From the outside-in:Epidermal targeting as a paradigm for atopic disease therapy

• 作者: Rachel MC Gillespie Sara J Brown
• 来源期刊: 世界皮肤病学杂志
• 学科: 医学
• 关键词: ATOPIC dermatitis ECZEMA FILAGGRIN Skin barrier KALLIKREIN THYMIC stromal lymphopoietin Allergic SENSITIZATION ATOPIC march
• 年，卷（期）: 2015,（1）
• 页码范围: 16-32
• 页数: 17页
• 分类号: R

摘要

Atopic dermatitis(AD)is a chronic inflammatory skin disorder which can precede asthma and allergic rhinitis in a disease trajectory known as the atopic march.The pathophysiology of AD includes cutaneous inflammation,disrupted epidermal barrier function,xerosis and propensity to secondary infections.AD had previously been thought to arise from the systemic atopic immune response and therapies are therefore directed towards ameliorating Th2-mediated inflammation.However in recent years the focus has shifted towards primary defects in the skin barrier as an initiating event in AD.Links between loss-of-function variants in the gene encoding filaggrin and disrupted activity of epidermal serine proteases and AD have been reported.Based on these observations,a mechanism has been described by which epidermal barrier dysfunction may lead to inflammation and allergic sensitization.Exogenous and endogenous stressors can further exacerbate inherited barrier abnormalities to promote disease activity.Pathways underlying progression of the atopic march remain unclear,but recent findings implicate thymic stromal lymphopoietin as a factor linking AD to subsequent airway inflammation in asthma.This new appreciation of the epidermis in the development of AD should lead to deployment of more specific strategies to restore barrier function in atopic patients and potentially halt the atopic march.