银屑病患者皮损处CD4^+ CD25^+ Foxp3^+调控T细胞的识别

Background: Depletion of CD4+CD25+Foxp3+naturally occurring regulatory T cells (Treg) induces autoimmune phenomena. These cells have not yet been fully characterized in the skin of psoriatic patients. Objectives: To prove that the Zenon immunofluorescent labeling technique is suitable for the demonstration of co-localization of T-cell markers and in particular to show the distribution of Treg in psoriatic skin. Methods: In biopsies derived from normal and psoriatic skin, CD4+CD25+, CD4+CD45RO+, CD8+CD25+, CD8+CD45RO+and CD4+CD25+Foxp3+cells in the dermis and in the epidermis were immunophenotyped, using a quantitative immunofluorescent labeling technique (Zenon), analyzed and compared using image analysis. Results: The immuno-fluorescent labeling technique was shown to be an easy and reliable tool to demonstrate co-localization of T-cell markers.In psoriasis, all pathogenic T-cell subsets (CD4+CD25+,CD4+CD45RO+, CD8+CD25+and CD8+CD45RO+cells) were significantly increased in the dermis and in the epidermis, as compared to normal skin (all p < 0.05). Using this labeling technique we were able to reveal CD4+CD25+Foxp3+Treg in psoriatic dermis, but not in the dermis of normal skin (p < 0.0001). Conclusions: The Zenon immunofluorescence technique in combination with image analysis is suitable for the demonstration of co-localization of T-cell markers in tissue. Increased numbers of pathogenic T cells (CD4+CD25+,CD4+CD45RO+, CD8+CD25+and CD8+CD45RO+) were shown in the dermis and epidermis, whereas CD4+CD25+Foxp3+Treg were identified in psoriatic skin with a predilection for the upper dermis.

联合Zenon标签技术和显微映像分析研究正常人和银屑病患者表皮细胞

Background: In order to better characterize epidermal cell populations in psoriatic vs. normal skin, fluorescent immunohistochemical techniques were extended with a new labeling technique. The Zenon technique conjugates primary antibodies rapidly and quantitatively after which they are used in the same manner as covalently labeled primary antibodies. Digital microscopic images of epidermal expression of keratin 10 and keratin 6 (differentiation), Ki-67 antigen (proliferation), and keratin 15 and β- 1 integrin (basal layer) were analyzed in a standardized way. Co-expression of different proteins was demonstrated. Methods: Sections of normal skin and psoriatic lesions were compared immunohistochemically. Antibodies against keratin 6, 10, and 15 were labeled with the Zenon technique. Antibodies against the Ki-67 antigen and β 1 integrin were covalently fluorescein isothiocyanate- labeled. Using standardized image analysis, intensity and positive surface area of the different antibodies in the epidermis were measured. Results: The number of Ki-67-antigen positive cells was significantly increased in lesional psoriatic skin. Intensity and positive surface area of keratin 10 and β -1 integrin were significantly decreased in comparison to normal epidermis. Differential expression of keratin 6 and keratin 15 was demonstrated. Conclusions: Using Zenon technology and image analysis, a description of morphology, co- expression, and quantification of representative markers for epidermal cell populations is possible.

随机对照研究复合制剂卡泊三醇和倍他米松二丙酸盐(Daivobet~/Dovobet~)对银屑病患者生活质量的影响

Background: Psoriasis is a common disease and may have a significant impact o n patients’quality of life (QoL). Objectives: To assess the impact on QoL of a new two-compound product (TCP) (Daivobet./Dovobet.; LEO Pharma) which combin es the topical vitamin D analogue calcipotriol (50 μ g g- 1) and theWorld Heal th Organization group III corticosteroid betamethasone dipropionate (0- 5 mg g - 1) in a single ointment vs. calcipotriol monotherapy using a placebo-contro lled study design. Methods: The Psoriasis Disability Index and the EuroQoL 5D qu estionnaire and visual analogue scale (VAS) were used in this study, which enrol led 828 patients with psoriasis vulgaris for treatment lasting up to 4 weeks. Th ese QoL instruments were completed by patients before and after treatment with t he TCP of calcipotriol and betamethasone dipropionate used once or twice daily, calcipotriol alone twice daily and vehicle twice daily. Results: The TCP used on ce or twice daily and calcipotriol used twice dailywere found to have statistica lly significant beneficial effects on patients’QoL over the course of treatme nt, and each was demonstrated to have a statistically significant benefit on QoL over vehicle. The TCP, applied once daily, was superior to calcipotriol twice d aily in terms of reductions on the EuroQoL 5D questionnaire andVAS. Conclusions: The results suggest that calcipotriol twice daily and the new TCP applied twice daily have a substantial effect on QoL. Once-daily application of the TCP is superior to calcipotriol twice daily terms of QoL, which reflects the superior e fficacy of this combination and the advantage of once-daily application when c ompared with twice-daily application.

2次/d应用钙泊三醇软膏和1次/d短期应用地蒽酚乳膏治疗:一项按日间用药程序指导性治疗寻常型银屑病的随机对照试验

Background: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. Objectives: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. Methods: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Results: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0%in the calcipotriol group vs. 63.6%in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15%of the patients treated with calcipotriol ointment and 25%of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). Conclusions: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.

脉冲染料激光治疗局限性顽固性斑块状银屑病的有效性:一项比较研究

Background: Localized chronic plaque psoriasis, resistant to local therapy, may be very hard to treat. The treatment of these lesions with a pulsed dye laser (PDL) has been described before, but a comparative study between the PDL and a potent topical treatment has never been performed. Objectives: To compare the efficacy of the PDL in the treatment of localized, recalcitrant plaque psoriasis with a potent topical therapy, using calcipotriol/betamethasone dipropionate (Dovobet ) as an active comparator. Methods: Eight patients with psoriasis were treated with both PDL(585 nm) and calcipotriol/ betamethasone dipropionate in an open, intrapatient, left-right comparison. A plaque severity score (sum score) and photographs were used to document the course of therapy. Patients reported pain on a visual analogue scale. Results: Both treatments were well tolerated, although one patient left the study due to post-PDL treatment pain. A significant difference in the sum score 12 weeks after treatment was seen in favour of the PDL (62% vs. 19% reduction; P < 0.05). Scores for erythema declined significantly at week 12 in both the PDL and the calcipotriol/betamethasone dipropionate group (P < 0.001). Induration and desquamation scores were significantly reduced at week 12 in the PDL group, without a statistically significant reduction in calcipotriol/betamethasone- treated lesions. The pain scores declined with progressive PDL treatments, although not statistically significantly. Conclusions: PDL treatment might be considered for the treatment of localized, recalcitrant plaque psoriasis, when other topical therapies have failed.

长疗程短波紫外线治疗白癜风对患者生活质量的影响

Long-term treatments for chronic diseases such as vitiligo need to be evaluated for their clinical efficacy. Assessment of the quality of life (QOL), however, may provide the most relevant information on the actual benefit for these patients. In this study we evaluated QOL after long-term narrowband ultraviolet (UV) B for the treatment of vitiligo. All patients, with long-term stable vitiligo vulgaris, who were treated at our clinic during the last 4 years received specifically for this study a designed QOL questionnaire, which included questions about general well-being, camouflage and psychosocial aspects; 71.4% of the patients responded. Most patients indicated an improvement on a psychological level, but an increase in camouflaging. The present study shows that, after long-term narrowband UVB phototherapy, skin appearance does not play a major role in the life of vitiligo patients, while well being only improved in a minority of patients.

地蒽酚治疗银屑病:对68例住院患者的观察

The irritant response of perilesional skin is a serious limitation of dithranol therapy in psoriasis. No data are available on the actual prevalence and severity of irritation during 24- h dithranol treatment in an inpatient setting. Using a retrospective analysis of 68 patients with psoriasis visiting our inpatient department for dithranol treatment, the occurrence of dithranol irritation was studied. We found a relatively high frequency of dithranol irritation. Furthermore, most irritation occurs at the start of the therapy with relatively low concentrations.