Basal cell carcinoma risk and solar UV exposure in occupationally relevant anatomic sites: do histological subtype, tumor localization and Fitzpatrick phototype play a role? A population-based case-control study.

BACKGROUND: A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates. OBJECTIVES: To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure. METHODS: Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated. RESULTS: Participants with high versus no (OR 2.08; 95% CI 1.24-3.50; p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15-3.65; p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses. CONCLUSION: The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. OBJECTIVES: To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. METHODS: Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. RESULTS: Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. CONCLUSIONS: Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.

Knowledge of outdoor workers on the effects of natural UV radiation and methods of protection against exposure.

The most important but influenceable risk factor in the development of skin cancer is the unprotected exposure to solar ultraviolet (UV) radiation. In order to assure adequate and effective protection against UV exposure, a level of knowledge about solar radiation and its effects is required. The objective of this study was to assess the knowledge of workers in outdoor professions on the effects of natural UV radiation and methods of protection against exposure. Forty outdoor workers were given a standardized questionnaire designed to ascertain their level of knowledge. The majority of participants knew exposure to solar radiation can be detrimental depending on exposure time. Eighty-three percentage recognized that people working regularly in an outdoor environment may be at risk due to high exposure. Long-sleeved clothing plus headgear and sunscreen containing sun-protecting substances were deemed adequate methods of protection by 83% and 85% respectively. Seventy percentage of the outdoor workers were familiar with the definition of the sun protection factor (SPF), yet only 25% correctly identified the amount of sunscreen needed to achieve the SPF as indicated on the product. A mere 8% of participants knew that symptoms of a sunburn first became apparent 3 h after sun exposure and only 18% were able to accurately gauge the amount of time they could spend in the sun before developing one. Although 30% had heard of the ultraviolet index (UVI), only 13% understood that protecting your skin using additional measures is recommended as of UVI 3. Overall, 30% of the outdoor workers thought themselves sufficiently protected against the harmful effects of the sun. While the participants of this study had a basic fundamental understanding of the effects of solar radiation and methods of protection against exposure, there remains an urgent need for further clarification across all demographic groups.

[Prevention of occupational solar UV radiation-induced epithelial skin cancer]. / Prävention von durch berufliche solare UV-Exposition bedingtem epithelialem Hautkrebs.

Malignancies of the skin, with an incidence of more than 200,000 newly registered cases/year, are the most frequently notified malignances in Germany. In Europe, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) account for about 30 cases/100,000 persons and 50-100 cases/100,000 persons, respectively. Ultraviolet (UV) exposure is the main risk factor to induce these cancers. Increased incidence rates were shown for persons having red/blonde hair as well as light eye colour, acquire sun burns easily, hardly tan and develop freckles. The majority of the malignancies and precursor lesions are acquired by UV exposure in leisure time. However, in highly occupationally UV-exposed outdoor workers, UV monitoring revealed that exposure levels are 2-3 times higher compared to the general population. Occupations likely to be highly exposed are farmers, forestry workers, gardeners, landscapers, fishermen and seafarers, construction workers, builders, tin smiths, sport teachers, mountain guides, etc. Recent metaanalyses showed that occupational UV exposure is a relevant and independent risk factor for SCC and to a lesser extent also for BCC. To prevent occupationally caused malignancies of the skin a significant reduction of occupationally acquired UV dosages in outdoor workers is mandatory. Relevant factors influencing the cumulative sun exposure in outdoor workers are the amount of UV exposure, the specific tasks to be performed in the sun as well as the UV protection habits of the workers. Besides adequate behavior, textile protection by headgear and clothing as well as the regular use of sunscreens and sun glasses are important.

Evaluation of methylprednisolone aceponate, tacrolimus and combination thereof in the psoriasis plaque test using sum score, 20-MHz-ultrasonography and optical coherence tomography.

BACKGROUND: Despite new treatment options with systemic disease modifiers, topical therapy - especially as combination therapy - plays an important role in psoriasis treatment. METHODS: Antipsoriatic efficacy of methylprednisolone aceponate ointment (MPA), tacrolimus 0.1% ointment (FK506) and their combination (MPA+FK506) were investigated in a double-blind randomized pilot study using the psoriasis plaque test. Agents and corresponding placebos were applied once daily under occlusion for 11 days. Test sites were evaluated by sum score (erythema, scaling, infiltration), objective assessment by 20-MHz-sonography and optical coherence tomography (OCT). RESULTS: After 11 days, the sum score significantly improved from baseline value in FK506-treated skin (9.6 vs. 2.9, p < 0.0001). MPA led to a significant improvement of the sum score (9.4 vs. 0.6, p < 0.0001). Combination therapy showed results similar to MPA monotherapy (9.4 vs. 0.4, p < 0.0001). These findings were confirmed by 20-MHz-sonography and OCT data. CONCLUSION: FK506 is moderately effective in chronic plaque-type psoriasis in our model. Combination therapy with FK506+MPA has no additive effect compared to MPA alone.

Demonstration of UVB-induced synthesis of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis.

Cutaneous vitamin D(3) (VD(3)) is generated by UVB-induced photolysis of 7-dehydrocholesterol (7-DHC). VD(3) then undergoes sequential hydroxylation to calcidiol (25-OHD(3)) in the liver and to hormonally active calcitriol (1 alpha,25-(OH)(2)D(3)) in the kidney. Recently, we have described the epidermal VD(3) metabolic pathway by demonstrating the autochthonous formation of calcitriol in cultured keratinocytes. In this study we sought to determine whether photolysis of 7-DHC induced by irradiation of human skin with monochromatic UVB at 300 nm results in epidermal synthesis of calcitriol in vivo. Using a microdialysis technique we demonstrated that UVB irradiation results in a dose- and time-dependent increase in the calcitriol concentration in the extracellular fluid of UVB-irradiated skin. Topical treatment of skin with an ointment containing 2% ketoconazole immediately after irradiation suppressed UVB-induced intraepidermal calcitriol synthesis. This study demonstrates for the first time UVB-triggered synthesis of calcitriol in human skin in vivo. The link between UVB irradiation and synthesis of calcitriol in the skin may be of great importance for regulation of biological processes such as cell growth, differentiation, apoptosis and immunological reactions.

UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model.

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol (1alpha,25-dihydroxyvitamin D3). This study was initiated to test whether the ultraviolet-B-induced photolysis of provitamin D3 (7-dehydrocholesterol), which results in the formation of vitamin D3, can generate calcitriol in an in vivo-like human skin equivalent model made of fibroblasts in a collagen matrix as the dermal component and keratinocytes as the epidermal component. Cultures were preincubated with increasing concentrations of 7-dehydrocholesterol (0.53-5.94 nmol per cm2 human skin equivalent) at 37 degrees C and irradiated with monochromatic ultraviolet B at wavelengths ranging from 285 to 315 nm (effective ultraviolet doses 7.5-45 mJ per cm2). In our in vitro model irradiation with ultraviolet B resulted in a sequential metabolic process with generation of previtamin D3 followed by the time-dependent formation of vitamin D3, 25-hydroxyvitamin D3, and ultimately calcitriol in the femtomolar range. Unirradiated cultures and irradiated cultures without keratinocytes generated no calcitriol. Irradiation of skin equivalents at wavelengths > 315 nm generated no or only trace amounts of calcitriol. The ultraviolet-B-triggered conversion of 7-dehydrocholesterol to calcitriol was strongly inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases. The amount of calcitriol generated was dependent on the 7-dehydrocholesterol concentration, on wavelength, and on ultraviolet B dose. Hence, keratinocytes in the presence of physiologic concentrations of 7-dehydrocholesterol and irradiated with therapeutic doses of ultraviolet B may be a potential source of biologically active calcitriol within the epidermis.

Determination of the calibration factor of polysulphone film UV dosemeters for terrestrial solar radiation.

Polysulphone film is used as a personal UV dosemeter in dermatological or epidemiological studies. The relative efficiency of this detector does not exactly match the action spectrum as proposed by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and to which the UV dose and exposure limits refer. Therefore, the calibration of the dosemeter depends on the spetrum. In the present paper the variation of the calibration factor for terrestrial solar UV spectra is analysed on the basis of a two year observation period at a site near Munich. Germany. A detailed error estimation is included. It is shown that the variation of the calibration factor within this class of spectra is the main contribution to the total uncertainty of the dose determination, which can be up to 40%. The shape of the spectrum of terrestrial solar UV radiation is mainly determined by the total ozone column and the solar elevation angle. It is shown how the calibration depends on these two parameters and how this additional information can help to reduce the measurement error to a residual uncertainty of 17%. Exposure studies of terrestrial solar UV radiation using polysulphone film as a dosemeter would gain in accuracy if total ozone column values at the study's site could be measured or taken from satellite or weather service data. The interpretation of the magnitude of the dose uncertainty depends on the further use of these data.

[Studies on the stabilization of the cornea in rabbits]. / Untersuchungen zur Verfestigung der Hornhaut am Kaninchen.

BACKGROUND: The mechanical stabilization of the cornea in keratoconus may delay progression of this disease. The cross-linking techniques optimized in corneas of enucleated porcine eyes were investigated under in vivo conditions in rabbits to estimate the biocompatibility and duration of the stiffening effect. METHODS: Twenty-eight rabbits were treated monocularly, the fellow eye serving as control. The epithelium was mechanically removed and 19 eyes were treated with riboflavin plus ultraviolet irradiation (365 nm, 2 mW/cm2) for 45 min and 9 eyes with 0.075% glutaraldehyde for 20 min. After treatment, the eyelids were sutured for 3 days. The healing process was controlled by slit-lamp examination and photographically documented. After 1 month, 20 animals and after 3 months 8 animals were sacrificed, the eyes enucleated, and the stress-strain relation of the corneas measured and compared to the fellow eye. RESULTS: The epithelium was closed after 4-5 days. The transparency of the corneas remained clear during follow-up, and there were no signs of inflammatory reaction. Stress for a strain of 6% was higher in the treated corneas by a factor of 1.3 +/- 0.66 (P = 0.319) in the glutaraldehyde group and by a factor of 1.6 +/- 0.75 (P = 0.0408) in the riboflavin group at 1 month, and by 1.3 +/- 0.48 (P = 0.07) at 3 months after treatment. CONCLUSIONS: The cross-linking technique using riboflavin plus UV irradiation is suitable for at least temporarily stiffening the cornea in vivo and seems to be a promising method for conservative treatment of keratectasia.

UVB-induced conversion of 7-dehydrocholesterol to 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in the human keratinocyte line HaCaT.

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol. The present study was initiated to test whether ultraviolet B (UVB)-induced photolysis of provitamin D3 (7-dehydrocholesterol, [7-DHC]) which results in the formation of vitamin D3 also leads to the generation of calcitriol in keratinocytes. Submerged monolayers of HaCaT keratinocytes were preincubated with 7-DHC (25 microM) at 37 degrees C and irradiated with monochromatic UVB at different wavelengths (effective UV-doses: 7.5-60 mJ/cm2), or a narrow-band fluorescent lamp Philips TL-01 (UVB-doses: 125-1500 mJ/cm2). Irradiation with both sources of UVB resulted in the generation of different amounts of previtamin D3 in our in vitro model followed by time-dependent isomerization to vitamin D3 and consecutive formation of calcitriol in the picomolar range. Unirradiated cultures or cultures exposed to wavelengths > 315 nm generated no or only trace amounts of calcitriol. The conversion of vitamin D3 generated after UVB irradiation to calcitriol is inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases in this chemical reaction. The generation of calcitriol was wavelength- and UVB dose dependent and reached approximately 18-fold higher levels after irradiation at 297 nm than at 310 nm (effective UVB dose: 30 mJ/cm2). Hence, keratinocytes may be a potential source of biologically active calcitriol within epidermis, when irradiated with therapeutical doses of UVB.

A novel pathway for hormonally active calcitriol.

Calcitriol [1alpha,25(OH)2D3], the hormonally active form of vitamin D3 (D3) is produced in both renal and extrarenal tissues. Our findings demonstrate that physiological doses of UVB radiation at 300 nm induce the conversion of 7-dehydrocholesterol (7-DHC) via preD3 and D3 into calcitriol in the pmol range in epidermal keratinocytes. The hydroxylation of photosynthesized D3 to calcitriol is strongly suppressed by ketoconazole, a known inhibitor of cytochrome P450 mixed function oxidases. The UVB-induced formation of calcitriol in human skin is demonstrable in vivo by the microdialysis technique. These results suggest that human skin is an autonomous source of hormonally active calcitriol.

Laboratory facilities and recommendations for the characterization of biological ultraviolet dosimeters.

A laboratory facility for characterizing biological dosimeters for the measurement of UV radiation has been built and tested. The facility is based on a solar simulator, stabilized by photofeedback, and monitored by a spectroradiometer, with a versatile filter arrangement. This enables the following characteristics of the dosimeters to be ascertained: spectral response, linearity, and reciprocity; angular acceptance and response; calibration in simulated sunlight. The system has been tested on a variety of dosimeters and has the potential to be used with other radiometers, subject currently to the size of their active surface.

[Measurement and evaluation of natural and artificial UV radiation]. / Messung und Bewertung natürlicher und künstlicher UV-Strahlung.

Natural and artificial UV radiation are environmental factors with both beneficial and harmful biological effects. This article will explain the physical measurement quantities and their relation to the biologically effective dose and will summarize the present technical state of the art of personal UV monitoring. In practical use are dosimeters based on polysulphone, a polymer which undergoes changes in its optical properties upon irradiation with UV. Other systems determine the UV dose by quantifying damage induced in Bacillus subtilis spores upon UV exposure. An electronic UV sensor represents a new and interesting development. Personal UV dosimeters will become an useful tool in both clinical and scientific areas within dermatology.

Biologically weighted personal UV dosimetry.

People are exposed to natural or artificial UV radiation in different ways; unintentionally or intentionally, at their workplace on their spare time. To quantify the amount of individual UV exposure, a personal dosimetry is necessary. In research, polysulphone film (PSF) dosimeters are the most frequently used personal UV dosimeters. We use calculated weighting factors in the measurement processing of polysulphone film dosimeters. The special weighting factor transforms the dosimeter reading from an equivalent UV dose to the biologically effective UV dose. The factor depends on the investigated problem (action spectrum of the photobiological effect and spectral distribution of the incident UV source), the calibration of PSF was carried out once by a monochromatic radiation (gamma = 295 nm). The equivalent dose readings are available from this calibration curve for any investigated question. A presented result of this method is the seasonal measurement of erythemally effective UV exposure by ambient solar radiation, and the individual exposure level in a "normal" person concerning UV exposure and also in groups with the risk of a lack of sunshine. Further applications are occupational measurements of the risk of health damage by UV radiation (with respect to the limit of the maximum permissible 8 h-exposure according to IRPA/INIRC-guidelines). We controlled the extent of UV exposure in workers in the area of arc welding workplaces. The biological weighting of PSF readings simplifies a routine use of PSF in personal UV monitoring to investigators without the expending special measurement technology (e.g. spectroradiometer).

In vivo evaluation of sunscreens by spectroscopic methods.

BACKGROUND/AIMS: The methods available for testing the efficacy of topical sunscreens have improved considerably in recent years. Nevertheless, so far no simple and rapid test has been proposed to measure in vivo transmission spectra of sunscreens in the UVA region. METHODS: Spectral changes that occur after sunscreen application were measured with a fluorescence spectrometer (LS 50B, Perkin Elmer, UK) equipped with a Y-shape quartz guide for in vivo measurements. Three sunscreens with different protection factors in the UVA range were tested. The excitation-emission maps of human collagen, skin and sunscreens were analysed. RESULTS: As a consequence of the human skin and sunscreen fluorescence map analysis, the optimal spectral regions (both for direct and indirect fluorescence measurements) were detected. In vivo fluorescence and remittance spectroscopy were used to investigate the time dependence in transmission spectra of epidermis with applied sunscreens. We also evaluated the feasibility of in vivo fluorescence measurements for the investigation of the sunscreens'water-resistance. CONCLUSION: The procedure is simple, and values obtained can be used to predict UVA protection on the basis of the mathematical algorithms.

Serum 25(OH)D3 and ultraviolet exposure of residents in an old people's home in Germany.

The 25(OH)D3 serum levels of 31 and 29 residents of an old people's home in Dresden were determined in February and in August 1991. The mean 25(OH)D3 levels in winter were below 10 ng/ml. Bedridden patients did not reach this level even in summer. Polysulphone films are useful indicators of a deficiency of ultraviolet light, which can result in a subsequent vitamin D deficiency.

[Ultraviolet exposure in the environment of welding work sites]. / UV-Strahlenbelastung in der Umgebung von Schweissarbeitsplätzen.

It has been checked if the "limits of the acceptable doses of ultraviolet radiation of monochromatic radiation at the workplace" (NIOSH-standard of USA) are adhered to in the vicinity of welders' work stations in a factory hall. For recording of UV-doses polysulphon films have been used. According to these investigations non-welders are exposed to doses of UV-radiation which exceed the limits recommended by about eight times. Clinical examinations of these persons showed chronic damage of the external parts of the eyes in a higher percentage than in a control group. It is pointed to the necessity of taking protective measures to shield persons working in the vicinity of welding job sites from ultraviolet radiation.

[References for the operating behavior of ultraviolet fluorescence tubes in phototherapy equipment]. / Hinweise zum Betriebsverhalten von UV-Fluoreszenzstrahlern in Phototherapiegeräten.

The working behaviour of the UV-fluorescent tubes type UVS 20-2, UVS 40-2 and UVS 65-2 (Manufacturer: VEB NARVA "Rosa Luxemburg" Leuchten- und Leuchtstoff-lampenwerk Brand-Erbisdorf) applicated in phototherapy equipments has been investigated in four commercially and two self-made devices. In the first 100 hours of the application of the fluorescent tubes an exponential decrease of the irradiation power reaching a value of 30 percent must be considered. After an exchange of old tubes (1,500 working hours) to new one a jump in the irradiation power with a factor 2.5 may be observed. The temperature of the fluorescent tube altering after the switch and daily instabilities in the supply power influence the irradiation power in a way that must not be neglected. The emission of equipments with good remove of the tube heat is constant after 5 minutes. In constructions causing and maintaining a high temperature of the tubes this time is about 20 minutes.