Development and characterisation of an irradiation device for biomedical studies covering the solar spectrum with individual regulated spectral bands.

To understand the importance of terrestrial solar exposure on human skin, not only individual spectral components need to be considered in biomedical studies, but also the relevance of the combined action profile of the complete solar spectrum (cSS) must be established. We therefore developed a novel irradiation device that combines the emission of four individual lamps (UVB, UVA, VIS and nIR) to achieve exposure from 280 to 1400 nm with individual controllable lamps. The integrated irradiance of each spectral band is similar to the solar spectrum. The lamps can be utilised individually or in any desired combination. Here we present the design, realisation, and validation of this irradiation device as well as biological results on cellular metabolism (MTT assay), cell cycle alterations, and clonogenic growth in HaCaT cells after exposures to the individual spectral bands as well as their simultaneous combinations. Thereby, we demonstrate that UVB combined with UVA is the main determinant for the metabolic activity within cSS. Also, UVB-dependent effects dominate cell cycle regulation in cSS, whilst UVA and nIR have little influence. Lastly, also clonogenic growth is dominated by the UVB action profile in cSS, despite nIR showing modulatory activity when applied in combination with UVB. Together, this highlights the regulatory influence of the different spectral bands on the three biological endpoints and demonstrates their modulation when being part of the complete solar spectrum.

Air pollution-induced tanning of human skin.

BACKGROUND: Melanism is more frequent in animals living in polluted areas on urban-industrial sites. Given that an increasing number of people are exposed to elevated air pollution levels, it is possible that environmental pollutants affect melanogenesis in human skin. Epidemiological studies have shown that exposure to traffic-related air pollutants such as diesel exhaust particles (DEP) is associated with more clinical signs of hyperpigmentation. However, mechanistic evidence linking DEP exposure to pigmentation has been elusive. OBJECTIVES: To develop an ex␣vivo skin model to allow for repetitive topical application of relevant ambient DEP, and to provide proof of concept in humans. METHODS: We measured skin pigmentation, melanin and pigmentation-associated gene expression, and evaluated oxidative stress. RESULTS: Repetitive exposure of ex␣vivo skin to DEP at nontoxic concentrations increased skin pigmentation. This increase was visible to the naked eye, time dependent, and associated with an increase in melanin content and the transcription of genes involved in de novo melanin synthesis. Similarly, in healthy participants (n = 76), repetitive topical application of DEP at nontoxic concentrations increased skin pigmentation. DEP-induced pigmentation was mediated by an oxidative stress response. After the application of DEP, epidermal antioxidants were depleted, lipid peroxidation and oxidative DNA damage were enhanced, and in a vehicle-controlled, double-blind clinical study DEP-induced pigmentation was prevented by the topical application of an antioxidant mixture. CONCLUSIONS: Similar to solar radiation, air pollutants cause skin tanning. As eumelanin is an antioxidant, it is proposed that this response serves to protect human skin against air pollution-induced oxidative stress.

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

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

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

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

[Sun-damaged skin (photoaging): what is new?] / Lichtalterung (Photoaging) der Haut: Was gibt es Neues?

Skin aging results from the interaction of genetic and nongenetic so-called exposomal, factors. Among the exposomal factors, chronic, life-long exposure to sunlight is of eminent importance for the development of skin aging characteristics. Importantly, photoaging of human skin is not only caused by ultraviolet (UV) B and A radiation, but is also the consequence of exposure to wavelengths beyond the UV spectrum. These include visible, i.e. blue light (400-440 nm) as well as the short part of infrared radiation, i.e. IRA (760-1200 nm). Here we summarize the scientific evidence supporting these conclusions and emphasize the resulting consequences for daily photoprotection of human skin. We also explain the clinical significance of the concept that is offered by the skin aging exposome, which e.g. takes into account the fact that sunlight interacts with other exposomal factors and that this interaction is important for photoaging of the skin.

Clinical and biological impact of the exposome on the skin.

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

Photoprotection of the future: challenges and opportunities.

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

Identification of factors associated with minimal erythema dose variations in a large-scale population study of 22 146 subjects.

BACKGROUND: Minimal erythema dose (MED) has substantial inter- and intraindividual variations, reflecting the influence of very diverse factors. However, related studies showed little consistency probably because of their limited sample size. OBJECTIVE: To identify the factors associated with MED variations in a large-scale population study. METHODS: The MED test was performed by following the international standard procedure on 22 146 subjects. The results were analysed in adjusted multivariable linear and logistic regression models. RESULTS: This large-scale study revealed that lower MED was consistently associated with lighter skin [ß-coefficient = -0.33, 95% confidence interval (CI) -0.36 to 0.30, P = 6.41 × 10-84 ]. Females had significantly higher MED than male (ß = 0.91, 0.32-1.50, P = 2.93 × 10-3 ). Stratified analyses showed that MED was not associated with age [female: odds ratio (OR) = 0.99, 0.98-1.01; male: OR = 0.99, 0.97-1.00]. MED was lower in summer than in other seasons (spring: OR = 1.08, 1.06-1.11; autumn: OR = 1.11, 1.08-1.13; winter: OR = 1.20, 1.18-1.22). Furthermore, MED was associated with air temperature (ß = -0.36, -0.49 to 0.23, P = 4.81 × 10-8 ) and air pressure (ß = -0.64, -0.82 to 0.46, P = 8.01 × 10-12 ) in summer only while not in other seasons. CONCLUSIONS: This study provides unprecedented evidence that MED is associated with skin colour, sex, season and meteorological factors, but not with age.

[Air pollution (particulate matter and nitrogen dioxide) and skin aging]. / Luftverschmutzung (Feinstaub, Stickstoffdioxid) und Hautalterung.

It has recently been discovered that air pollution can contribute to skin aging. This conclusion is based on both epidemiological and mechanistic evidence. Specifically, exposure to ambient relevant particulate matter and to nitrogen dioxide (NO2) is associated with an increased risk to develop facial pigment spots. In addition, genetic studies indicate the involvement of gene-environment interactions because women carrying certain genetic variants of the aryl hydrocarbon receptor (AHR) signaling pathway have a higher risk to develop facial pigment spots in response to exposure to particulate matter (PM2.5). Mechanistic studies prove a cause/effect relationship because topical exposure of human skin ex vivo or in vivo to non-toxic concentrations of a standardized diesel exhaust mixture increased skin pigmentation by inducing melanin de novo synthesis via an oxidative stress response. In line with this, cosmetic anti-pollution products containing anti-oxidants, but also AHR antagonists are effective in reducing or preventing this increase in skin pigmentation. Ultraviolet (UV) radiation is another important environmental factor which can cause skin aging and pigment spot formation. In a real exposure situation, human skin is exposed to both environmental factors simultaneously. Corresponding epidemiological studies show that particulate matter present in the troposphere and solar UV radiation interact with each other. These results emphasize that environmentally induced skin aging results from a highly complex process.

Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study.

BACKGROUND: Increasing evidence suggests photoprotection by oral supplementation with ß-carotene and lycopene. OBJECTIVES: To examine the capacity of lycopene-rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. METHODS: In a placebo-controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2-week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. RESULTS: TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0·05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. CONCLUSIONS: Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.

[New approaches for the prevention of actinic keratosis]. / Neue Ansätze zur Prävention aktinischer Keratosen.

Actinic keratosis is one of the most common skin diseases. Because of the ongoing demographic changes, it is anticipated that the incidence will further increase. Prevention of actinic keratoses is thus of great importance. By far the most important cause of actinic keratoses is the chronic cumulative irradiation of human skin with ultraviolet B and A radiation from natural sunlight. There is no doubt that use of sunscreens is effective in preventing actinic keratoses. Recent studies indicate that in high-risk groups the regular use of medical devices which are characterized by a very high SPF and which contain liposomally encapsulated DNA repair enzymes are effective in preventing the development of new actinic keratoses even when field cancerization is already present in human skin. There is also evidence that oral photoprotective strategies based on the regular intake of vitamin B3 may be used to prevent actinic keratoses.

[Environmentally induced (extrinsic) skin aging]. / Umweltinduzierte (extrinsische) Hautalterung.

Chronic exposure to ultraviolet light, particularly as a component of natural sunlight, is a major cause of environmentally induced aging of the skin. In addition, other environmental factors for premature skin aging include longer wavelength radiation in the visible light region and in particular in the shortwave infrared radiation region. Furthermore, particulate and gaseous components of air pollution significantly contribute to the aging process.

Ectoine-containing cream in the treatment of mild to moderate atopic dermatitis: a randomised, comparator-controlled, intra-individual double-blind, multi-center trial.

INTRODUCTION: The natural cyclic tetrahydropyrimidine, ectoine, is a low-molecular, water-binding, organic osmolyte. Previously, topical application of ectoine to healthy human skin was shown to improve skin hydration as well as skin barrier function. OBJECTIVES: We therefore speculated that topical application of ectoine would be beneficial for patients with atopic dermatitis (AD), in which a genetically defined defect in skin barrier function is of major pathogenetic relevance. We assessed the efficacy of an ectoine-containing cream (EHK02-01) in the management of 65 patients with mild to moderate AD in a randomized, intra-individual, double-blind, multi-center trial, in which the efficacy of ectoine was compared to a nonsteroidal anti-inflammatory cream previously found to primarily act on skin barrier function and therefore with a comparable mode of action. METHODS: Sixty-five patients with mild to moderate AD aged 18-65 years were enrolled. The patients applied EHK02-01 and the control cream on two symmetrical lesions twice daily for 28 days. At the beginning, after 7 and after 28 days, treated skin areas were assessed by modified, objective local SCORAD (Scoring Atopic Dermatitis) and IGA (Investigator's Global Assessment) as well as the patients' judgment of efficacy and their assessment of pruritus. RESULTS: EHK02-01 was found to be very well tolerated. Even more important, efficacy of EHK02-01 treatment was equivalent to that achieved with the reference product. CONCLUSION: These results indicate that topical treatment with EHK02-01 may represent a novel option for the treatment of patients with AD.

Attitudes and behaviors regarding sun exposure in Japan compared to Europe and North America.

The objective of our study was to assess the attitudes and behaviors in Japan regarding sun exposure and compare them to those in Europe and North America. The study population was a representative sample of individuals aged >18 years from Ipsos panels in Japan (N = 1000), North America (N = 1000), and Europe (N = 6000) using the quota method. Questionnaires covered habits, practices, and perceptions regarding sun exposure. Results revealed that the majority of people (80.1%) believed that the sun gives them energy, and 61.1% considered that being tanned made them look healthier. However, there was a significant difference between men and women regarding the appeal of tanned skin, with 54.95% of men versus 34.67% (p < 0.001) of women seeing a tan as an aesthetic asset. People aged <40 years were less likely to find a tan attractive (30.3%) compared to those aged ≥40 years (48.9%) (p < 0.001). Of those questioned, 45.70% of used sunscreen with a much higher use among women (70.10%) than men (18.74%) (p < 0.001). Almost 54% of people said they stayed in the shade to protect themselves from the sun with this behavior being more prevalent among women (67.05%) and fair-skinned individuals (56.13%). Fear of the risks of sun exposure was more common among women, with 84.8% fearing premature skin aging, compared to 71.8% of men (p < 0.001). In Japan, 44.30% of those questioned said tanned skin was attractive (p < 0.001); for Europeans and North Americans the proportions were 81.1% and 77.6%, respectively. Only a quarter (25.80%) thought it essential to return from vacation with a tan. On the other hand, Europeans showed a strong recognition of the energy the sun brings (83.18%), and widely believed that tanned skin is attractive (82.32%) and healthy (73.15%). In North America, attitudes were similar to those in Europe regarding the attractiveness of tanned skin (77.65%) and the importance of returning tanned from vacation (48.15%). Compared to Europeans and North Americans, the Japanese seemed to be more cautious about sun-induced hazards and considered lighter skin to be more attractive.

Algorithm for dermocosmetic use in the management of cutaneous side-effects associated with targeted therapy in oncology.

Currently, numerous patients who receive targeted chemotherapy for cancer suffer from disabling skin reactions due to cutaneous toxicity, which is a significant problem for an increasing number of patients and their treating physicians. In addition, using inappropriate personal hygiene products often worsens these otherwise manageable side-effects. Cosmetic products for personal hygiene and lesion camouflage are part of a patients' well-being and an increasing number of physicians feel that they do not have adequate information to provide effective advice on concomitant cosmetic therapy. Although ample information is available in the literature on pharmaceutical treatment for cutaneous side-effects of chemotherapy, little is available for the concomitant use of dermatological skin-care products with medical treatments. The objective of this consensus study is to provide an algorithm for the appropriate use of dermatological cosmetics in the management of cutaneous toxicities associated with targeted chemotherapy such as epidermal growth factor receptor inhibitors and other monoclonal antibodies. These guidelines were developed by a French and German expert group of dermatologists and an oncologist for oncologists and primary care physicians who manage oncology patients. The information in this report is based on published data and the expert group's opinion. Due to the current lack of clinical evidence, only a review of published recommendations including suggestions for concomitant cosmetic use was conducted.

Sun exposure, a relevant exposome factor in acne patients and how photoprotection can improve outcomes.

BACKGROUND: Acne pathophysiology includes a complex interaction among inflammatory mediators, hyperseborrhea, alteration of keratinization and follicular colonization by Propionibacterium acnes. AIMS: To describe the impact of the exposome on acne and how photoprotection can improve outcomes. METHODS: A narrative review of the literature was carried out; searches with Google Scholar and Pubmed from January 1992 to November 2022 were performed. The keywords used were "acne," "sunscreens," "photoprotection," "cosmetics," "cosmeceuticals," "pathogenesis," "etiology," "exposome," "sunlight," "stress," "lack of sleep," "diet," "postinflammatory hyperpigmentation," "pollution," "exposome," "ultraviolet radiation," and "visible light." RESULTS: Environmental factors such as solar radiation, air pollution, tobacco consumption, psychological stress, diverse microorganisms, nutrition, among others, can trigger or worsen acne. Solar radiation can temporarily improve lesions. However, it can induce proinflammatory and profibrotic responses, and produce post-inflammatory hyperpigmentation and/or post-inflammatory erythema. While photoprotection is widely recommended to acne patients, only four relevant studies were found. Sunscreens can significantly improve symptomatology or enhance treatment and can prevent post-inflammatory hyperpigmentation. Furthermore, they can provide camouflage and improve quality of life. Based on acne pathogenesis, optimal sunscreens should have emollient, antioxidant and sebum controlling properties. CONCLUSIONS: The exposome and solar radiation can trigger or worsen acne. UV light can induce post-inflammatory hyperpigmentation/erythema, and can initiate flares. The use of specifically formulated sunscreens could enhance adherence to topical or systemic therapy, camouflage lesions (tinted sunscreens), decrease inflammation, and reduce the incidence of post-inflammatory hyperpigmentation/erythema.