Tacastacas Joselin D, Oyetakin-White Patricia, Soler David C, Young Andrew, Groft Sarah, Honda Kord, Cooper Kevin D, McCormick Thomas S
Department of Dermatology, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Photodermatol Photoimmunol Photomed. 2017 Jul;33(4):193-202. doi: 10.1111/phpp.12299. Epub 2017 Apr 20.
BACKGROUND/PURPOSE: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques.
AIMS/OBJECTIVES: In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques.
Eucerin Original Moisturizing Lotion (topical vehicle) or Aldara (imiquimod 5% topical cream) were applied for 5 days once daily to a maximum contiguous area of 25 cm (5 cm × 5 cm area). Patients were provided with sachets containing 12.5 mg of imiquimod each and were instructed to apply imiquimod (I) to two psoriasis plaques (5 sachets of imiquimod allotted to each plaque). A PHAROS excimer Laser EX-308 (Ra Medical Systems, Inc. Carlsbad, CA, USA) with an output of monochromatic 308-nm light and pulse width of 20-50 ns was used for all patients. Punch biopsies of psoriatic lesions (6 mm) were taken at 4 and 48 h after final application of topical treatment with or without excimer laser treatment. Real-time quantitative RT-PCR was performed according to manufacturer's instructions and Inmunohistochemistry was used as described before.
Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses.
The observation that psoriasis involvement was not aggravated by usage of topical IMQ was encouraging. Additional observational studies might be necessary to further tailor the combination of IMQ with NB-UVB therapy to reliably improve the psoriatic pathology.
背景/目的：银屑病仍是一种使人衰弱的皮肤病，影响着1%至3%的美国人口。尽管目前几种生物疗法的有效性已将这种病理描述为一种由白细胞介素-23、肿瘤坏死因子-α和辅助性T细胞17介导的疾病，但侵入性较小的方法仍在使用且需要改进。其中一种方法是使用窄谱中波紫外线（NB-UVB）疗法，特异性清除表皮内的CD3+、CD4+和CD8+细胞，以清除银屑病斑块。
为了改进NB-UVB疗法，我们试图确定用Toll样受体7激动剂咪喹莫特（IMQ）对皮肤进行预处理是否有助于提高前者清除银屑病斑块的效率。
将优色林原保湿乳液（外用赋形剂）或爱达乐（5%咪喹莫特外用乳膏）每天涂抹一次，持续5天，涂抹面积最大为25平方厘米（5厘米×5厘米区域）。为患者提供每包含12.5毫克咪喹莫特的药包，并指示患者将咪喹莫特（I）涂抹于两块银屑病斑块上（每块斑块分配5包咪喹莫特）。所有患者均使用输出单色308纳米光、脉冲宽度为20至50纳秒的PHAROS准分子激光EX-308（美国加利福尼亚州卡尔斯巴德市拉医疗系统公司）。在最后一次外用治疗（无论是否进行准分子激光治疗）后4小时和48小时，对银屑病皮损进行6毫米的打孔活检。根据制造商的说明进行实时定量逆转录聚合酶链反应，并如前所述使用免疫组织化学方法。
我们的结果表明，尽管IMQ似乎如前所述激活了I型干扰素途径，但其与NB-UVB联合用于清除银屑病皮肤无效。尽管基因MxA、GRAMD1A和DMXL2的上调表明IMQ治疗确实引起了银屑病患者皮肤的变化，但可能需要更优化的IMQ和NB-UVB剂量才能获得理想的治疗反应。
外用IMQ不会加重银屑病病情这一观察结果令人鼓舞。可能需要进一步的观察性研究，以进一步调整IMQ与NB-UVB疗法的联合使用，从而可靠地改善银屑病病理状况。
