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The article published in the British Journal of Dermatology explores the association between prescribed oral antidiabetic medication (OADM) for type 2 diabetes mellitus and the risk of developing skin cancer. The systematic review and meta-analysis included studies from various geographical locations and ethnicities, focusing on basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma. The findings suggest that metformin may decrease the risk of skin cancer compared to other OADM, with a dose-response relationship observed for metformin and rosiglitazone exposure. However, the certainty of evidence remains low, indicating the need for further research to confirm causality between OADM and skin cancer risk. [Extracted from the article]

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18–40 years) and 10 older (65–89 years) adults, phototype I–III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years. [ABSTRACT FROM AUTHOR]

The article discusses the impact of the systemic photoprotective agent afamelanotide on the vitamin D status of patients with erythropoietic protoporphyria (EPP). EPP is a rare condition that causes severe pain when the skin is exposed to visible light. Afamelanotide has been shown to increase the length of time patients can spend in the sun without pain and improve their quality of life. However, the study found that afamelanotide had no impact on vitamin D status, suggesting that vitamin D assessment and supplementation are still necessary for patients with EPP. [Extracted from the article]

Information about the prevalence of photodermatoses is lacking, despite their substantial impact on life quality. Our objective was to systematically review the literature to establish what is known regarding prevalence and incidence of photodermatoses. We searched Medline, CINAHL and Embase from inception to 2021 to identify original population‐based studies in English literature reporting the prevalence and/or incidence of photodermatoses. Information was extracted according to geographical location and risk of bias was assessed using a 10‐point risk of bias tool for prevalence studies. Primary outcome was the population prevalence of photodermatoses. Prevalence data for polymorphic light eruption (PLE) were used to calculate the global pooled prevalence of PLE. Twenty‐six studies were included; 15 reported prevalence of photodermatoses based on samples of the general population and 11 on prevalence and/or incidence from national and international registry data. The general population studies involved PLE (nine studies), unspecified photosensitivity (2), actinic prurigo (2), juvenile spring eruption (1), chronic actinic dermatitis (1) and variegate porphyria (1), while registry studies reported on cutaneous porphyrias and genophotodermatoses (nine and two studies, respectively). Worldwide the prevalence of PLE between countries ranged from 0.65% (China) to 21.4% (Ireland). The pooled estimated prevalence of PLE was 10% (95% CI 6%–15%) among the general population (n = 19,287), and PLE prevalence increased with distance from the equator (r = 0.78, p < 0.001). While several photodermatoses are rare, photosensitivity can be prevalent at wide‐ranging world locations, including Egypt where photosensitivity was found in 4% of children and 10% of adults. This study showed that PLE is highly prevalent in many populations and that its prevalence shows a highly significant correlation with increasing northerly or southerly latitude. Available population‐based studies for photodermatoses suggest they can be prevalent at a range of world locations; more attention is required to this area. [ABSTRACT FROM AUTHOR]

This article presents a patient's perspective on living with solar urticaria, a rare condition characterized by an extreme sensitivity to sunlight. The patient describes the progression of their symptoms over time and the impact it had on their daily life. After being diagnosed with solar urticaria, the patient tried various treatments and self-management strategies, but found limited relief. Eventually, they were approved for omalizumab therapy, which significantly improved their condition and allowed them to have more outdoor exposure without reacting. The article also includes comments from clinicians about the condition and its management. [Extracted from the article]

Background: UVB absorption by 7-dehydrocholesterol (7DHC) in the skin triggers the production of vitamin D and its metabolites, which maintain calcium homeostasis. Detection and measurement of 7DHC in skin using modern liquid chromatography–tandem mass spectrometry (LC–MS/MS) techniques have been lacking, yet there is need for such a technique to provide more information on 7DHC concentration and its UVB responses in human skin. Objectives: To develop and validate a reliable method to measure 7DHC concentration in skin. Methods: Human skin punch biopsies of 5 mm diameter obtained through the Manchester Skin Health Biobank were utilised. 7DHC was extracted with ethyl acetate:methanol 1:1 (v/v) and derivatised using 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), to allow for improved ionisation of 7DHC through Electrospray Ionisation Mass Spectrometry (ESI–MS). Solid supported liquid extraction (SLE) was also employed to allow the removal of larger lipids from 7DHC and minimise potential matrix effects. Results: The LC–MS/MS assay satisfied International Council for Harmonisation research standards for method validation. Calibration curve was linear with a typical r2 of 0.997, coefficient of variation was 11.1% and 4.32% for inter-assay and intra-assay imprecision, respectively. Lower limit of quantification was 1.6 µg/g and upper limit of quantification was 100 µg/g, SLE recovery of 7DHC was on average 91.4%. Conclusions: We have developed a robust, precise and accurate assay for the detection and quantification of 7DHC in small samples of human skin (0.2 cm2 surface area). This novel method of extraction and quantification will be valuable to future vitamin D photobiology research. [ABSTRACT FROM AUTHOR]

Background: Loss and remodelling of the dermal extracellular matrix (ECM) are key features of photodamaged human skin. Green tea catechins (GTCs) have been explored for their anti‐inflammatory and chemopreventive properties, but data on the impact of GTCs on ultraviolet radiation (UVR)‐induced changes to the dermal ECM are lacking. Aim: To investigate the effect of an inflammatory dose of solar‐simulated UVR on human dermal ECM and potential for protection by GTCs in a double‐blind randomized controlled trial. Methods: In total, 50 healthy white (Fitzpatrick skin type I–II) adults aged 18–65 years were randomized to a combination of GTCs 540 mg plus vitamin C 50 mg or to placebo twice daily for 12 weeks. The impact of solar‐simulated UVR at 3 × minimal erythema dose on the dermal collagen and elastic fibre networks was assessed by histology and immunohistochemistry in all participants at baseline. The impact of GTC supplementation on UVR‐induced effects was compared between the groups post‐supplementation. Results: The area of papillary dermis covered by collagen and elastic fibres was significantly lower (P < 0.001) in UVR‐exposed skin than in unexposed skin. Significantly lower levels of fibrillin‐rich microfibrils (P = 0.02), fibulin‐2 (P < 0.001) and fibulin‐5 (P < 0.001) were seen in UVR‐exposed than unexposed skin, while procollagen‐1 deposition was significantly higher in UVR‐exposed skin (P = 0.01). Following GTC supplementation, the UVR‐induced change in fibulin‐5 was abrogated in the active group but not the placebo group, with no difference between the two groups for other components. Conclusions: Acute UVR induced significant changes in the human dermal collagen and elastic fibre networks, whereas oral GTCs conferred specific UVR protection to fibulin‐5. Future studies could explore the impact of GTCs on the effects of repeated suberythemal UVR exposure of human skin. [ABSTRACT FROM AUTHOR]

Background: The use of indoor tanning devices causes melanoma and other skin cancers with resulting morbidity, mortality and increased healthcare costs. Policymakers require robust economic evidence to inform decisions about a possible ban of such devices to mitigate these burdens. Objectives: To assess the health costs and consequences of introducing a policy‐based intervention across England to ban commercial indoor tanning with an accompanying public information campaign. Methods: A cost‐effectiveness analysis, adopting a healthcare system perspective, was conducted using a decision model to track a national cohort of 18‐year‐olds over a lifetime time horizon. A nationwide ban on commercial indoor tanning combined with a public information campaign (the policy‐based intervention) was compared with the status quo of availability of commercial indoor tanning. The expected costs (currency, GBP; price year, 2019) and quality‐adjusted life‐years (QALYs) were calculated. Net monetary benefit (NMB) (net benefit measured in cost compared with an accepted threshold) and net health benefit (NHB) (net gain in QALYs compared with an accepted threshold) of implementation were calculated. A probabilistic sensitivity analysis was used to calculate the probability that the intervention was cost‐effective. Results: Compared with the current situation, a ban on commercial indoor tanning combined with a public information campaign would result in 1206 avoided cases of melanoma, 207 fewer melanoma deaths and 3987 averted cases of keratinocyte cancers over the lifetime of all 18‐year‐olds (n = 618 873) living in England in 2019. An additional 497 QALYs would be realized along with healthcare cost‐savings of £697 858. This intervention would result in an NMB of £10.6m and an NHB of 530 QALYS. Multiple sensitivity analyses confirmed the robustness of the findings. At a cost‐effectiveness threshold of £20 000, there is a 99% likelihood of this policy‐based intervention being cost‐effective. Conclusions: The implementation of a ban on commercial indoor tanning across England with an accompanying public information campaign would be an effective use of healthcare resources. [ABSTRACT FROM AUTHOR]

Purpose: To determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2). Methods: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D3 (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. Results: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41–71 nmol/L mean difference [95% confidence interval] − 15% [− 26, − 3%]; 1,25(OH)2D ≤ 120 vs ≥ 157 pmol/L − 12% [− 24%, − 1%]). Vaccine response was also poorer in winter than summer (− 18% [− 31%, − 3%]), when serum 25(OH)D and 1,25(OH)2D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [− 21%, 14%]). Conclusion: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. Clinical trial registry number: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103. [ABSTRACT FROM AUTHOR]

Background: Systemic drugs are a potentially reversible cause of photosensitivity. We explore prevalence, impact, phototest findings and culprit drugs. Methods: Retrospective review of patients was diagnosed with drug‐induced photosensitivity in a specialist photoinvestigation centre (2000‐2016), using data recorded in standardized pro forma. Patients underwent detailed clinical evaluation. Monochromator phototesting was performed to 300 ± 5 nm, 320 ± 10 nm, 330 ± 10 nm, 350 ± 20 nm, 370 ± 20 nm, 400 ± 20 nm, 500 ± 20nm and 600 ± 20 nm. Broadband UVA and solar‐simulated radiation (SSR) testing were performed, and photopatch testing and laboratory tests examined for other causes of photosensitivity. DLQI was evaluated. Results: Prevalence of drug‐induced photosensitivity was 5.4% (122/2243) patients presenting with photosensitivity. Patients with drug‐induced photosensitivity were 52.5% female; median 62 years (range 11‐86); phototype I (17.2%), II (39.3%), III (26.2%), IV (6.5%), V (4.1%). Fifty‐five (45.1%) patients had reduced erythemal thresholds on monochromator phototesting: 83.6%% to UVA alone, 14.5% to both UVA and UVB, 1.8% to UVA and visible light; 61.4% (n = 75) showed abnormal response to broadband UVR. Drugs implicated: quinine (11.5%), diuretics (10.7%; thiazide 9.8%), antifungals (9.8%), proton‐pump‐inhibitors (9.8%), angiotensin‐converting enzyme inhibitors (7.4%), anti‐inflammatory drugs (6.6%), statins (5.7%), selective serotonin reuptake inhibitors (4.9%), calcium channel antagonists (3.3%), anti‐epileptics (3.3%), tricyclic antidepressants (3.3%), beta‐blockers (2.5%), antibiotics (2.5%), others (≤1.6% cases each). Emerging culprits included azathioprine (2.5%) and biologics (TNF‐α inhibitors, denosumab; 2.5%). Median DLQI was 11 (range 2‐27) for the past year. Conclusion: Classically described photosensitizing drugs such as thiazides and quinine remain common offenders, while emerging culprits include biologics such as TNF‐a inhibitors and proton‐pump‐inhibitors. There is very large impact on life quality; identification facilitates measures including drug cessation and implementation of appropriate photoprotection. [ABSTRACT FROM AUTHOR]

Background: Cutaneous exposure to sunlight is a major source of vitamin D. Individuals with photosensitivity disorders have symptoms provoked by sunlight and may not achieve the brief sunlight exposures that convey vitamin D acquisition. Objective: To explore knowledge, behaviour and attitudes towards vitamin D and its acquisition in patients with photosensitivity. Methods: Patients (n = 19) diagnosed with solar urticaria, erythropoietic protoporphyria or polymorphic light eruption at a specialist photoinvestigation centre participated in semi‐structured focus groups to discuss vitamin D knowledge, acquisition behaviours and attitudes towards vitamin D acquisition through sunlight and diet. Discussions were analysed by thematic analysis using MAXQDA11. Results: Knowledge of vitamin D was variable. There was good awareness that sunlight exposure is an important source but knowledge of dietary sources was poor. Patients had little concern for their own vitamin D status prior to attending the photoinvestigation centre. Most patients avoided sunlight exposure, were unable to achieve the guidance on sun exposure for healthy individuals and were aware this could affect their vitamin D status. Use of oral vitamin D supplements was common, and all were willing to consider supplements if required. Patients recommended improving education of clinicians to increase patient awareness of vitamin D, Conclusions: More targeted guidance is required on acquisition of vitamin D for patients with photosensitivity, supported by increased patient and clinician education. [ABSTRACT FROM AUTHOR]

Objectives: Solar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR‐induced inflammation are well‐documented, the mediation of its resolution and longer‐term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation. Methods: To investigate the self‐resolving events of UVR inflammation in vivo, human skin was exposed to a single pro‐inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post‐UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry. Results: We identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR‐induced inflammation in humans involves a post‐resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T‐cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post‐UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure. Conclusion: We have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T‐cell subpopulations are recruited to UVR‐inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T‐cell subpopulations and also the persistent alteration of the lipid microenvironment post‐UVR. [ABSTRACT FROM AUTHOR]

Long-term exposure of human skin to ultraviolet radiation (UVR) in sunlight negatively impacts its appearance and function with photoaged skin having a characteristic leathery, rough appearance, with deep wrinkles. These clinical features of photodamage are thought to result from UVR-induced remodelling of the dermal extracellular matrix, particularly the elastic fibre system. There are few in vivo human data on the impact of acute UVR exposure on this fibre system and particularly solar-simulated radiation (SSR)-mediated effects. We examined the differential effect of broadband UVB and SSR on the human dermal elastic fibre system, and specifically the microfibrillar components fibrillin-1, fibulin-2 and fibulin-5. Healthy white Caucasian adults (skin type II–III) were recruited and irradiated with 3× their minimal erythema dose of broadband UVB (n = 6) or SSR (n = 6) on photoprotected buttock skin. Punch biopsies were taken 24 h after irradiation and from unirradiated control skin. Overall, histological assessment of elastic fibres revealed significantly less elastic fibre staining in broadband UVB (P = 0.004) or SSR (P = 0.04) irradiated skin compared to unirradiated control skin. Significantly less staining of fibrillin-1-positive microfibrils was also observed in the papillary dermis of UVB irradiated skin (P = 0.02) but not skin exposed to SSR. Conversely, immunohistochemistry for fibulin-5-positive microfibrils revealed significantly less expression in skin exposed to SSR (P = 0.04) but not to broadband UVB. There was no significant change in fibulin-2-positive microfibrils following either broadband UVB or SSR irradiation. Thus, broadband UVB and SSR mediate differential effects on individual components of the dermal elastic fibre network in human skin. Further human studies are required to explore the mechanisms underlying these findings and the impact of potential photoprotective agents. [ABSTRACT FROM AUTHOR]

Summary: Background: Solar urticaria (SU) is a rare chronic inducible urticaria triggered via uncharacterized chromophores. We detail responses of a large patient series to monochromator phototesting and broadband ultraviolet radiation (UVR); relationship to life quality is explored. Methods: Retrospective review of all SU patients undergoing standardized diagnostic photoinvestigation at a specialist centre during 2000‐2016. From 2011, patients completed dermatology life quality index (DLQI) questionnaires for the past week and year. Results: In 145 patients (mean: 35.8, range: 3‐69 years; 18 aged <18 years; 100 female), combined phototesting with broadband UVR and monochromator sources successfully provoked 74.5% patients, with 65.6% provoked by broadband UVR alone and 57.9% by monochromated radiation alone. The narrow wavebands most frequently eliciting wheal and flare response were between 370 and 400 nm, with 25% patients at 300 ± 5 nm, 53.6% at 320 ± 10 nm, 66.7% at 330 ± 10 nm, 77.4% at 350 ± 20 nm, 83.3% at 370 ± 20 nm, 86.9% at 400 ± 20 nm, 44% at 500 ± 20 nm and 17.8% at 600 ± 20 nm. In 62 patients, the DLQI revealed 56.1% had very to extremely large impact in the past week (all patients: mean score: 11.1, range: 0‐29) rising to 69.8% for the past year (12.5, 0‐30); adults and children were similarly affected. Patients with positive photoprovocation had higher DLQI score than those who were negative (DLQI for past week: mean: 12.6 ± SEM 1.1 vs 4.6 ± 1.4, P < .01). Conclusion: SU is predominantly provoked by longer UVA‐shorter visible radiation, which penetrates window‐glass and where sunscreens are less effective; impact on life quality is considerable. Photoprotective agents effective against this spectrum are needed. [ABSTRACT FROM AUTHOR]

While we agree that adequate vitamin D is essential for health, clearly sunbeds are not a viable source of vitamin D production in the skin given that the same emitted ultraviolet B wavelengths that promote vitamin D also cause skin cancer.[[6]] The World Health Organization has classified indoor tanning devices as carcinogenic[7] and has recommended that interventions be applied to curtail their use.[8] We assessed the potential impact of a policy-based intervention to reduce skin cancer using evidence from meta-analyses[[9]] that have quantified the increased risk of skin cancer from indoor tanning. Dear Editor, Lindqvist I et al i .[1] claim that our model-based economic evaluation does not account for beneficial effects of indoor tanning.[2] Their contention that indoor tanning is associated with reduced mortality is based on a prospective cohort study conducted by them. Cost-effectiveness of a policy-based intervention to reduce melanoma and other skin cancers associated with indoor tanning. [Extracted from the article]

Background Solar UVR is a major cause of skin cancer but also an important source of vitamin D (VitD), essential for musculoskeletal health. Conflicting public health messages may confuse patients with skin cancer prone to further skin cancer. Objective To explore the knowledge, behaviour and attitudes of patients with skin cancer to sunlight exposure and VitD sources. Methods Patients ( n = 10) previously treated for multiple basal cell cancer in a hospital setting participated in focus group sessions with semi-structured discussions to explore: knowledge of VitD, sun-avoidance behaviour and attitude towards sunlight exposure messages. Thematic data analysis was performed using software programme MAXQDA11. Results Pre-existing knowledge of VitD was low. Most patients practised sun avoidance and were not inclined to increase exposure. Patients did not perceive VitD deficiency as a substantial risk to their own health, or a need to take VitD supplements. They aimed to increase VitD status through dietary intake, but knowledge of food VitD content was lacking. Conclusions The patients with skin cancer, appropriate to their heightened skin cancer risk, appeared unlikely to increase their sun exposure to gain VitD. However, education is required regarding the generally low levels of VitD in foodstuffs, and the requirement for supplements/fortified foods if strict sun avoidance is employed. [ABSTRACT FROM AUTHOR]

Solar ultraviolet radiation (UVR) exposure of human skin has beneficial and harmful effects on health, including impact on immune function, inflammation and reportedly mood, but these are not fully elucidated. Since the endocannabinoid system is implicated in many activities including mood alteration, our objective was to (i) determine and quantify circulating levels of a wide range of endocannabinoid and N-acyl ethanolamine (NAE) species (ii) evaluate whether these are modulated by cutaneous UVR exposures, as attained through repeated low level summer sunlight exposure. Wearing goggles to prevent eye exposure, 16 healthy volunteers (23–59 y; 10 light skin, phototype II, and 6 dark skin, phototype V) received the same UVR exposures (1.3 SED, 95% UVA/5% UVB) thrice weekly for 6 weeks, whilst casually dressed to expose ∼35% skin surface area. Blood samples were taken at baseline, days 1, 3 and 5 of week one, then at weekly intervals, and analysed by LC-MS/MS. Eleven endocannabinoids and NAEs were detected and quantified at baseline, with N-palmitoyl ethanolamine the most abundant (30% of total). Levels did not vary according to phototype (p ＞ 0.05), except for the NAE docosapentaenoyl ethanolamide, which was higher in phototype II than V (p = 0.0002). Level of the endocannabinoid, 2-AG, was elevated during the UVR exposure course (p ＜ 0.05 vs. baseline for all subjects; p ＜ 0.01 for each phototype group), with maximum levels reached by week 2–3, while NAE species did not significantly alter. These findings suggest differential involvement of the cutaneous endocannabinoid system in low dose solar UVR responses in humans. [ABSTRACT FROM AUTHOR]

Skin exposure to ultraviolet radiation (UVR) triggers conversion of precursor 7-dehydrocholesterol (7DHC) to vitamin D3, which then enters the bloodstream. The aim of this study was to assess if skin 7DHC concentration differs between younger and older adults, and to explore the impact of solar-simulated UVR (SSR) on 7DHC (in skin) and vitamin D3 (cholecalciferol; in serum) in these age groups. Younger (n = 10, 18–40 years) and older (n = 11; 65–89 years) adults of skin phototype I–III were exposed to a suberythemal dose of SSR (95% UVA, 5% UVB, 1.3 standard erythemal dose) over 35% body surface area in the UK winter. Six 5-mm buttock skin punch biopsies were taken: two from unexposed skin, two immediately post-UVR and two at 24 h post-UVR. Blood was taken at baseline, 24 h and 7 days post-UVR. Skin and serum samples were assayed using high-performance liquid chromatography–tandem mass spectrometry. Baseline mean (SD) 7DHC concentrations were 0.22 (0.07) µg mg–1 and 0.25 (0.08) µg mg–1 in younger and older adults, respectively. Immediately post-UVR, 7DHC concentrations were 0.27 (0.10) µg mg–1 and 0.22 (0.08) µg mg–1 in younger and older adults, respectively, and 24 h post-UVR they were 0.27 (0.08) µg mg–1 and 0.28 (0.13) µg mg–1, respectively. Baseline serum vitamin D3 concentrations in younger adults were 1.5 (1.5) nmol L–1 vs. 1.5 (1.7) nmol L–1 in older adults; 24 h post-UVR they were 3.1 (2.0) nmol L–1 in younger adults vs. 2.5 (2.0) nmol L–1 in older adults and 7 days post-UVR they were 2.0 (2.1) vs. 1.7 (1.2) nmol L–1, respectively. No significant difference was seen in any parameter between age groups. Thus, in contrast to previous assumptions, skin 7DHC concentration is not a limiting factor for vitamin D3 synthesis in healthy older adults relative to younger adults. The early vitamin D3 biosynthetic pathway does not appear to differ between these age groups. [ABSTRACT FROM AUTHOR]

Langerhans cells ( LCs) are sentinels of skin's immune system, their loss from epidermis contributing to UVR suppression of cell-mediated immunity ( CMI). Omega-3 polyunsaturated fatty acids show potential to reduce UVR suppression of CMI in mice and humans, potentially through modulation of LC migration. Our objectives were to examine whether eicosapentaenoic acid ( EPA) ingestion influences UV-mediated effects on epidermal LC numbers and levels of immunomodulatory mediators including prostaglandin ( PG)D2, which is expressed by LC. In a double-blind randomised controlled study, healthy individuals took 5-g EPA-rich (n=40) or control (n=33) lipid for 12 weeks; UVR-exposed and unexposed skin samples were taken pre- and postsupplementation. Epidermal LC numbers were assessed by immunofluorescence for CD1a, and skin blister fluid PG and cytokines were quantified by LC- MS/ MS and Luminex assay, respectively. Presupplementation, UVR reduced mean ( SEM) LC number/mm2 from 913 (28) to 322 (40) ( P<.001), and mean PGD2 level by 37% from 8.1 (11.6) to 5.1 (5.6) pg/μL; P<.001), while IL-8 level increased ( P<.001). Despite confirmation of EPA bioavailability in red blood cells and skin in the active group, no between-group effect of EPA was found on UVR modulation of LC numbers, PGD2 or cytokine levels postsupplementation. Thus, no evidence was found for EPA reduction of photoimmunosuppression through an impact on epidermal LC numbers. Intriguingly, UVR exposure substantially reduced cutaneous PGD2 levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD2 levels could reflect LC loss from the epidermis and/or altered dendritic cell activity and may be relevant for phototherapy of skin disease. [ABSTRACT FROM AUTHOR]

Background: Safe systemic protection from the health hazards of ultraviolet radiation (UVR) in sunlight is desirable. Green tea is consumed globally and is reported to have anti-inflammatory properties, which may be mediated through the impact on cyclooxygenase and lipoxygenase pathways. Recent data suggest that green tea catechins (GTCs) reduce acute UVR effects, but human trials examining their photoprotective potential are scarce. Objective: We performed a double-blind, randomized, placebo-controlled trial to examine whether GTCs protect against clinical, histologic, and biochemical indicators of UVR-induced inflammation. Design: Healthy adults (aged 18-65 y, phototypes I-II) were randomly allocated to 1350 mg encapsulated green tea extract (540 mg GTC) with 50 mg vitamin C or placebo twice daily for 3 mo. Impact on skin erythema, dermal leukocytic infiltration, and concentrations of proinflammatory eicosanoids was assessed after solar-simulated UVR challenge, and subject compliance was determined through assay of urinary GTC metabolite epigallocatechin glucuronide. Results: Volunteers were assigned to the active (n = 25) or the placebo (n = 25) group. After supplementation, median (IQR) sunburn threshold (minimal erythema dose) was 28 (20-28) and 20 (20-28) mJ/cm2 in the active and placebo groups, respectively (nonsignificant), with no difference in AUC analysis for measured erythema index after a geometric series of 10 UVR doses. Skin immunohistochemistry showed increased neutrophil and CD3+ T-lymphocyte numbers post-UVR in both groups (P < 0.01) with no statistically significant differences between groups after supplementation. Cyclooxygenase and lipoxygenase metabolites prostaglandin E2 (vasodilator) and 12-hydroxyeicosatetraenoicacid (chemoattractant), respectively, increased after UVR (P < 0.05), with no differences between supplementation groups. Conclusion: Oral GTC (1080 mg/d) with vitamin C over 3 mo did not significantly reduce skin erythema, leukocyte infiltration, or eicosanoid response to UVR inflammatory challenge. This trial was registered at clinicaltrials.gov as NCT01032031. [ABSTRACT FROM AUTHOR]

A detailed map of the available UV across the UK from 2003 to 2012 is provided. A suite of data derived from climatologies and satellite observations are used to calculate spectral UV irradiance and related weighted doses (erythema, DNA damage, vitamin D). The result is a well-validated tool that has two advantages: (i) the output is simulated spectral UV irradiance that can be weighted with any action spectrum for use in any research studies that require ambient UV data, (ii) reliance on instruments with planned operational lives of at least several years that ensures data and method homogeneity for extension to future studies. The model-derived doses are satisfactory validated against spectral ground-based measurements at two sites. According to the calculated climatology, the southern part of the UK receives 1.5–2 times more UV than the north during spring, summer and autumn. During wintertime, the UV doses in the far north are an order of magnitude lower than southern values. Even for the same latitude, regional variations of cloudiness result in doses at coastal sites being up to 25% higher than inland areas. [ABSTRACT FROM AUTHOR]

Skin cancers have a higher incidence than all other cancers combined and are a major cause of morbidity worldwide. Laboratory data suggest certain dietary constituents, notably omega-3 polyunsaturated fatty acids (n-3 PUFAs), could potentially protect against skin malignancy, although no large-scale review has been conducted in humans. The objective of this review and meta-analysis was to determine the relationship between dietary n-3 PUFAs and skin cancer incidence. It considered all published randomized controlled trials and observational studies up to March 2013. Five studies (two case-control and three cohort) were identified pertaining to oral n-3 PUFA consumption and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (or a combination) and were included in a random-effects meta-analysis. A further six studies considering nondietary n-3 PUFA exposure ( e.g. by tissue analysis) and/or recognized biological markers of skin cancer risk ( e.g. p53 expression) were analyzed qualitatively. Dietary n-3 PUFAs were not associated with BCC (pooled OR 1.05, 95% CIs 0.86-1.28). Consumption of high levels of n-3 PUFAs were inversely associated with melanoma, although with only one estimate available (OR 0.52, 95% CI 0.34-0.78), and SCC, although nonsignificantly (pooled OR 0.86, 95% CIs 0.59-1.23). Available evidence is suggestive, but currently inadequate, to support the hypothesis that n-3 PUFAs protect against skin malignancy. [ABSTRACT FROM AUTHOR]

Skin cancer is a major public health concern, and the primary aetiological factor in the majority of skin cancers is ultraviolet radiation ( UVR) exposure. UVR not only induces potentially mutagenic DNA damage but also suppresses cell-mediated immunity ( CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role, and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar-simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomized controlled trials and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to photodistributed telangiectasia in a person induced with the calcium channel blocker (CCB) amlodipine.

Green tea catechins (GTC) reduce UV radiation (UVR)-induced inflammation in experimental models, but human studies are scarce and their cutaneous bioavailability and mechanism of photoprotection are unknown. We aimed to examine oral GTC cutaneous uptake, ability to protect human skin against erythema induced by a UVR dose range and impact on potent cyclo-oxygenase- and lipoxygenase-produced mediators of UVR inflammation, PGE2 and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively. In an open oral intervention study, sixteen healthy human subjects (phototype I/II) were given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks. Pre- and post-supplementation, the buttock skin was exposed to UVR and the resultant erythema quantified. Skin blister fluid and biopsies were taken from the unexposed and the UVR-exposed skin 24 h after a pro-inflammatory UVR challenge (three minimal erythema doses). Urine, skin tissue and fluid were analysed for catechin content and skin fluid for PGE2 and 12-HETE by liquid chromatography coupled to tandem MS. A total of fourteen completing subjects were supplement compliant (twelve female, median 42·5 years, range 29–59 years). Benzoic acid levels were increased in skin fluid post-supplementation (P= 0·03), and methylated gallic acid and several intact catechins and hydroxyphenyl-valerolactones were detected in the skin tissue and fluid. AUC analysis for UVR erythema revealed reduced response post-GTC (P= 0·037). Pre-supplementation, PGE2 and 12-HETE were UVR induced (P= 0·003, 0·0001). After GTC, UVR-induced 12-HETE reduced from mean 64 (sd 42) to 41 (sd 32) pg/μl (P= 0·01), while PGE2 was unaltered. Thus, GTC intake results in the incorporation of catechin metabolites into human skin associated with abrogated UVR-induced 12-HETE; this may contribute to protection against sunburn inflammation and potentially longer-term UVR-mediated damage. [ABSTRACT FROM PUBLISHER]

Background: Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status. Objective: We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity. Design: In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated. Results: At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6 ng/mL; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL. Conclusions: Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the ISRCTN Register (www.isrctn.org) as 07565297. [ABSTRACT FROM AUTHOR]

In order to establish a consensus recommendation for performing photopatch testing, a photopatch test taskforce group was established under the joint umbrella of the European Society for Contact Dermatitis and the European Society for Photodermatology in 2000. After proposing the most adequate methodology in 2004 and completing a European multicentre photopatch test study in 2011, this taskforce is recommending a list of photoallergens that should form part of a baseline series for photopatch testing in Europe. It contains mainly ultraviolet filters and drugs, mostly non-steroidal anti-inflammatory drugs. The choice of chemicals was based on the results of a recent multicentre study, previous published cases of photoallergy, and use of the substances in the European market. It is suggested that an extended list of photoallergens should be photopatch tested in selected cases, along with patients' own products. Two contact allergens, cinnamyl alcohol and decyl glucoside, should be simultaneously patch tested in order to clarify photopatch and patch test reactions, respectively, to ketoprofen and methylene bis-benzotriazolyl tetramethylbutylphenol (Tinosorb M™). [ABSTRACT FROM AUTHOR]

Background: Skin cancer is a major public health concern, and the majority of cases are caused by solar ultraviolet radiation (UVR) exposure, which suppresses skin immunity. Omega-3 (n-3) PUFAs protect against photoimmunosuppression and skin cancer in mice, but the impact in humans is unknown. Objectives: We hypothesized that EPA-rich n-3 PUFA would abrogate photoimmunosuppression in humans. Therefore, a nutritional study was performed to assess the effect on UVR suppression of cutaneous cell-mediated immunity (CMI) reflected by nickel contact hypersensitivity (CHS). Design: In a double-blind, randomized controlled study, 79 volunteers (nickel-allergic women, 22-60 y old, with phototype I or II) took 5 g n-3 PUFA-containing lipid (70% EPA plus 10% DHA) or a control lipid daily for 3 mo. After supplementation, nickel was applied to 3 skin sites preexposed on 3 consecutive days to 1.9, 3.8, or 7.6 J/cm of solar-simulated radiation (SSR) and to 3 unexposed control sites. Nickel CHS responses were quantified after 72 h and the percentage of immunosuppression by SSR was calculated. Erythrocyte [red blood cell (RBC)] EPA was measured by using gas chromatography. Results: SSR dose-related suppression of the nickel CHS response was observed in both groups. Photoimmunosuppression appeared less in the n-3 PUFA group than in the control group (not statistically significant [mean difference (95% CI): 6.9% (-2.1%, 15.9%)]). The difference was greatest at 3.8 J/cm2 SSR [mean difference: 11% (95% CI: 0.5%, 21.4%)]. Postsupplementation RBC EPA was 4-fold higher in the n-3 PUFA group than in the control group (mean difference: 2.69% (95% CI: 2.23%, 3.14%), which confirmed the EPA bioavailability. Conclusion: Oral n-3 PUFAs appear to abrogate photoimmunosuppression in human skin, providing additional support for their chemo-preventive role; verification of study findings is required. This trial was registered at clinicaltrials.gov as NCT01032343. [ABSTRACT FROM AUTHOR]

The long-chain n-3 PUFA, EPA, is believed to be important for skin health, including roles in the modulation of inflammation and protection from photodamage. FFQ and blood levels are used as non-invasive proxies for assessing skin PUFA levels, but studies examining how well these proxies reflect target organ content are lacking. In seventy-eight healthy women (mean age 42·8, range 21–60 years) residing in Greater Manchester, we performed a quantitative analysis of long-chain n-3 PUFA nutrition estimated from a self-reported FFQ (n 75) and correlated this with n-3 PUFA concentrations in erythrocytes (n 72) and dermis (n 39). Linear associations between the three n-3 PUFA measurements were assessed by Spearman correlation coefficients and agreement between these measurements was estimated. Average total dietary content of the principal long-chain n-3 PUFA EPA and DHA was 171 (sd 168) and 236 (sd 248) mg/d, respectively. EPA showed significant correlations between FFQ assessments and both erythrocyte (r 0·57, P< 0·0001) and dermal (r 0·33, P= 0·05) levels, as well as between erythrocytes and dermis (r 0·45, P= 0·008). FFQ intake of DHA and the sum of n-3 PUFA also correlated well with erythrocyte concentrations (r 0·50, P< 0·0001; r 0·27, P= 0·03). Agreement between ranked thirds of dietary intake, blood and dermis approached 50 % for EPA and DHA, though gross misclassification was lower for EPA. Thus, FFQ estimates and circulating levels of the dietary long-chain n-3 PUFA, EPA, may be utilised as well-correlated measures of its dermal bioavailability. [ABSTRACT FROM PUBLISHER]

This article reviews recent data on the expression, regulation and activation of antimicrobial peptides (AMP) in human skin, and considers their potential protective and pro-inflammatory roles following upregulation by ultraviolet radiation (UVR). Antimicrobial peptides are small peptides that are key components of the innate immune system, originally identified by their vital role in protecting the body-environment interface from infection. However, it has now become clear that AMP have more extensive actions, including the provision of pivotal links with the adaptive immune system. Moreover, aberrant AMP expression may contribute to immuno-modulated inflammatory dermatoses including psoriasis, eczema and the photoaggravated condition lupus erythematosus. Recent work has demonstrated the direct upregulation of AMP in healthy skin by cutaneous UVR exposure. This may serve to protect the skin from risks imposed by both the biophysical barrier-compromise and the immunosuppression that are attributable to UVR exposure. Furthermore, it is observed that UVR provokes upregulation of AMP in an atypical manner in the photosensitivity disorder polymorphic light eruption. Dysregulated UVR responses of these pro-inflammatory proteins may play a role in the pathogenesis of certain immune-mediated diseases caused or aggravated by sunlight. [ABSTRACT FROM AUTHOR]

Background: The cutaneous synthesis of vitamin D is dependent on UVB from sunlight, but melanin reduces the penetration of UVB and thus contributes to vitamin D insufficiency in individuals with darker skin. The national guidance provided on amounts of sunlight exposure in the United Kingdom is for the light-skinned population, and in the absence of dedicated information, darker-skinned people may attempt to follow this guidance. Objectives: We determined the relative effect of a simulation of UK recommendations of summer sunlight exposure on the vitamin D status of individuals of South Asian ethnicity compared with that of whites. Design: In a prospective cohort study, simulated summer sunlight exposures were provided under rigorous dosimetric conditions to 15 adults (aged 20-60 y) of South Asian ethnicity, and serum 25-hydroxyvitamin D [25(OH)D] was measured weekly. Dietary vitamin D intake was estimated. Outcomes were compared with those of 109 whites (aged 20-60 y) treated with the identical UV-radiation exposure protocol. Results: At baseline (winter trough), all South Asians were vitamin D-insufficient [25(OH)D concentrations <20 ng/mL], and 27% of South Asians were vitamin D-deficient [25(OH)D concentrations <5 ng/mL]; although 25(OH)D concentrations increased postcourse (P < 0.0001), all South Asians remained vitamin D-insufficient. The mean increase in 25(OH)D was 4.3 compared with 10.5 ng/mL in the South Asian and white groups, respectively (P < 0.0001), and 90% of the white group reached vitamin D sufficiency postcourse. The median dietary vitamin D intake was very low in both groups. Conclusions: Sunlight-exposure recommendations are inappropriate for individuals of South Asian ethnicity who live at the UK latitude. More guidance is required to meet the vitamin D requirements of this sector of the population. This study was registered at www.isrctn.org as ISRCTN 07565297. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) in sunlight has deleterious effects on skin, while behavioural changes have resulted in people gaining more sun exposure. The clinical impact includes a year-on-year increase in skin cancer incidence, and topical sunscreens alone provide an inadequate measure to combat overexposure to UVR. Novel methods of photoprotection are being targeted as additional measures, with growing interest in the potential for systemic photoprotection through naturally sourced nutrients. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are promising candidates, showing potential to protect the skin from UVR injury through a range of mechanisms. In this review, we discuss the biological actions of n-3 PUFA in the context of skin protection from acute and chronic UVR overexposure and describe how emerging new technologies such as nutrigenomics and lipidomics assist our understanding of the contribution of such nutrients to skin health. [ABSTRACT FROM AUTHOR]

Exposure to sunlight, specifically the ultraviolet radiation, has both positive and negative health effects. Maximizing the benefits (vitamin D synthesis) while minimizing the damage is a multifaceted problem in which many of the elements are poorly quantified. Here we show how rigorously conducted large sample size laboratory studies of the effect of ultraviolet radiation dose on vitamin D status can be applied to real-life situations. This was achieved by modeling the radiation incident on different surfaces for different solar locations, and equating with the controlled exposures in the laboratory studies. Results from both model and experimental data show that relatively short exposures of a modest amount of unprotected skin to summer sunlight in northern climes, on a regular basis during lunchtime hours, increases vitamin D to sufficiency status (≥20 ng mL) in the white Caucasian population. While both sun exposure conditions and human skin responses are variable in real life, these quantitative findings provide a guide for authorities devising sunlight exposure recommendations. [ABSTRACT FROM AUTHOR]

Excessive ultraviolet radiation (UVR) exposure induces erythema, mediated in part by prostaglandin-E2 (PGE2). While keratinocytes are a major PGE2 source, epidermal melanocytes (EM) also express PGE2-production machinery. It is unclear whether EM-produced PGE2 contributes to UVR-induced skin inflammation, and whether this is correlated with melanogenesis. Epidermal melanocytes were cultured from skin phototype-1 and -4 donors, followed by assessment of PGE2 production and melanogenesis. Epidermal melanocytes expressed cytoplasmic phospholipase-A2, cyclooxygenase-1, cytoplasmic prostaglandin-E synthase and microsomal prostaglandin-E synthase-1, -2. Epidermal melanocytes produced PGE2 under basal conditions, which increased further after arachidonic acid stimulation. Epidermal melanocytes expressed cyclooxygenase-2 (COX-2) mRNA and a selective COX-2 inhibitor (NS-398) reduced PGE2 production. Ultraviolet B-induced PGE2 production was positively correlated with skin phototype-1, despite variability between individual EM donors. By contrast, there was no correlation between PGE2 production by EM and their melanogenic status. Thus, EM may contribute to UVR-induced erythema, with role of donor skin phototype more important than their melanogenic status. [ABSTRACT FROM AUTHOR]

The article describes the case of patients diagnosed with pompholyx, a type of eczema characterized by a pruritic vesicular eruption occurring on the lateral fingers, hands and feet. Topics discussed include the aetiological factors and aggravating factors, effect of seasonal changes on pompholyx, medical history of patients and standard management of pompholyx eczema and photoprotection advice.

Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE2, PGF2a, and PGE3 accompany the erythema in the first 24-48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution. [ABSTRACT FROM AUTHOR]

Objective: To compare 5-year lesion recurrence rates in primary nodular basal cell carcinoma treated with topical methyl aminolevulinate photodynamic therapy (PDT) or simple excision surgery. Design: Prospective, randomized, multicenter study. Setting: University hospital dermatology departments. Patients: A total of 97 patients, 50 with 53 lesions treated with methyl aminolevulinate PDT and 47 with 52 lesions treated by excision surgery, were included in the per protocol analysis. Of the lesions treated with methylaminolevulinate PDT and surgery, 49 and 52, respectively, showed complete clinical response at 3 months after treatment and were observed for long-term outcome evaluation. Interventions: Topical methyl aminolevulinate cream, 160 mg/g, applied for 3 hours before illumination (75 J/cm² of red light at 570 to 670 nm) on 2 or 4 occasions (12 [23%] of 53 lesions); or excision surgery. Main Outcome Measures: Histologically confirmed lesion recurrence, sustained lesion complete response rate (time-to-event analysis), and investigator assessment of cosmetic outcome, 5 years after the last treatment. Results: At 5 years, recurrence was documented in 7 (14%) of 49 lesions (95% confidence interval [CI], 6%-27%) treated with methyl aminolevulinate PDT vs 2 (4%) of 52 lesions (95% CI, 1%-13%) treated with excision surgery (P=.09). Estimated sustained lesion complete response rates were 76% (95% CI, 59%-87%) and 96% (95% CI, 84%-99%), respectively (P=.01). More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome: 27 (87%) of 31 patients (95% CI, 70%-96%) vs 19 (54%) of 35 patients (95% CI, 37%-71%) (P=.007). Conclusions: Long-term follow-up indicates superior efficacy of surgery to methyl aminolevulinate PDT in nodular basal cell carcinoma. However, methyl aminolevulinate PDT is also an effective treatment for this indication and exhibits a more favorable cosmetic outcome. [ABSTRACT FROM AUTHOR]