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外用皮质类固醇对短接触高剂量地蒽酚疗法的影响。

The influence of a topical corticosteroid on short-contact high-dose dithranol therapy.

作者信息

Swinkels O Q, Prins M, Tosserams E F, Gerritsen M J, Van Der Valk P G, Van De Kerkhof P C

机构信息

Department of Dermatology, University Hospital Nijmegen, P.O.Box 9101, 6500 HB Nijmegen, The Netherlands.

出版信息

Br J Dermatol. 2001 Jul;145(1):63-9. doi: 10.1046/j.1365-2133.2001.04282.x.

Abstract

BACKGROUND

Dithranol (anthralin) has been known to be effective in the treatment of psoriasis for more than 80 years. However, perilesional and uninvolved skin often show irritation during dithranol treatment, which limits its use. As the relapse rate of psoriasis is worsened by adding corticosteroids to a dithranol regimen, the use of topical corticosteroids to reduce dithranol irritation is controversial.

OBJECTIVES

The aim of the present study was to investigate the clinical and cell biological effect of clobetasol-17-propionate 0.05% ointment on dithranol-treated lesional and perilesional skin.

METHODS

For 17 consecutive days, 2% dithranol cream was applied on two test sites. A third site was left untreated on all participating patients (n = 8). All sites consisted of a psoriasis lesion as well as a 3-cm zone of perilesional skin localized on the back. After 1 h, the cream was washed off, and subsequently one of the dithranol-treated sites was treated once a day with clobetasol-17-propionate 0.05% ointment. The second site was treated once daily with the vehicle. On day 17, punch biopsies were taken from all three lesions and from the perilesional zone of all test sites in order to perform an immunohistochemical investigation, using markers to assess proliferation, differentiation and inflammation.

RESULTS

The SUM score (erythema + induration + scaling) of the lesion treated with dithranol/clobetasol showed a pronounced reduction, which was significantly greater than the SUM score of the lesion treated with dithranol/vehicle. However, the scores of both sites were equal by 6 weeks of follow-up. Comparing the two treated lesions, we observed a lower number of cycling epidermal cells in the dithranol/clobetasol lesion and a significantly lower perivascular dermal score of T lymphocytes. Comparing the perilesional skin of the two treated sites we observed less cycling epidermal cells in the dithranol/clobetasol-treated site. Regarding perilesional differentiation, the interpapillary involucrin expression was higher in the dithranol/clobetasol-treated site. With respect to perilesional inflammation the expression of dermal polymorphonuclear leucocytes, monocytes, macrophages and T lymphocytes in the dermal infiltrate were significantly lower in the dithranol/clobetasol-treated site.

CONCLUSIONS

The addition of clobetasol-17-propionate enhanced the antipsoriatic efficacy of dithranol by interfering with T-cell accumulation and epidermal proliferation. The addition of a corticosteroid reduced perilesional dithranol inflammation at the cellular level, although clinically detectable dithranol erythema was not reduced.

摘要

背景

蒽林治疗银屑病已有80多年历史,疗效显著。然而,在蒽林治疗期间,皮损周围和未受累皮肤常出现刺激反应,限制了其应用。由于在蒽林治疗方案中添加皮质类固醇会使银屑病复发率升高,因此使用外用皮质类固醇减轻蒽林刺激存在争议。

目的

本研究旨在探讨0.05%丙酸氯倍他索软膏对蒽林治疗的皮损及皮损周围皮肤的临床和细胞生物学作用。

方法

连续17天,在两个测试部位涂抹2%蒽林乳膏。所有参与研究的患者(n = 8)均有一个部位不做处理。所有部位均位于背部,包括一处银屑病皮损及3 cm宽的皮损周围皮肤区域。1小时后,将乳膏洗净,随后其中一个用蒽林治疗的部位每天涂抹一次0.05%丙酸氯倍他索软膏,另一个部位每天涂抹赋形剂。第17天,从所有三个皮损部位及所有测试部位的皮损周围区域取打孔活检组织,进行免疫组织化学研究,使用标志物评估增殖、分化和炎症情况。

结果

蒽林/丙酸氯倍他索治疗的皮损SUM评分(红斑 + 硬结 + 脱屑)显著降低,明显低于蒽林/赋形剂治疗的皮损SUM评分。然而,随访6周时,两个部位的评分相等。比较两个治疗部位的皮损,我们观察到蒽林/丙酸氯倍他索治疗的皮损中循环表皮细胞数量较少,真皮血管周围T淋巴细胞评分显著较低。比较两个治疗部位的皮损周围皮肤,我们观察到蒽林/丙酸氯倍他索治疗部位的循环表皮细胞较少。关于皮损周围分化,蒽林/丙酸氯倍他索治疗部位的乳头间内聚蛋白表达较高。关于皮损周围炎症,蒽林/丙酸氯倍他索治疗部位真皮浸润中的真皮多形核白细胞、单核细胞、巨噬细胞和T淋巴细胞表达显著较低。

结论

添加丙酸氯倍他索通过干扰T细胞聚集和表皮增殖增强了蒽林的抗银屑病疗效。添加皮质类固醇在细胞水平上减轻了皮损周围蒽林炎症,尽管临床上可检测到的蒽林红斑并未减轻。

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