlation and slope obtained with the low-roughness plates confirmed the previous results obtained by COLIPA. Across all laboratories, higher UVAPF values were obtained on the high-roughness plates (P

Skin exposure to sunlight can cause many adverse effects. It is now recognized that both Ultraviolet A (UVA) and UVB wavelengths are responsible for the detrimental effects of solar radiation on skin. With our increasing knowledge on the harmful effects of UVA, the need for effective, well-balanced photoprotection has become more crucial. Numerous clinical studies showed that well-balanced sunscreen, with a SPF/UVAPF ratio ≤ 3, provide the most effective protection against pigmentation (especially on dark skin), DNA damage, UV-induced skin immunosuppression and photodermatoses. The calculation of UVA protection required in Asia revealed its particular importance in India, and gives clear evidence that the SPF value alone is not sufficient to evaluate the efficacy of a sunscreen.

This review of published in vitro and in vivo studies concerning the biological effects of ultraviolet A (UVA; 320–400 nm) radiation illustrates the evidence for combining UVA and UVB filters in sun-protection products. These data have led to the development of new sunscreens as well as methods to evaluate their efficacy. After listing the UVA filters available and briefly noting the requirements for a high SPF, broad-spectrum sunscreen, the methods for evaluating the level of UVA protection will be described. This article also summarizes several studies looking at the prevention of erythema, pigmentation, DNA damage, photoimmunosuppression, photoaging and photodermatoses. These data demonstrate in vitro and in vivo that only well-balanced UVA-UVB sunscreens, absorbing over the entire UV spectrum are able to prevent or significantly reduce the associated biological damage.

There is a continuing need to measure and communicate reliably the UVA protection offered by commercial sunscreens. To that end, the COLIPA (European Cosmetics Trade Association) 'In Vitro Sun Protection Methods' group has developed a new in vitro method for measuring UVA protection in a standardized, reproducible manner. The method is based on in vitro UV substrate spectrophotometry and convolution of resulting absorbance data with the action spectrum for the in vivo Persistent Pigment Darkening (PPD) endpoint to provide an in vitro UVA protection factor (UVAPF) which is correlated with an in vivo measure. This method has been published as a COLIPA guideline, used currently in European geographies for testing and labelling sunscreen products. This article summarizes two 'ring' studies, involving eight separate testing laboratories, which both defined critical parameters for the method and validated it. In Ring Study 1, eight laboratories tested the in vitro UV transmission of a total of 24 sunscreens and, from the data, a unit dose of UVA (D(0) of 1.2 J cm(-2)) was defined to provide a single irradiation step which, by taking into account potential sunscreen photo-instability, gave the closest agreement with in vivo UVAPF values. In Ring Study 2, eight laboratories tested the in vitro UV transmission of a total of 13 sunscreens using this single irradiation step and established a very good correlation (r(2) = 0.83; slope = 0.84, P < 0.0001) between resulting in vitro UVAPF values and corresponding values derived from the in vivo PPD method. This new method, therefore, can be used to provide a reliable in vitro metric to describe and label UVA efficacy in sunscreen products, in line with the EU Commission recommendation 2006/247/EC.

The importance of adequate UVA protection is apparent with improved understanding of UVA-induced skin damage. This has led to the development of new sunscreen ingredients. A number of regulatory bodies or experts from the industry and academia have proposed methods to assess the efficacy of sunscreens against UVA radiation. In addition different proposals have been made regarding the labeling for UVA protection. The purpose of this paper is to describe several in vitro methods for measuring UVA protection of sunscreen products and to consider their validity. The different proposals in terms of UVA labeling are also presented and discussed. This review illustrates the need for standardization of the measurement conditions and harmonization to convey to consumers the most appropriate information on UVA protection.

UVA protection afforded by 6 different sunscreens with a sun protection factor of 21 or more was compared by means of the persistent pigmentation darkening method. Colorimetric and visual assessment showed significant differences in UV radiation-induced pigmentation at 2 hours. The labeled sun protection factor of the tested sunscreens was not predictive of UVA protection level.

Background/Purpose: The aims of the present studies were to check that persistent pigment darkening (PPD) method can produce accurate and reproducible results for high UVA protection factors (UVAPF) and to provide data on the variability between laboratories and on the influence of skin types. Methods: The Japanese Cosmetic Industry Association (JCIA) PPD method was used to determine the UVAPF in different laboratories of different sunscreen formulations with increasing UVAPF. Two formulations were tested at seven independent laboratories and five products within two laboratories. The influence of skin types on the UVAPF of two products was tested within one laboratory on two panels of volunteers. All laboratories complied with the JCIA method specifications. Results: Reproducible results have been obtained between the different labs and a low and satisfactory variability was achieved with a panel size of 10 subjects. Furthermore, skin type was demonstrated to have no influence within the defined selection criteria. Conclusions: From this multiple center testing, the PPD method has been shown to be appropriate for testing sunscreen formulations with UVAPFs above 20. It is reasonable to expect that test results will be consistent if an identical protocol is used between laboratories.

In vitro and in vivo studies provide a body of evidence that adequate protection of the skin against ultraviolet (UV)-induced damage requires photostable broad-spectrum sunscreens with a proper level of UVA protection. UVA alone and UV solar simulated radiation (SSR) induce DNA lesions in keratinocytes and melanocytes as reflected by the comet assay and p53 accumulation. UVA and SSR impair the immune system as shown by significant alteration of Langerhans cells and inhibition of contact hypersensitivity response to chemical allergens and delayed-type hypersensitivity response to recall antigens. Any of these detrimental effects is more efficiently prevented by sunscreens with a higher level of protection in the UVA range. The involvement of UVA (fibroblast alteration, increased metalloproteinase expression) and the pivotal need for well-balanced UVA/UVB sunscreens were further demonstrated using reconstructed three-dimensional skin models.

SummaryBackground Ultraviolet (UV) exposure of human skin induces local and systemic immune suppression. This phenomenon has been well documented when UVB radiation (290–320 nm) is used. The mechanism is thought to involve Langerhans cells (LCs), the epidermal dendritic cells that play a crucial role in antigen presentation. A variety of studies have clearly demonstrated that UVB radiation decreases LC density and alters their morphology and immunological function, but little is known about the effects of the entire UV spectrum (ultraviolet solar simulated radiation, UV-SSR or UVB + UVA) or UVA (320–400 nm) radiation alone. Objectives The purpose of this study was to analyse and compare the effects of a single exposure of human volunteers to UV-SSR, total UVA or UVA1 (340–400 nm) in the human epidermal LC density and morphology. Methods Immunohistochemistry on epidermal sheets with various antibodies and transmission electron microscopy (TEM) were used. Results Immunostaining for class II antigen revealed that a single UV-SSR exposure, corresponding to twice the minimal erythemal dose (MED), induced a significant reduction in LC density with only slight morphological alterations of remaining cells. After a single UVA exposure, LC density showed a dose-dependent reduction with a significant effect at 60 J cm−2 (well above the MED). Moreover, the reduction of LC dendricity was also dose-dependent and significant for doses exceeding 30 J cm−2. UVA1 radiation was as effective as total UVA for the later endpoint. As demonstrated by TEM, the location of Birbeck granules containing epidermal cells was modified in UVA-exposed areas. They were located in the spinous rather than in the suprabasal layer. In addition, the morphology of these cells was altered. We observed a rounding up of the cell body with a reduction of dendricity. Alterations of mitochondrial membrane and ridges were also seen. Conclusions A single exposure of human skin in vivo to UV-SSR, UVA or UVA1 radiation results in different alterations of density and/or morphology of LCs. All these alterations may impair the antigen-presenting function of LCs leading to an alteration of immune response.

The issue of the photostability of sunscreens has been frequently raised because of the possible loss of photoprotection, mainly in the UVA range, during sun exposure. Up to now, in vitro techniques have been mainly proposed to evaluate photostability. These techniques have generated controversial debates concerning the predictive value of these in vitro observations in relation to the in vivo reality during sun exposure.Diffuse reflectance spectroscopy (DRS) is a recently developed technique that allows measurement of the UVA efficacy of sunscreen products in vivo on human volunteers. The absorption spectrum of the product is obtained by measuring the change in reflection of the skin with and without product. From this absorption spectrum, the UVA protective efficacy of the test product can be calculated for an appropriate source and a given biological action spectrum. We have used the DRS technique in vivo to determine the photostability of sunscreen products by measuring reflection spectra in the UVA range (320-400 nm) before and after product application and before and after UV exposure of the test products. Comparison between these spectra or between the corresponding calculated UVA protection factors has made it possible to determine the remaining level of protection in the UVA range after exposure. This study was designed to compare in vivo the protective efficiency and the photostability of three marketed sunscreen products (SPF 23-30) after solar-simulated exposure for SPF testing or after actual sun exposure. These in vivo data were then compared to in vitro photoinstability results.According to the in vitro measurements, one sunscreen product was found photostable and two products photo-unstable. After UVe exposure for in vivo SPF determination, a decrease in UVA absorption and UVA-PF was observed for the two photo-unstable products, while the photostable product did not present any decrease in UVA absorption. These results were confirmed through exposure to actual sun.Our study confirms the prediction of the in vitro methods previously used to assess the photostability of sunscreen products. In addition, DRS provides a powerful new tool for the in vivo simultaneous evaluation of photostability and estimation of the UVA protection factor of sunscreen products performed during the test for SPF determination.

The prevention of photodermatoses implies that the exposure to ultraviolet (UV) light of photosensitive patients is reduced to levels below the threshold of induction of light reactions. The four principal measures of prevention are the following: “ avoidance of sun exposure around midday; “ UV-protective clothes; “ hats; “ use of sunscreen products. Protection of photosensitive patients by sunscreen products play an important role. This is particularly true for the prevention of photodermatoses, which are elicited by UVA. About 50% of the exposure to UVA occurs in the shade, i.e. in the absence of direct sunlight. The amount of UVA in sunlight is high from sunrise to sunset, whereas the intensity of UVB peaks more sharply at midday. Whereas window and car glass materials offer an effective shield against UVB, they are transparent for UVA. Moreover, due to the presence of subclinical and/or apparent eczema in already affected skin areas, the natural protective capacity of the horny layer may be reduced or lost, which will further increase the light sensitivity of the afflicted skin. Which are the ideal properties of state-of-theart sun protection products? Such compounds should be: (i) well tolerated; (ii) cosmetically pleasant; (iii) non-toxic; (iv) equally effective against UVA and UVB; (v) photostable; (vi) water resistant; (vii) with a high ‘Sun Protection Factor’. These criteria should be briefly commented on (adverse properties listed under (i)–(iii) are exclusion criteria). (i) Good tolerance is of primary importance, since such products are often applied under stress conditions to sensitive skin. Skin tolerance requires careful testing and optimisation, since preparations with high protection factors contain relatively large amounts of UV filter substances (see later). Many promising filter substances are rejected at an early stage of development due to their irritant, photoirritant or photoallergic potential. * Corresponding author. Tel.: +33-1-47567701; fax: +331-47567630.

Publisher Summary Changes in lifestyle and the development of leisure activities and holiday habits have led to an increase in daily exposure of the skin to ultraviolet (UV) light, affecting an ever larger section of the population. At the same time, sun protective products have undergone improvements in their ability to protect skin against sunburn as reflected by continuous increases in sun protection factors (SPF). Though there is a plethora of end points related to UVB damage, most of them being directly or indirectly linked to DNA damage, there are only few specific UVA-related phenomena in the skin that can be quantified. In the field of photoprotection, considerable progress was made in the investigation of UVA damage when potent filter substances with maximum absorption in the range of longer than 320 nm became available. It became clear that some subchronic to chronic skin disorders are mainly because of UVA exposure (polymorphous light eruption being a typical and frequent example). This chapter discusses those methods of quantification of the impact of UV light on the skin, which are sufficiently discriminative to distinguish between mere UVB and complete UVB + UVA photoprotection and that are of use in the assessment of the efficacy of photoprotection.

The trans to cis photoisomerization of urocanic acid (UCA) in skin is considered to play an important role in the mechanism of immunosuppression. We have investigated the effects of skin type and various sunscreens with low sun protection factor (SPF) on the UV-induced cis-UCA formation in human skin after exposure to artificial UV light. The rate of cis-UCA formation depends little on the skin type and is reduced by topical application of sunscreens. The rate of cis-UCA formation decreases with increasing SPF and only broad-spectrum, highly protective sunscreens offer protection against the UV-induced formation of cis-UCA, which accumulates in the stratum corneum after multiple UV exposures. A theoretical approach to estimate the distribution of cis-UCA after irradiation indicates that this compound may diffuse into the deeper layers of the epidermis with D approximately 10(-17) m2/s, and that its elimination from the stratum corneum is mainly due to desquamation.