Skin, hair and beyond: the impact of menopause.

The skin is an endocrine organ and a major target of hormones such as estrogens, androgens and cortisol. Besides vasomotor symptoms (VMS), skin and hair symptoms often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life. Skin and mucosal menopausal symptoms include dryness and pruritus, thinning and atrophy, wrinkles and sagging, poor wound healing and reduced vascularity, whereas skin premalignant and malignant lesions and skin aging signs are almost exclusively caused by environmental factors, especially solar radiation. Hair menopausal symptoms include reduced hair growth and density on the scalp (diffuse effluvium due to follicular rarefication and/or androgenetic alopecia of female pattern), altered hair quality and structure, and increased unwanted hair growth on facial areas. Hormone replacement therapy (HRT) is not indicated for skin and hair symptoms alone due to the risk-benefit balance, but wider potential benefits of HRT (beyond estrogen's effect on VMS, bone, breast, heart and blood vessels) to include skin, hair and mucosal benefits should be discussed with women so that they will be able to make the best possible informed decisions on how to prevent or manage their menopausal symptoms.

A dermocosmetic formulation containing Vichy volcanic mineralizing water, Vitreoscilla filiformis extract, niacinamide, hyaluronic acid, and vitamin E regenerates and repairs acutely stressed skin.

The exposome has an impact on skin from life-long exposure. Acute short-term exposure to exposome stressors can also alter skin functions such as skin physical barrier and immune defenses, leading to skin dryness, sensitivity, flares of inflammatory skin conditions, or viral reactivations. Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. An extract produced by lysing Vitreoscilla filiformis (VfeV) cultured in Vichy volcanic mineralizing water (VVMW) has properties of probiotic fractions. In this review, we present in vivo and ex vivo studies with a dermocosmetic formulation containing 80% VVMW, 5% VfeV, 4% niacinamide (vitamin B3), 0.4% hyaluronic acid, and 0.2% vitamin E (M89PF) to evaluate the clinical efficacy in preventing and repairing stressed skin. Skin barrier benefits of M89PF were shown in studies after the skin was exposed to sudden thermal changes, after skin irritation by tape stripping, and in sleep-deprived women. M89PF significantly accelerated skin renewal compared to untreated skin. Skin antioxidant defense activity of M89PF was shown after exposure to stress from UVA plus cigarette smoke aggression. Skin microbiome recovery after acute stress from a harsh cleanser was significantly better in M89PF-treated skin compared to bare skin. Clinical benefits of M89PF on correcting clinical signs of stressed skin were shown in both Caucasian and Asian women exposed to a stressful lifestyle and various external (pollution, tobacco smoking, solar radiation) and internal (poor sleep, stressful work, unbalanced diet, and alcohol consumption) exposome factors. M89PF also showed depigmenting properties on dark spots in Asian women. Further clinical studies are now warranted to evaluate the efficacy of M89PF as adjuvant care to prevent and repair skin barrier disruption and reinforce skin defenses in skin exposed to acute stresses.

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.

Effectiveness of a formulation containing peptides and vitamin C in treating signs of facial ageing: three clinical studies.

OBJECTIVE: Vitamin C and peptides are widely used in cosmetic products but there is a paucity of clinical studies showing that the formulations are effective in treating signs of facial ageing. These 3 clinical studies evaluated the effectiveness of an anti-ageing formula containing natural vitamin C (10%), biopeptides (rice and lupin), hyaluronic acid, and Vichy volcanic mineralising water, in amber glass ampoules with no preservatives (Peptide-C ampoules). METHODS: Dansyl chloride fluorescence labelling compared cell turnover for Peptide-C ampoules vs untreated skin in 32 female subjects. Study 2, an open clinical study, evaluated the efficacy on wrinkles of Peptide-C ampoules by investigator clinical scoring based on Dynamical Atlas visual assessment (N = 40) and subject self-assessment questionnaires (N = 47). Study 3, an open clinical study, evaluated wrinkles by instrumental quantification with 3D fringe projection analysis (N = 40) and subject questionnaires (N = 51). RESULTS: The mean cell turnover was faster for skin treated with Peptide-C ampoules compared to untreated skin (17.1 days vs. 19.2 days; P < 0.0001). In study 2, after 28 days application of Peptide-C ampoules, clinical grading of crow's-feet wrinkles, forehead wrinkles and nasolabial folds decreased by 9%, 11% and 5%, respectively (all P < 0.05 vs baseline). Of 47 subjects, 77%, 64% and 79% indicated their skin seemed smoothed out, fine lines were less visible, and skin complexion was more radiant, respectively. In study 3, the number of wrinkles decreased by 11.5% after 29 days application of Peptide-C ampoules vs baseline (P < 0.05) and 65% of subjects responded the fine lines were less visible. CONCLUSION: This formulation of a combination of anti-ageing ingredients in ampoules, allowing a minimalist formula, showed significant results on improving facial wrinkles and radiance.

OBJECTIF: La vitamine C et les peptides sont régulièrement utilisés dans les produits dermocosmétiques mais il existe peu d'études cliniques sur l'efficacité des formulations sur les signes du vieillissement cutané du visage. Trois études cliniques ont évalué l'efficacité d'une formule anti-âge contenant de la vitamine C naturelle (10%), des biopeptides (riz et lupin), de l'acide hyaluronique et de l'eau minéralisante volcanique de Vichy, dans un format d'ampoules en verre ambré, sans conservateur (ampoules Peptide-C). MÉTHODES: Une première étude a comparé par la technique de chlorure de Dansyl le renouvellement cellulaire avec la formulation ampoules Peptide-C et la peau non traitée chez 32 sujets féminins. La seconde étude, en ouvert, a évalué l'efficacité clinique sur les rides des ampoules Peptide-C en se reposant sur les Atlas Dynamiques (N=40) et les questionnaires d'auto-évaluation des sujets (N=47). La troisième étude, ouverte, a évalué les rides par quantification instrumentale avec l'analyse de projection de franges 3D (N=40) et les questionnaires d'autoévaluation des sujets (N=51). RÉSULTATS: Le renouvellement cellulaire était plus rapide pour la peau traitée avec des ampoules de Peptide-C comparées à la peau non traitée (17.1 jours contre 19.2 jours ; p<.0001). Dans l'étude 2, après 28 jours d'application des ampoules Peptide-C, l'évaluation clinique des rides de la patte d'oie, du front et des plis naso-labiaux a montré une amélioration de 9 %, 11 % et 5 %, respectivement (tous p<0,05 vs baseline). Sur 47 sujets, 77%, 64% et 79% ont indiqué que leur peau semblait respectivement lissée, que les ridules étaient moins visibles et que le teint de la peau était plus radieux. Dans l'étude 3, le nombre de rides a diminué de 11,5 % après 29 jours d'application des ampoules Peptide-C par rapport à la baseline (p<0,05) et 65 % des sujets ont répondu que les ridules étaient moins visibles. CONCLUSION: Cette combinaison d'ingrédients anti-âge dans un format d'ampoules, et une formulation minimaliste, a montré des résultats significatifs sur l'amélioration des rides faciales et de l'éclat du teint.

Daylight photodynamic therapy with methyl aminolevulinate cream is as effective as conventional photodynamic therapy with blue light in the treatment of actinic keratosis: a controlled randomized intra-individual study.

BACKGROUND: We know the efficacy of daylight phototherapy dynamic (DL-PDT) in the treatment of actinic keratosis (AK). But the almost studies have compared daylight with red light using methyl aminolevulinate cream and not with blue light. PDT with blue light is another conventional PDT that is effective in the treatment of AKs. OBJECTIVES: The aim of this study is to assess the efficacy and the safety of DL-PDT vs. PDT in blue light in the treatment of AKs. METHODS: This randomized, controlled, intra-individual efficacy and safety study enrolled 26 subjects. AKs on the face/scalp were treated once, with DL-PDT on one side and c-PDT on the contralateral side. Primary endpoints for DL-PDT at week 12 were efficacy with clearance of AKs and safety with assessment of pain. Lesions with complete response 12 weeks after one treatment session were followed until week 24. RESULTS: More than 1000 AK were studied. At week 12, the raw number of disappeared AK lesions at 3-month follow-up was 19.6 (±6.0) for DL-PDT and 20.0 (±6.9) for c-PDT with P = 0.8460 (90.5% vs. 94.2% of AK disappearance, respectively). The response was maintained at 6 months (90.0% and 94.6% of AK reduction, respectively). DL-PDT was nearly painless than c-PDT with light blue: 1.2 vs. 5.1, respectively (P < 0.0001). CONCLUSIONS: Daylight-PDT seems as effective as c-PDT with light blue and DL-PDT is less painful. The response of DL-PDT was sustainable until 6 months.

The conventional protocol vs. a protocol including illumination with a fabric-based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study.

BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.

The role of exposome in acne: results from an international patient survey.

BACKGROUND: Acne severity and its response to treatment may be influenced by internal and external factors: the exposome. OBJECTIVES: The aim of this international real-life survey was to assess the most involved exposome factors in acne. METHODS: Eleven thousand individuals, aged between 15 and 39 years, with clinically confirmed acne or without acne, defined by age, gender and prevalence, were invited to participate in an Internet survey of 63 questions in order to assess the frequency of identified acne exposome factors. RESULTS: Data from 6679 questionnaires were used for statistical analysis purposes: 2826 from the acne group and 3853 from the control group. Nibbling, consumption of dairy products, sweets, alcohol or whey proteins, as well as exposure to pollution, stress, certain mechanical factors and humid or hot weather or sun exposure, were significantly (all P ≤ 0.05) more frequently reported for the acne group than for the control group. This was not the case for tobacco consumption. Data regarding the impact of cannabis consumption were insufficient for drawing any conclusions. CONCLUSIONS: Data from this international, anonymized Internet questionnaire conducted with more than almost 6700 participants add new arguments to assumptions made that certain exposome factors have an impact on acne. Nutrition, pollution, stress and harsh skincare, as well as climate and sun exposure may be considered the most frequent factors related to acne.

Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.

Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) of actinic keratosis (AK) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy (c-PDT), using methyl aminolevulinate (MAL) cream. OBJECTIVES: To demonstrate the efficacy and safety of DL-PDT vs. c-PDT in treating mild facial/scalp AK. MATERIALS AND METHODS: This 24-week randomized, controlled, investigator-blinded, multicentre, intra-individual efficacy (non-inferiority) and safety (superiority regarding pain) study enrolled 100 subjects. AKs on the face/scalp were treated once, with DL-PDT on one side and c-PDT on the contralateral side. Primary end points for DL-PDT at week 12 were efficacy [non-inferiority regarding complete lesion response (mild AK)] and safety (superiority regarding subject's assessment of pain). Lesions with complete response 12 weeks after one treatment session were followed until week 24. The safety evaluation included incidence of adverse events. Subject satisfaction was classified using a questionnaire. RESULTS: At week 12, the complete lesion response rate with DL-PDT was non-inferior to c-PDT (89·2% vs. 92·8%, respectively; 95% confidence interval -6·8 to -0·3), confirmed by intention-to-treat analysis. Additionally, regardless of the treatment used, 96% of mild lesions were maintained in complete response 24 weeks after the PDT session. For DL-PDT, subject-reported pain was significantly lower (0·8 vs. 5·7, respectively; P < 0·001), with better tolerability and significantly higher subject satisfaction regarding convenience and outcome. CONCLUSIONS: Daylight-mediated PDT was not inferior in efficacy to Metvix c-PDT (mild AK response rate), better tolerated, nearly painless and more convenient for patients.

Photodynamic therapy for actinic keratosis in organ transplant patients.

BACKGROUND: The incidence of actinic keratoses (AK) and non-melanoma skin cancer (NMSC) in organ transplant recipients (OTRs) is significantly higher than in immunocompetent patients. Rates of progression and recurrence following treatment are higher too, in part due to the effects of the immunosuppressant drugs. Conventional therapies for AK, using curettage, cryotherapy, surgical excision, topical therapies and photodynamic therapy (PDT), are often less effective, and may be inappropriate, for treating the greater numbers and extent of lesions in OTRs. Moreover, there are no specific protocols for treating this patient population that take into account the need for more frequent treatment and the increased pain associated with treating larger areas. OBJECTIVES: Recently, a pan-European group of dermatologists with expertise in this area met to share current best practice in PDT for the treatment of AK in OTRs. METHODS: The group identified areas where PDT currently is not meeting the needs of these patients and discussed how these gaps might be addressed. RESULTS/CONCLUSIONS: This position article summarizes those discussions and makes recommendations concerning a standardized protocol for treating OTRs, for a large randomized controlled trial to provide robust data on safety, efficacy and optimal pain control, and to provide pharmaco-economics data that can be used to support extended reimbursement in this patient group. The authors also recommend a second clinical trial to further investigate induced immunosuppression with PDT in healthy volunteers.

Visceral lesions occurring during follow-up of melanoma patients: a true place for other diagnosis than melanoma metastasis.

BACKGROUND: Diagnosis of melanoma metastasis is often based on a combination of clinical and radiological examinations in patients with a past history of melanoma. Chemotherapeutic treatment is often proposed without histological proof of the metastatic status. OBJECTIVE: The aim of this study was to investigate a cohort of melanoma patients with invasive diagnostic procedures (IDPs) for pathological confirmation of metastasis in case of suspicious visceral lesions. METHODS: A total of 109 melanoma patients with IDPs for suspicious visceral lesion(s) were included. Data about primary melanoma, IDPs characteristics, pathological result and therapeutic consequence were collected. Patients with AJCC Stage I-III melanoma at the time of the IDP were statistically analysed for various characteristics according to the final diagnosis yielded by the IDP. RESULTS: A total of 64 diagnostic surgical resections, 38 CT-guided core-needle biopsies, 15 ultrasound-guided core-needle biopsies, 6 surgical biopsies and 6 per-endoscopic biopsies were performed. Main target organs were the lungs (43.5%), breasts (8.5%) and liver (8%). IDPs were well tolerated and provided adequate samples for reliable diagnoses. Among the 105 IDPs in stage I-III patients, 56 melanoma metastases (53%), 25 benign lesions (24%) and 23 other cancers (22%) were found. One IDP was not informative. Multivariate analysis showed that nodular type of the primary melanoma, time-lag between primary melanoma and IDP over 12 months and the presence of suspicious lesions outside the organ biopsied were significantly associated with melanoma metastasis diagnosis. CONCLUSION: Suspected melanoma metastasis was ruled out for benign lesion or second cancer in nearly half of the stage I-III patients having undergone an IDP, therefore modifying the medical treatment.

[Unilateral acneiform rash in facial palsy]. / Éruption acnéiforme unilatérale sur paralysie faciale.

BACKGROUND: Cetuximab is a chimeric monoclonal antibody selective for epidermal growth factor receptor (EGFR). It is increasingly used in epithelial cancer, often in combination with radiotherapy or chemotherapeutic agents, since it induces a broad range of cellular responses that enhance tumour sensitivity to these therapies. However, it can cause numerous adverse effects, the most common being acneiform eruption on the face and trunk, which is generally bilateral and symmetric. PATIENTS AND METHODS: Herein we present the first case of unilateral cetuximab-induced acneiform eruption in facial palsy. DISCUSSION: To our knowledge the medical literature contains no other such cases. Our hypothesis is that lymphoedema associated with facial palsy reduces lymphatic drainage, promoting the deposition of cetuximab on EGFR and persistence of local signs.

Kaposi's sarcoma after long-acting steroids: time until remission and drug washout.

Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we report a case of Kaposi's sarcoma (KS) and severe immunosuppression after a chronic triamcinolone acetonide (TA) treatment. Six months after withdrawal, traces of TA were still detected in the serum by HPLC mass spectrometry. At 8 months, the drug became undetectable, and clinical and biological signs of immune recovery - beginning of KS regression, normalization of IgG levels and CD4 T lymphocyte counts - became noticeable. We then provide a review of the literature on the time until remission of KS after immunosuppression reduction. We also reviewed the cases of KS induced by TA, and the metabolic side effects of TA when compared to standard glucocorticoids.