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Actinic Keratosis: Rationale and Management

机译:光化性角化病:基本原理和管理

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Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the ‘field’. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.
机译:光化性角化病(AKs)是常见的皮肤损伤,预示着发生鳞状细胞癌(SCC)和其他皮肤恶性肿瘤的风险增加,这主要归因于过度的紫外线(UV)暴露。它们主要存在于皮肤白皙的个体中,并且日益成为免疫抑制的问题。 AKs可能自发退变,保持稳定或转变为浸润性SCC。具有5个以上AK的人发生SCC的风险增加,并且大多数SCC都来自AK。 AK形成的主要机制是炎症,氧化应激,免疫抑制,细胞凋亡受损,诱变,细胞生长和增殖失调以及组织重塑。人乳头瘤病毒也与某些AKs的形成有关。了解这些机制可指导目前可用的AK疗法的基本原理。 AKs管理的主要原则之一是野外癌化。随着年龄的增长,大面积的皮肤暴露于越来越多的紫外线和其他环境损害中。对于头部,颈部和前臂尤其如此。这些侮辱不仅针对单个病变发展的皮肤,而且还针对可能出现AK作物的大面积区域。病变之间的皮肤也受到相同的伤害,并且可能包含尚未发现的临床前病变或增生细胞区域。整个受影响的区域称为“田地”。因此,管理分为病变导向治疗和现场导向治疗。当前的疗法包括病变定向的冷冻疗法和/或切除术,以及局部领域定向的乳膏:5-氟尿嘧啶,咪喹莫特,双氯芬酸,光动力疗法和丁二酸丁二醇酯。结合病灶和野外定向疗法已取得了良好的结果,几种新型疗法正在研究中。处理方法是可变的,并且针对个人量身定制,这使得黄金标准管理算法难以设计。这篇文献综述文章旨在根据目前对病理生理学和流行病学的理解,描述针对AK的最佳可用疗法背后的原理。在2000年1月1日至2013年9月18日之间进行了PubMed和MEDLINE文献检索。在适当的情况下,引用了在此之前发表的文章。这不是系统的综述或荟萃分析,而是旨在强调对AK疾病及其管理的最新了解。

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