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.

Burned bodies: post-mortem computed tomography, an essential tool for modern forensic medicine.

Currently, post-mortem computed tomography (PMCT) has become an accessible and contemporary tool for forensic investigations. In the case of burn victims, it provides specific semiologies requiring a prudent understanding to differentiate between the normal post-mortem changes from heat-related changes. The aim of this pictorial essay is to provide to the radiologist the keys to establish complete and focused reports in cases of PMCT of burn victims. Thus, the radiologist must discern all the contextual divergences with the forensic history, and must be able to report all the relevant elements to answer to the forensic pathologist the following questions: Are there tomographic features that could help to identify the victim? Is there evidence of remains of biological fluids in liquid form available for toxicological analysis and DNA sampling? Is there another obvious cause of death than heat-related lesions, especially metallic foreign bodies of ballistic origin? Finally, what are the characteristic burn-related injuries seen on the corpse that should be sought during the autopsy? TEACHING POINTS: • CT is highly useful to find features permitting the identification of a severely burned body. • PMCT is a major asset in gunshot injuries to depict ballistic foreign bodies in the burned cadavers. • CT is able to recognise accessible blood for tests versus heat clot (air-crescent sign). • Heat-related fractures are easily differentiated from traumatic fractures. • Epidural collections with a subdural appearance are typical heat-related head lesions.

[Orbital myositis associated with ipilimumab]. / Myosite orbitaire associée à un traitement par ipilimumab.

BACKGROUND: Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) that allows increased survival and, occasionally, complete remission, in the treatment of metastatic melanoma. The most frequent adverse effects are attributed to dysimmunity. We report the case of a female patient who developed orbital myositis during treatment with ipilimumab. PATIENTS AND METHODS: A woman on ipilimumab for a heel melanoma with mediastinal metastases was referred for evaluation of painful diplopia and proptosis that began three days after the fourth infusion of ipilimumab. The clinical examination disclosed a left abductiondeficit associated with conjunctival hyperaemia and palpebral oedema. Orbital MRI disclosed enlargement of the left lateral rectus, enhancing after contrast. An extensive work-up did not find any evidence for thyroid-related eye disease, as well as other orbital inflammatory processes, orbital cellulitis or orbital metastases. Treatment with high-dose oral steroids resulted in complete clinical recovery within a few days. DISCUSSION: To our knowledge, this is the first clinical report of orbital myositis as an adverse event related to anti-CTLA-4 antibody treatment. Both timing and usual profile of adverse events support the hypothesis that orbital myositis has to be attributed there to ipilimumab. Several dysimmune toxicities were observed with ipilimumab. Ophtalmic toxicity has unusually been described. Most cases were uveitis. Whether immune-related adverse events correlate with clinical response to ipilimumab treatment remains to be determined.

A preliminary investigation of the impact of oily skin on quality of life and concordance of self-perceived skin oiliness and skin surface lipids (sebum).

OBJECTIVE: This preliminary study investigated both the impact of oily skin on quality of life (QoL) and the agreement between subjective oily skin self-assessment and objective skin surface sebum measurement in young to middle-aged Chinese women in Beijing. METHODS: A 18-item Chinese version of the Oily Skin Self-Image Questionnaire (OSSIQ) was used to assess the impact of oily skin on QoL in 300 healthy female subjects (age groups: 20-25; 26-30; 31-35,). The subjects were divided equally into the oily skin group and the non-oily skin group based on their self-perception of skin oiliness. The level of skin surface lipids (SSL) was measured on the middle of the forehead, and both cheeks using the Sebumeter(®). In order to assess the agreement between self-perceived skin oiliness and measured SSL, we tentatively used the SSL median value as a dividing point to regroup all subjects. RESULTS: The results indicate that the Chinese version of the OSSIQ distinguished the oily skin group from the non-oily skin group. Subjects in the oily skin group had significant higher emotional status score and behavior score when compared with subjects in the non-oily skin group. Subjects in the oily skin group had higher SSL when compared with subjects in the non-oily skin group, especially in younger age groups. The agreement between self-perceived skin oiliness and measured SSL was moderately strong in younger age groups, and declined with age. CONCLUSION: These results strongly suggest that having oily skin can cause a significant negative impact on QoL among Chinese women. The Chinese version of the OSSIQ is a reliable and valid tool for assessing the impact of oily skin on QoL. The accuracy of oily skin self-assessment declines with age.

[Dermatology, cosmetic and well-being]. / Dermatologie, cosmétique et bien-être.

BACKGROUND: To the extent that they help improve our appearance, cosmetics can affect how we relate to ourselves and to others, and as such can improve quality of life. Such benefits may be objectively demonstrated using validated methods and quality-of-life scales. GOAL: The aim of this review is to assess the effects of cosmetics on well-being in various situations based on studies using objective measurement methods. METHOD: Literature review. RESULTS: In pathological settings, the use of cosmetics can significantly improve the quality of life and well-being of patients, resulting in better acceptance of their disease and better therapeutic compliance. The use of cosmetics has also been shown to exert positive effects on self-esteem and social relations. A growing body of studies also demonstrates the beneficial effects of cosmetics on well-being under normal physiological conditions. DISCUSSION: Today, the effects and benefits of cosmetics can be measured objectively using quality-of-life scales, allowing initiation of actions for the rediscovery of well-being and self-esteem.

Cellulite and skin ageing: is there any interaction?

OBJECTIVE: This study aimed to identify the characteristics of cellulite in women of different age and to appreciate whether cellulite could interfere with skin ageing or not. METHODS: 94 Healthy females, divided into three age groups (21-30yrs; 31-40yrs; 51-60yrs) and two grade groups of cellulite (grade 2; grade 0 or control group), were investigated using non invasive techniques. The "orange peel appearance" was quantified by measuring the shadowed surfaces under low angle light. The biomechanichal properties were measured (extensibility-retractability-elasticity). The thicknesses of the skin structures were also evaluated using ultrasound. Echogenicity of the dermis was recorded and dermis density determined in two bands (superficial and low dermis). RESULTS: In grade 2, the shadowed surfaces are significantly different according to age; i.e. smaller and more numerous after age of 30; the total skin thickness including hypodermis is increased of about 30% irrespective to age, compared to control group. The biomechanical properties of the skin are significantly modified as age increases without any grade effect. In grade 2, retractability and elasticity parameters are altered from age 30 whilst only from age 50 in the control group. Echogenicities of the superficial and deep dermis also decrease from age 30 and become significantly lower than the ones of grade 0. CONCLUSION: Population with cellulite presents earlier skin ageing characteristics than the control population. Two sub-populations may exist: the under 30 age with large dimpled surfaces, normal biomechanical and density properties; and the over 30 age with smaller and numerous dimpled surfaces and already altered dermis properties. This premature skin ageing should be prevented accordingly.

An epidemiological study of acne in female adults: results of a survey conducted in France.

BACKGROUND: Acne is usually perceived as a disease of teenagers, and most epidemiological studies have focused on adolescents. OBJECTIVE: The primary objective was to investigate the prevalence of acne in a representative sample of French females. Information about skin type, life-style factors influencing acne and quality of life were also recorded. METHODS: A self-administered questionnaire was sent to 4,000 adult women aged 25-40 years, after a validation test by three dermatologists. A definition of acne severity, according to questionnaire answers, was established before the questionnaire was sent out. RESULTS: A total of 3394 women completed the questionnaire of which 3,305 were useable. The data showed a prevalence of acne in 17% of the population, and physiological acne in 24%. Thus, the total acne prevalence was 41%. Forty-nine per cent of the acne patients had acne sequelae (scars and/or pigmented macules). Forty-one per cent of adult acne patients had not experienced acne during their adolescence. A premenstrual flare and stress was recorded as causing acne in 78% and 50%, respectively. Twenty-two per cent of acne subjects were currently receiving therapy. For most patients, acne did not severely impair their quality of life. CONCLUSION: This study shows a prevalence of acne in 41% of women in the general population. A high proportion of these acne cases are late onset acne.

Adapalene 0.1% gel has low skin irritation potential even when applied immediately after washing.

The purpose of this study was to evaluate the difference, if any, in facial skin tolerance of adapalene 0.1% gel applied immediately after washing, compared to delayed application as recommended for the other topical retinoids: tretinoin and isotretinoin. Twenty-five acne patients with mild to moderate acne vulgaris were included in this intra individual randomized comparison study where adapalene 0.1% gel was applied immediately after washing on one half of the face and 20-30 min after washing on the contralateral half-face, for 22 consecutive days. No difference between the two regimens was detected by the investigator or by 21 of the 22 patients who completed the study. It was concluded that application of adapalene gel 0.1% is well tolerated even when applied immediately after washing.

Evaluation of clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life.

A randomized, multicentre, investigator-masked study was conducted in 105 patients with mild to moderate acne vulgaris to compare the efficacy and safety of adapalene 0.1% gel with tretinoin 0.025% gel after three months of treatment, with particular emphasis on reduction in inflammatory lesion counts after one week of treatment and impact on quality of life. In terms of efficacy, adapalene gel was found to be superior to tretinoin gel after one week of treatment, with respect to reduction in inflammatory lesion counts (32% vs. 17%, respectively; P = 0.001), total lesion counts (28% vs. 22%, respectively; P = 0.042) and global severity grade (28% vs. 16%, respectively; P = 0.001). No significant difference between the two treatments was found after 12 weeks of treatment for any of these variables. Evaluation of facial skin tolerance parameters showed significant differences between the two treatments in favour of adapalene for dryness, erythema, immediate and persistent burning and pruritus for at least one time point. One patient in the adapalene group and three patients in the tretinoin group experienced medical events which lead to discontinuation of treatment (skin irritation; NS). Quality of life scores improved more rapidly in the adapalene group than in the tretinoin group, with significant differences (P < 0.05) appearing at week 1 for questions related to problems with partners, close friends or relatives and to skin symptoms. There was also a significantly greater improvement in social and leisure activity in the adapalene group at week 12. Adapalene 0.1% gel reduced inflammatory and total lesion counts more rapidly than tretinoin 0.025% gel, and was also better tolerated. These differences appear to result in an earlier and greater quality of life improvement for the patients receiving adapalene.

Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris.

A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.

A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials.

The purpose of this meta-analysis was to determine if adapalene 0.1% gel (Differin) provided superior efficacy and better tolerability than tretinoin 0.025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0.1% gel, 450 treated with tretinoin 0.025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran-Mantel-Haenszel test. All statistical tests were two-sided, with the 0.05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.

Adapalene 0.1% gel has low skin-irritation potential.

BACKGROUND: Adapalene is a new naphthoic acid derivative with potent retinoid and antiinflammatory properties, developed for the topical treatment of acne vulgaris. OBJECTIVE: We compare the cutaneous safety of adapalene in different gel vehicles with tretinoin 0.025% gel. METHODS: A total of 42 healthy human subjects were enrolled in two randomized, double-blind, controlled, intraindividual studies. In the first study (study A), adapalene aqueous 0.03% and 0.1% gels were evaluated for their 21-day cumulative irritation potential compared with vehicle alone, patch alone, and tretinoin 0.025% gel under occlusion. In the second study (study B), adapalene aqueous (0.03% and 0.1%) gels and adapalene alcoholic (0.03% and 0.1%) gels were evaluated for their 5-day cumulative irritation potential compared with their respective vehicles and tretinoin 0.025% gel. Transepidermal water loss (TEWL) was measured daily at each visit. RESULTS: In study A, adapalene had a slight irritation potential that was in the same range as the gel vehicle and the patch alone, whereas tretinoin 0.025% gel was a severe irritant. In study B, no irritation was seen with either adapalene aqueous gels or adapalene gel vehicles or patch alone. The adapalene alcoholic gels were slightly irritating, and tretinoin gel produced intense irritation reactions in the majority of subjects. TEWL increased fourfold at the tretinoin site but remained unchanged at all adapalene sites. CONCLUSION: Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel.

Skin tolerance of adapalene 0.1% gel in combination with other topical antiacne treatments.

BACKGROUND: Adapalene (Differin gel) is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We assessed, in healthy volunteers, the skin irritancy potential of three combinations, each including adapalene 0.1% gel and one topical marketed antiacne product. METHODS: Twenty-five healthy volunteers were enrolled in a 21-day cumulative irritancy study performed in a double-blind, randomized, controlled, intraindividual design. Five days a week, the three materials (benzoyl peroxide, clindamycin phosphate, and erythromycin) were applied in a nonocclusive manner either alone or in combination with adapalene gel on seven cutaneous sites on the upper back. Adapalene was applied in the evening whereas the three other materials were applied in the morning. Irritation was evaluated and scored daily except on weekends. RESULTS: All materials were well-tolerated when tested alone. The combinations of adapalene 0.1% gel and either benzoyl peroxide, clindamycin phosphate, or erythromycin were also well-tolerated. The mean cumulative irritancy indices indicated that all three combinations were nonirritating. CONCLUSION: Under the conditions of the study, all tested treatments alone or in combination appeared nonirritating.

Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients.

BACKGROUND: Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris. METHODS: A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products. RESULTS: A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p < 0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported. CONCLUSION: The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

[Comparative study of the efficacy and tolerability of 0.1 and 0.03 p.100 adapalene gel and 0.025 p.100 tretinoin gel in the treatment of acne]. / Etude comparative de l'efficacité et de la tolérance de gels d'adapalène à 0.1 et 0.03 p. 100 et d'un gel de trétinoïne à 0.025 p. 100 dans le traitement de l'acné.

INTRODUCTION: Adapalene is a new chemical entity with retinoid activity. PATIENTS AND METHODS: 0.1 p. 100 adapalene gel (Différine gel), 0.03 p. 100 adapalene gel and a commercially available 0.025 p. 100 tretinoin gel (Aberel gel) were compared in 89 male and female patients with acne. RESULTS: Inflammatory, non inflammatory, total lesion counts, and the global facial acne grade regularly decreased as a function of time in the three treatment groups. No statistically or clinicaly significant differences were observed for these parameters between 0.1 p. 100 adapalene gel and 0.025 p. 100 tretinoin gel following a 12-week treatment. Conversely, both of these gels were significantly more effective than 0.03 p. 100 adapalene gel with regards to inflammatory and total lesion counts, and the global facial acne grade. The differences of efficacy seen between both adapalene gels demonstrate a dose-dependent activity of the drug in the topical treatment of acne. The three products induced retinoid-like skin irritation with significant differences in intensity in favour of adapalene for erythema, dryness, scaling and burning after application and in favour of tretinoin for persistent burning. No treatment-related medical events were reported and adapalene plasma levels were lower than 0.15 ng/ml (limit of detection of the analytical method). CONCLUSIONS: The topical treatment of acne with adapalene gels was found to be safe and effective, with a dose-related response. The efficacy of 0.1 p. 100 adapalene gel and of 0.025 p. 100 tretinoin gel are not different but skin tolerance of 0.1 p. 100 adapalene gel is superior.

Chronic topical application of all-trans-retinoic acid in man does not affect corneocyte surface area.

The potential therapeutic activity of topically applied novel analogues of retinoic acid is currently measured in many different animal models. In most cases, the technique used is invasive and biopsy specimens are required. Furthermore, efficacy in these models is not a guarantee of success in treatment of humans. Therefore, predictive human pharmacology tests are required in order to quantify a retinoid effect on human skin before conducting large clinical trials. The aim of this study was to determine whether changes in corneocyte surface area could be used as a predictive measure for the efficacy of topical retinoids in man. Topical applications of all-trans retinoic acid gel (Aberel), salicylic acid gel and the gel vehicle were made once daily for 4 weeks to skin of the lumbar region of healthy human volunteers. Corneocytes were recovered from these three treated zones as well as from one zone of untreated skin, and their surface areas were measured by image analysis using a MOP-Videoplan. The results showed that at no point during the 4 weeks of daily application to healthy human skin was there a statistically significant difference in the surface area of corneocytes recovered from Aberel, salicylic acid-, vehicle-treated or untreated sites. No specific effect of retinoic acid could be detected. However, although no between-treatment differences were found, significant cyclical changes in the mean surface areas with respect to baseline were observed.

[Hyperandrogenism and pilosebaceous follicles]. / Hyperandrogénie et follicule pilo-sébacé.

The characteristic of skin is that it is both a site of the metabolism and the target-organ of the androgens which it receives or produces. In the skin, so called "weak" androgens are transformed into more powerful ones, such as androstenedione, testosterone and 5 alpha-dihydrotestosterone. Hyperandrogeny is often found in association with the three main androgenodependent dermatoses: acne, androgenic alopecia and hirsutism. However, the problem of the receptivity of the target-organ, the pilosebaceous follicle, is highlighted in diseases without symptoms of hyperandrogeny. The androgen receptors have been identified in the basal cells of the sebaceous gland and in the hair shaft. The presence of androgen receptors in the keratinocytes and in the cutaneous fibroblasts arises the problem, unresolved to date, of the interactions between the different cutaneous structures.