Subclinical effects of adapalene-benzoyl peroxide: a prospective in vivo imaging study on acne micromorphology and transfollicular delivery.

BACKGROUND: Adapalene-benzoyl peroxide (A-BPO) is a first-line topical treatment for acne vulgaris. In vivo reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) detect micromorphological changes over time and visualize transfollicular delivery. OBJECTIVES: To visualize temporal, subclinical effects of A-BPO on acne micromorphology using RCM and OCT, and evaluate their impact on transfollicular delivery of microparticulate carrier systems. METHODS: Fifteen patients with mild to moderate acne received a 6-week course of A-BPO. Micromorphological changes were evaluated at time 0, 3 and 6 weeks with RCM (n = 1190 images) and OCT (n = 210 scans). Transfollicular delivery of microparticles was assessed at baseline and week 6. RESULTS: In vivo imaging visualized steady normalization of skin micromorphology in response to A-BPO over 6 weeks, including decreased hyperkeratinization of follicular borders (RCM median decrease -71.2%, P < 0.05), reduced intrafollicular keratinous content (RCM median decrease -47.7%, P < 0.05) and increased epidermal thickness (OCT median increase of 25.25%, P < 0.05). Imaging visualized microparticles in the follicular unit. Despite a visible reduction in keratin and sebum, transfollicular microparticle delivery appeared unaffected. CONCLUSIONS: Reflectance confocal microscopy and OCT detect A-BPO-induced changes in micromorphology and visualize transfollicular microparticle delivery. Keratolysis and sebolysis did not have a measurable effect on transfollicular delivery of microparticles.

Basal cell carcinoma treated with combined ablative fractional laser and ingenol mebutate - an exploratory study monitored by optical coherence tomography and reflectance confocal microscopy.

BACKGROUND: Basal cell carcinomas (BCCs) have previously been treated off-label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non-invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low-risk BCCs. METHODS: Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2 -laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits. RESULTS: At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients. CONCLUSION: Two treatments of combined AFL and IM show potential to treat low-risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short-term follow-up.

Sunscreen applied at ≥ 2 mg cm-2 during a sunny holiday prevents erythema, a biomarker of ultraviolet radiation-induced DNA damage and suppression of acquired immunity.

BACKGROUND: Sun protection factor (SPF) is assessed with sunscreen applied at 2 mg cm-2 . People typically apply around 0·8 mg cm-2 and use sunscreen daily for holidays. Such use results in erythema, which is a risk factor for skin cancer. OBJECTIVES: To determine (i) whether typical sunscreen use resulted in erythema, epidermal DNA damage and photoimmunosuppression during a sunny holiday, (ii) whether optimal sunscreen use inhibited erythema and (iii) whether erythema is a biomarker for photoimmunosuppression in a laboratory study. METHODS: Holidaymakers (n = 22) spent a week in Tenerife (very high ultraviolet index) using their own sunscreens without instruction (typical sunscreen use). Others (n = 40) were given SPF 15 sunscreens with instructions on how to achieve the labelled SPF (sunscreen intervention). Personal ultraviolet radiation (UVR) exposure was monitored electronically as the standard erythemal dose (SED) and erythema was quantified. Epidermal cyclobutane pyrimidine dimers (CPDs) were determined by immunostaining, and immunosuppression was assessed by contact hypersensitivity (CHS) response. RESULTS: There was no difference between personal UVR exposure in the typical sunscreen use and sunscreen intervention groups (P = 0·08). The former had daily erythema on five UVR-exposed body sites, increased CPDs (P < 0·001) and complete CHS suppression (20 of 22). In comparison, erythema was virtually absent (P < 0·001) when sunscreens were used at ≥ 2 mg cm-2 . A laboratory study showed that 3 SED from three very different spectra suppressed CHS by around ~50%. CONCLUSIONS: Optimal sunscreen use prevents erythema during a sunny holiday. Erythema predicts suppression of CHS (implying a shared action spectrum). Given that erythema and CPDs share action spectra, the data strongly suggest that optimal sunscreen use will also reduce CPD formation and UVR-induced immunosuppression.

Optimal sunscreen use, during a sun holiday with a very high ultraviolet index, allows vitamin D synthesis without sunburn.

BACKGROUND: Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status. OBJECTIVES: To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday. METHODS: The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D3 [25(OH)D3 ] was assessed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D3 (28·0 ± 16·5 nmol L-1 ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L-1 25(OH)D3 , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L-1 25(OH)D3 . CONCLUSIONS: Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D3 concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission.

Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D3 , after a summer holiday in Northern Europe.

BACKGROUND: Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children. OBJECTIVES: To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV). METHODS: Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy. RESULTS: The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol µmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday. CONCLUSIONS: Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.

Sun behaviour on the beach monitored by webcam photos.

OBJECTIVES: To prevent skin cancer, the general population is recommended to limit time in the sun, to wear clothes and to seek shade around noon. This study aimed to investigate the number of beachgoers, the duration of sun exposure, and clothing worn during the day on a beach in Copenhagen. STUDY DESIGN: Observational, descriptive study. METHODS: On 11 beach days in 2014 and 2015, beachgoers were counted every hour from 8:00 to 20:00. It was noted if they wore clothes or swimwear. To estimate the duration of sun exposure, it was noted how long cars were parked by the beach. RESULTS: Of the counted beachgoers 46% were present from noon to 15:00. The number of beachgoers peaked at 15:00 on weekend days (Saturdays and Sunday) and at 16:00 on working days (Monday to Friday). Both on weekend days and working days, the percentage of beachgoers wearing clothes was lowest at 13:00 when about 90% wore only swimwear. Cars were parked for 117 min on average. Around noon, the mean time expanded to 142 min. We assume this to reflect the duration of a beach visit. CONCLUSION: The results indicate a weak tendency to limit time in the sun and to seek shade when the ultraviolet radiation is strongest in the midday sun. Hopefully information about actual sun behaviour can be used to adjust campaigns.

UVR: sun, lamps, pigmentation and vitamin D.

Exposure to ultraviolet radiation (UVR) has important and significant consequences on human health. Recently, there has been renewed interest in the beneficial effects of UVR. This perspective gives an introduction to the solar spectrum, UV lamps, UV dosimetry, skin pigment and vitamin D. The health benefits of UVR exposure through vitamin D production or non-vitamin D pathways will be discussed in this themed issue in the following articles.

Defining "intermittent UVR exposure".

BACKGROUND: Cutaneous malignant melanoma (CMM) has been associated with "intermittent UVR exposure", which in previous studies has mainly been assessed by retrospective questionnaire data. Further, there is no uniform definition of the term "intermittent UVR exposure". OBJECTIVES: We aimed to define and quantify "intermittent UVR exposure" by an objective measure. METHODS: A broad study population of adults and children had data collected during a summer period. Data were personal UVR dosimetry measurements, from which the number of "intermittent days" was derived, sun behaviour diaries and retrospective questionnaires. Two definitions of intermittent UVR exposure were tested: (1) days when UVR dose exceeded 3 times individual average daily UVR dose, and (2) days when UVR dose exceeded individual constitutive skin type. Measures of nevi and lentigines were used as surrogates for CMM. RESULTS: Using the first definition based solely on UVR dosimetry data we found 1241 "intermittent days" out of a total of 17 277 days (7.2%) among 148 participants. The numbers for nevi and lentigo density were significantly predicted by the number of intermittent days (R(2) = 0.15 and R(2) = 0.40, p < 0.001). The corresponding numbers for prediction of nevi and lentigo density by retrospective questionnaire data was lower (R(2) = 0.11, R(2) = 0.26, p < 0.001). CONCLUSIONS: We introduce a well-defined objective measure of intermittent UVR exposure. This measure may provide a better prediction of solar skin damage and CMM than retrospective questionnaire data.

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate.

BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n = 120). A 2,940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ-E), superficial-dermis (26 mJ/channel, MAZ-DS), and mid-dermis (256 mJ/channel, MAZ-DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full-thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC-activated MTX-fluorescence (254 nm) and semi-quantify MTX distribution in skin. RESULTS: AFXL increased topical MTX-delivery (P < 0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07 mg/cm(2) , increasing sixfold (MAZ-E), ninefold (MAZ-DS), and 11-fold (MAZ-DM) after AFXL (P < 0.001). Deeper MAZs increased MTX-concentrations in all skin layers (P < 0.038) and favored maximum accumulation in deeper skin layers (MAZ-E: 1.85 mg/cm(3) at 500 µm skin-level vs. MAZ-DM: 3.75 mg/cm(3) at 800 µm, P = 0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth (P = 0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6-47 µm, P ≥ 0.438). CONCLUSION: AFXL greatly increases topical MTX-delivery. Deeper MAZs deliver higher MTX-concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519-529, 2016. © 2016 Wiley Periodicals, Inc.

Adjuvant eflornithine to maintain IPL-induced hair reduction in women with facial hirsutism: a randomized controlled trial.

BACKGROUND: Photoepilation is the treatment of choice for hair removal in patients with hirsutism, but it remains a challenge to prevent regrowth of hairs. OBJECTIVES: The objective of this study was to investigate whether topical eflornithine maintains hair reduction in hirsute patients after cessation of intense pulsed light (IPL) therapy. METHODS: A randomized, split-face, single-blinded controlled trial on topical eflornithine vs. no eflornithine treatment (control) after 5-6 IPL-treatments in 22 women with facial hirsutism. Application of eflornithine was initiated after the final IPL-treatment (baseline) and applied twice daily for 6 months to half of the face. Patients were assessed at baseline and 1, 3 and 6 months after the final IPL-treatment. The primary endpoint was difference in facial hair counts between eflornithine vs. no treatment. Secondary endpoints were patient-evaluated efficacy, patient satisfaction and safety. RESULTS: A total of 18 patients completed the study protocol. At 1 month after final IPL-treatment, eflornithine reduced hair regrowth by 14% (P = 0.007, n = 20 patients), at 3 months by 9% (P = 0.107, n = 19) and at 6 months by 17% (P = 0.048, n = 18) compared to no treatment. Patient-evaluated efficacy supported blinded hair counts and patients were satisfied with eflornithine treatment throughout the study (median VAS 5-6). Eflornithine was generally well tolerated, but blinded evaluation demonstrated deterioration of acne in two patients at final assessment. CONCLUSION: Topical eflornithine provides a self-administered treatment with a potential to maintain IPL-induced hair reduction in hirsute patients.

Protoporphyrin IX formation after topical application of methyl aminolaevulinate and BF-200 aminolaevulinic acid declines with age.

BACKGROUND: Topical photodynamic therapy (PDT) is a popular treatment modality in dermatology. The effect of PDT in epidermal cells depends on formation of protoporphyrin IX (PpIX) from 5-aminolevulinic acid (ALA). A variety of physiological changes in epidermal function occur with increasing age, but no studies have investigated whether PpIX formation is age-related. OBJECTIVES: To investigate a possible relationship between age and PpIX formation. METHODS: Methyl aminolaevulinate cream (MAL) and 5-ALA gel (BF-200 ALA) were applied to two identical fields on the forearm of 30 healthy volunteers for 24 h. The volunteers were divided into two age groups: a young group under 55 years (range 18-54) and an older group over 55 years (range 65-85). PpIX formation was measured noninvasively every hour from 1-5 h, and after 18, 21 and 24 h. Skin phototype, stratum corneum hydration and ultraviolet (UV) damage were also assessed. Treatment efficacy in relation to age was evaluated in 100 basal cell carcinomas (BCCs) treated with MAL-PDT. RESULTS: Both photosensitizers induced significantly more PpIX formation in the younger group. Linear regression revealed a significant age-related decline in PpIX formation after the standard application time of 3 h (P < 0.001 for both treatments). Skin phototype, stratum corneum hydration and UV damage were not associated with PpIX formation. The treatment efficacy of BCCs 3 months after MAL-PDT was higher in young patients (P = 0.012). CONCLUSIONS: PpIX formation in human skin declines with age. No explanation could be attributed to skin phototype, stratum corneum hydration or UV damage. The consequence might be reduced efficacy of PDT in the elderly.

Quantitative assessment of growing hair counts, thickness and colour during and after treatments with a low-fluence, home-device laser: a randomized controlled trial.

BACKGROUND: At-home laser and intense pulsed-light hair removal continues to grow in popularity and availability. A relatively limited body of evidence is available on the course of hair growth during and after low-fluence laser usage. OBJECTIVES: To assess growing hair counts, thickness and colour quantitatively during and after cessation of low-fluence laser treatment. METHODS: Thirty-six women with skin phototypes I-IV and light to dark-brown axillary hairs were included. Entire axillary regions were randomized to zero or eight self-administered weekly treatments with an 810-nm home-use laser at 5·0-6·4 J cm(-2). Standardized clinical photographs were taken before each treatment and up to 3 months after the final treatment for computer-aided quantification of growing hair counts, thickness and colour. RESULTS: Thirty-two women completed the study protocol. During sustained treatment, there was a reduction in growing hair that reached a plateau of up to 59%, while remaining hairs became up to 38% thinner and 5% lighter (P < 0·001). The majority of subjects (77%) reported 'moderately' to 'much less hair' in treated than untreated axilla, and assessed remaining hairs as thinner and lighter (≥ 60%). After treatment cessation, hair growth gradually returned to baseline levels, and 3 months after the final treatment the count and thickness of actively growing hair exceeded pretreatment values by 29% and 7%, respectively (P ≤ 0·04). CONCLUSIONS: Sustained usage of low-fluence laser induced a stable reduction of growing hair counts, thickness and colour. The reduction was reversible and hairs regrew beyond baseline values after cessation of usage. Computer-aided image analysis was qualified for quantification of hair counts, thickness and colour after laser epilation.

Combination of ablative fractional laser and daylight-mediated photodynamic therapy for actinic keratosis in organ transplant recipients - a randomized controlled trial.

BACKGROUND: Topical photodynamic therapy (PDT) for actinic keratoses (AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients (OTR). OBJECTIVES: We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-dPDT) compared with daylight PDT (dPDT), conventional PDT (cPDT) and AFL alone (AFL) in field treatment of AK in OTR. METHODS: In each patient, four areas in the same region were randomized to one treatment with AFL-dPDT, dPDT, cPDT and AFL. AFL was delivered with a 2940-nm AFL at 2·3 mJ per pulse, 1·15 W, two stacks, 50-µs pulse-duration, 2·4% density. In dPDT and AFL-dPDT, methyl aminolaevulinate (MAL) was applied for 2·5 h without occlusion during daylight exposure. For cPDT, MAL was occluded for 3 h followed by red-light (630 nm) irradiation at 37 J cm(-2). The primary end-point was complete response (CR) 3 months post-treatment. RESULTS: Sixteen patients with 542 AK (grades I-III) in field-cancerized skin of the scalp, chest and extremities were treated during August and September 2012. After 3 months, CR (AK I-III) rates were 74% after AFL-dPDT, 46% after dPDT, 50% after cPDT and 5% after AFL (P < 0·001). CR rates in AFL-dPDT, dPDT and cPDT were also significantly different (P = 0·004). Median maximal pain scores differed significantly during AFL-dPDT (0), dPDT (0), AFL (0) and cPDT (5) (P < 0·001). Erythema and crusting were more intense following AFL-dPDT than dPDT and cPDT, but only transient hypopigmentation was observed. CONCLUSIONS: AFL-dPDT is a novel PDT modality that enhances CR with excellent tolerability compared with dPDT and cPDT in difficult-to-treat AK in OTR.

UVR exposure and vitamin D in a rural population. A study of outdoor working farmers, their spouses and children.

BACKGROUND: Living and working in the countryside may result in excessive UVR exposure, with increased risk of skin cancer. Some sun exposure is, however, recommended, since vitamin D production is UVB-dependent. OBJECTIVES: To examine UVR exposure and vitamin D levels in a rural population of outdoor working male farmers, their indoor working spouses and their children, expected to receive high UVR exposure. METHODS: Prospective, cohort study. During the summer 2009 daily, personal UVR exposure and sun behaviour were recorded by dosimetry and diaries (17 403 days). Vitamin D was measured at the end of summer and the following winter. RESULTS: Risk behaviour (= exposure of shoulders/upper body to the sun), beach days, sunscreen use and sunburns were infrequent. Farmers and boys had the highest daily UVR exposure (both 1.5 SED per day), likewise on work days. On non-work days the UVR exposure was even higher (up to 2.0 SED per day). Farmers, girls and boys had a higher chronic UVR exposure than the spouses, who had more intermittent high UVR exposure. Vitamin D levels did not differ between family members. At the end of summer 16% of the participants were vitamin D insufficient, the following winter, 61%. Some UVR exposure variables correlated positively, but weakly, with vitamin D levels. CONCLUSIONS: UVR exposure was generally high among this study population, however, vitamin D levels still dropped below the recommended level during winter for most participants. Differences in UVR exposure between the groups did not result in differences in vitamin D levels.

Determinants of personal ultraviolet-radiation exposure doses on a sun holiday.

BACKGROUND: A great number of journeys to sunny destinations are sold to the Danish population every year. We suspect that this travel considerably increases personal annual ultraviolet-radiation (UVR) exposure doses. This is important because such exposure is the main cause of skin cancer, and studies have shown a correlation between intermittent solar UVR exposure and malignant melanoma. OBJECTIVES: To prospectively monitor the behaviour of a group of sun seekers during a winter sun holiday and to study the impact of behaviour on personal UVR exposure doses. METHODS: In this observational study 25 Danish sun seekers were closely monitored by on-site investigators for 6 days during a winter sun holiday in the Canary Islands, thus avoiding the possible recall bias of retrospective studies with questionnaires. The volunteers recorded their location, clothing and sunscreen use in diaries, and their UVR doses were measured by personal UVR dosimeters worn on the wrist. This resulted in 3450 half-hour registrations during 150 participation days. RESULTS: On average, each volunteer received a total UVR dose of 57 standard erythema doses over 6 days, which is 43% of the annual UVR dose of a Danish indoor worker. Their exposed body area, sunscreen use and percentage of body with sunscreen application were positively correlated with their personal UVR doses, and there was also a strong relationship between location and UVR doses received. CONCLUSIONS: The behaviour of the volunteers had a major impact on their personal UVR doses. Our results emphasize the importance of changing the behaviour of sun seekers with protanning attitudes to reduce their personal annual UVR exposure doses, and possibly their risk of skin cancer.

Sun behaviour after cutaneous malignant melanoma: a study based on ultraviolet radiation measurements and sun diary data.

BACKGROUND: It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. OBJECTIVES: In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun behaviour. METHODS: The study population consisted of 24 patients recently diagnosed with CMM during the 7 months preceding the start of the study; 51 controls who matched these recently diagnosed patients in age, sex, occupation and constitutive skin type; and 29 patients diagnosed with CMM between 12 months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. RESULTS: The UVR dose of recently diagnosed patients on days with body exposure was one-third lower, and the number of days using sunscreen was double that of matched controls. However, in patients diagnosed more than 12 months earlier, the UVR dose on days with body exposure was one-third higher and the number of days using sunscreen was half that of recently diagnosed patients. CONCLUSIONS: Patients with CMM limited their UVR dose on days with body exposure, and by using sunscreen further reduced UVR reaching the skin, although only immediately after diagnosis.

Diagnosis of malignant melanoma and basal cell carcinoma by in vivo NIR-FT Raman spectroscopy is independent of skin pigmentation.

There is a general need for methods to obtain fast in vivo diagnosis of skin tumours. Raman spectroscopy measures molecular structure and may thus have potential as a tool for skin tumour diagnosis. The purpose of this study was to investigate how skin pigmentation influenced the Raman spectra and skin tumour diagnostics in vivo. We obtained Raman spectra in vivo from the normal skin of 55 healthy persons with different skin pigmentation (Fitzpatrick skin type I-VI) and in vivo from 25 basal cell carcinomas, 41 pigmented nevi and 15 malignant melanomas. Increased skin pigmentation resulted in a higher spectral background caused by fluorescence, which could be removed by background correction. After background correction, we found only a negligible effect of pigmentation on the major spectral bands, and the comparison of the intensity of these bands allowed us to differentiate between normal skin and the different skin lesions independent of skin type. The diagnosis of skin lesions is possible due to significant (p < 0.05) differences found in the water band around 3250 cm(-1), the protein specific band around 1250 cm(-1) (amide-III) and the amide-III ratio that describes the protein/lipid ratio by comparing bands around 1250 cm(-1) with bands around 1300 cm(-1). We have shown that NIR-FT Raman spectroscopy is useable for malignant melanoma and basal cell carcinoma diagnostics in vivo and that pigmentation of the skin or lesion does not influence the diagnosis, but larger data sets are required to establish accurate diagnostic power.

A small suberythemal ultraviolet B dose every second week is sufficient to maintain summer vitamin D levels: a randomized controlled trial.

BACKGROUND: It is known that ultraviolet (UV) B radiation increases serum 25-hydroxyvitamin D(3) [25(OH)D] level. However, there is uncertainty about the relationship between the maintenance of vitamin D status and UVB. OBJECTIVES: To define the frequency of UVB exposure necessary for maintaining summer 25(OH)D levels during the winter. METHODS: In total, 60 participants were included from October 2008 to February 2009 (16weeks) and randomized for UVB exposure of 1 standard erythema dose (SED) to ∼88% body area once a week (n=15 completed), every second week (n=14 completed) or every fourth week (n=12 completed). The controls (n=14 completed) had no intervention. Vitamin D was measured at baseline, every fourth week before exposure, and 2days after the last UVB exposure. RESULTS: The 25(OH)D levels (mean) after UVB exposure once a week increased significantly (from 71·9 to 84·5nmolL(-1) ) (P<0·0001), whereas UVB exposure every second week maintained 25(OH)D levels (P=0·16). A significant decrease in mean 25(OH)D levels (from 56·4 to 47·8nmolL(-1) ) (P<0·0001) was found after UVB exposure once every fourth week and for the control group (from 64·8 to 40·1nmolL(-1) ) (P<0·0001). The development in 25(OH)D levels during the 16-week study period were negatively correlated with baseline 25(OH)D (P<0·0001). Further, the increase in 25(OH)D after the last UVB exposure was negatively correlated with the 25(OH)D level just before the last UVB exposure (P<0·0001). CONCLUSIONS: Exposure to a UVB dose of 1 SED every second week to ∼88% body area is sufficient for maintaining summer 25(OH)D levels during the winter.

The relation between sunscreen layer thickness and vitamin D production after ultraviolet B exposure: a randomized clinical trial.

BACKGROUND: Sunscreens absorb ultraviolet B (UVB) and it is a major concern that sunscreen use may lead to vitamin D deficiency. OBJECTIVES: To investigate the relation between the amount of sunscreen applied and the vitamin D serum level in humans after UVB exposure under controlled conditions. METHODS: Thirty-seven healthy volunteers with fair skin types were randomized to receive an inorganic sunscreen with sun protection factor (SPF) 8 of 0 mg cm(-2) , 0.5 mg cm(-2) , 1 mg cm(-2) , 1.5 mg cm(-2) , or 2 mg cm(-2) thickness on the upper body, approximately 25% of the body area. Participants were irradiated with a fixed UVB dose of 3 standard erythema doses 20 min after sunscreen application. This procedure was repeated four times with a 2- to 3-day interval. Blood samples were drawn before the first irradiation and 3 days after the last to determine the serum vitamin D level expressed as 25-hydroxyvitamin D(3) [25(OH)D]. RESULTS: The vitamin D serum level increased in an exponential manner with decreasing thickness of sunscreen layer in response to UVB exposure. For all thicknesses of sunscreen, the level of 25(OH)D increased significantly after irradiation (P<0.05), except for the group treated with 2 mg cm(-2) , in which the increase in 25(OH)D was not statistically significant (P=0.16). CONCLUSIONS: Vitamin D production increases exponentially when thinner sunscreen layers than recommended are applied (<2 mg cm(-2) ). When the amount of sunscreen and SPF advised by the World Health Organization are used, vitamin D production may be abolished. Re-evaluation of sun-protection strategies could be warranted.

Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. OBJECTIVES: In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. METHODS: One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. RESULTS: No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P < 0·0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3·5 J cm(-2). CONCLUSIONS: Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.