Donald Allan

Recommended summer sunlight exposure levels can produce sufficient (?20 ng ml-1) but not the proposed optimal (?32 ng ml-1) 25(OH)D levels at UK latitudes

Recommendations on limitation of summer sunlight exposure to prevent skin cancer may conflict with requirements to protect bone health through adequate vitamin D levels, the principal source being UVB in summer sunlight. We determined whether sufficient (> or =20 ng ml(-1)) and proposed optimal (> or =32 ng ml(-1)) 25(OH)D levels are attained by following UK guidance advising casual short exposures to UVB in summer sunlight, and performed the study under known conditions to enhance the specificity of future recommendations. During wintertime, when ambient UVB is negligible, 120 white Caucasians, aged 20-60 years, from Greater Manchester, UK (53.5 degrees N) received a simulated summers sunlight exposures, specifically 1.3 standard erythemal dose, three times weekly for 6 weeks, while wearing T-shirt and shorts. The baseline winter data predict that 5% (confidence interval (CI): 2.7-8.6) of Greater Manchester white Caucasians have deficient (<5 ng ml(-1)) 25(OH)D, 62.5% (CI: 55.2-69.4) have insufficient, and only 2.9% (CI: 1.4-5.6) have proposed optimal levels. After the simulated summer exposures, 90 (CI: 84.9-93.7) and 26.2% (CI: 20.1-33.2) reached 20 and 32 ng ml(-1) 25(OH)D, respectively. Assuming midday UVB levels, sufficient but suboptimal vitamin D status is attained after a summers short (13 minutes) sunlight exposures to 35% skin surface area; these findings will assist future public health guidance on vitamin D acquisition.

Recommended summer sunlight exposure amounts fail to produce sufficient vitamin D status in UK adults of South Asian origin

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.

Efficacy of a dose range of simulated sunlight exposures in raising vitamin D status in South Asian adults: implications for targeted guidance on sun exposure

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.

Efficacy of Photodynamic Therapy as a Treatment for Gorlin Syndrome-related Basal Cell Carcinomas

AIMS The management of the multiple basal cell carcinomas (BCCs) that develop throughout life of patients with Gorlin syndrome can be challenging. Surgical excision can result in significant disfigurement from scarring and tissue defects. Radiotherapy is contraindicated because of enhanced radiation tumourigenesis in these patients. Photodynamic therapy (PDT) is a simple, repeatable out-patient procedure, which is associated with minimal skin deterioration. It is now routinely used to treat superficial sporadic BCCs, using a topically-applied photosensitiser and external light, but its role in the management of Gorlin syndrome-related BCCs has yet to be established. In particular, Gorlin syndrome is often associated thick, nodular lesions which can be resistant to treatment with topical PDT. MATERIALS AND METHODS We report our outcome data for 33 Gorlin patients (138 lesions) treated with PDT. Lesion thicknesses were assessed using ultrasound, both prior to treatment and during follow-up, to quantify treatment response and to guide the choice of treatment methods. Topical PDT was used to treat superficial lesions (<2 mm thick) and a systemic photosensitiser +/- light delivered by interstitially-placed optical fibres was employed for thicker lesions (>2 mm). RESULTS AND CONCLUSIONS Local control rates of 56.3% at 12 months were achieved overall. The use of a systemic photosensitiser +/- interstitial light delivery extended the remit of PDT, allowing thicker lesions (>2 mm) to be treated, resulting in local control rates of 59.3% in this group. PDT can be considered as a treatment option for patients with multiple BCCs as a result of Gorlin syndrome. The use of ultrasound to accurately assess lesion thickness helps to select the optimum treatment method. Systemic photosensitisers and interstitial optical fibres can be used to treat thicker lesions, offering a treatment option for patients with thick nodular tumours who wish to avoid surgery.

Addition of novel degenerate electrical waveform stimulation with photodynamic therapy significantly enhances its cytotoxic effect in keloid fibroblasts: first report of a potential combination therapy.

BACKGROUND We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW) on differential gene expression in keloid fibroblasts. OBJECTIVE In this study, we evaluated the in vitro cytotoxic effect of PDT at 5J/cm(2) and 10J/cm(2) of red light (633 ± 3nm) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) with and without DW, on keloid fibroblasts compared to normal skin fibroblasts. METHODS The rate of intracellular photosensitizer (protoporphyrin IX, PPIX) generation and disintegration, reactive oxygen species (ROS) generation, LDH cytotoxicity, WST-1 cytoproliferation, apoptosis by Caspase-3 activation, mitochondrial membrane potential assessment by JC-1 aggregates, qRT-PCR, flow cytometry and In-Cell Western Blotting were performed. RESULTS PPIX accumulation and disintegration rate was higher in keloid than normal fibroblasts after incubation with MAL compared to ALA. Increased cytotoxicity and decreased cytoproliferation were observed for keloid fibroblasts after PDT+DW treatment compared to PDT alone. ROS generation, mitochondrial membrane depolarization, apoptosis (Caspase-3 activation) and collagens I and III gene down-regulation were higher in keloid compared to normal skin fibroblasts after MAL-PDT+DW treatment. An increase in the number of cells entering apoptosis and necrosis was observed after PDT+DW treatment by flow cytometry analysis. All positive findings were statistically significant (P<0.05). CONCLUSION The cytotoxic effect of PDT on keloid fibroblasts can be enhanced significantly with addition of DW stimulation, indicating for the first time the utility of this potential combinational therapy.

Guidelines on the measurement of ultraviolet radiation levels in ultraviolet phototherapy: report issued by the British Association of Dermatologists and British Photodermatology Group 2015

Guidelines on the measurement of ultraviolet radiation levels in ultraviolet phototherapy: report issued by the British Association of Dermatologists and British Photodermatology Group 2015 H. Moseley, D. Allan, H. Amatiello, A. Coleman, H. du Peloux Menag e, C. Edwards, L.S. Exton, J. Ferguson, T. Garibaldinos, C. Martin and M.F. Mohd Mustapa The Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. The Christie NHS Foundation Trust and University of Manchester, Manchester Academic Health Science Centre, Wilmslow Road, Manchester M20 4BX, U.K. Radiation Physics and Protection Group, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, U.K. Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, U.K. Lewisham and Greenwich NHS Trust, High Street, London SE13 6LH, U.K. Royal Gwent Hospital, Cardiff Road, Newport NP20 2UB, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. Department of Clinical Physics and Bio-Engineering, University of Glasgow, Glasgow G12 8QQ, U.K.

Systemic photodynamic therapy with Photofrin for naevoid basal cell carcinoma syndrome—A pilot study

BACKGROUND Treatment of basal cell carcinomas in naevoid basal cell carcinoma syndrome (NBCCS) poses several challenges. The sheer numbers of such lesions in these patients makes traditional therapeutic modalities like surgery, impractical. Topical photodynamic therapy (PDT) with δ-5-amino levulinic acid has increasingly been recognised as and safe and effective choice in the treatment of BCC. The probability of local control of BCC treated by PDT depends strongly on lesion thickness, thick nodular lesions being less responsive. Response to treatment is monitored by the reduction in the lesional size, but histopathological confirmation of regression is often required. METHOD We used systemic photodynamic therapy with Porfimer Sodium (Photofrin(®), Axcan Pharma Inc., Quebec, Canada), a systemic photosensitizer for treating multiple BCC in seven patients with NBCCS. Treatment response was monitored using a high resolution 20MHz ultrasound. RESULTS There was a substantial reduction in the number of superficial basal cell carcinomas with complete US regression after one treatment. A 74.2% reduction was seen in the size of thick lesions treated with external light. Thick nodular lesions in two patients treated with interstitial optical diffuser fibres in addition to external light showed 87.6% reduction in size as measured by high resolution ultrasound. CONCLUSIONS Our preliminary results indicate that systemic photodynamic therapy using Photofrin and external light either alone or with interstitial optical diffuser fibres; may be effective in treatment of multiple, thick and nodular BCC lesions in Naevoid basal cell carcinoma syndrome. Further studies are needed to confirm our observations. We found high resolution ultrasound an effective alternative to histopathological analysis in monitoring the response to treatment.

An ultrasound analysis of the response of Gorlin syndrome-related and sporadic basal cell carcinomas to aminolaevulinic acid photodynamic therapy

BACKGROUND Gorlin Syndrome (naevoid basal cell carcinoma syndrome, NBCCS) predisposes the patient to the development of basal cell carcinomas (BCCs) throughout their life. The standard treatment for isolated lesions is surgical excision. However, when numerous surgical procedures are required over time, the patient can be left with multiple disfiguring scars. Photodynamic therapy (PDT) offers a non-invasive treatment option for patients with this condition, in which ionizing radiation is contraindicated. This study evaluates PDT as a treatment modality for Gorlin Syndrome and compares the treatment response of Gorlin-related basal cell carcinomas with that of the sporadic lesions. METHODS In this un-randomized study, basal cell carcinomas in 25 Gorlin syndrome patients (with 36 lesions) and 145 sporadic patients (with 189 lesions) were treated by photodynamic therapy, using δ-5-aminolaevulinic acid (ALA) as a photosensitizer and 100Jcm(-2) of red light (630±15nm). The maximum thickness of the BCC was measured by 20MHz pulsed ultrasound prior to treatment and again 4-6 weeks and 12 months following treatment. The response of Gorlin syndrome lesions was compared to those in the overall sporadic population and then to a subpopulation matched as closely as possible for age, lesion thickness and site. RESULTS For both populations, the average pre-treatment BCC thickness by US was 1.5mm (overall range 0.3-5.3), and the average thickness at 4-6 weeks post-treatment was 0.5mm (overall range 0-4.3). Those BCC less than 1.5mm thick prior to treatment were significantly more likely to have no US evidence of disease at 4-6 weeks than and were more likely to be controlled at 12 months. CONCLUSIONS The average response to ALA PDT of Gorlin syndrome-related BCC closely resembles that for the sporadic population, with the same wide range of responses for a given dose. Ultrasound parameters measured at treatment and at 4-6 weeks post-treatment aid prediction of outcome and necessity for further treatment.

Systemic photodynamic therapy in folliculitis decalvans.

Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary cicatricial alopecia. The role of dysfunctional immune activity and the presence of bacteria, particularly Staphylococcus aureus, appear pivotal. We describe a 26‐year‐old man with a 4‐year history of FD that was recalcitrant to numerous systemic and topical therapies, whose disease was virtually cleared during a follow‐up of 25 months following a course of treatment with systemic photodynamic therapy (PDT) using ultraviolet light (100–140 J/cm2) with porfimer sodium 1 mg/kg as monotherapy. This is the first report of the use of systemic PDT as a treatment for FD. Systemic PDT has potent antibacterial effects with little or no resistance. In addition, systemic PDT provides local immunomodulation and improved scar healing. Significant adverse effects following systemic PDT with appropriate aftercare are rare. This case demonstrates that systemic PDT is a useful therapy option in the treatment of recalcitrant FD.