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Background: The suspected link between human papillomavirus (HPV) and the development of premalignant and malignant skin lesions remains inadequately examined in clinical settings. This case series describes HPV vaccination as an off-label adjuvant therapy for actinic keratosis (AK)., Methods: Twelve immunocompetent AK patients underwent HPV vaccination at a private dermatology clinic in Naestved, Denmark. Prior to vaccination, all patients demonstrated a high AK burden that required regular control visits. At 0, 2, and 6 months, the patients received an intramuscular injection of a commercially available 9-valent HPV vaccine. Concurrently, patients continued conventional AK therapies at 3-month intervals. Clinical response, consisting of reduction in AK number and general change in skin appearance, was assessed by a dermatologist over 12 months following first vaccination., Results: All patients (mean age 76.2 years; 10 M and 2 F) completed the vaccine schedule. Overall, an average 85% reduction in total AK burden was recorded 12 months after beginning vaccination. Median AK burden thus fell from 56 (IQR: 44-80) to 13.5 (IQR: 1-18) lesions after 12 months. Lesion reduction was observable by the second inoculation at month 2 (34 AKs; IQR 22-80), continuing steadily until month 6 (15 AKs; IQR 5-30) and plateauing between 6 and 12 months. Clinically, HPV vaccination elicited fading of lesions' erythematous background after the first dose, often followed by sloughing of hyperkeratotic elements in subsequent weeks. Patients reported no adverse effects related to HPV vaccination., Conclusion: This case series introduces the possibility that 9-valent HPV vaccination in combination with conventional treatments may be used as a therapeutic strategy for AK., Competing Interests: E. Wenande, N.B. Thomsen, K. Togsverd-Bo, and M. Haedersdal have no conflicts of interest to declare. The authors have no relevant financial activities outside the submitted work or during the 3 years prior to submission. All authors have no financial or nonfinancial (political/personal) interests, relationships, or affiliations relevant to the subject of the manuscript. Specifically, the commercial manufacturer of the 9-valent HPV vaccine has neither been informed nor financially involved in the planning, conduction, or reporting of this case series. The authors have no relevant conflicts of interest in regard to employment, stock, royalties, or consultant arrangements with any HPV vaccine manufacturer. The manuscript's contents have not previously been presented elsewhere., (Copyright © 2021 by S. Karger AG, Basel.)

Objective: To investigate the clinical performance and safety of a new silver-containing wound-contact layer, Physiotulle -Ag (Coloplast), in the treatment of chronic venous leg ulcers with delayed healing and signs of critical colonisation., Method: This was an open prospective non-comparative multicentre clinical study. Patients were treated for four weeks with Physiotulle -Ag, which was covered by Alione Hydrocapillary Dressing (Coloplast)., Results: Thirty patients were recruited into the study. One ulcer healed after three weeks of treatment. The mean relative ulcer area reduced by 55% after four weeks. Over the study period the mean amount of healthy granulation tissue increased from 26% to 62%, and the mean amount of fibrin decreased from 63% to 32%. The ratio of malodorous wounds was 50% at inclusion, 20% after one week and 3% after four weeks. The dressing was considered easy or very easy to apply in 100% and easy to remove in 89% of dressing evaluations. The dressing combination showed good exudate-management properties. Incidence and severity of maceration, erythema and eczema decreased during the study and no device-related adverse events were recorded., Conclusion: Physiotulle -Ag is safe and easy to use in chronic venous leg ulcers in which healing is delayed and with signs of critical colonisation.

The study compared the effect of a sustained silver-release foam dressing (Contreet Foam) with a foam dressing (Allevyn Hydrocellular) without added silver in critically colonised venous leg ulcers with delayed healing. The study was a multicentre, open, randomised, controlled study lasting for 4 weeks. Ulcer area and healing were assessed weekly. Odour, maceration, absorption capacity and leakage were evaluated at dressing changes. All adverse events were recorded. One hundred and twenty-nine patients were included (Contreet Foam: 65, Allevyn Hydrocellular: 64). The two groups were comparable in all respects. After 4 weeks, there was a significantly greater reduction in ulcer area in the Contreet Foam group (45%) than in the Allevyn Hydrocellular group (25%). After 1 and 4 weeks, odour was present in significantly less of the ulcers in the Contreet Foam group (17% and 19%, respectively) compared with the Allevyn Hydrocellular group (47% and 39%, respectively) and at the final visit there were significantly fewer leakages in the Contreet Foam group (19%) compared with the Allevyn Hydrocellular group (49%). Also, less maceration was observed after 1 and 4 weeks in the Contreet Foam group (34% and 37%, respectively) compared with the Allevyn Hydrocellular group (55% and 48%, respectively). The occurrence and cause of adverse events were equally distributed between the study groups. The present study provides evidence of the superior performance of the silver-releasing dressing, Contreet Foam, compared with a traditional moist foam wound healing dressing in the treatment of critically colonised, chronic venous leg ulcers. The results of this randomised, controlled study suggest an important role of sustained silver-releasing dressings in the treatment of critically colonised chronic wounds.

In a randomized, open, left-right comparison study, 20 patients with atopic dermatitis were treated with UVB. One side of the body received UVB in a conventional regimen with fixed dosage increments, the other side was given UVB dosages according to skin reflectance measurements of skin pigmentation and erythema. Clinical outcome was assessed by SCORAD. The initial, final and cumulative UVB dosages, time to 50% reduction in SCORAD, and side effects were compared. The initial UVB dosage was somewhat higher in the skin reflectance-guided treatment than in the conventional UVB regimen, although not significantly. There was no difference in the reduction of SCORAD comparing the two treatment options; however, the final UVB dosage and the cumulative UVB dosages were significantly lower in the optimized regimen. This new technique offers the same therapeutic advantage and security as a dose regimen guided by minimal erythema dose testing. However, measurement of skin pigmentation by skin reflectance is a rapid method, which can easily be operated by nurses.

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.

The pulsed dye laser is the treatment of choice for port-wine stains. In this study we evaluate the importance of preoperative skin pigmentation and skin redness for the development of side effects from one treatment with the pulsed dye laser. A risk assessment is performed and skin reflectance measurement objectifies postoperative pigmentary changes. Fourteen human volunteers (skin types I to V) were laser-treated on the inside of the proximal brachium. Photographic documentation was used for blinded, clinical evaluation of side effects 3 and 6 months postoperatively. Skin was artificially reddened using topical application of 10% nicotinic acid cream. The development of pigmentary alterations and texture changes depended on the preoperative pigmentation and redness degrees. The risk of inducing clinically visible pigmentary alterations and texture changes increased with higher preoperative skin pigmentation and redness degrees, and with the application of increasing laser doses. Pigmentary alterations were induced at a lower fluence level than texture changes. The risk of side effects was higher 3 months postoperatively than 6 months postoperatively, substantiating a gradual disappearance of side effects. Skin reflectance measurements documented postoperative hyperpigmentation that faded partially from 3 to 6 months postoperatively. This is the first human experimental model for port-wine stains which provides quantitative data on the relationship between preoperative skin colours and postoperative clinically disturbing side effects.

Laser therapy is today considered the treatment of choice for vascular skin lesions, which commonly are located on the face and, therefore, frequently are exposed to sunlight. The purpose of this study was to examine whether preoperative and postoperative ultraviolet irradiation influences the development of laser-induced side effects. We laser-treated hairless mice with a copper vapor laser; three different intensities were used at a constant pulse duration. Simulated solar ultraviolet radiation was administered either before the laser treatment (3 consecutive days, daily doses of 2.48 J/cm2) or after the laser treatment (four times weekly in 4 weeks, daily doses of 1.66 J/cm2). Laser-induced wounds, scars, and hyperpigmentation were evaluated by macroscopic, histologic, and biochemical examinations. Preoperative ultraviolet exposure enlarged the laser-induced wounds and the areas with texture change at some of the laser intensities used. However, the most pronounced effect was seen for postoperative ultraviolet-irradiated mice. These mice developed, at some of the laser intensities, a higher incidence of bulging infiltration as well as higher degrees of fibrosis and hyperpigmentation, thus developing a poor cosmetic appearance. Furthermore, ultraviolet irradiation after laser treatment resulted in slowly healing wounds of reduced size, indicating deep, constricted skin damage. We conclude that ultraviolet exposure before and after copper vapor laser treatment increases the risk of inducing side effects from dermatological laser treatment.

Background and Objective: To clarify whether epidermal thickness is of importance to the purpuric reaction from treatment with the pulsed dye laser (PDL)., Study Design/materials and Methods: Fifteen fairly pigmented volunteers were laser treated in two test regions of varying epidermal thicknesses: normal buttock skin and ultraviolet B (UVB)-exposed buttock skin. Laser treatments were performed with the flashlamp-pumped PDL (585 nm). Fluences ranged from 3-6.5 J/cm2, spot size was 7 mm, and each volunteer received at least six fluences in each treatment region. Assessment of the response was based on clinical evaluation (threshold dose to purpura 10 minutes and 1 day after treatment) and skin reflectance-evaluated redness (1 and 6 days, 2 and 6 weeks after treatment)., Results: The total epidermal thickness differed between the unexposed buttock skin (median, 72.7 microm) and the UVB-exposed buttock skin (87.2 microm) (P < 0.01). There was no correlation between the epidermal thickness and the threshold dose to induce purpura 10 minutes and 1 day after laser exposure. Skin reflectance revealed no correlation between the epidermal thickness and the skin reflectance evaluated redness on 1, 6 days, and 2 weeks postoperatively. A dose-response relation was seen within the two test regions; 6 weeks after laser exposure, there was no remaining laser-induced skin redness., Conclusion: The epidermal thickness is unimportant to the purpuric reaction after PDL treatment.

Photodynamic therapy (PDT) with topical application of delta-aminolevulinic acid (ALA) followed by irradiation with visible light (ALA-PDT) is a relatively new and promising experimental treatment of superficial premalignant and malignant skin neoplasms. The purpose of this study was to determine whether ALA-PDT can prevent photocarcinogenesis in hairless mice exposed to solar UV. A total of 140 mice was divided into seven groups of 20 mice each. Group 1: solar-UV exposure. Group 2: solar UV and a cream base+visible light once a week. Group 3: solar UV and ALA-PDT once a week. Group 4: solar UV and ALA-PDT once every second week. Group 5: solar UV and ALA-PDT every fourth week. Group 6: ALA-PDT once a week. Group 7: no treatment. The time to first and to second tumor > or = 1 mm was registered. Predefined endpoints, such as one tumor > or = 4 mm or an area of small confluent tumors on the back of the mice were criteria for withdrawal from the experiment. The time to first and to second tumor was significantly longer in the ALA-PDT-treated mice than in mice only exposed to solar UV and solar-UV/cream base-visible light (P < 0.005). However, we observed an increased death and accident rate in the ALA-PDT-treated groups compared to the groups not treated with ALA-PDT (chi-square test, P = 0.0250). Significantly more ALA-PDT-treated mice were withdrawn because of a tumor > or = 4 mm (P = 0.0005). The UV unexposed mice developed no tumors. Repetitive treatments with ALA-PDT delay photoinduced carcinogenesis in mice.

Background and Objective: The intention of the present study was to clarify whether UV-exposure prior to laser treatment of albino mouse skin may influence laser-induced side effects and if a possible influence may be explained by epidermal thickening., Study Design/materials and Methods: Albino, hairless mice were irradiated 0, 8, and 22 consecutive times with simulated solar UV (1.4 J/cm2 per treatment). Subsequently, two areas on the back of the mice (1.26 cm2 each) were treated with a copper vapor laser that was connected to a Hexascan. The beam diameter was 1 mm, pulse duration 200 msec, and intensities 0.6 W, 0.8 W, and 1.0 W. Laser-induced wounds, scars, and histologically evaluated fibrosis were evaluated., Results: We found that mice irradiated with UV before laser treatment developed smaller wounds, smaller texture change areas, and less fibrosis as compared with nonirradiated control groups, and significant, negative correlations were demonstrated between epidermal thicknesses (stratum corneum, the cellular part of epidermis, and the entire epidermis) and laser-induced skin reactions. A dose response was obtained between laser intensities and laser-induced skin reactions, which tended to be more severe in the cranial back location as compared with the caudal back location. Epidermal layers increased significantly after eight consecutive times of UV irradiation and increased to a steady level after 22 times of irradiation., Conclusion: We conclude that UV exposure prior to laser treatment of albino mice reduced laser-induced side-effects, which could be explained by increased epidermal thickening. Variations in epidermal thickness might thus contribute to variations in clinical response to dermatological laser treatment with the copper vapor laser.

Background and Design: A fundamental idea of laser treatment of tattoos is that the wavelength must be well absorbed by the tattoo color. In this study, absorption by different tattoo colors was therefore measured in vivo by skin reflectance to establish optimal laser wavelengths for different tattoo colors. Spectral reflectance by tattooed skin and by normal, uninvolved skin was measured in 10-nm steps in a wavelength range from 300 to 800 nm on eight human volunteers with a total of 13 tattoos, which consisted of 14 different tattoo colors. Wavelength ranges for maximal absorption were established., Results: We found that tattoos absorbed maximally in the following ranges: red tattoos, from 505 to 560 nm (green spectrum); green tattoos, from 630 to 730 nm (red spectrum); and a blue-green tattoo, in two ranges from 400 to 450 nm and from 505 to 560 nm (blue-purple and green spectrums, respectively). Yellow tattoos absorbed maximally from 450 to 510 nm (blue-green spectrum), purple tattoos-absorbed maximally from 550 to 640 nm (green-yellow-orange-red spectrum), blue tattoos absorbed maximally from 620 to 730 nm (red spectrum), and orange tattoos absorbed maximally from 500 to 525 nm (green spectrum). Black and gray absorbed broadly in the visible spectrum, but these colors were most effective from 600 to 800 nm. Optimal and suboptimal laser wavelengths are proposed., Conclusions: We recommend that wavelength ranges should be established for maximal tattoo absorption before laser treatment of decorative tattoos to select the most optimal laser wavelength present.

A case of solar pruritus is reported. Severe pruritus of the back, shoulders and upper lateral aspects of the arms, without any eruption, developed in a 28-year-old outdoor worker during 4 to 6 weeks of intensive solar exposure. The pruritus was intense and described as a burning sensation deep in the skin. Only a few excoriations and slight xerosis were found. Solar pruritus or brachioradial pruritus is a condition primarily seen in Caucasian people living in the tropics or subtropics. Previously the disease has only been reported once outside these areas.

Khellin is used together with either UVA irradiation or sun exposure in the treatment of vitiligo. The purpose of this study was to investigate the carcinogenic effect of topically applied khellin together with UVA or solar simulated radiation (SSR) in lightly pigmented C3H/Tif mice. For comparison purposes a 0.1% 8-methoxypsoralen (8-MOP) cream was also tested in combination with SSR. Fifty microliters of a 5% khellin cream, a 0.1% 8-MOP cream, or a cream without active substances were spread uniformly on the back of the mice 30 minutes before UVA or SSR irradiation. All mice were irradiated 3 times a week until age or skin tumor development necessitated killing. Treatment with topical khellin and UVA irradiation was carcinogenic to lightly pigmented hairless mice, time to 50% of the mice had developed one tumor (t50) was 507 days. This indicates that the combination of topical khellin and UVA radiation, formerly expected to be rather innocuous, is carcinogenic to mice. Also the combination of khellin and SSR (t50 = 268 days) enhanced skin tumor development significantly compared with control cream and SSR (t50 = 330 days), P < 0.05. In addition, the combination of khellin and SSR was found to have the same carcinogenic effect as treatment with 0.1% 8-MOP and SSR (t50 = 262 days). This study shows that topically applied khellin increases the carcinogenic effect of both UVA and sunlight.

The carcinogenic and melanogenic effects of a filtered metal halide source (UVASUN) that emits UV radiation in a range from 340 to 400 nm and a bank of Philips TL 09R tubes (TL 09) emitting in a range from 310 to 400 nm were studied in lightly pigmented hairless hr/hr C3H/Tif mice. Both the carcinogenic effect of the two UVA radiation sources alone and in combination with a UV source, consisting of one Philips TL 12 and five Bellarium-S SA-1-12 tubes emitting radiation somewhat similar to the UV part of the solar spectrum (SOLAR UV), were investigated. Finally, the melanogenic effect of exposure to the two UVA sources were studied. The mice were exposed to the UVA sources 30 min/day 5 days/week, in equal erythemogenic doses, calculated by using the Commission Internationale de l'Eclairage human erythema action spectrum. Equal erythemogenic doses of TL 09 and UVASUN induced the same degree of skin pigmentation, but skin tumor development was enhanced in mice exposed to TL 09 compared with UVASUN (P < 0.0005). For all but one tumor, endpoint pretreatment with TL 09 or UVASUN for 91 days did not influence tumor development during subsequent exposure to SOLAR UV radiation 10 min/day, 4 days/week. Exposure to the two UVA radiation sources after 91 days of SOLAR UV exposure significantly enhanced skin tumor development. Overall, the data on the interaction between exposure to the UVA sources and SOLAR UV indicated that the risk of SOLAR UV-induced carcinogenesis was independent of the type of prior-UVA exposure and post-UVA exposure.

A new in vivo method of visual scoring of pigmentation in hairless hr/hr mice with a C3H/Tif background is described. The mice were placed under a bank of 6 Philips TL08 fluorescent ultraviolet A (UVA) tubes in a dark room, and the pigmentation of the skin was compared with a Kodak Gray Scale with 20 different shades from white to black. The radiation from the tubes changed both the color of the back of the mouse and the gray scale into purple hues. The purple color of the back of each mouse could then be classified as one of 20 shades on the gray scale. An experiment was conducted exposing 3 groups of 20 mice to different doses of UV radiation from Philips TL01 tubes. One group of 20 mice was not irradiated and served as control. The pigmentation of each mouse was scored by one investigator every 2-3 weeks. After a few weeks of exposure a clear distinction between the groups was seen. To evaluate the inter- and intrapersonal variation of the method, 30 mice with various degrees of pigmentation were scored independently and blindly by two investigators. This was done twice during the study with a few days' interval. No interpersonal difference was found, but one investigator scored differently the first and second time by only 0.5 points. The described method provides a reproducible in vivo method, with very good discrimination, for estimation of pigmentation in hairless mice.

The carcinogenic effect of 4 ultraviolet (UV) sources was studied in lightly pigmented hairless mice. Two narrow-band UV sources, Philips TL01 and Philips TL12 with a Tempax filter, and two broad-spectrum UV sources, Philips TL12 and Bellarium S, were used. Exposure doses were calculated from the CIE erythema action spectrum. Four groups of mice (n = 20) were exposed to a nonerythemogenic dose (low dose), and 4 groups were exposed to an erythemogenic dose (high dose) of each of the 4 UV sources. One group (control) was not irradiated. The mice in the 4 low-dose groups were all exposed to 0.6 basic minimal erythema doses (B-MED) 5 days/week, and all the mice in the high-dose groups to 1.2 B-MED 5 days/week. After 16 weeks of acclimatization, the doses were doubled. Bellarium S and Philips TL12 were equally carcinogenic in the low-dose regimen and the high-dose regimen. Mice exposed to Philips TL12 with a Tempax filter developed tumors significantly earlier compared with Bellarium and Philips TL12. Philips TL01 was more carcinogenic than any of the other UV sources. Equally erythemogenic doses calculated from the CIE erythema action spectrum seem to be more carcinogenic when derived from narrow-band UVB sources than from broad-band UV sources.

Background and Design: Twenty-eight subjects were phototested to determine their erythemal responses to oral methoxsalen with UV-A and UV-B irradiation. Skin pigmentation was measured by skin reflectance at 550 and 660 nm before irradiation. The smallest UV radiation dose to produce erythema (minimal phototoxic dose and minimal erythema dose, respectively) was determined. The serum concentration of methoxsalen was measured at the time of UV-A irradiation., Results: There was a positive correlation between skin pigmentation and both 72-hour minimal phototoxic dose and 24-hour minimal erythema dose. No correlation was demonstrated between methoxsalen serum concentration and minimal phototoxic dose. The combination of skin pigmentation and methoxsalen level did not give a better prediction of minimal phototoxic dose than skin pigmentation alone., Conclusions: Skin pigmentation measurements can be used to predict the minimal phototoxic and erythema doses. Skin pigmentation measurements are easy to perform and should be included in both phototherapy and photochemotherapy to improve the efficiency and reliability of the treatment.

The melanogenic potential of multiple suberythemogenic doses of 6 different ultraviolet (UV) sources was investigated. The UV sources emitted different amounts of UVA and UVB. The backs of 12 volunteers were exposed to the 6 UV sources 10 times during 4 weeks. Every volunteer was exposed to the same suberythemogenic dose (0.75 basic minimal erythema dose) of each of the UV sources. The changes in pigmentation and minimal erythema dose of the UV exposed test sites were registered during the 10 sessions. Three UVA sources with a low emission in the UVB area (0.2-3.1%) had a high melanogenic potential. Two UVB sources (UVB emission 74.3% and 94.5%) were unable to induce a significant increase in skin pigmentation. The 3 UVA sources with a low UVB output increased skin pigmentation significantly better than a UVA source with a UVB output of 6.9%. All 6 lamps were able to increase photoprotection significantly. The increase in photoprotection was not significantly different between any of the 6 UV sources. This study shows that, if humans are exposed to equally suberythemogenic doses of different types of UV radiation, then radiation obtained from UVA sources greatly enhances melanogenesis, whereas UVB radiation sources are unable to induce pigmentation.