Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis.
Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis.
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DOI：
10.1007/s12016-010-8231-1
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发表时间：
2011-12
影响因子：
9.1
通讯作者：
Wakefield JS
中科院分区：
文献类型：
--
作者：
Elias PM;Wakefield JS
过度的 Th2 细胞信号传导和 IgE 产生在特应性皮炎 (AD) 的发病机制中发挥着关键作用。然而，最近的信息表明，AD 中的炎症实际上是由对屏障的遗传性损伤引发的，包括 Netherton 综合征中 FILAGGRIN 和 SPINK5 突变之间的密切相关性，后者提供了 AD 是由丝氨酸蛋白酶活性过度引起的重要线索。但对屏障的后天应激源也可能是引发 AD 炎症所必需的，此外，金黄色葡萄球菌的微生物定植不仅会加剧炎症，还会进一步对 AD 中的屏障造成压力。这些见解的治疗意义如下：虽然目前的治疗主要针对改善 Th2 介导的炎症和/或瘙痒，但这些疗法充满了短期和潜在的长期风险。相比之下，使用以神经酰胺为主的角质层脂质三重脂质混合物的“屏障修复”疗法更符合逻辑，已被证实有效，并且安全性大大提高。
Excessive Th2 cell signaling and IgE production play key roles in the pathogenesis of atopic dermatitis (AD). Yet, recent information suggests that the inflammation in AD instead is initiated by inherited insults to the barrier, including a strong association between mutations in FILAGGRIN and SPINK5 in Netherton syndrome, the latter of which provides an important clue that AD is provoked by excess serine protease activity. But acquired stressors to the barrier may also be required to initiate inflammation in AD, and in addition, microbial colonization by Staphylococcus aureus both amplifies inflammation, but also further stresses the barrier in AD. Therapeutic implications of these insights are as follows: While current therapy has been largely directed toward ameliorating Th2-mediated inflammation and/or pruritus, these therapies are fraught with short-term and potential long-term risks. In contrast, “barrier repair” therapy, with a ceramide-dominant triple-lipid mixture of stratum corneum lipids, is more logical, of proven efficacy, and it provides a far-improved safety profile.