Estimating personal solar ultraviolet radiation exposure through time spent outdoors, ambient levels and modelling approaches.

BACKGROUND: Evidence on validation of surrogates applied to evaluate the personal exposure levels of solar ultraviolet radiation (UVR) in epidemiological studies is scarce. OBJECTIVES: To determine and compare the validity of three approaches, including (i) ambient UVR levels, (ii) time spent outdoors and (iii) a modelling approach integrating the aforementioned parameters, to estimate personal UVR exposure over a period of 6 months among indoor and outdoor workers and in different seasons (summer/winter). METHODS: This validation study was part of the European Commission-funded ICEPURE project and was performed between July 2010 and January 2011 in a convenience sample of indoor and outdoor workers in Catalunya, Spain. We developed linear regression models to quantify the variation in the objectively measured personal UVR exposure that could be explained, separately, by the ambient UVR, time spent outdoors and modelled UVR levels. RESULTS: Our 39 participants - mostly male and with a median age of 35 years - presented a median daily objectively measured UVR of 0·37 standard erythemal doses. The UVR dose was statistically significantly higher in summer and for outdoor workers. The modelled personal UVR exposure and self-reported time spent outdoors could reasonably predict the variation in the objectively measured personal UVR levels (R2 range 0·75-0·79), whereas ambient UVR was a poor predictor (R2 = 0·21). No notable differences were found between seasons or occupation. CONCLUSIONS: Time outdoors and our modelling approach were reliable predictors and of value to be applied in epidemiological studies of the health effects of current exposure to UVR.

Ultraviolet radiation exposure to the face in patients with xeroderma pigmentosum and healthy controls: applying a novel methodology to define photoprotection behaviour.

BACKGROUND: In xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR). Protection is most important for the face. OBJECTIVES: We aimed to assess how well patients with XP adhere to medical advice to protect against UVR by objectively estimating the mean daily dose of UVR to the face. METHODS: We objectively estimated the UVR dose to the face in 36 patients with XP and 25 healthy individuals over 3 weeks in the summer. We used a new methodology which combined UVR dose measurements from a wrist-worn dosimeter with an activity diary record of face photoprotection behaviour for each 15-min period spent outside. A protection factor was associated with each behaviour, and the data were analysed using a negative binomial mixed-effects model. RESULTS: The mean daily UVR dose (weighted for DNA damage capacity) to the face in the patients with XP was 0·13 standard erythemal doses (SEDs) (mean in healthy individuals = 0·51 SED). There was wide variation between patients (range < 0·01-0·48 SED/day). Self-caring adult patients had a very similar UVR dose to the face as cared-for patients (0·13 vs. 0·12 SED/day), despite photoprotecting much more poorly when outside, because the self-caring adults were outside in daylight much less. CONCLUSIONS: Photoprotection behaviour varies widely within the XP group indicating that nonadherence to photoprotection advice is a significant issue. The timing and duration of going outside are as important as photoprotective measures taken when outside, to determine the UVR exposure to the face. This new methodology will be of value in identifying the sources of UVR exposure in other conditions in which facial UVR exposure is a key outcome, particularly in patients with multiple nonmelanoma skin cancers.

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.

Daylight photodynamic therapy of actinic keratosis without curettage is as effective as with curettage: a randomized clinical trial.

BACKGROUND: Guidelines for photodynamic therapy (PDT) of actinic keratosis (AK) recommend pretreatment with curettage. The impact of curettage on cure rate is, however, not well established. OBJECTIVE: The present study aimed to evaluate whether daylight PDT without curettage could be as effective as daylight PDT with curettage. METHODS: Twenty-five patients with multiple AKs were treated in two even-sized areas on the face and scalp. One area was treated with standard daylight PDT starting with curettage followed by incubation with methyl aminolevulinate (MAL) for 30 min before 2 h of daylight exposure. The other area was incubated with MAL for 1 h without prior curettage before 2 h of daylight exposure. The longer incubation time was used to obtain a sufficiently high protoporphyrin IX concentration in the non-curettaged area. RESULTS: There was no difference in cure rate 3 months after daylight PDT in areas pretreated with curettage (86%) compared to non-curettaged areas (84%) (P = 0.1). Neither was there any difference between reported pain during daylight exposure (P > 0.7) or clinically evaluated erythema the day after treatment (P = 1.0). CONCLUSION: Daylight PDT without curettage but with 1 h of MAL incubation before daylight exposure was shown to be as effective in treatment of thin AKs on the face and scalp as standard daylight PDT with curettage. This modification of daylight PDT eases the task for the clinic and makes it more convenient for the patients as well, creating the possibility of performing daylight PDT as an entirely home-based treatment for AKs of the face and scalp without training the patients to perform pretreatment.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

BACKGROUND: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. OBJECTIVES: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. METHODS: OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. RESULTS: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. CONCLUSIONS: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.

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.

Increased protoporphyrin IX accumulation does not improve the effect of photodynamic therapy for actinic keratosis: a randomized controlled trial.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is highly effective for treating actinic keratosis (AK) on the face/scalp, but less effective on the extremities. Insufficient accumulation of protoporphyrin IX (PpIX) may cause these inferior efficacy rates. However, it is possible to increase PpIX accumulation by extending the MAL application time and/or pretreating the skin with curettage. OBJECTIVES: To investigate whether increased PpIX accumulation improves the effect of MAL-PDT for AKs in a randomized intra-individual study. METHODS: Twenty-two patients with 533 AKs on both hands were treated with MAL-PDT. To obtain different concentrations of PpIX, four symmetrical areas on each patient were randomly allocated to different regimens: (i) 3-h MAL application without prior curettage (3hC-); (ii) 3 h with curettage (3hC+); (iii) 21 h without curettage (21hC-); and (iv) 21 h with curettage (21hC+). Treatment efficacy was evaluated after 3 months, whereas PpIX fluorescence, pain and erythema were assessed during and after PDT. RESULTS: Extended MAL application with and without curettage increased PpIX accumulation significantly compared with the standard 3hC+ regimen (P = 0·001 and P = 0·002, respectively). However, the median total clearance rates did not improve accordingly: 3hC+ (55·0%), 21hC- (55·0%) and 21hC+ (53·6%). Conversely, insufficient PpIX accumulation in the 3hC- regimen led to a significantly lower clearance rate (33·3%) than the other regimens (P < 0·045). Furthermore, pain and erythema were correlated to PpIX accumulation. CONCLUSIONS: Increased PpIX accumulation does not improve the effect of MAL-PDT for AKs on the hands, but leads to worse adverse events. Different strategies are needed to improve PDT on the extremities.

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.

Protoporphyrin IX in the skin measured noninvasively predicts photosensitivity in patients with erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disease that causes severe sensitivity to visible light as a result of protoporphyrin IX (PpIX) accumulation in the skin. OBJECTIVES: To establish a noninvasive method to measure PpIX in the skin of patients with EPP and to investigate how skin PpIX relates to erythrocyte PpIX and photosensitivity. METHODS: Skin PpIX was measured in 25 patients with EPP by calculating the difference in PpIX fluorescence before and after complete photobleaching of PpIX using controlled illumination. The patients reported symptoms during the illumination and skin erythema was measured before and after illumination. Confirmation of the presence of PpIX was obtained in seven patients by measuring the in vivo fluorescence emission spectrum. This method was used to examine skin PpIX during the hours after an illumination in seven patients. RESULTS: We established a noninvasive method to measure skin PpIX based on measurements of PpIX fluorescence before and after complete PpIX photobleaching. The patients had an average skin PpIX of 2·0 units and skin emission spectra confirmed the presence of skin PpIX (peak emission 632 nm). Skin PpIX was associated with erythrocyte PpIX (P = 0·002, R2 = 0·34), skin erythema (P = 0·001, R2 = 0·47) and symptoms during illumination. Furthermore, skin PpIX increased during the hours after illumination. CONCLUSIONS: We have developed a noninvasive method to measure skin PpIX in patients with EPP. Skin PpIX is dependent on erythrocyte PpIX and exposure of the skin to light. This method can be used for objective monitoring of treatment effect.

Pulse photodynamic therapy reduces inflammation without compromising efficacy in the treatment of multiple mild actinic keratoses of the face and scalp: a randomized clinical trial.

BACKGROUND: The main side-effects of photodynamic therapy (PDT) for actinic keratoses (AKs) are post-treatment erythema and oedema, and pain during illumination. Severe erythema after PDT enhances the down time associated with the treatment. OBJECTIVES: To evaluate in a randomized intraindividual study whether pulse-PDT and corticosteroid pulse-PDT would reduce treatment-induced erythema compared with conventional PDT. METHODS: Twenty-two patients with multiple mild AKs on the face and scalp were treated with methyl aminolaevulinate (MAL)-PDT in three similar areas. Two areas were incubated with MAL for 30 min (pulse-PDT) and one area was incubated with MAL for 3 h (conventional PDT). All areas were illuminated with red light after 3 h. In one of the pulse-PDT areas a superpotent corticosteroid was applied before and just after PDT (S-pulse-PDT). RESULTS: Pulse-PDT significantly reduced PDT-induced erythema (P = 0·020), and erythema was even further reduced by S-pulse-PDT (P < 0·001). The complete lesion response rate 3 months after PDT did not differ significantly between the three treated areas. CONCLUSIONS: Pulse-PDT and S-pulse-PDT reduced erythema 24 h after treatment of multiple mild AKs on the face and scalp. The use of a short MAL application time and topical corticosteroid did not affect the efficacy of PDT and may be an easy way to make PDT treatment of large visible areas more acceptable.

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.

The European Status Quo in legal recognition and patient-care services of occupational skin cancer.

BACKGROUND: Skin cancer is the most common malignancy in Caucasian populations worldwide and ultraviolet radiation (UVR) is known for being the number one carcinogen. As, especially in outdoor workers, UVR is an inevitable carcinogen, the prevention and management of UVR-related skin cancers in these at-risk populations represent a collective challenge for dermatologists and healthcare policymakers likewise. OBJECTIVE: To provide an overview on the current regulations on the acknowledgement and management of work-related skin cancer in 11 European countries. METHODS: Dermatologists from 11 countries networking within the EU Horizon 2020 COST Action TD1206 'StanDerm' contributed to a standardized survey regarding current national regulations, implemented for the recognition, prevention and management as well as possible compensation regulations in their individual country of residence. RESULTS: Ten of 11 participating countries in this survey reported the existence of an established programme available on certain occupational diseases; work-related skin diseases were only specifically recognized in eight countries. Seven of 11 countries recognize cutaneous squamous cell carcinoma in outdoor workers as 'occupational skin cancer'. Basal cell carcinoma (6 of 11), actinic keratosis (5 of 11), Bowen's disease (5 of 11) and malignant melanoma (5 of 11) are not as regularly approved as potentially 'work-induced'. Only a few of the countries included into this survey established a general documentation system (national registry) on occupational skin diseases. So far, representatives of only three countries of this survey referred to a specific established national programme for the prevention, management or compensation of occupational skin cancers acquired during work-related UVR exposure. CONCLUSION: This survey highlights the need for mandatory regulations on the prevention, management and potential compensation of work-related UV-induced skin cancer across Europe. Against the background of a joint European domestic market, equal standards of occupational safety across Europe should include binding regulations for the protection and management of work-related skin cancer. The design of a common regulation to meet the increasing incidence of skin cancers in outdoor workers should become part of the European agenda, ensuring equal working and living conditions in the member states.

Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy: a randomized controlled trial.

Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p = 0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n = 43) compared with PDT-treated skin (n = 8), p = 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR.

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.

Cutaneous leishmaniasis responds to daylight-activated photodynamic therapy: proof of concept for a novel self-administered therapeutic modality.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Israel, with hundreds of new cases reported in recent years. Photodynamic therapy (PDT) is highly effective for treatment of CL, but requires equipment available only at specialized centres. Daylight-activated PDT (DA-PDT) abolishes the need for artificial light sources and allows the patient to administer the treatment with no professional assistance. OBJECTIVES: The objective of this single-centre, open study was to establish proof of concept for the efficacy of DA-PDT in the treatment of CL using clinical, microbiological and molecular clearance as outcome measures. METHODS: Thirty-one patients with CL (11 Leishmania major and 20 Leishmania tropica) underwent DA-PDT. Fourteen patients were treated in the hospital garden under professional supervision and 17 patients underwent DA-PDT as a self-administered treatment modality at home. Following application of a thick layer of 16% methyl aminolaevulinate and 30-min occlusion, the lesions were exposed to daylight for 2·5 h. Treatment sessions were repeated at weekly intervals until clinical and microbiological cure. Control lesions were either treated with cryotherapy or left untreated. RESULTS: The overall cure rate for DA-PDT was 89% (intention-to-treat cure rate 77%); this was 86% for the hospital-based treatment group and 92% for the self-administered group. CONCLUSIONS: DA-PDT proved to be effective in the treatment of CL caused by L. major and L. tropica. More patients were treated according to a self-administered protocol, suggesting that DA-PDT can be adopted even in technologically deprived countries where the majority of Leishmania infections are encountered.

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.