Does imiquimod pretreatment optimize 308-nm excimer laser (UVB) therapy in psoriasis patients?

Photodermatology Pub Date : 2017-07-01 Epub Date: 2017-04-20 DOI:10.1111/phpp.12299
Joselin D Tacastacas, Patricia Oyetakin-White, David C Soler, Andrew Young, Sarah Groft, Kord Honda, Kevin D Cooper, Thomas S McCormick
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Abstract

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.

Materials and methods: 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 cm2 (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.

Results: 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.

Conclusion: 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.

咪喹莫特预处理是否优化了308 nm准分子激光(UVB)治疗银屑病患者的效果?
背景/目的:牛皮癣仍然是一种使人衰弱的皮肤病,影响了美国1-3%的人口。尽管目前几种生物疗法的有效性已经将这种病理描述为IL-23、TNF-a和th17介导的疾病,但侵入性较小的方法仍在使用中,需要改进。其中之一是使用窄带中波紫外线(NB-UVB)治疗,专门消耗表皮内CD3+、CD4+和CD8+细胞,以清除银屑病斑块。目的:为了改善NB-UVB治疗,我们试图确定用TLR7激动剂咪喹莫特(IMQ)进行皮肤预处理是否有助于提高前者解决银屑病斑块的效率。材料和方法:Eucerin®Original Moisturizing Lotion(外用载体)或Aldara®(咪喹mod 5%外用乳膏)涂抹5天,每日1次,最大连续面积为25 cm2 (5 cm × 5 cm面积)。为患者每人提供含有12.5 mg咪喹莫特的小袋,并指示将咪喹莫特(I)应用于两个牛皮癣斑块(每个斑块分配5小袋咪喹莫特)。A PHAROS准分子激光器EX-308 (Ra医疗系统公司)carsbad, CA, USA),输出单色308 nm光,脉冲宽度为20-50 ns。采用准分子激光治疗或不采用准分子激光治疗,在最终应用局部治疗后4和48小时对银屑病病变(6 mm)进行穿孔活检。按照说明书进行实时定量RT-PCR,免疫组织化学方法如前所述。结果:我们的研究结果表明,尽管IMQ似乎像前面描述的那样激活了I型干扰素途径,但它与NB-UVB同时使用来清除银屑病皮肤是无效的。虽然MxA、GRAMD1A和DMXL2基因的上调表明IMQ治疗确实诱导了银屑病患者的皮肤变化,但IMQ和NB-UVB的更优剂量可能需要达到预期的治疗效果。结论:局部使用IMQ治疗后,银屑病的受累程度没有加重,这是令人鼓舞的。可能需要更多的观察性研究来进一步调整IMQ与NB-UVB治疗的组合,以可靠地改善银屑病病理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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