Current problems in dermatology最新文献

Cutaneous malignant melanoma (CMM) and nonmelanoma skin cancers (NMSC), squamous cell and basal cell carcinomas, have been increasing at exponential rates for as long as the International Agency for Research on Cancer (IARC) have been collecting data starting from 1955 in some northern European countries and 1960 in most other European countries. Different strains of the human papilloma virus (HPV) have been found in CMM and NMSC biopsies and implicated in the carcinogenic process as a "hit-and-run" mechanism and can spread at exponential rates, especially since the 1960s' sexual revolution. This chapter covers only IARC data for CMM in the European countries from 1960 to 2018, plotted by regions (northern, middle, and southern latitudes and eastern versus western longitudes), countries latitudes, and each country over time, which shows that about half have linear and the other half have exponential increases in CMM. From this analyzed data and published data in the literature, the major risk factors of CMM appear to be light hair color, especially red and white hair (reactive oxygen species and UVA; 320-400 nm), low cutaneous vitamin D3 levels, and HPV after 1960, while there was no apparent risk from exposure to UVB (290-320 nm) or sunburns.

Black skin, compared with white skin, is generally assumed to be more resistant to the consequences of sun exposure due to its epidermal melanin content. However, recent scientific evidence shows that black skin is not completely impervious to sunlight. Both clinical and -experimental data have reported sun-induced effects on black skin. Black skin can warm, burn and peel when -exposed to the sun. Exposure to the sun can also cause hyperpigmentation and photoageing manifestations. The current misconceptions expressed by most black individuals about their resistance to sun-induced effects prevent their engagement in sun safe behaviours. Therefore, the demystification of the harmful effects of the sun needs to be supported by more research studies showing the effectiveness of sun protection strategies for the black population.

Sunscreen application to UV-exposed skin is promoted to prevent skin cancer and sun damage, within a comprehensive photoprotection strategy that also includes sun avoidance and wearing UV protective clothing. The benefits of sunscreen are verified in preventing sunburn but appear to be largely presumptive in skin cancer prevention. Contemporary science establishes UVA as a primary driver of melanoma and photoaging. Consequentially, the traditional UVB-skewed protection of sunscreens provides an intellectual and logical explanation for rising skin cancer rates and, in particular, their failure to protect against melanoma. Better protection could be achieved with more balanced UVB/UVA sunscreens, toward spectral homeostasis protection. Greater balanced protection has another advantage of attenuating fewer UVB rays, which aid synthesis of vitamin D and nitric oxide. Percutaneous absorption of Soluble Organic UV Filters leads to systemic exposure, which becomes the relevant safety consideration. It is minimized by selecting Insoluble UV Filters with low absorption potential from a molecular weight above 500 Da. The filters must also be very hydrophilic, very lipophilic, or consist of particles. The risk-benefit ratio is a medical imperative, more so for cosmetics or sunscreens, since in principle there should be no risk from their use. The production of ideal sunscreens that mimic the effective, balanced UVB/UVA attenuation of textiles and shade is now possible, while maintaining an acceptable therapeutic margin of safety in humans and a favorable ecologic profile. Sunscreens with a favorable risk-benefit ratio and good esthetic properties or other consumer-friendly attributes will improve compliance and may achieve substantial clinical benefits.

Sunlight comprises radiation of different wavelengths, of which UVA and UVB are most important with respect to human skin diseases. Next to erythema, edema, and sunburns, UV radiation causes skin cancer. UV radiation of any wavelength is now considered as a class I carcinogen to humans. The mutagenic effects of UV radiation depend on DNA damage following direct absorption by nuclear DNA, resulting in cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts that, if not repaired by nucleotide excision repair pathway, result in characteristic UV signature mutations (C→T or CC→TT transition). In addition, increased formation of reactive oxygen species by UV exposure may cause formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine leading to T→G transversion. In addition, UV radiation has been shown to induce a number of immune modulations that largely result in local and potentially also in systemic immunosuppression, which may not only impair control of dysplastic and neoplastic skin lesions but also affect immuno-pathological and infectious skin diseases. Recent find-ings have shown that ambient doses of high-energy visible light, beyond the UV range, may also cause damage to human skin.

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.

In photodermatology, UV radiation is the component of the solar system that has attracted the most interest as it represents the greatest risk of skin damage from solar exposure. Efficient protection strategies have therefore been developed to protect skin against powerful solar radiation. Recently, there has been increasing evidence to suggest that less energetic radiation, such as visible light and infrared radiation, might also influence skin physiology. Yet, it remains unclear, regarding risk assessment, whether visible light irradiation induces positive or negative effects in skin and when appropriate protection is needed. This review focuses primarily on blue light as part of the visible spectrum and sets out current mechanistic understanding of the benefits and risks of blue-light exposure to skin. Furthermore, it discusses phototherapies and potential strategies for protecting against detrimental effects of blue light such as hyperpigmentation and premature skin aging.

Vitamin D is generally accepted in its importance on the regulation of calcium homeostasis and bone metabolism. Moreover, further health effects due to vitamin D are under discussion. In its effect, vitamin D is more like a hormone. In the classic view, a vitamin is an essential nutrient, which cannot be synthesized independently in the body. Besides nutrition, vitamin D will be produced in the body itself. The skin contains the provitamin D3 7-dehydrocholesterol, a precursor of vitamin D. Provitamin D3 will be photoconverted to previtamin D3 by UVB radiation that penetrates the skin superficially. In this way, the vitamin D metabolism will be started independent of the nutrition. In everyday life, this photosynthesis will be carried out due to the solar UVB radiation penetrating the uncovered skin. In the same spectral waveband range of UVB radiation, which causes the beneficial health effect of starting the vitamin D metabolism, the UVB radiation causes simultaneously acute and chronic harmful health effects as UV erythema (sunburn), skin aging and skin cancer. There is no vitamin D production in the skin without simultaneous DNA damage in the skin. Against this background, risks and benefits have to be balanced carefully.

This chapter is focused on those products that are sold primarily as sun protection products and considers the additional claims made for these that are intended to differentiate and imply additional benefits. It is essentially an overview, as each claim would require an individual chapter to deal with in detail. We do not consider products with another intended primary use, such as moisturizer or colour comments, which are, in themselves "secondary sunscreens," defined specifically in Australia [AS/NZS 2604:2012 Sunscreen products - Evaluation and classification] or Canada. Primarily, the chapter serves as a reference guide. An argument is presented for the potential negative impact on the credibility of the whole product category brought about by the marketing strategy of attempting to segment on the basis of either criticism of competitor products and/or targeting niche groups of consumers. The European Union (EU) Regulation 655/2013 [Commission Regulation (EU) No 655/2013 laying down common criteria for the justification of claims used in relation to cosmetic products] states 6 criteria for representation of products. These are Legal Compliance, Truthfulness, Evidential Support, Honesty, Fairness and Informed Decision Making. More specifically to sunscreens, the EU Synthesis Document makes recommendation on efficacy and related claims [European Union Synthesis Document - Commission recommendation on the efficacy of sunscreen products and claims related thereto]. This chapter does not consider or test these criteria but does include a table of claims and suggested ways to substantiate these.

The Precautionary Principle is a decision-making device designed to help us when we deal with uncertain risks. Despite a number of case-control and prospective studies over several years, there remains some uncertainty as to whether sunscreens are unequivocally effective in reducing the risk of skin cancer, and we examine how useful the principle is in deciding whether sunscreen should be included in the sun protection toolbox as a public health measure. We conclude that the Precautionary Principle can be a useful tool supporting public health recommendations to use sunscreen as a means of reducing the morbidity and mortality of skin cancer, but we show that it is not without its shortcomings.

Adverse reactions to sunscreens are uncommon in relation to their widespread use [Loden et al. Br J Dermatol. 2011;165(2):255-62; Jansen et al. J Am Acad Dermatol. 2013;69(6):867 e861-814; quiz 881-862] and can be related to both active and inactive ingredients in sunscreen products [DiNardo et al. J Cosmet Dermatol. 2018;17(1):15-19; Barrientos et al. Contact Dermatitis. 2019;81(2):151-52]. Pathogenetically, the main cutaneous adverse reaction patterns to sunscreens can be divided into allergic and irritant contact dermatitis, phototoxic and photoallergic contact dermatitis, contact urticaria, and, in solitary cases, anaphylactic reactions [Lautenschlager et al. Lancet. 2007;370(9586):528-37]. A summary is provided in Table 1. Nearly all adverse effects due to active sunscreen ingredients reported to date are related to the organic UV filters, which are sometimes also referred to as "chemical UV filters." This imbalance is attributable to the lipophilic character and small molecular size of the organic UV filters that allow skin penetration, which is the basic requirement to initiate the sensitization [Stiefel et al. Int J Cosmet Sci. 2015;37(1):2-30]. In contrast, cutaneous adverse reactions to inorganic UV filters, initially termed "physical UV filters" owing to their firstly known "physical" mechanism of action through reflection and scattering [Stiefel et al. Int J Cosmet Sci. 2015;37(1):2-30], are only reported by case reports. Neither zinc oxide nor titanium dioxide possesses relevant skin-irritating properties or sensitization potential [Lau-tenschlager et al. Lancet. 2007;370(9586):528-37]. Adverse reactions to UV filters currently approved in the European Union as listed in the Annex VI (updated November 7, 2019) are summarized in Table 2.