Department of Dermatology D92, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
JAMA Dermatol. 2017 Apr 1;153(4):270-278. doi: 10.1001/jamadermatol.2016.5268.
Skin pretreatment is recommended for adequate penetration of topical photosensitizing agents and subsequent protoporphyrin IX (PPIX) accumulation in photodynamic therapy (PDT).
To compare the relative potential of different physical pretreatments to enhance PPIX fluorescence in normal skin.
DESIGN, SETTING, AND PARTICIPANTS: This intraindividual, randomized clinical trial was performed from November 28 to December 20, 2014, at Bispebjerg Hospital, Copenhagen, Denmark, among 12 healthy volunteers 18 years or older. Analysis was based on intention to treat. All participants completed the study protocol.
Participants were each exposed to standardized skin preparation with curettage, microdermabrasion with abrasive pads, microneedling with dermarollers, ablative fractional laser (AFXL), non-AFXL, and no pretreatment, followed by 3 hours of methyl aminolevulinate hydrochloride incubation and subsequent red light illumination.
The primary outcome measure was methyl aminolevulinate-induced PPIX fluorescence accumulation. Secondary outcome measures were PPIX photobleaching and clinical local skin reactions, supported by noninvasive reflectance measurements of percentage of skin redness, transepidermal water loss, and participant-assessed pain.
Among the 12 healthy study participants (8 men; 4 women; mean [SD] age, 33 [15] years), histologic findings confirmed standardization of interventions with partial removal of the stratum corneum after curettage and microdermabrasion and similar vertical penetration depths for microneedling, AFXL, and non-AFXL (median, 125 μm). PPIX fluorescence reached highest intensities in skin pretreated with AFXL (median, 8661 arbitrary units [AU]) compared with microdermabrasion (median, 6731 AU), microneedling (median, 5609 AU), and curettage (median, 4765 AU) (P < .001), among which similar enhancement was shown. Comparatively lower fluorescence levels were demonstrated for skin pretreated with non-AFXL (median, 2898 AU), methyl aminolevulinate-treated controls (median, 2254 AU), and untreated controls (median, 239 AU) (P < .03). Increasing laser densities (2% vs 4% vs 6%) and the number of pretreatment passes (1, 2, and 3 passes) did not enhance PPIX fluorescence. Local skin reactions were most intensified in AFXL-pretreated skin and correlated with PPIX fluorescence and degree of PPIX photobleaching.
Under standardized conditions, PPIX accumulation was most enhanced after AFXL pretreatment, followed by microdermabrasion, microneedling, and curettage. Increasing the number of pretreatment passes and laser densities did not further augment PPIX accumulation. These results may indicate relatively enhanced PDT response by AFXL pretreatment in diseased skin.
clinicaltrials.gov Identifier: NCT02372370.
皮肤预处理被推荐用于充分渗透局部光敏剂，并随后在光动力疗法（PDT）中积累原卟啉 IX（PPIX）。
比较不同物理预处理方法在增强正常皮肤中 PPIX 荧光的相对潜力。
设计、地点和参与者：这是一项于 2014 年 11 月 28 日至 12 月 20 日在丹麦哥本哈根比斯加普伯格医院进行的个体间、随机临床试验，共有 12 名 18 岁或以上的健康志愿者参与。分析基于意向治疗。所有参与者都完成了研究方案。
参与者分别接受标准化的皮肤准备，包括刮除术、带研磨垫的微晶磨皮术、带滚针的微针穿刺术、消融性分数激光（AFXL）、非 AFXL 和无预处理，随后进行 3 小时的盐酸氨基酮戊酸孵育和随后的红光照射。
主要结果测量是甲基氨基酮戊酸诱导的 PPIX 荧光积累。次要结果测量是 PPIX 光漂白和临床局部皮肤反应，由皮肤红斑百分比、经表皮水分流失和参与者评估的疼痛的非侵入性反射测量支持。
在 12 名健康研究参与者（8 名男性；4 名女性；平均[SD]年龄，33[15]岁）中，组织学发现证实了干预措施的标准化，刮除术和微晶磨皮术导致部分角质层去除，微针穿刺术、AFXL 和非 AFXL 的垂直穿透深度相似（中位数，125μm）。与微晶磨皮术（中位数，6731AU）、微针穿刺术（中位数，5609AU）和刮除术（中位数，4765AU）相比，AFXL 预处理的皮肤 PPIX 荧光达到最高强度（中位数，8661 个任意单位[AU]）（P<.001），其中显示出相似的增强效果。经非 AFXL 预处理（中位数，2898AU）、接受盐酸氨基酮戊酸处理的对照组（中位数，2254AU）和未处理对照组（中位数，239AU）的皮肤荧光水平较低（P<.03）。皮肤反应在 AFXL 预处理的皮肤中最为强烈，并与 PPIX 荧光和 PPIX 光漂白程度相关。
在标准化条件下，AFXL 预处理后 PPIX 积累增加最多，其次是微晶磨皮术、微针穿刺术和刮除术。增加预处理次数和激光密度不会进一步增加 PPIX 积累。这些结果可能表明 AFXL 预处理在疾病皮肤中相对增强了 PDT 反应。
clinicaltrials.gov 标识符：NCT02372370。
