Validation of skin surface microtopography as a measure of skin photoaging in a subtropical population aged 40 and over.

BACKGROUND: Evidence suggests that skin surface microtopography is a valid measure of photoaging among young adults, but whether this applies to older adults is unknown. METHODS: We investigated the association between degree of photoaging as measured by histological dermal elastosis and skin microtopography grades by decade of age from 40 to 89 years in a community sample in Australia. Skin surface replicas and punch biopsies were taken from 664 participants of the Nambour Skin Cancer Study. The association was assessed using ordinal logistic regression with proportional odds assumption, using histological dermal elastosis grades as outcome. RESULTS: There was significant increase in odds of higher skin surface microtopography grades with higher dermal elastosis grades for age groups below 70 years [40 to 49 years: odds ratio (OR) 2.96, 95% confidence interval (CI) 1.68-5.22; 50 to 59 years: OR 3.78, 95% CI 2.28-6.26; 60 to 69 years: OR 2.47, 95% CI 1.41-4.35). The association was not significant for those 70 years or older. CONCLUSION: Skin surface microtopography grading system is a valid measure of degree of dermal elastosis for middle-aged and older adults up to 69 years but appears not to be valid for adults 70 years or more living in a high sun exposure setting.

Dietary Antioxidant Capacity and Skin Photoaging: A 15-Year Longitudinal Study.

The long-term effect of diet on skin aging is largely unknown, but evidence suggests that the antioxidants from foods may mitigate the main component of skin aging caused by sun exposure. We assessed the association between the total antioxidant capacity of foods people eat and the photoaging of their skin. In a community-based, prospective study among 777 Australian adults aged <55 years at baseline, we estimated the total dietary antioxidant capacity of participants' diets in 1992, 1994, and 1996 and graded photoaging severity using microtopography in 1992, 1996, and 2007. We used ordinal logistic regression and applied generalized estimating equations to estimate change in the degree of photoaging associated with increasing total antioxidant capacity compared with the group with the lowest antioxidant capacity, separately in younger (≤45 years) and older (>45 years) adults. In the 15-year study period, the overall prevalence of severe skin photoaging increased from 42% at baseline to 88%. Adults aged >45 years who consumed foods with high antioxidant capacity experienced approximately 10% less photoaging over 15 years than those who ate foods with low antioxidant capacity. No association was found among adults aged ≤45 years. Foods rich in antioxidants as measured by antioxidant capacity may retard skin aging among healthy men and women aged >45 years.

Broad-spectrum sunscreens provide better protection from solar ultraviolet-simulated radiation and natural sunlight-induced immunosuppression in human beings.

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

The benefit of daily photoprotection.

BACKGROUND: It is now recognized that both ultraviolet (UV)-A and UVB wavelengths participate in the generation of photodamaged human skin during sun exposure. During usual daily activities, an appropriate protection against solar UV exposure should prevent clinical, cellular, and molecular changes potentially leading to photoaging. OBJECTIVE: This study was designed to evaluate in human beings the protection afforded by a day cream containing a photostable combination of UVB and UVA filters and thus protect against the UV-induced skin alterations. RESULTS: In solar-simulated radiation exposed and unprotected skin sites we observed melanization. The epidermis revealed a significant increase in stratum corneum and stratum granulosum thickness. In the dermis, an enhanced expression of tenascin and a reduced expression of type I procollagen were evidenced just below the dermoepidermal junction. Although no change in elastic fibers in exposed buttock skin was seen, a slightly increased deposit of lysozyme and alpha-1 antitrypsin on elastin fibers was observed using immunofluorescence techniques. A day cream with photoprotection properties was shown to prevent all of the above-described alterations. LIMITATIONS: This study was performed on a limited number of patients (n = 12) with specific characteristics (20-35 years old and skin type II and III). Two dermal alterations were evaluated by visual assessment and not by computer-assisted image analysis quantification. CONCLUSION: Our in vivo results demonstrate the benefits of daily photoprotection using a day cream containing appropriate broad-spectrum sunscreens, which prevent solar UV-induced skin damages.

Sunscreens containing the broad-spectrum UVA absorber, Mexoryl SX, prevent the cutaneous detrimental effects of UV exposure: a review of clinical study results.

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

Measurement of sunscreen immune protection factors in humans: a consensus paper.

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

Standard ultraviolet daylight for nonextreme exposure conditions.

The skin is exposed to ultraviolet radiation (UVR) from natural or artificial sources on a daily basis. The effects of chronic low dose exposure merit investigation, even when these effects are neither conspicuous nor clinically assessable. The purpose of the present study was to define a relative spectral UV irradiance that is representative of frequent nonextreme sun exposure conditions and therefore more appropriate for studies of the long-term and daily effects of solar UV on the skin. Solar spectral UV irradiance values were calculated for different dates and locations by using a radiative transfer model. The spectral irradiance values obtained when the solar elevation is lower than 45 degrees were averaged. An important feature is the dUVA (320-400 nm) to dUVB (290-320 nm) irradiance values ratio, which was found to be 27.3 for the overall average. When the months corresponding to extreme irradiance values (low or high) were excluded from the calculations, the dUVA to dUVB ratio ranged from 27.2 to 27.5. The mean spectral irradiance of the model presented here represents environmental UV exposure conditions and can be used both as a standard to investigate the biological effects of a nonextreme UVR and to assess the effectiveness of products for daily skin protection.

High ultraviolet A protection affords greater immune protection confirming that ultraviolet A contributes to photoimmunosuppression in humans.

Solar radiation causes immunosuppression that contributes to skin cancer growth. Photoprotective strategies initially focused on the more erythemogenic ultraviolet B. More recently, the relationship of ultraviolet A and skin cancer has received increased attention. We hypothesized that if ultraviolet A contributes significantly to human ultraviolet-induced immune suppression, then increased ultraviolet A filtration by a sunscreen would better protect the immune system during ultraviolet exposure. Two hundred and eleven volunteers were randomized into study groups and received solar-simulated radiation, ranging from 0 to 2 minimum erythema dose, on gluteal skin, with or without sunscreen, 48 h prior to sensitization with dinitrochlorobenzene. Contact hypersensitivity response was evaluated by measuring the increase in skin fold thickness of five graded dinitrochlorobenzene challenge sites on the arm, 2 wk after sensitization. Clinical scoring using the North American Contact Dermatitis Group method was also performed. Solar-simulated radiation dose-response curves were generated and immune protection factor was calculated using a nonlinear regression model. Significance of immune protection between study groups was determined with the Mann-Whitney-Wilcoxon exact test. The sunscreen with high ultraviolet A absorption (ultraviolet A protection factor of 10, based on the in vivo persistent pigment darkening method) and a labeled sun protection factor of 15 demonstrated better immune protection than the product that had a low ultraviolet A absorption (ultraviolet A protection factor of 2) and a labeled sun protection factor of 15. Nonlinear regression analysis based on skin fold thickness increase revealed that the high ultraviolet A protection factor sunscreen had an immune protection factor of 50, more than three times its sun protection factor, whereas the low ultraviolet A protection factor sunscreen had an immune protection factor of 15, which was equal to its labeled sun protection factor. This study demonstrates that ultraviolet A contributes greatly to human immune suppression and that a broad-spectrum sunscreen with high ultraviolet A filtering capacity results in immune protection that exceeds erythema protection. These results show that high ultraviolet A protection is required to protect against ultraviolet-induced damage to cutaneous immunity.

Standardized protocols for photocarcinogenesis safety testing.

Solar ultraviolet radiation (UVR) is recognized as a major cause of non-melanoma skin cancer in man. Skin cancer occurs most frequently in the most heavily exposed areas and correlates with degree of outdoor exposure. The incidence of skin cancer is also increased by contact with photosensitizing drugs and chemicals such as psoralens, coal tars and petroleum stocks. Other substances which do not act as photosensitizers, such as immunosuppressants taken by organ transplant recipients, also increase the risk of skin cancer. The U.S. Food and Drug Administration requests, on a case-by-case basis, that risk of enhanced photocarcinogenesis is assessed for many classes of drugs. Health Canada's Therapeutic Products Programme has issued a Notice of Intent to regulate pharmaceutical products which may enhance carcinogenicity of the skin induced by ultraviolet radiation. Other national regulatory agencies review such data when they exist, but their own requirements emphasize batteries of short-term in vitro and in vivo tests. While they may support drug development strategies, short-term tests have yet to be validated as predictors of the ability of drugs or chemicals to enhance photocarcinogenesis. Published protocols now describe study designs and procedures capable of determining whether test agents enhance the rate of formation of UVR-induced skin tumors.

Changes in matrix gene and protein expressions after single or repeated exposure to one minimal erythemal dose of solar-simulated radiation in human skin in vivo.

Damage to the skin extracellular matrix (ECM) is the hallmark of long-term exposure to solar UV radiation. The aim of our study was to investigate the changes induced in unexposed human skin in vivo after single or repeated (five times a week for 6 weeks) exposure to 1 minimal erythemal dose (MED) of UV solar-simulated radiation. Morphological and biochemical analyses were used to evaluate the structural ECM components and the balance between the degrading enzymes and their physiologic inhibitors. A three-fold increase in matrix metalloproteinase 2 messenger RNA (mRNA) (P < 0.02, unexposed versus exposed) was observed after both single and repeated exposures. Fibrillin 1 mRNA level was increased by chronic exposure (P < 0.02) and unaltered by a single MED. On the contrary, a single MED significantly enhanced mRNA levels of interleukin-1alpha (IL-1alpha), IL-1beta (P < 0.02) and plasminogen activator inhibitor-1 (P < 0.05). Immunohistochemistry demonstrated a significant decrease in Type-I procollagen localized just below the dermal-epidermal junction in both types of exposed sites. At the same location, the immunodetected tenascin was significantly enhanced, whereas a slight increase in Type-III procollagen deposits was also observed in chronically exposed areas. Although we were unable to observe any change in elastic fibers in chronically exposed buttock skin, a significant increase in lysozyme and alpha-1 antitrypsin deposits on these fibers was observed. These results demonstrate the existence of a differential regulation, after chronic exposure compared with an acute one, of some ECM components and inflammatory mediators.

Food intake, dietary patterns, and actinic keratoses of the skin: a longitudinal study.

BACKGROUND: Actinic keratoses (AKs) are premalignant actinic tumors of the skin. Evaluation of the role of diet in their development is lacking. OBJECTIVE: The objective was to determine whether intake of certain food groups or dietary patterns retard the occurrence of AKs over a 4.5-y period. DESIGN: In a community-based study of skin cancer in Queensland, Australia, food intake of 1119 adults was assessed in 1992, 1994, and 1996 by using a validated food-frequency questionnaire. Dermatologists counted prevalent AKs during full-body skin examinations in 1992 and 1996. The relative ratio (RR) of AK counts in 1996 relative to 1992 was compared across increasing intakes of 26 food groups, and for 3 dietary patterns identified by principal components analysis, with the use of generalized linear models with negative binomial distribution, allowing for repeated measures. All analyses were adjusted for confounding factors, including skin color and sun exposure indexes. RESULTS: AK acquisition decreased by 28% (RR: 0.72; 95% CI: 0.55, 0.95) among the highest consumers of oily fish (average of one serving every 5 d) compared with those with minimal intake. Similarly, the rate of acquisition of AKs was reduced by 27% (RR: 0.73; 95% CI: 0.54, 0.99) in those with the highest consumption of wine (average of half a glass a day in this study population). There was no consistent association of dietary pattern with AK acquisition. CONCLUSION: Moderate intake of oily fish and of wine may decrease the acquisition of AKs and thus complement sun protection measures in the control of actinic skin tumors.

Biological effects of simulated ultraviolet daylight: a new approach to investigate daily photoprotection.

BACKGROUND: The irradiance of standard ultraviolet daylight (UV-DL) is representative of most frequently encountered UV exposure conditions and simulators of UV-DL can now be used to properly investigate the biological effects of a non-extreme UV radiation. One of the characteristics of the simulated UV-DL used in this study is its dUVA to dUVB irradiance ratio, which amounts to 24, instead of close to 10, for the simulated zenithal UV radiation (UV-SSR). PURPOSE/METHODS: The aim of our study was to compare photobiological effects induced, in human skin, by acute and semi-chronic exposure to simulated UV-DL with those induced by UV-SSR. RESULTS: Differences between UV doses needed to induce given biological effects after exposure to simulated UV-DL compared with UV-SSR indicate that the spectral distribution of the UV spectrum is of primary importance with regard to biological endpoints in the epidermis (SBC, p53, thymine dimers, Langerhans cells, and melanocyte alterations, etc.) and in the dermis (collagen, tenascin, etc.). Significant biological damage was noticed after 19 cumulative exposures to 0.5 minimum erythemal dose (MED) of UV-DL over 4 weeks. 0.5 MED of UV-DL corresponds to 1/9 of the daily typical dose received in Paris in April, emphasizing the need for an efficient daily UV protection. CONCLUSION: Simulated UV daylight is a relevant new tool for daily photoprotection studies.

Skin surface topography grading is a valid measure of skin photoaging.

BACKGROUND: The technique of grading the surface topography of sun-exposed skin using silicone impressions of the skin surface is a simple, non-invasive method for measuring skin damage because of sun exposure, but it has never been validated in a community setting. OBJECTIVE: To investigate the repeatability and validity of using standardly-graded skin impressions as a means of assessing skin photoaging. PATIENTS/METHODS: A random sample of 195 adults aged 18-79 years and living in Nambour, Australia (latitude, 26 degrees South) had a silicone impression taken of the back of the left hand and a 2 mm punch biopsy of the skin at the same site. Silicone impressions were graded twice independently and histological photoaging was determined by two pathologists. RESULTS: Grading of silicone impressions of skin surface topography was highly repeatable (weighted kappa > 0.8). Compared with those with low skin impression grades (least degeneration), people with high grades were three times more likely to show a high degree of dermal elastosis on skin histology (odds ratio 3.1, 95% confidence interval 1.6, 5.7) after adjusting for age, sex, skin colour, tanning ability, occupational exposure, smoking and height-adjusted weight. Other photoaging changes in the stratum corneum and dermis were also strongly correlated with high grades of damage on skin impressions. CONCLUSION: Grading silicone impressions of skin surface topography is a highly reliable and a valid measure of photoaging and enables prediction of dermal elastosis in a population setting.

Effects of UVA radiation on an established immune response in humans and sunscreen efficacy.

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

Iron chelation can modulate UVA-induced lipid peroxidation and ferritin expression in human reconstructed epidermis.

BACKGROUND/PURPOSE: As ferritin has been identified as an important factor in antioxidant defense in cultured human skin cells, we evaluated UVA-induced lipid hydroperoxides (LPO) production and ferritin expression in reconstructed human epidermis in vitro. RESULTS: Ferritin is regularly present in the basal layer of unirradiated epidermis both in the human skin in vivo and in the reconstructed human epidermis in vitro. Following acute UVA exposure, ferritin expression increased in basal epidermal cells in both models. Quantitative analysis showed that, in reconstructed human epidermis, LPO and ferritin levels increased linearly with the UVA dose. An iron chelator, OR10141, inhibited these inductions. CONCLUSION: These findings demonstrate that reconstructed human epidermis is a useful in vitro model to study UVA-induced oxidative stress and protection afforded by iron chelators, antioxidants or UVA absorbers.