Bovenschen H J, Gerritsen W J, van Rens D W A, Seyger M M B, de Jong E M G J, van de Kerkhof P C M
Department of Dermatology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands.
Arch Dermatol Res. 2007 Feb;298(9):457-63. doi: 10.1007/s00403-006-0716-7. Epub 2006 Nov 30.
The aim of this study was to explore the additional effect of betamethasone dipropionate cream in the early phase of an intramuscular (IM) alefacept course, on plaque severity and on modulating T-cell subsets, cells expressing NK-receptors, epidermal proliferation and keratinocyte differentiation in lesional psoriatic skin. Therefore, sixteen patients with moderate-to-severe chronic plaque psoriasis received 15 mg alefacept IM for 12 weeks, followed by a 12-week follow-up period. The first 4 weeks, patients were randomized 1:1 to either betamethasone dipropionate, or the vehicle cream, once daily. Plaque severity (SUM) was assessed and serial biopsies were immunohistochemically stained for T-cell subsets (CD3, CD4, CD8, CD45RO, CD45RA, CD2, CD25, GITR), cells expressing NK-receptors (CD94 and CD161), epidermal proliferation (Ki67) and differentiation (K10), which were quantified using manual and digital image analysis. Alefacept monotherapy resulted in statistically significant improvement in plaque severity. Subsequently, immunohistochemical assessments on T-cell subsets, epidermal proliferation (Ki67) and keratinization (K10) revealed marked time-related improvements with respect to the mentioned parameters, without significant differences between both treatment regimens. Alefacept monotherapy induces improvement of plaque severity, which is accompanied by a reduction in activated (CD2+, CD25+, CD45RO+) dermal CD4+ and activated epidermal CD8+ T cells, epidermal proliferation and differentiation. Once daily treatment with betamethasone dipropionate cream during the first 4 weeks of an intramuscular alefacept course did not provide substantial additional clinical and immunohistochemical improvement.
本研究的目的是探讨丙酸倍他米松乳膏在肌内注射阿法赛特疗程早期,对斑块严重程度以及对银屑病皮损中T细胞亚群、表达自然杀伤细胞受体的细胞、表皮增殖和角质形成细胞分化的调节作用。因此,16例中重度慢性斑块状银屑病患者接受15mg阿法赛特肌内注射,疗程为12周,随后进行12周的随访。在最初4周,患者按1:1随机分为两组,分别每日一次外用丙酸倍他米松乳膏或赋形剂乳膏。评估斑块严重程度(SUM),并对连续活检组织进行免疫组织化学染色,检测T细胞亚群(CD3、CD4、CD8、CD45RO、CD45RA、CD2、CD25、糖皮质激素诱导的肿瘤坏死因子受体)、表达自然杀伤细胞受体的细胞(CD94和CD161)、表皮增殖(Ki67)和分化(K10),采用手动和数字图像分析进行定量。阿法赛特单药治疗使斑块严重程度有统计学意义的改善。随后,对T细胞亚群、表皮增殖(Ki67)和角化(K10)的免疫组织化学评估显示,上述参数有明显的时间相关改善,两种治疗方案之间无显著差异。阿法赛特单药治疗可改善斑块严重程度,同时伴有活化的(CD2 +、CD25 +、CD45RO +)真皮CD4 +和活化的表皮CD8 + T细胞减少、表皮增殖和分化。在肌内注射阿法赛特疗程的前4周,每日一次外用丙酸倍他米松乳膏并未带来显著的额外临床和免疫组织化学改善。