Optimized UVB treatment of psoriasis: a controlled, left-right comparison trial.

In a randomized, controlled, left-right comparison study, 20 patients with chronic plaque psoriasis were treated with UVB. One side of the body received UVB in a conventional regimen with fixed dose increments, the other side was given UVB doses according to measurements of skin pigmentation. Skin pigmentation was quantified by the skin reflectance technique. The relationship between skin pigmentation and sensitivity to UV radiation was used to optimize and individualize the initial UVB exposure dose. Clinical outcome, initial, final and cumulative UVB doses, time to 50% reduction in PASI score, and side-effects were compared. The consequence of the optimization of the UVB doses with a skin reflectance meter was that the initial UVB dose was significantly higher than in the conventional UVB regimen. PASI scoring demonstrated a more rapid improvement during the first 2 weeks of treatment on the half body receiving the optimized treatment compared to the other side (P < 0.05). This new technique offers the same therapeutical advantages and security as a dose regimen guided by minimal erythema dose testing. However, measurement of skin pigmentation by skin reflectance is a quick method which can be operated easily by nurses.

Sunscreen protection against cis-urocanic acid production in human skin.

Commercial sunscreens may offer some protection from immunosuppression induced by ultraviolet (UV) radiation, but agreement concerning the degree of protection is lacking. Cis-urocanic acid, formed by the photoisomerization of transurocanic acid is considered an important mediator of the cutaneous immunomodulation resulting from exposure to UV radiation. We investigated the effect of sunscreens on the isomerization of urocanic acid in 17 human subjects. Two sunscreens containing chemical filters, sun protection factor (SPF) 4 and SPF 10, and a SPF 10 sunscreen with a physical filter were applied at a thickness of 2 mg/cm2. The effect of a thin layer (0.5 mg/cm2) of the chemical SPF 10 sunscreen was also evaluated, as the amount of sunscreen applied in practice may be considerably less than recommended. All areas were irradiated with a single UV dose of 3.6 SED (standard erythema doses). In irradiated unprotected skin the median net production of cis-urocanic acid was 52% (relative amount). In the sites treated with the chemical sunscreens, the production of cis-urocanic acid was 7.4% (SPF 4) and 3.5% (SPF 10), and isomerization was thus reduced more efficiently at a higher SPF (p<0.01). The physical sunscreen reduced the formation of cis-UCA to 15%, and was significantly less effective than both the chemical SPF 10 sunscreen (p<0.01) and the SPF 4 sunscreen (p<0.01). The production of cis-urocanic acid in the area treated with the thin layer of the chemical SPF 10 sunscreen was 22%. The protection against the production of cis-urocanic acid was therefore reduced significantly (p<0.01) when the sunscreen was applied in an amount lower than recommended.

Isomerization of urocanic acid after ultraviolet radiation is influenced by skin pigmentation.

Exposure to ultraviolet (UV) radiation may induce erythema, DNA damage and suppression of immune responses. Melanin pigmentation offers protection against the first two of these effects, but immunosuppression seems to occur irrespective of the subject's pigmentation. Cis-urocanic acid (cis-UCA), produced by isomerization of trans-UCA in the stratum corneum on UV exposure, initiates some of the immunomodulatory effects of UV radiation. In the present study the relationship between skin pigmentation and UCA isomerization has been examined in 28 healthy individuals of skin types I-IV. Pigmentation is measured in five areas of not recently exposed back skin before irradiation with 0, 0.45, 0.9, 1.8 and 3.6 standard erythema dose (SED) of filtered broadband UV-B (1 SED = 10 mJ cm-2 at 298 nm). The concentration of UCA isomers is measured immediately after the irradiation. With 3.6 SED, the relative production of cis-UCA is close to the maximum obtainable, irrespective of skin type. A significant negative correlation is found between pigmentation and relative production of cis-UCA at 0.45 and 1.8 SED, and between pigmentation and absolute production of cis-UCA at 0.45 SED. At doses of 0.45 and 0.9 SED the relative and absolute production of cis-UCA are higher in the group with skin types I and II when compared with the group with skin types III and IV. The higher isomerization in the lightly pigmented subjects than in the more pigmented ones may indicate that people with fair skin are at a relatively higher risk of immunosuppression when exposed to low doses of UV radiation.

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma.

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.

Urocanic acid isomers and photosensitivity in healthy children.

Episodes of intense sun exposure, particularly in childhood, seem to carry a risk for the development of malignant melanoma in later life. However, little is known about photosensitivity and natural photoprotection in children. In adult subjects, photoprotection is provided mainly by the epidermal content of melanin and the thickness of the stratum corneum, while the amount of urocanic acid (UCA), a major ultraviolet-absorbing component of the stratum corneum, is not thought to contribute significantly to photoprotection. The minimal erythema dose (MED) was determined in 22 healthy children aged 6-13 years and in 36 healthy adults (mean age 28.1 years). Pigmentation was measured at six body sites by use of reflectance spectroscopy and the concentration of UCA isomers was measured in a sun-exposed area (upper back) and in unexposed buttock skin. No significant differences between children and adults were found, either in pigmentation at exposed and unexposed body sites, or in MED. The concentration of total UCA was significantly higher in the children than in the adults on the buttock (median 22.2 vs. 13.6 nmol/cm2), but not on the back. On exposed back skin, the children had a significantly higher percentage of cis-UCA than the adults (median 60.1 vs. 28.3%), while no difference was found on the buttock. In both groups, a significant correlation was found between pigmentation and MED (children: Spearman correlation coefficient 0. 58, P = 0.006; adults: Spearman correlation coefficient 0.69, P < 0. 0001), indicating that pigmentation is of major importance in determining photosensitivity in children as well as in adults. The concentration of total UCA did not correlate with the MED in either group.

Skin temperature of UV-induced erythema correlated to laser Doppler flowmetry and skin reflectance measured redness.

BACKGROUND/AIMS: The sensitivity of human skin to UV radiation is investigated by visual grading of the resulting erythema reactions 24 h after exposure to a series of increasing UV doses. Visual erythema assessment is, however, subjective and depends on pigmentation and redness of the adjacent un-irradiated skin and can be aided by skin reflectance spectroscopy and laser Doppler blood flow measurements. Erythema is accompanied by a raised skin temperature, and this reaction might be utilised as a simple objective measurement of UV sensitivity. METHODS: Sixteen patients with cutaneous malignant melanoma, 16 patients with basal cell carcinoma, and 36 healthy people were phototested with simulated sunlight on previously UV un-exposed buttock skin. The resulting erythema reactions were graded visually 20-24 h post-exposure and measured by skin reflectance spectroscopy and laser Doppler flowmetry, and the surface skin temperature was determined in the erythema reactions and in adjacent un-irradiated skin by a contact thermometer. RESULTS: Skin surface temperature in UV-induced erythema reactions was dose dependent, was statistically identical in skin cancer patients and in healthy people, and was age independent. The average temperature increase in barely perceptible erythema was 0.7°C (SD=1.1°C), and in bright red erythema it was 3.5°C (SD=2.0°C). Skin surface temperature increases were correlated to measurements by skin reflectance spectroscopy and by laser Doppler flowmetry. CONCLUSIONS: Skin surface temperature changes can be used as a simple objective measurement of UV sensitivity in healthy people and in skin cancer patients and may be particularly useful in heavily pigmented people where visual assessment of erythema is difficult or impossible.

Epidermal thickness measured by light microscopy: a methodological study.

BACKGROUND/AIMS: Epidermal thickness is frequently measured by light microscopy. The preservation and staining methods may alter the proportions of the specimens and thereby influence the measurements. The aim of the present study was to describe: 1) a standardized light microscopic method to quantify the thicknesses of the stratum corneum and the cellular epidermal layers, 2) the variations according to preparation and staining techniques, and 3) the observer variability. METHODS: One hundred and sixty skin biopsies from 67 human volunteers were included. The cellular epidermis and the stratum corneum were estimated in sections preserved by freezing and subsequent preparation with cryostat or formalin-paraffin techniques. The slides were stained with haematoxylin-eosin or er-ythrocin, and thicknesses of the stratum corneum and the cellular epidermis were measured by a calibrated ruler and an ocular grid, respectively. RESULTS: The formalin fixation gave slightly higher values for the cellular epidermis than the cryostat technique. In comparison to erythrocin staining, haematoxylin-eosin gave a significantly thinner stratum corneum. No significant inter- or intra-observer variation was found for the thickness of the stratum corneum assessed twice by two experienced observers. However, the two observers differed slightly from each other on the thickness of the cellular epidermis. CONCLUSION: It is found that thickness measurements of the stratum corneum and the cellular epidermis are reliably performed on cryostatic cut sections stained with haematoxylin-eosin.

Urocanic acid isomers: relation to body site, pigmentation, stratum corneum thickness and photosensitivity.

Urocanic acid (UCA), present in the stratum corneum as trans-UCA, absorbs ultraviolet (UV) radiation and isomerizes to cis-UCA. Cis-UCA has been demonstrated to initiate suppression of selected immune responses in several experimental systems. Topical application of UCA-containing products reduces UV-induced erythema, but a role for endogenous UCA in photoprotection has not been reported. In this study the relationship between UCA isomers, pigmentation, minimal erythema dose (MED), and stratum corneum thickness was investigated. Pigmentation, concentration of total UCA, and the percentage present as the cis-isomer was measured in 36 healthy subjects, skin type I-IV, at six UV-exposed and nonexposed body sites: forehead, chest, back, outer upper arm, inner upper arm, and buttock. The MED was determined by phototesting on buttock skin, and a punch biopsy for measurement of stratum corneum thickness was taken adjacent to the site of the phototest. The percentage of cis-UCA was significantly higher in UV-exposed than on nonexposed areas. A small intraindividual variation in total UCA was found, being high on the buttock and the arm, lowest on the forehead. The subject to subject variation of total UCA was considerable at all body sites. No correlation was found between total UCA and MED, skin type, pigmentation, or stratum corneum thickness.

Epidermal thickness, skin pigmentation and constitutive photosensitivity.

The important factors for UV sensitivity in humans are considered to be the skin pigmentation and the epidermal thickness. In this study on 73 Caucasians (age 20-85 years), we investigated in UV unexposed buttock skin the relationship between the UV sensitivity and constitutive skin pigmentation and thickness of the stratum corneum and the cellular part of the epidermis, in 34 normal people and in 39 skin cancer patients (20) patients with cutaneous malignant melanoma and 19 patients with basal cell carcinoma of the skin). Skin pigmentation was measured by skin reflectance spectroscopy, and UV sensitivity by phototest with a solar simulator. Thicknesses of the stratum corneum and the cellular part of the epidermis were determined by light microscopic evaluation of skin biopsies from the phototest areas. We found that epidermal thickness was independent of skin type and was not correlated to constitutive skin pigmentation. Thickness of the stratum corneum was statistically not different in normal persons and in skin cancer patients (P = 0.41) and was independent of gender (P = 0.61) and age (P = 0.56), while thickness of the cellular epidermis decreased with age (P < 0.01). Stratum corneum thickness was found to be of minor importance for the constitutive UV sensitivity (accounting for on average 11% of the total photoprotection), which was mainly determined by the constitutive skin pigmentation (goodness-of-fit for correlation r = 0.83). A theoretical model for the relationship of UV dose to induction of clinical erythema grade and skin pigmentation and thickness of the stratum corneum was developed. Objective measurements of skin pigmentation in UV unexposed skin by skin reflectance spectroscopy in Caucasians, normal people and people with cutaneous malignant melanoma and basal cell carcinoma of the skin predicts the constitutive UV sensitivity with a high degree of precision.

Seasonal variation in urocanic acid isomers in human skin.

Urocanic acid (UCA) is a major chromophore for UV in the skin and has been suggested to act as an initiator of UV-induced immunosuppression. It converts from the naturally occurring trans-isomer to the cis-isomer on UV exposure. Isomerization is dose dependent until the photostationary state is reached, and the seasonal variation in irradiance from the sun may lead to changes in the percentage of UCA present as cis-UCA throughout the year. Thirty young healthy subjects, skin types I-IV, were followed from early summer till spring. At each of six visits (June, July, August, October, December, March), pigmentation and the concentration of UCA isomers were measured at six body sites: forehead, upper chest, upper back, outer upper arm, inner upper arm and buttock. In exposed as well as unexposed regions a variation in pigmentation was found, peak values being recorded in August. Total UCA concentration was lower in July and August than in the rest of the year, irrespective of body site. In July, the percentage of cis-UCA was close to the maximal obtainable (50-60%) at all sites except the buttock. In the three winter months the percentage of cis-UCA was below 7% in all regions except for the forehead, where the mean cis-UCA was 18% in October and March. No consistent relationship was found between UCA isomers and pigmentation or skin type.

UV induced erythema evaluated 24 h post-exposure by skin reflectance and laser Doppler flowmetry is identical in healthy persons and patients with cutaneous malignant melanoma and basal cell cancer.

Twenty-one patients with invasive cutaneous malignant melanoma and 19 patients with basal cell skin cancer and 29 healthy volunteers were phototested on non-UV exposed buttock skin to examine their 24 h reaction to a series of increasing doses of simulated sunlight with 25% dose increments. Skin pigmentation at the phototest sites was determined by skin reflectance before testing to assure an equal level of constitutive skin pigmentation in the 3 groups. Erythema reactions were scored visually 24 hours post-exposure and objective measurements of erythema were performed by skin reflectance and laser Doppler flowmetry. In adjacent non-irradiated skin the redness was also quantified to determine the increase in redness in irradiated skin compared to non-irradiated skin. Constitutional skin pigmentation correlated well to UV sensitivity (r = 0.75) and skin redness measured by skin reflectance technique correlated to laser Doppler flowmetry (r = 0.86). No significant differences in UV doses to barely perceptible erythema or to the higher erythema grades were found between the two skin tumour groups and the control group, and no significant differences were found in skin reflectance measured redness or in laser Doppler flowmetry of any erythema reactions between the 3 groups. The 24 h erythema reaction to sunlight can therefore not be used to distinguish patients with invasive cutaneous malignant melanoma or basal cell carcinoma from normal persons.

Water protective effect of barrier creams and moisturizing creams: a new in vivo test method.

Frequent exposure to water is an important risk factor for the development of irritant hand eczema. Evaluation of cream efficacy in protecting against water is difficult. A new non-irritant, non-invasive method is introduced, based on evaluation of colour intensities when an aqueous solution of crystal violet is applied to the skin, after pretreatment with different creams. By skin reflectance measurement, differences in colour intensity were objectified. Measurements of transepidermal water loss were also performed, 2 barrier creams and a moisturizer were tested on the dorsal and volar aspects of the hands. One barrier cream contained silicone, the other solid particles. The moisturizer had a high content of lipid. In one experiment, the immediate effect of the creams in protecting against water was evaluated. In a second experiment, the water resistancy of the creams was tested, using a standardized water immersion procedure (4 x 20 min). The barrier cream with particles gave the best immediate protection (dorsal 76%, volar 69%). The moisturizer was intermediately protective (dorsal 57%, volar 34%), while very little protection was found for the silicone-containing cream (dorsal 16%, volar 10%). The water immersion procedure resulted in only minor changes in protection for each cream. When comparing transepidermal water loss in the treated areas with pretreatment values, a reduction was recorded only for the particle-containing barrier cream. The colour method described may be used as a quick and easy test of the protective effect of creams against water.

Skin temperature and phototest evaluation.

The degree of erythema following UV irradiation is known to depend upon skin temperature at the time of UV exposure. We investigated whether changes in skin temperature at the time of erythema assessment influenced the level of erythema. Twenty-two healthy people (mean age 26 years) were irradiated with solar stimulated radiation on previously UV un-exposed buttock skin. The erythematous reactions were evaluated 20-24 h after irradiation by visual scoring and by measurements of skin reflectance and laser Doppler flowmetry. The readings were done at the baseline level at 21 degrees C room temperature where skin temperature was 30.0 +/- 1.7 degrees C and subsequently after skin warming to 37.2 +/- 2.5 degrees C and after cooling to 22.8 +/- 2.6 degrees C. After skin warming, a clinically evaluated erythema grade [0, (+), +, ++, + + +] was scored higher for at least one reaction in 10 of 22 individuals (45%). In the same proportion of subjects, changes to lower erythema grades were detected upon cooling. Skin warming caused an increase in laser Doppler blood flux, but skin cooling did not have a significant effect on cutaneous perfusion. Skin redness measured by skin reflectance was relatively stable during the cooling phase, but a significant increase in skin redness was noted for 0 reaction upon skin warming. For ++ and + + + reactions a small but significance decrease in reflectance was noted. Our results indicate that alterations in skin temperature, especially a temperature increase, modulates the degree of UV-induced erythema moderately. The temperature-dependent changes as an assessment of the (+) reaction are of practical significance, since this reaction is used for the assessment of cutaneous photosensitivity.

The sunscreening effect of urocanic acid.

Urocanic acid (UCA), present in the stratum corneum, is a major absorber of ultraviolet (UV) radiation and, on UV exposure, is induced to isomerize from the naturally occurring trans-isomer to the cis-isomer. Cis-UCA has been shown to have immunosuppressive properties, while trans-UCA may act as a natural sunscreen due to its UV-absorbing properties. The photoprotective capacity of UCA was investigated in this study. Minimal erythema dose (MED) was determined on normal buttock skin in 36 healthy subjects and the concentration of UCA isomers was measured on the skin adjacent to the test site. On the contralateral buttock. MED was determined 20 min after application of trans-UCA 5% in a cream base. The UCA cream gave a sun protection factor of 1.58. The amount of UCA applied was, however, 20-200 times higher than the amount of UCA found in normal skin, making a sunscreening effect of naturally occurring UCA very low. This was further supported, by a lack of correlation between naturally occurring UCA and the UV sensitivity of each subject determined by the MED.

Mast cells and elastosis in ultraviolet-irradiated hairless mice.

Earlier studies of ultraviolet (UV) irradiated hairless mice have suggested a relation between elastosis and mast cells. To examine whether such a relation exists, we examined groups of hairless mice irradiated with equal doses of UV. The narrow UV bands had peaks at 292, 300, 307, 317 and 336 nm. The groups were irradiated 5 times per week during 1 year. It was shown that the shorter the wavelengths, the more pronounced was the degree of elastosis. Sections from dorsal skin were prepared for light microscopy and stained with orcein, making it possible to detect the elastosis at the same time as the mast cells. We used a projection microscope and a computer analyzing system connected to a video scanner for the calculations. The mast cell count was higher in the irradiated groups than in the control group. The number of mast cells was higher in the groups irradiated with the shortest wavelengths (292 and 300 nm). In groups irradiated with wavelengths shorter than 307 nm a subepidermal clearance zone containing significantly fewer mast cells than the rest of the upper dermal layer was found. We suggest that the mast cells might have a digesting function, as this layer was cleared of elastotic fibers and few mast cells were seen here.

Rat bites.

Rat bites are rarely reported. In this case report, an eighty-three-year-old woman was hospitalized with multiple lesions from rat bites. Implications of rat bites are reviewed briefly.

Skin barrier function and dermal inflammation. An experimental study of transepidermal water loss after dermal tuberculin injection compared with SLS patch testing.

The reaction of the skin water barrier to dermal inflammation was studied in 15 healthy volunteers. Dermal inflammation was induced either by injection of tuberculin (Mantoux test) or by a 24-h sodium lauryl sulphate (SLS) patch test on the volar forearm. Measurement of transepidermal water loss (TEWL) was used for evaluation of the skin barrier function. Inflammation was quantified by assessment of blood flow by laser-Doppler flowmetry. Measurement from uninvolved skin in the test region > 7 cm distant from the test sites served as control. Measurements were performed twice, separated by an interval of 6 days. Throughout the study, TEWL values were higher in the SLS test sites than in the Mantoux reactions, although the blood flow was significantly increased in Mantoux reactions compared with SLS test sites. This indicates that the impaired skin barrier function caused by SLS is due to a direct cytotoxic effect, and cannot be explained by the inflammatory response alone. At control sites, blood flow and TEWL were significantly higher on the arm with the Mantoux test than the arm with the SLS patch test. The significant inflammation caused by the Mantoux reaction may cause functional alterations in the clinically normal skin > 7 cm distant from the test area.

[Effect of a safe-sex campaign on women attending a clinic of venereology. Sex behavior and prevalence of sexually transmitted diseases in women examined at the Venereaklinik in Copenhagen in 1984 and 1988]. / "Sikker sex"-kampagnens virkning blandt kvinder på en venereaklinik. Seksuel adfoerd og proevalens af seksuelt overførte sygdomme hos kvinder undersøgt på Københavns Venereaklinik i 1984 og 1988.

Consecutive female patients attending the Copenhagen Venereal Disease Clinic were interviewed about sexual behaviour in 1984 (981 women) and in 1988 (684 women). Details of symptoms, age at coitarche, number of sexual partners, contraceptive methods, and obstetric history were recorded together with the results of the venereological examination. A substantially higher proportion of women used condoms in 1988 (51%) than in 1984 (11%), but otherwise the safe sex campaigns had had a limited effect on the sexual behaviour in this group of women until 1988. The prevalence of gonorrhea decreased significantly (from 22% to 6%, p < 0.01), whereas an increase in the prevalence of genital warts was observed (from 4% to 10%, p < 0.01).

Skin reactivity to metallic cobalt in patients with a positive patch test to cobalt chloride.

458 consecutive patients were patch tested with a metallic cobalt disc as a supplement to the standard series. 23 patients had a positive reaction to CoCl2 1% pet. Of these, 19 were tested with the cobalt disc. 11 had a positive reaction and 5 a questionable reaction. There were no positive reactions to the cobalt disc in patients with a negative patch test to CoCl2 1% pet. Patch testing with CoCl2 1% pet. diagnoses all patients with allergy to metallic cobalt, but the test method is limited by a high number of irritant and questionable reactions.