Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan; Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, Chiba, Japan.
Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan; Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, Chiba, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan.
Allergol Int. 2022 Jul;71(3):265-277. doi: 10.1016/j.alit.2022.04.003. Epub 2022 May 25.
Atopic dermatitis is a skin disorder caused by skin dryness and barrier dysfunction, resulting in skin inflammation and chronic itch (or pruritus). The pathogenesis of atopic dermatitis is thought to be initiated by a lowering of the itch threshold due to dry skin. This lowering of the itch threshold is at least partially due to the increase in intraepidermal nerve fibers and sensitization of sensory nerves by interleukin (IL)-33 produced and secreted by keratinocytes. Such skin is easily prone to itch due to mechanical stimuli, such as rubbing of clothing and chemical stimuli from itch mediators. In patients with atopic dermatitis, once itch occurs, further itch is induced by scratching, and the associated scratching breaks down the skin barrier. Disruption of the skin barrier allows entry into the epidermis of external foreign substances, such as allergens derived from house dust mites, leading to an increased induction of type 2 inflammatory responses. As a result, type 2 cytokines IL-4, IL-13, and IL-31 are mainly secreted by Th2 cells, and their action on sensory nerve fibers causes further itch sensitization. These sequences of events are thought to occur simultaneously in patients with atopic dermatitis, leading to a vicious itch-scratch cycle. This vicious cycle becomes a negative spiral that leads to disease burden. Therefore, controlling itch is essential for the treatment of atopic dermatitis. In this review, we summarize and discuss advances in the mechanisms of peripheral itch sensitization in atopic dermatitis, focusing on skin barrier-neuro-immune triadic connectivity.
特应性皮炎是一种由皮肤干燥和屏障功能障碍引起的皮肤疾病，导致皮肤炎症和慢性瘙痒（或瘙痒）。特应性皮炎的发病机制被认为是由皮肤干燥引起的瘙痒阈值降低引起的。这种瘙痒阈值的降低至少部分是由于表皮内神经纤维的增加和角质形成细胞产生和分泌的白细胞介素 (IL)-33 对感觉神经的敏化。这种皮肤很容易因机械刺激（如衣物摩擦）和瘙痒介质的化学刺激而引起瘙痒。在特应性皮炎患者中，一旦出现瘙痒，搔抓会进一步引起瘙痒，相关的搔抓会破坏皮肤屏障。皮肤屏障的破坏允许外部异物（如尘螨衍生的过敏原）进入表皮，导致 2 型炎症反应的诱导增加。结果，2 型细胞因子 IL-4、IL-13 和 IL-31 主要由 Th2 细胞分泌，它们对感觉神经纤维的作用导致进一步的瘙痒敏化。这些事件序列被认为同时发生在特应性皮炎患者中，导致瘙痒-搔抓恶性循环。这种恶性循环成为导致疾病负担的负向螺旋。因此，控制瘙痒是特应性皮炎治疗的关键。在这篇综述中，我们总结和讨论了特应性皮炎外周瘙痒敏化机制的进展，重点关注皮肤屏障-神经-免疫三连锁关系。
