The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data

BACKGROUND: Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans. OBJECTIVES: To determine the skin cancer incidence in a population treated with TL-01 phototherapy. PATIENTS AND METHODS: All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex. RESULTS: Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0.04-13). The median cumulative number of TL-01 treatments and dose were 23 (1-199) and 13 337 (30-284 415) mJ cm(-2), respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4.7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102-391); P < 0.05]. CONCLUSIONS: A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.     

Phototherapy and PUVA photochemotherapy in children

The use of phototherapy and photochemotherapy in children has been limited due to concerns over their long-term carcinogenic potential. Furthermore, the method of administration is disconcerting to some children, particularly as phototherapy treatment units are seldom rendered 'child-friendly'. Despite these reservations, ultra-violet therapies can be useful treatment options for children with selected dermatological conditions provided they are used under carefully controlled conditions.     

不同剂型EGCG对UVB照射引起小鼠皮肤细胞凋亡的抑制作用

目的:考察不同剂型表没食子儿茶素没食子酸酯(EGCG)对中波紫外线(UVB)照射后小鼠皮肤细胞凋亡的抑制作用及丝裂原活化蛋白激酶p38(p38 MAPK)和TNF-α表达的影响。方法:将BALB/c小鼠分为8组,不同剂型EGCG(丙酮溶液、乳膏及脂质体)局部外用于小鼠背部皮肤后给予UVB(180 mJ/cm2)照射1次,取小鼠背部皮肤,TUNEL法检测凋亡细胞,Western blotting法检测p38 MAPK磷酸化水平,酶联免疫吸附法检测TNF-α水平。结果:UVB照射可诱导小鼠皮肤细胞凋亡,p38 MAPK磷酸化及TNF-α表达增高,EGCG丙酮溶液可降低凋亡指数,p38 MAPK磷酸化水平及TNF-α的表达,而乳膏和脂质体则未显示此作用(P<0.05)。结论:EGCG丙酮溶液外用可在一定程度上抑制UVB照射所致的细胞凋亡作用,从而发挥对皮肤的保护作用。     

Timecourse study of UVB-induced cytokine induction in whole mouse skin

Ever since the skin was recognized as a site of immunologic activity, a number of laboratories have studied the production of cytokines by skin cells and the effects of chemicals, allergens, contact irritants and UVB radiation on their production. Most research to date has been carried out using either purified populations of primary cells, or established cell lines. Cytokines, however, do not function in isolation but they appear in human tissues within the context of other cytokines that can, in turn, strongly influence the final biological outcome. Therefore, in vivo studies using whole skin are more physiologically relevant since all cell types are present and interactions among them are allowed to proceed. We report here the results of a detailed timecourse study using whole mouse skin, consisting of both dermis and epidermis, irradiated with either a low or high dose of UVB and analyzed using a Multi-probe RNase protection assay system. The results show that in whole skin the kinetics of cytokine induction are different than what was previously observed in tissue culture. In addition to already known skin-associated cytokines, we report here the presence and UVB induction of cytokines not previously reported.     

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.     

Photo(chemo)therapy in private practice in Belgium, France and The Netherlands

Photo(chemo)therapy is used widely, and ultraviolet (UV) sources, protocols and indications are numerous. A survey was carried out to examine how photo(chemo)therapy is employed in private practice and to determine whether safety guidelines are respected. A questionnaire survey sent to Belgian, French and Dutch dermatologists generated 593 useful responses. UV sources, doses of UV and 8-methoxypsoralen (8-MOP), as well as the frequency of the treatment, were all different in the three countries. UV starting doses were rarely chosen according to the minimal phototoxic dose (MPD) or to the minimal erythema dose (MED). Total cumulative UV doses were not always determined. Maintenance PUVA therapy for psoriasis was still performed by 15 to 40% of dermatologists in the respective countries. Another striking fact was that genital protection is not universal. On the other hand, the irradiance of tubes is checked regularly, and contraindications are respected. Despite the availability of guidelines, clinicians seem to be inconstant in their assessment of the carcinogenic risk of UV radiation.     

Protection against endogenous and UVB-induced oxidative damage in stratum corneum lipids by an antioxidant-containing cosmetic formulation

A 16-week human clinical study was carried out to determine the ability of antioxidants in a cosmetic vehicle to inhibit the induction of lipid peroxidation in stratum corneum lipids. The study consisted of a twice daily application of material for 12 weeks followed by a 4-week regression phase. Stratum corneum lipids were collected and then exposed to 500 mJ/cm2 of ultraviolet B (UVB) radiation in order to avoid excessive erythemal damage to the subjects. Lipid peroxides were assayed by a methylene blue derivative assay and expressed per unit area of skin. During the treatment period, decreases in the level of lipid peroxides were observed on the sites treated with the compositions containing antioxidants, as compared to the untreated sites, and expressed as percent differences. Decreases were observed in endogenous as well as UV-induced lipid peroxides followed by a return to baseline levels. These results demonstrate that antioxidants in a topical cosmetic formulation were effective in protecting human stratum corneum lipids against endogenous oxidation or if challenged by 500 mJ/cm2 UVB.     

Vitamin D production in psoriasis patients increases less with narrowband than with broadband ultraviolet B phototherapy

Background: Phototherapy of psoriasis is an effective treatment. In addition to standard broadband ultraviolet radiation B (UVB), (280–320 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) has become an important treatment for psoriasis. The same wavelength range of UVB (290–315 nm) induces synthesis of vitamin D. The aim was to compare the effect of broadband with NBUVB therapy on vitamin D synthesis in patients with psoriasis.
Methods: Sixty-eight Caucasian patients (17 women and 51 men) mean age 54.1 ± 16.0 years, with active plaque psoriasis, were treated with broadband UVB ( n =26) or NBUVB ( n =42) two to three times/week for 8–12 weeks. The serum concentrations of 25-hydroxyvitamin D (25(OH)D3), 1,25-dihydroxyvitamin D (1,25(OH)₂D3), intact parathyroid hormone (PTH), calcium and creatinine were measured before the first exposure and after the last dose of radiation.
Results: In broadband UVB treated patients, 25(OH)D3 increased from 37.9 ± 16.9 to 69.4 ± 19.7 ng/ml ( P <0.0001) and in patients treated with NBUVB from 34.8 ± 11.9 to 55.3 ± 17.6 ng/ml ( P <0.0001) and P =0.008 between the treatment groups. PTH decreased on broadband UVB ( P <0.05). The serum concentrations of 1,25(OH)₂D3, calcium or creatinine remained unaltered.
Conclusion: Serum 25(OH)D3 in psoriasis patients increased less with NBUVB than with broadband UVB phototherapy. Psoriasis improved on both regimens.