Editorial: The Value of New Knowledge.

is missing (Editorial).

Size of the exposed body surface area, skin erythema and body mass index predict skin production of vitamin D.

BACKGROUND: Cholecalciferol (vitamin D3), produced in the skin by UVB irradiation (290-315nm) of 7-dehydrocholesterol, is metabolized in the liver into 25-hydroxyvitamin D [25(OH)D] which is a major circulating metabolite. AIM: To examine changes in serum concentrations of cholecalciferol and its metabolites after UVB exposure of different skin areas. METHODS: 21 healthy Caucasians (skin type II and III, aged 23-47years) were exposed to broadband UVB (290-320nm) and randomized to either exposure to one minimal erythema dose given as a single dose, or a suberythemic dose given for 3 subsequent days. The following areas were exposed: face and back of hands, upper half of the body and the whole body, respectively. Serum cholecalciferol and 25(OH)D were measured immediately before start and 24h after the 1st and last exposure, respectively. RESULTS: Subjects with whole body exposure had an average S-cholecalciferol increase per dose unit of 0.18ngml(-1)mJ(-1)cm(2), 0.95 CI: (0.16, 0.20), upper body treatment 0.13ngml(-1)mJ(-1)cm(2), 0.95 CI: (0.10, 0.15) and face and hands exposure 0.013ngml(-1)mJ(-1)cm(2), 0.95 CI: (-0.012, 0.037). The increase in cholecalciferol correlated positively to the UVB dose and skin erythema and negatively to body mass index (BMI) when controlling for other factors. Exposure of face and hands induces smaller cholecalciferol production in comparison with exposure of larger skin areas. CONCLUSION: Size of the exposed skin area, UVB dose, skin erythema and BMI were the major determinants for serum levels of skin synthesized cholecalciferol. Exposure of hands and face induces smaller cholecalciferol production in comparison with exposure of larger skin areas.

Vitamin D production after UVB exposure - a comparison of exposed skin regions.

BACKGROUND: Cholecalciferol is an essential steroid produced in the skin by solar ultraviolet B radiation (UVB 290-315nm). Skin production of cholecalciferol depends on factors affecting UVB flux, age and exposed skin area. PURPOSE: Serum cholecalciferol and 25-hydroxyvitamin D3 [25(OH)D3] concentrations were measured after UVB irradiation of 3 different skin areas to compare the skin capacity to produce vitamin D in different anatomic sites in the same individuals. METHOD: Ten voluntary Caucasians (skin photo type II & III, aged 48±12years (±SD)) were exposed to broadband UVB (280-320nm) between February and April. Hands and face, upper body and whole body were exposed to a suberythemic dose of UVB (median 101mJ/cm(2) (min 66, max 143)) (for 3 subsequent days 24h apart with a wash out period of about 3weeks (median 18days (min 11, max 25)) between the exposures of respective area. Serum concentrations of cholecalciferol and 25(OH)D3, were measured immediately before the first and 24h after the last dose of radiation. RESULTS: There was a significantly higher increase in serum cholecalciferol after UVB exposure of the two larger skin areas compared to face and hands, but no difference in increase was found between upper body and whole body exposures. CONCLUSION: Exposure of a larger skin area was superior to small areas and gave greater increase in both serum cholecalciferol and serum 25(OH)D3 concentrations. However, exposure of face and hands, i.e. only 5% of the body surface area, was capable of increasing serum concentrations of 25(OH)D3.

Cryosurgery of eyelid basal cell carcinomas including 781 cases treated over 30 years.

PURPOSE: To present the results of a 30-year prospective study in which eyelid basal cell carcinomas were treated with cryosurgery. METHODS: Basal cell carcinomas with well-defined borders on the eyelids or medial canthus, diagnosed by punch biopsy, were included. Cryosurgery was performed using liquid nitrogen sprayed into a cone circumscribing the tumours. The tumours were treated in a double freeze-thaw cycles technique. The minimum thawing time of the frozen area outside the tumour margin was at least 60 seconds. During the first 20 years of the study, patients were re-examined for up to 10 years. In the last 10 years of the study, most patients were followed up for 1 year, and if there was no visible scarring in the treated area at the 1-year check-up, follow-ups were implemented at the patient's request following self-assessment. RESULTS: In total, 781 tumours in 768 patients were treated. The median age of the patients at treatment was 73 years, mean 70.9 years (range 22-102 years). More women (58%) were treated than men. The median tumour size was 8 mm, mean 9.1 mm (range 2-25 mm). There were few side-effects requiring intervention. Twelve patients underwent surgery due to ektropion during follow-up. In 101 patients, treatment of the tumour resulted in conjunctival growth on the skin side, which required correcting operations in 28 patients. Three recurrences have occurred. CONCLUSION: Cryosurgery is an effective treatment modality for eyelid basal cell carcinomas, resulting in few recurrences and good cosmetic and functional outcomes at a low cost.

The risk of skin cancer in psoriasis patients treated with UVB therapy.

Phototherapy is an effective and widely used treatment for generalised plaque psoriasis. Despite the mutagenic effects of UVB this type of therapy is still assumed to be a safe treatment option. We have performed a cross sectional study to assess the risk of skin cancer in the cohort of psoriasis patients treated with UVB. A total of 162 white patients (116 men and 46 women, mean ± standard deviation age 56.0 ± 13.5 years) were included in the study. All patients have previously been treated with UVB at least 100 times in the last 5 years. Eight patients (4.9%, 0.95 CI: 2.2-9.5%) out of the 162 included in the study had histopathologically verified skin cancer. We found that the risk of skin cancer in psoriasis patients treated with UVB correlated with the number of treatments (controlling for age) but not with the type of UVB lamp. How-ever, the overall risk of malignancy in the UVB-treated patients was not greater than in the general population.

Fluorescence diagnostics of basal cell carcinomas comparing methyl-aminolaevulinate and aminolaevulinic acid and correlation with visual clinical tumour size.

Fluorescence diagnostics based on aminolaevulinic acid (ALA) fluorescence has been suggested as an in vivo pre-surgical tool for tumour demarcation. We performed fluorescence diagnostics of 35 basal cell carcinomas (BCCs) undergoing photodynamic therapy (PDT) using methyl-aminolaevulinate (MAL). In addition, a semi-automated thresholding algorithm was implemented to detect the potential tumour region. The mean tumour fluorescence contrast was found to be 1.65 ± 0.06 during the first MAL-PDT session, and increased to 1.84 ± 0.07 at the second treatment (p < 0.01). This could imply that disruption of the skin barrier and inflammatory responses after the first session of PDT led to higher accumulation of proto-porphyrin IX during the second session of PDT. The tumour areas detected based on fluorescence in small BCCs (< 1 cm(2)) were in general (n = 18/23) larger than the visual clinical tumour size. In addition, the fluorescence contrast using MAL (1.65 ± 0.06) was found to be significantly higher (p<10(-4)) than the contrast (data from previous study) after application of ALA (1.20 ± 0.06). Thus, MAL generally provides higher tumour contrast than ALA in BCCs, and should be preferred for use in fluorescence diagnostics. Correlation between fluorescence, lack of treatment response and/or pain was not observed.

Vitamin D status in psoriasis patients during different treatments with phototherapy.

BACKGROUND: Phototherapy (broadband UVB (BUVB), narrowband UVB (NBUVB) and heliotherapy) is commonly used treatment modalities for widespread psoriasis. Vitamin D3, cholecalciferol, is produced in the epidermis by ultraviolet radiation (290-315 nm) of 7-dehydrocholesterol. 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] are the major circulating metabolites. Sun exposure is the strongest factor influencing 25(OH)D. The similar wavelength spectrum of UVB responsible for D vitamin synthesis (BUVB, 280-315 nm) has been successfully used for years to treat psoriasis. PURPOSE: The aim was: (1) To increase the knowledge about the effects of phototherapy on vitamin D production during treatment of psoriasis. (2) To examine if there were differences between the effect of BUVB, NBUVB and heliotherapy on vitamin D synthesis in psoriasis patients. METHODS: Serum concentrations of 25(OH)D, 1,25(OH)(2)D, PTH, calcium and creatinine, measured before and after phototherapy in white Caucasian patients with moderate to severe active plaque psoriasis, were aggregated from three studies. RESULTS: Psoriasis improved in all patients, with a reduction in PASI ((Psoriasis Area and Severity Index) score of about 75% on all regimes. Serum 25(OH)D increased and PTH decreased after the phototherapy. The increase in 25(OH)D was higher in the BUVB treated patients compared with NBUVB. There was no correlation between the dose of UVB and the increase of 25(OH)D. CONCLUSION: UVB and heliotherapy improved the psoriasis score, increased the serum 25(OH)D levels and reduced the serum PTH concentrations. Vitamin D production in psoriasis patients increased less with NBUVB than with BUVB phototherapy.

Vitamin D production in psoriasis patients increases less with narrowband than with broadband ultraviolet B phototherapy.

BACKGROUND: Phototherapy of psoriasis is an effective treatment. In addition to standard broadband ultraviolet radiation B (UVB), (280-320 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) has become an important treatment for psoriasis. The same wavelength range of UVB (290-315 nm) induces synthesis of vitamin D. The aim was to compare the effect of broadband with NBUVB therapy on vitamin D synthesis in patients with psoriasis. METHODS: Sixty-eight Caucasian patients (17 women and 51 men) mean age 54.1 +/- 16.0 years, with active plaque psoriasis, were treated with broadband UVB (n=26) or NBUVB (n=42) two to three times/week for 8-12 weeks. The serum concentrations of 25-hydroxyvitamin D (25(OH)D3), 1,25-dihydroxyvitamin D (1,25(OH)(2)D3), intact parathyroid hormone (PTH), calcium and creatinine were measured before the first exposure and after the last dose of radiation. RESULTS: In broadband UVB treated patients, 25(OH)D3 increased from 37.9 +/- 16.9 to 69.4 +/- 19.7 ng/ml (P<0.0001) and in patients treated with NBUVB from 34.8 +/- 11.9 to 55.3 +/- 17.6 ng/ml (P<0.0001) and P=0.008 between the treatment groups. PTH decreased on broadband UVB (P<0.05). The serum concentrations of 1,25(OH)(2)D3, calcium or creatinine remained unaltered. CONCLUSION: Serum 25(OH)D3 in psoriasis patients increased less with NBUVB than with broadband UVB phototherapy. Psoriasis improved on both regimens.

Review of photodynamic therapy in actinic keratosis and basal cell carcinoma.

The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT) using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field.

Risk factors for osteoporosis and bone status in postmenopausal women with psoriasis treated with UVB therapy.

The aims of this study were to examine whether postmenopausal women with psoriasis who were exposed to regular ultraviolet light B (UVB) therapy had greater bone mineral density than women of similar age from the same region, and to estimate the influence of risk factors on bone status. A total of 35 randomly selected women, age (mean +/- SD) 69.3 +/- 6.29 years (age range 60-82 years), with active psoriasis, mean onset at 37.0 years (+/- 23.5 SD) were studied. The patients had been previously exposed to broadband or narrowband UVB. Age-matched, women (n = 2448) from Göteborg, examined at the Geriatric out-patient clinic during the years 2001 and 2002, were used as controls. Bone mineral density was examined by Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and the lumbar spine. Medical history and lifestyle factors were assessed with a questionnaire. Postmenopausal women with psoriasis were found to have higher bone mineral density than age-matched controls. Higher body weight, physical activity and UVB exposure could explain this finding.

Solid-phase extraction and reverse-phase HPLC: application to study the urinary excretion pattern of benzophenone-3 and its metabolite 2,4-dihydroxybenzophenone in human urine.

BACKGROUND: Benzophenone-3 (BZ-3) is a common ultraviolet (UV) absorbing compound in sunscreens. It is the most bioavailable species of all UV-absorbing compounds after topical application and can be found in plasma and urine. OBJECTIVES: The aim of this study was to develop a reverse-phase high performance liquid chromatography (HPLC) method for determining the amounts BZ-3 and its metabolite 2,4-dihydroxybenzophenone (DHB) in human urine. The method had to be suitable for handling a large number of samples. It also had to be rapid and simple, but still sensitive, accurate and reproducible. The assay was applied to study the urinary excretion pattern after repeated whole-body applications of a commercial sunscreen, containing 4% BZ-3, to 25 healthy volunteers. METHODS: Each sample was analyzed with regard to both conjugated/non-conjugated BZ-3 and conjugated/non-conjugated DHB, since both BZ-3 and DHB are extensively conjugated in the body. Solid-phase extraction (SPE) with C8 columns was followed by reverse-phase HPLC. For separation a Genesis C18 column was used with an acethonitrile-water mobile phase and the UV-detector was set at 287 nm. RESULTS: The assay was linear r(2) > 0.99, with detection limits for BZ-3 and DHB of 0.01 micromol L(-1) and 0.16 micromol L(-1) respectively. Relative standard deviation (RSD) was less than 10% for BZ-3 and less than 13% for DHB. The excretion pattern varied among the human volunteers; we discerned different patterns among the individuals. CONCLUSIONS: The reverse-phase HPLC assay and extraction procedures developed are suitable for use when a large number of samples need to be analyzed and the method fulfilled our objectives. The differences in excretion pattern may be due to differences in enzyme activity but further studies, especially about genetic polymorphism, need to be performed to verify this finding.

UVB therapy increases 25(OH) vitamin D syntheses in postmenopausal women with psoriasis.

BACKGROUND: Vitamin D3 is produced in the epidermis by ultraviolet (UV) radiation (290-315 nm) of 7-dehydrocholesterol. A similar range of 290-320 nm (broadband UVB) has been successfully used for years to treat psoriasis. The aim of this study was to investigate whether UVB therapy was able to influence vitamin D synthesis in psoriasis patients. METHODS: Twenty-four postmenopausal, white Caucasian women, aged 69 +/- 5.9 (mean +/- SD), with active plaque psoriasis, were treated with broadband UVB two to three times per week for 8-12 weeks. The serum concentrations of calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), intact parathyroid hormone (PTH), thyroid hormones, osteocalcin, calcium and creatinine were measured before the first and after the last dose of radiation. Bone density was measured using Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and lumbar spine. RESULTS: Serum levels of 25(OH)D3 increased from 36.8 +/- 17 ng/ml (mean +/- SD) to 59.6 +/- 18.7 ng/ml (P<0.001) after the UVB treatment period. Serum PTH decreased from 62.8 +/- 25.7 ng/l to 48.2 +/- 17.4 ng/l (P<0.001). Secondary hyperparathyroidism (PTH>65 ng/l) was revealed in seven patients (29%) in whom PTH values were suppressed by the UVB therapy. The serum levels of calcitriol, calcium, osteocalcin, thyroid hormones and creatinine were unaltered. CONCLUSION: UVB therapy in elderly psoriatic women improved psoriasis, increased serum 25(OH)D3 synthesis and reduced serum PTH concentrations.

Photodynamic therapy for acne vulgaris: a pilot study of the dose-response and mechanism of action.

Acne vulgaris does not always respond to conventional therapy. Photodynamic therapy (PDT) has been proposed as a treatment option. The aim of this study was to determine the optimal light dose for effective PDT treatment of acne and to investigate whether PDT reduces sebum excretion and the amount of Propionibacterium acnes. Fifteen patients (9 men, 6 women, age range 16-44 years, mean age 25 years) with mild to severe acne were enrolled in an open, unblinded study. Aminolaevulinic acid cream (20% in Unguentum Merck) was applied on two circular areas 3 h before PDT. The areas of investigation were irradiated with red light (635 nm) from a Waldman PDT 1200 lamp. Ten patients with facial acne were treated with a light dose of 50 J/cm(2) on the right cheek and 30 J/cm(2) on the left cheek. Five patients with acne on their back were treated either with 50 J/cm(2) or with 70 J/cm(2). Clinical follow-up was performed for at least 10 weeks. In the patients with facial acne, sebum excretion was determined before PDT and at every follow-up visit. The amount of P. acnes was measured in a skin surface biopsy using a cyano-acrylate polymer to extract the content of the sebaceous follicles. In 9 patients with facial acne the improvement of lesions was the same for the two light doses. According to the patients' own assessment, 8 improved after PDT (p=0.02). No difference was found between the two doses in patients with acne on the back. Hyperpigmentation was more common at higher doses of light, and pain was experienced more often by the patients when higher doses were used. No significant reduction in P. acnes or sebum excretion was found at any time after PDT. It is concluded that PDT could be an alternative treatment of acne lesions. The lowest possible light dose should be used for minimal side-effects. Other mechanisms of action for PDT than eradication of P. acnes and sebosuppression should be considered.

Human papilloma virus in skin, mouth and uterine cervix in female renal transplant recipients with or without a history of cutaneous squamous cell carcinoma.

Some human papillomaviruses are thought to be associated with skin cancer. In this pilot study, 21 female renal transplant carriers, 10 with a history of skin squamous cell carcinoma and 11 without, together with 9 age-matched healthy women were investigated for human papillomavirus DNA in sun-exposed (forehead) and less sun-exposed (buttock) skin, mouth and uterine cervix. Paraffin-embedded tumours from 9 of the patients with a history of squamous cell carcinoma were analysed. Healthy skin from both the healthy and the immunosuppressed individuals harboured a wide variety of papillomaviruses. In the healthy individuals, samples from less sun-exposed skin showed a lower prevalence of human papillomavirus DNA than corresponding samples from the immunosuppressed patients (4/9 and 7/9, respectively). Among the immunosuppressed patients, human papillomavirus DNA was found as frequently in buttock samples (17/21) as in forehead samples (17/20). There was no increased prevalence of human papillomavirus in the cervix or mouth samples from the immunosuppressed patients.