University of Miami Miller School of Medicine, Miami, and Center for Clinical and Cosmetic Research, Aventura, FL, USA.
Clin Cosmet Investig Dermatol. 2012;5:111-22. doi: 10.2147/CCID.S28905. Epub 2012 Aug 24.
Actinic keratosis is a common disease in older, fair-skinned people, and is a consequence of cumulative ultraviolet exposure. It is part of a disease continuum in photodamaged skin that may lead to invasive squamous cell carcinoma. Treatment options frequently used include cryosurgery and topical pharmacologic agents, which are examples of lesion-directed and field-directed strategies. Ingenol mebutate gel was recently approved by the US Food and Drug Administration for topical treatment of actinic keratosis. While the mechanism of action of ingenol mebutate is not fully understood, in vitro and in vivo studies using tumor models indicate it has multiple mechanisms. Ingenol mebutate directly induces cell death by mitochondrial swelling and loss of cell membrane integrity preferentially in transformed keratinocytes. It promotes an inflammatory response characterized by infiltration of neutrophils and other immunocompetent cells that kills remaining tumor cells. The ability of ingenol mebutate to eliminate mutant p53 patches in ultraviolet-irradiated mouse skin suggests that it may have the potential to treat chronically ultraviolet-damaged skin. In human studies, ingenol mebutate achieved high clearance of actinic keratosis on the head and body after 2-3 consecutive daily treatments when measured by complete or partial clearance of lesions. Localized inflammatory skin responses were generally mild to moderate and resolved in less than a month.
光化性角化病是一种常见于老年、皮肤白皙人群的疾病，是紫外线暴露累积的结果。它是光损伤皮肤疾病谱的一部分，可能导致侵袭性鳞状细胞癌。常用的治疗方案包括冷冻疗法和局部药物治疗，它们分别是病变导向和区域导向策略的范例。美国食品和药物管理局最近批准了 ingenol mebutate 凝胶用于光化性角化病的局部治疗。虽然 ingenol mebutate 的作用机制尚未完全阐明，但使用肿瘤模型的体外和体内研究表明其具有多种机制。ingenol mebutate 通过线粒体肿胀和细胞膜完整性丧失，直接诱导转化角质细胞优先发生细胞死亡。它促进以中性粒细胞和其他免疫活性细胞浸润为特征的炎症反应，从而杀死残留的肿瘤细胞。ingenol mebutate 能够消除紫外线照射的小鼠皮肤中的突变 p53 斑块，这表明它可能具有治疗慢性紫外线损伤皮肤的潜力。在人体研究中，ingenol mebutate 在连续 2-3 天每日治疗后，头部和身体的光化性角化病清除率很高，病变完全或部分清除。局部炎症性皮肤反应通常为轻度至中度，在不到一个月内消退。
