The current options in the management of actinic keratosis.

Actinic keratosis is a precursor for squamous cell skin cancer. Hence, it is important to treat. For single actinic keratoses, cryo surgery is recommended. For widespread actinic keratoses, imiquimod, photodynamic therapy (PDT) or 5-FU may be used. ''One-shot'' treatments are advocated as prolonged treatment over several weeks probably diminishes patient compliance. Consequently, cryo surgery for single actinic keratoses and PDT for widespread actinic keratoses should primarily be recommended.

Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell carcinomas: a perfusion study using microdialysis in vivo.

BACKGROUND: Photodynamic therapy is becoming a popular treatment for superficial nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic results. Nevertheless, the reported cure rates vary and the transdermal penetration of drugs has been discussed as a limiting factor, particularly for treatment of nodular basal cell carcinoma (BCC). OBJECTIVES: To investigate the transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were compared and the effect of curettage was studied. METHODS: Twenty patients with 27 histologically verified BCCs (13 superficial, 14 nodular) were included. All lesions were located at the front of the body (head and face excluded). The first 10 patients included were treated with MAL (13 BCCs), and the following 10 patients with ALA (14 BCCs). A light curettage was performed on every second lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates were collected at 15-30-min intervals for 4 h and the interstitial concentrations of MAL and ALA were determined using high-performance liquid chromatography. RESULTS: No significant difference in interstitial drug concentration was observed between lesions treated with ALA or MAL during the 4-h measurement period. However, for the lesions with deeper catheter locations, i.e. at or below 1 mm (n = 11), drug concentrations above the detection limit were obtained in only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not found to be correlated with the depth of the catheters. No difference was found when comparing superficial and nodular BCCs, and the effect of curettage was found to be negligible. CONCLUSIONS: The results imply that there is no significant difference in transdermal penetration of ALA and MAL in tumour tissue. Detectable levels of drug were not obtained in almost 50% of the lesions where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to affect the interstitial concentration, indicating that penetration of drug indeed might be a problem when treating BCCs thicker than 1 mm.

Changes in ultraviolet absorption of sunscreens after ultraviolet irradiation.

The incidence of skin cancer is increasing rapidly and sunscreens have been recommended in order to reduce damage from sunlight. In this investigation we have studied the change in the absorption spectrum of some photoactive organic species in sunscreens after ultraviolet A and ultraviolet B irradiation in a dose normally encountered during a full day in the sun. Samples of a number of photoactive compounds commonly used in sunscreens were irradiated with ultraviolet A and ultraviolet B light. A UVASUN 2000 MUTZHAS sunlamp was used for ultraviolet A irradiation and an Esshå Corona mini, equipped with two Philips TL12 20 W lamps, was used as the ultraviolet B source. The ultraviolet A dose was 100 J per cm2. The ultraviolet B dose corresponded to 20 minimal erythema doses. The absorption spectra of the compounds were recorded before and after irradiation. The absorbance of 2-ethylhexyl 4-methoxycinnamate was reduced significantly, whereas 3-(4-methylbenzyliden)camphor seemed to be rather stable. The benzophenones studied seemed to be relatively stable. In the case of 4-tert. butyl-4'-methoxy-dibenzoylmethane there was a rapid decrease in the ultraviolet A absorption leading to unsatisfactory protection in the ultraviolet A region. 4-Isopropyl-dibenzoylmethane also lost most of its ultraviolet protective capacity after irradiation with ultraviolet A. Ultraviolet B seemed to have a minor effect on all the samples. It is important for the clinician not only to know the initial absorption spectrum in the ultraviolet region for a specific sunscreen substance, but also whether it is altered during irradiation and in what way. This study including gas chromatography and mass spectrometry analysis indicates that some of the photoactive organic species commonly used today in sunscreens are unstable following ultraviolet irradiation.

Premalignant and malignant skin lesions in renal transplant patients.

Among 129 renal transplant patients with 3-16 years of posttransplant observation time, and residents in a low ultraviolet radiation area, 25 (19.4%) had premalignant or malignant skin lesions, a 3-fold increase over a control population collected randomly. Thirteen (10.1%) had skin cancer, a 7-fold increase. Nine patients had multiple lesions; none had metastatic disease. Multiple regression analysis revealed age, outdoor occupation, and transplantation/immunosuppression to be equally significant risk factors for skin malignancy. Transplant patients should be educated and periodically examined for early detection of skin malignancies.

Sunscreen application and its importance for the sun protection factor.

To achieve a good sun protection, a layer thickness of 2 mg/sq cm is often recommended. Fifty individuals were asked to apply five different sunscreens ad libitum. Ten percent dihydroxyacetone was added to the sunscreens in order to make them fluoresce when irradiated with Wood's light. The layer thickness was calculated by dividing the amount applied by the area. The thicknesses of the sunscreen layers varied little between different parts of the body and different brands; in general it was close to 1 mg/sq cm. The corresponding protection factor was measured for two sunscreens on 20 persons. The results indicate that the sun protection factor under ad libitum conditions is only 50% of what would be achieved using a layer thickness of 2 mg/sq cm.

Comparison of the carcinogenic potential of trioxsalen bath PUVA and oral methoxsalen PUVA. A preliminary report.

BACKGROUND AND DESIGN: There is an increasing concern about the long-term carcinogenic effect of oral psoralen with long-wave UV radiation in the A range (PUVA). Most follow-up investigations indicate a definite risk of squamous cell carcinoma of the skin with long-term PUVA treatment. In a recently published study of 4799 Swedish patients who had received PUVA, it was noted that 833 patients who had received trioxsalen bath or oral trioxsalen did not show any increased risk of skin cancer in contrast to oral methoxsalen. This finding has been further investigated in this study. We compared four dermatologic university clinics in Sweden with regard to the carcinogenic potential of the PUVA regimen used. One clinic used trioxsalen bath PUVA exclusively and the other three used oral methoxsalen. Information on their PUVA-treated patients was collected and linked with information from the Swedish Cancer Registry to identify individuals with squamous cell carcinoma of the skin. RESULTS: A total of 18 squamous cell carcinomas of the skin were reported in 2975 PUVA-treated patients until 1987. The expected number was 3.1. The center using bath PUVA only had no increased risk of squamous cell carcinoma of the skin in contrast to the three centers using oral methoxsalen-PUVA. The increased risk for male subjects from those centers varied from six to 13 times that in the general population, but for female subjects a significant increased relative risk was found only at one center. CONCLUSION: In this preliminary report, PUVA treatment with trioxsalen bath seems to be less carcinogenic than the oral dosage. However, differences in the patient populations might also have affected the outcome of the study. More information on this field is needed.

Basal cell carcinoma of the eyelids and solar ultraviolet radiation exposure.

AIMS: To compare the distribution of eyelid basal cell carcinoma (BCC) with the relative ultraviolet radiation (UVR) exposure to different sites on the eyelids. METHODS: The location of BCC on the eyelids was allocated to one of seven regions. The UVR exposure was recorded with a polymer film attached to the eyelids at seven sites in a manikin and in human subjects. RESULTS: Localisation of the 329 tumours was mainly on the lower eyelids (225 tumours), and the medial canthal regions (87 tumours). There was no association between UVR doses at the seven sites of the eyelids and the location of BCCs. The UVR exposure was similar on the upper and lower eyelids, while the number of tumours on the lower eyelids outnumbered the upper lids by a factor of 13 (17 upper, 225 lower) CONCLUSION: UVR exposure only partially explains the aetiology of periorbital BCC.

Phototoxicity of skin microorganisms tested with a new model.

A new standardized method for testing phototoxicity of chemicals against microorganisms is described. The inoculum size of the microorganism, application of test chemicals, prediffusion time, incubation time and incubation period are defined. Staphylococcus aureus, S. epidermidis, Candida albicans, and Pityrosporum orbiculare were studied. Both 8-methoxypsoralen and trimethylpsoralen were phototoxic against all microorganisms tested, while tetracycline and doxycycline were not phototoxic. C. albicans may be chosen for phototoxicity testing because it has been used earlier, it is easy to maintain in culture, it grows easily when tested, and its pathogenicity is low. The phototoxicity of S. aureus, S. epidermidis, Pseudomonas aeruginosa, Propionibacterium acnes, C. albicans, and P. orbiculare against each other were also investigated. Only P. orbiculare was inhibitory. It inhibited the growth of S. aureus, S. epidermidis, and Ps. aeruginosa - both in the dark and after irradiation. The growth inhibition was markedly enhanced after UVA irradiation, indicating phototoxicity. The phototoxic effect of P. orbiculare may play a role in the ecology of the human skin flora.

Treatment of superficial basal cell carcinomas using topically applied delta-aminolaevulinic acid and a filtered xenon lamp.

OBJECTIVE: To evaluate the treatment of superficial basal cell carcinomas (SBCC) using photodynamic therapy with topically applied delta-aminolaevulinic acid (ALA) and a filtered short arc xenon lamp as a light source. METHOD: An oil-in-water emulsion containing 20% ALA was applied topically to the lesion sites which were then occluded for 3 h. Irradiation was performed in a single session of 10 min using 125 or 166 mW/cm2 in the wavelength range (620-670 nm, giving a radiation dose of 75 or 100 J/cm2, respectively. Urine samples obtained in connection with the treatment were examined for traces of porphobilinogen and porphyrin. The therapy outcome was determined by histological examination of punch biopsies or by clinical verification. A follow-up scheduled for 5 years was initiated. PATIENTS: A group of 37 patients with histologically verified SBCCs were included. A total of 190 SBCCs were treated. Also included were six patients with 10 nodular basal cell carcinomas and five patients with 18 Mb. Bowen. The urine samples from three patients showed traces of porphyrins. RESULTS: Of the 157 SBCCs followed-up for 6 months, 144 were cleared giving a clearance rate of 92%. Of the nodular basal cell carcinomas and Mb. Bowens, 2 of ten and 11 of 18 were cleared, respectively. CONCLUSION: Photodynamic therapy is well suited to the treatment of SBCCs giving good cosmetic results regardless of lesion size. The filtered xenon lamp proved to be particularly suitable for photodynamic therapy.

Treatment of chronic urticaria with PUVA or UVA plus placebo: a double-blind study.

Chronic urticaria is a disease for which the available range of treatment modalities is limited. Ultraviolet radiation has recently been shown to affect histamine release from mast cells. We therefore studied the effects of PUVA and UVA on chronic urticaria. Nineteen patients took part in the study, which was designed as a randomized double-blind study. Eleven patients received PUVA, and 8 received UVA plus a placebo. In the PUVA group, 7 patients showed improvement, 3 noticed no change, and 1 became worse. In the group that received UVA plus placebo, 5 patients experienced an improvement, whereas the other 3 showed no change. The differences between the groups were not statistically significant. However, the probability of achieving this degree of improvement in both groups just by chance is less than 1%. Consequently, the improvement noted could have been due to either UVA alone or a placebo effect. It is concluded that PUVA is not better than UVA in the treatment of chronic urticaria.

Problem sites: scalp, palm and sole, and nail.

The scalp, palms and soles, and nails are problem sites in the everyday therapy of psoriasis. This article reviews the pathogenesis, differential diagnosis, and latest treatment.

No difference in skin cancer incidence with or without cyclosporine--a 5-year perspective.

In the short perspective of 5 years, there was no difference in the incidence of malignant and premalignant skin lesions among patients with Aza- vs CyA-based immunosuppressive protocols, or when these drugs were combined. However, the risk of acquiring skin cancer increases with the length of immunosuppressive therapy. Another 5 to 10 years of experience with CyA will be needed to decide on any change in the established pattern of posttransplant skin complications.

Phototherapy of psoriasis - clinical aspects and risk evaluation.

The study gives information on the healing frequency and time to relapse in a day care centre for UVB, UVB plus dithranol, and PUVA treatment. Psoriasis treatment must be repeated for many years and a psoriasis patient must come to terms with the fact that during a substantial part of the rest of his life, he must use some type of treatment. This makes it important that the treatment is pleasant and easy to carry out. The combination of sauna and UVB in a day care centre, or treatment with home solaria fulfill these demands. In view of this background I think that UVB treatment of psoriasis could be the treatment of choice for many psoriasis patients. About 80 percent of the patients heal with this treatment. For the rest of the patients, addition of dithranol or a switch to PUVA has proven to be effective. Median time to healing was about 8 weeks with UVB and UVB + dithranol whereas 12 weeks was necessary to achieve healing among PUVA patients with a poor response to UVB given earlier. The remission times were 9, 12 and 25 weeks for UVB, UVB + dithranol and PUVA-treatment respectively. In Gothenburg, we give 35.000 UVB treatments annually. An important question is the potential hazards connected with the therapy as we know that UV radiation is carcinogenic. According to our studies, the median amount of UVB radiation actually received per year from therapy is of the same magnitude as during outdoor work or certain outdoor activities. If UVB treatment is expanded we can expect an increased incidence of skin cancer of squamous cell type among this type of psoriasis patient even if the retrospective study we made showed no increased risk among people extensively treated with UVB in the past. The risk for psoriasis patients on a life long UVB treatment will probably be of the same order of magnitude as for outdoor workers. In comparison with other every day risks, the risk of dying from a skin cancer seems to be negligible. Regular check-ups by a dermatologist can reduce this risk close to zero.

Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation.

BACKGROUND: Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and can be found in the urine. The amount varies between 0.4% and 2%. This seems to be the main metabolic pathway in rats. OBJECTIVES: To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted. METHODS: Twenty-five volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm(-2), and UVB between 0.46 and 2.0 J cm(-2). BZ-3 in urine was analysed with a high-performance liquid chromatography method. RESULTS: The volunteers excreted 1.2-8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P < 0.99, t-test). CONCLUSIONS: We show that a large amount of BZ-3 is absorbed. BZ-3 is accumulated in the body as the volunteers excreted BZ-3 5 days after the last application.