Sunscreen use: controversies, challenges and regulatory aspects.

Mismatches between skin pigmentation and modern lifestyle continue to challenge our naked skin. One of our responses to these challenges is the development and use of sunscreens. The management of sunscreens has to balance their protective effect against erythema, photocarcinogenesis and photoageing owing to the potential toxicity of the ultraviolet (UV) filters for humans and the environment. The protection against UV radiation offered by sunscreens was recently standardized in the European Union (EU) based on international harmonization of measurement techniques. Four different categories of sun protection have been implemented along with recommendations on how to use sunscreen products in order to obtain the labelled protection. The UV filters in sunscreens have long been authorized for use by the EU authority on the basis of data from studies on acute toxicity, subchronic and chronic toxicity, reproductive toxicity, genotoxicity, photogenotoxicity, carcinogenicity, irritation, sensitization, phototoxicity and photosensitization as well as on environmental aspects. New challenges with respect to the safety of UV filters have arisen from the banning of animal experiments for the development of cosmetics. Future debates on sunscreens are likely to focus on nanoparticles and environmental issues, along with motivation campaigns to persuade consumers to protect their skin. However, more efficient sunscreen use will also continue to raise questions on the benefit in preventing vitamin D synthesis in the skin induced by sunlight.

Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.

BACKGROUND: alpha-lipoic acid (LA) or the reduced form dihydrolipoate (DHLA) is a potent scavenger with anti-inflammatory properties. Previous uncontrolled studies with topical treatment with 5% LA-containing creams indicate a beneficial effect on photoageing skin. OBJECTIVE: The purpose of this study was to investigate whether a cream containing 5% LA showed any advantages concerning a number of the criteria associated with ageing of the facial skin, compared with an identical cream lacking LA. MATERIAL AND METHODS: Thirty-three women, mean age 54.4 years, were included in this controlled study. After randomization half the face was treated twice daily for 12 weeks with the LA cream and the other half with the control cream. The following methods of assessment were used: self-evaluation by the test subjects, clinical evaluation, photographic evaluation and laser profilometry. Profilometry was performed before the start of treatment and at the end. RESULTS: All four methods of assessment showed a statistically significant improvement on the LA-treated half of the face. Laser profilometry, the most objective method used, showed an average decrease in skin roughness of 50.8% (44.9-54.0) on the LA-treated side, compared with 40.7% (32.4-48.7) on the placebo-treated half of the face P < 0.001 (Wilcoxon matched pairs test). CONCLUSIONS: It is indicated that 12 weeks of treatment with a cream containing 5% LA improves clinical characteristics related to photoageing of facial skin.

Expression of p21WAF1/CIP1, p53, bcl-2 and Ki-67 in venous leg ulcers with and without squamous cell carcinoma.

In order to gain understanding of the cellular mechanisms of malignant transformation in chronic venous leg ulcers, we analysed by immunohistochemistry the presence of p21, p53, bcl-2 and Ki-67 in ulcers with and without squamous cell carcinoma. The material consisted of 41 archived histopathological samples from 33 patients with chronic venous leg ulcers and 28 samples from 21 patients suffering from squamous cell carcinoma in chronic venous leg ulcers. All samples derived from the chronic ulcers were negative for p53, p21 and bcl-2. Cells positive for Ki-67 were seen in certain ulcer areas. In the cancers, 14 samples showed immunopositivity for p53 and 22 samples were positive for p21, with expression mainly in the suprabasal layer. Expression of p21 seemed independent of p53. None of the samples was bcl-2-positive. Ki-67 was positive with basal expression in 16/28 of the tumour samples, 15 of which also expressed p21. There was no perilesional p53 or p21 activity in the cancer samples. The results regarding perilesional expression are different from those reported in UV-induced squamous cell carcinomas and probably reflect a different carcinogen.

Human papillomavirus in venous ulcers with and without squamous cell carcinoma.

Malignant transformation of chronic wounds is a well-known, albeit rare, phenomenon. We examined archival paraffin blocks of samples of squamous cell carcinoma (SCC) in chronic venous leg ulcers previously taken from 23 patients and of chronic noncancerous venous leg ulcers from 35 patients for the presence of human papillomavirus (HPV) DNA. The methods used were the polymerase chain reaction (PCR) with GP05+/06+ (mucosal) and nested PCR with CP65/70 and CP66/69 (EV-associated) primers. A subsequent nonradioactive Southern blot hybridization was used to confirm the specificity of the PCR. With PCR three samples were positive on the gel, and with Southern blotting, a further seven samples were positive, to give a total of ten samples. All of the positive samples were from the noncancerous ulcers and with the primers GP05+/06+. HPV infection is probably not the carcinogen responsible for the malignant transformation of venous leg ulcers. The difference in positivity between the ulcers and the SCCs was statistically significant (P = 0.01) and raises the question as to whether HPV-positive cells are eliminated in the interaction between the SCC and the immune system. Further studies on the carcinogenic effects of chronic proliferation and the role of HPV infection therein, are needed.

Squamous cell carcinoma complicating chronic venous leg ulceration: a study of the histopathology, course and survival in 25 patients.

We have studied 25 cases of squamous cell carcinoma in chronic venous leg ulcers. Twenty-three of the patients were dead and two were alive. The mean age at cancer diagnosis was 78.5 years. The median survival was 1 year. Eleven tumours were well-differentiated, 10 moderately and four poorly. All patients with a poorly differentiated tumour died within a year. Metastases were certain in eight cases. The disease was lethal in 10 cases which included all poorly differentiated tumours. The survival of the study group was significantly shortened compared with a control group of patients with lower limb non-melanoma skin cancer (n = 433) from the Swedish Cancer Registry (P = 0.0084). When diagnosed, squamous cell carcinoma in chronic leg ulcers merits a thorough investigation of the degree of differentiation and spread. Assertive treatment is indicated as poorly differentiated tumours and some moderately differentiated tumours may be fatal.

Sunbed use in relation to phenotype, erythema, sunscreen use and skin diseases. A questionnaire survey among Swedish adolescents.

Sunbed use was studied in relation to phenotype, erythema, sunscreen use and skin disease. The study population comprised 14-19 year-old Stockholm adolescents in 60 randomly selected classes, with 1252 students providing information. More than half (57%) reported sunbed use > or = 4 times during the previous year. Skin type III dominated (64%). Excessive exposure (> or = 10 times/year) was not correlated to skin type. Sunscreens were most commonly used by sunbed users. Of all sunbed users, 44% reported erythema. Adolescents with acne/seborrhoca, eczema or psoriasis used sunbeds more than others without skin diseases. The proportion with sunbed erythema (44%) indicates an unrecognized susceptibility to artificial ultraviolet radiation (UVR) among adolescents. The association between high exposure to UVR and sunscreen use stresses the importance of sunscreens being used as supplementary protection, not as a tool for tanning.

A qualitative ultrastructural study of melanocytes after grenz-ray and UVA irradiation.

Seven female human subjects were irradiated with 4 Gy of grenz rays and 30J/cm2 of long-wave ultraviolet (UVA) radiation once a week for three weeks. 6/7 subjects when irradiated on the back developed a clearly visible pigmentation due to both grenz-ray and UVA pigmentation. The effect on epidermal melanocytes was observed with transmission electron microscopy. Ultrastructural changes in melanocytes following both grenz-ray and UVA irradiation were an increase in the number of premature and mature melanosomes, elongation and protrusion of cytoplasm, sometimes indented nuclei, and the development of multilamella of basal lamina. Compared with UVA-irradiated skin, in the same individuals the melanocytes seemed somewhat more hypertrophic after grenz-ray irradiation. In general the observed qualitative ultrastructural differences between UVA- and grenz-ray-irradiated melanocytes were limited, indicating that the influence of grenz-rays is similar to that of UVA.

Reviews.

NURSING PRACTICE BEN-OCH FOTSAR Diagnos-Klinik-Terapi.

A transmission electron microscopic study of macromelanosomes in sporadic dysplastic naevi.

Melanosomes in sporadic dysplastic nevi were examined by transmission electron microscope. In particular the structure of macromelansomes was observed. Macromelanosomes were present in both nevus cells and keratinocytes. They were round and consisted of a core structure and a cortex structure. The core was composed of electron-dense amorphous material and electron-lucent microvesicles. The cortex contained grains of different sizes and electron densities. Occasionally small melanosomes were observed in the cortex. Electron-lucent microvesicles were also present in small spherical and ellipsoid melanosomes. Melanosome complexes observed in nevus cells contained degrading melanosomes with electronlucent microvesicles, dispersed microvesicles and grains. Melanosome complexes with structures resembling those found in macromelanosomes were also present. The result of the investigation suggests that melanosome complexes found in nevus cells might become macromelanosomes through autophagy.

[Spurious hyperphosphatemia in multiple myeloma].

We present a 68-year-old woman with Ig A-K multiple myeloma and a laboratory report of extreme hyperphosphatemia (29 mg/dl), but no clinical manifestations attributable to such a high serum phosphorus. The hyperphosphatemia was demonstrated to be spurious and due to interference of monoclonal immunoglobulin with the phosphomolybdate calorimetric assay for phosphorus of some automated systems. In this case, after removal of serum proteins phosphorus values were normal. Normal values of phosphorus were also obtained with the phosphomolybdate calorimetric assay after reduction of paraprotein levels in this patient by chemotherapy. Knowledge of this phenomenon may obviate unnecessary testing and treatment. It may also suggest the presence of dysproteinemia.

A case report of acute febril neutrophilic dermatosis (Sweet's syndrome) and Crohn's disease.

A case of Crohn's disease complicated by Sweet's syndrome is presented. The main ultrastructural findings were the multiplication of basal lamina surrounding the venulea, interendothelial gaps and in perivascular locations mixed infiltrates of neutrophiles and erythrocytes. The changes indicate that the initial site of the reaction was the walls of the dermal vessels.

Ultrastructural changes in Darier's disease induced by ultraviolet irradiation.

A male patient with clinically and histopathologically verified Darier's disease and a history of deterioration after sun exposure was irradiated on uninvolved skin with 25, 50 and 75 J/cm2 of UVA once a week for five weeks. He also received 3 and 5 times his individually established MED of UVB. Since no signs of keratosis follicularis were detected one week after the last irradiation, he was then exposed to 10 times his MED with UVB, whereupon clinically characteristic lesions of keratosis follicularis developed. One week after this exposure, biopsies were taken from the UV-induced lesions and processed for light and transmission electron microscopic investigation. Light microscopy revealed suprabasal lacunae, corps ronds and grains. In the electron microscope, gaps in the basal lamina beneath the suprabasal lacunae were also observed, through which cytoplasmic processes of lymphocyte- and fibroblast-like cells and basal keratinocytes protruded. Parts of keratinocytes with disruptive cell membranes were localized in the gaps of the basal lamina. Also, multiplication of the basal lamina was frequent.