Longitudinal Assessment of the Prevalence of Actinic Keratosis and Extensive Risk Factor Evaluation: An Update from the Rotterdam Study.

Population-based studies available to analyze the prevalence, risk factors, and longitudinal outlook of actinic keratoses (AKs) are limited. These features mentioned earlier were assessed using Rotterdam study participants aged ≥40 years who underwent a full-body skin examination by a dermatology-trained physician. ORs with 95% confidence intervals were calculated for the associations between risk factors and the presence of AK. Among 8,239 eligible participants, the prevalence of one or more AKs was 21.1% (95% confidence interval = 20.2-22.0) and was higher in men. Male sex, age, lighter hair and eye color, baldness, genetic risk score, and digital photoaging measures (digitally assessed pigmented spots, telangiectasias, and global facial wrinkling) had a positive association with AK. Cigarette smokers had reduced odds of having AK, with current smokers having the lowest risk. Among patients with two AK assessments, there was no difference in the presence of AK during follow-up between treated and untreated participants. In conclusion, genetic risk score and digital photoaging measures showed associations with increased lesion count. At the individual level, patients were most likely to decrease in AK severity group over time, possibly regardless of whether or not participants were treated.

Stimulating Sunscreen Use Among Outdoor Construction Workers: A Pilot Study.

Background: Outdoor workers (OW) receive a higher dose of ultraviolet radiation (UVR) compared to indoor workers (IW) which increases the risk of non-melanoma skin cancer (NMSC). Regular sunscreen use reduces the NMSC risk, however, adequate sun-safety behavior among OW is poor. The main objective was to conduct method- and intervention-related elements of a future intervention trial among OW, based on providing sunscreen and assessing sunscreen use on group- and individual level. Methods: This pilot study was conducted at a construction site in the Netherlands from May-August 2021. Nine dispensers with sunscreen (SPF 50+) were installed at the worksite. OW (n = 67) were invited to complete two (cross-sectional) questionnaires on sun-safety behavior, before and after providing sunscreen. Stratum corneum (SC) samples for the assessment of UV-biomarkers were collected from the forehead and behind the ear from 15 OW and 15 IW. The feasibility of the following elements was investigated: recruitment, (loss to) follow-up, outcome measures, data collection, and acceptability of the intervention. Results: The first questionnaire was completed by 27 OW, the second by 17 OW. More than 75 percent of the OW were aware of the risks of sun exposure, and 63% (n = 17) found sunscreen use during worktime important. The proportion of OW never applying sunscreen in the past month was 44.4% (n = 12) before, and 35.3% (n = 6) after providing sunscreen. A majority of OW (59.3%, n = 16) found sunscreen provision encouraging for sunscreen use, the dispensers easy to use (64.7%, n = 17) and placed in practical spots (58.8%, n = 18). Collecting SC-samples was fast and easy, and several UV-biomarkers showed higher levels for sun-exposed compared to less exposed body parts. There was no significant difference in UV-biomarker levels between OW and IW. Conclusions: This pilot study revealed low sunscreen use among OW despite providing sunscreen, overall satisfaction with the sunscreen, and the sufficient awareness of the risks of UVR-exposure. Collecting SC-samples at the workplace is feasible and several UV-biomarkers showed to be promising in assessing UVR-exposure. The low participation rate and high loss to follow-up poses a challenge for future intervention studies.

Research Techniques Made Simple: Stratum Corneum Tape Stripping.

Stratum corneum (SC)-derived biomarkers can provide relevant information on the skin's antimicrobial, physical, and immunological barriers. The SC is easily accessible, and collection by adhesive tapes (tape stripping [TS]) is robust and minimally invasive. Given its minimal invasiveness and simplicity, TS is particularly useful for studies in the pediatric population and when repetitive sampling over time is desirable, for example, in clinical trials. The palette of SC biomarkers is expanding in a wide variety of research areas, benefiting from advances in multiplex immunoassays and omics approaches, including proteomics, lipidomics, and transcriptomics. Although there is increasing interest in collecting SC samples, the lack of TS standardization hampers its broader implementation in research and clinical practice. In this article, we address the TS procedure as well as methodological challenges that should be considered in the development of an optimal sampling strategy.

Protection Against Solar Ultraviolet Radiation in Outdoor Construction Workers: Study Protocol for a Non-randomized Controlled Intervention Study.

Introduction: Non-melanoma skin cancer (NMSC) incidence is increasing, and occupational solar exposure contributes greatly to the overall lifetime ultraviolet radiation (UVR) dose. This is reflected in an excess risk of NMSC showing up to three-fold increase in outdoor workers. Risk of NMSC can be reduced if appropriate measures to reduce UVR-exposure are taken. Regular use of sunscreens showed reduced risk of NMSC. However, sun-safety behavior in outdoor workers is poor. The objective of this study is to investigate the effectiveness of an intervention aiming at increasing sunscreen use by construction workers. Methods: This non-randomized controlled intervention study is comprised of two intervention and two control groups recruited at four different construction sites in the Netherlands. The study population comprises ~200 construction workers, aged 18 years or older, followed during 12 weeks. The intervention consists of providing dispensers with sunscreens (SPF 50+) at construction sites and regular feedback on the application achieved by continuous electronic monitoring. All groups will receive basic information on UV-exposure and skin protection. Stratum corneum (SC) samples will be collected for measurement of biomarkers to assess internal UV-dose. External UV-dose will be assessed by personal UV-sensors worn by the workers during work-shifts in both groups. To detect presence of actinic keratosis (AK) or NMSC, a skin check of body parts exposed to the sun will be performed at the end of the study. The effect of the intervention will be assessed from data on self-reported sunscreen use by means of questionnaires collected on baseline and after 12 weeks of intervention (primary outcome). Levels of SC biomarkers of internal UV-dose, external UV-dose, number of sunburn episodes, and prevalence of NMSC including AK will be assessed as secondary outcomes. The electronically monitored sunscreen consumption will be assessed as process outcome. Discussion: This study is intended to provide evidence of the effectiveness of a technology-driven intervention to increase sunscreen use in outdoor construction workers. Furthermore, it will increase insight in the UV-protective behavior, external and internal UV-exposure, and the prevalence of NMSC, including AK, in construction workers. Trial Registration: The Netherlands Trial Register (NTR): NL8462 Registered on March 19, 2020.

Tape stripping the stratum corneum for biomarkers of ultraviolet radiation exposure at sub-erythemal dosages: a study in human volunteers.

PURPOSE: Prevalence of skin cancer is rapidly increasing. There is a need for non-invasive biomarkers to assess efficacy of prevention strategies aiming at reduction of exposure to ultraviolet radiation (UVR). Recently, stratum corneum (SC) biomarkers were applied in various inflammatory skin diseases. Here, we explore their suitability as candidate biomarkers for UVR. MATERIAL AND METHODS: Twelve volunteers were exposed to a UVB-dose of 0.72 SED, three times a week, during three weeks. As candidate biomarkers, cis-isomers of urocanic acid (cUCA) and 25 immunological mediators were measured in the SC. RESULTS: Eight immunological markers significantly changed from baseline. Of them, IL-1RA/IL-1α and a placental growth factor (PIGF) showed gradual changes during UVR-exposure (p < 0.01 for linear trend). cUCA increased sharply already after the first exposure, however, reached a plateau in the second week. CONCLUSIONS: SC represents a promising, non-invasive alternative to skin biopsy in detecting UVR-induced changes. cUCA is the marker of choice for assessment of single UVR-exposure; however, it is less suitable for cumulative UVR-dose. Immunological markers including IL-1RA/IL-1α and PIGF showed gradual changes, and therefore are convenient for monitoring chronic UVR-exposure. These candidate biomarkers might facilitate assessment of the efficacy of preventive measures in the workplace and general population.

Actinic keratosis and surrounding skin exhibit changes in corneocyte surface topography and decreased levels of filaggrin degradation products.

Actinic keratosis (AK) is a frequent premalignant skin lesion mainly caused by chronic sun exposure. AK lesions are often surrounded by invisible, subclinical alterations, called field of cancerization (FoC). Definition of FoC is of importance for therapy management; however, the criteria and non-invasive tools to characterize FoC are lacking. Atomic force microscopy (AFM) proved to be a suitable tool for detection of changes in the corneocyte surface topography in inflammatory skin diseases, which share similar clinical features with AK such as hyper- and parakeratosis. Therefore, in this study we applied AFM to investigate AK and surrounding skin obtained by non-invasive collection of the stratum corneum (SC) with adhesive tapes. Furthermore, we determined degradation products of structural protein filaggrin (natural moisturizing factor, NMF), which previously showed association with the changes in corneocyte surface topography. Ten patients with multiple AK on the face were recruited from the outpatient clinic. SC samples were collected from the AK lesion, skin sites adjacent to the AK, 5 cm from the AK and retroauricular area. Corneocyte surface topography was determined by AFM, and NMF by liquid chromatography. The AK lesion showed alterations of the corneocyte surface topography characterized by an increased number of nanosize protrusions, which gradually decreased with the distance from the lesion. NMF levels show an inverse pattern. Atomic force microscopy showed to be a suitable tool to detect changes in the corneocyte surface topography on the AK lesion and surrounding skin in a non-invasive manner.

Percutaneous penetration of drugs applied in transdermal delivery systems: an in vivo based approach for evaluating computer generated penetration models.

Human skin is a viable pathway for administration of therapeutics. Transdermal delivery systems (TDS) have been approved by the US-FDA since 1981. To enable the risk assessment of dermal exposure, predictive mathematical models are used. In this work the accuracy of predicted flux of the models is compared to experimental human in vivo data of drugs applied in US-FDA approved TDS. A database of pharmacokinetic data of drugs applied in TDS was used and updated. Three mathematical models (QSAR) were used to calculate predicted fluxes, and compared to the human in vivo data. For more than half of the drugs applied in TDS, the predicted flux by the mathematical models was an underestimation compared to the flux calculated with the experimental in vivo data. The flux was over- or underestimated by a factor 10-100. All mathematical models were significantly correlated with the experimental in vivo data. The process of percutaneous penetration has several influencing factors, TDS minimize some of these factors. Limitations are discussed. Further research is needed, with a focus on validation and standardization of the permeability coefficient. This work offers observations that should give a stimulus for refinement on the appropriate usage and limitations of mathematical models.