Division of Allergy-Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, Colo.
J Allergy Clin Immunol Pract. 2017 Nov-Dec;5(6):1477-1487. doi: 10.1016/j.jaip.2017.08.031.
Atopic dermatitis (AD), a common chronic pruritic inflammatory skin disease, impacts the quality of life of patients and caregivers and has become a global health problem. It is increasingly recognized as a disease not only of children but also of adults who may have a persistent or relapsing course from childhood or who develop new-onset adult disease. Besides well-established atopic comorbidities, associations with a number of nonatopic comorbidities have been reported. AD is characterized by both immune dysregulation and epidermal barrier dysfunction. The findings that nonlesional skin in AD has both terminal keratinocyte differentiation defects and immune abnormalities as well as multiple markers of immune and inflammatory activation in the circulation point to the systemic nature of the disease and have important translational implications. Although AD is predominantly associated with type 2 immune responses, activation of other cytokine pathways including T1, T22, and T17/IL-23 has been reported, suggesting potential therapeutic targets and provide a rationale for treatment with novel biologics. Dupilumab, a fully human mAb targeting the IL-4 Rα subunit, blocks signaling of both IL-4 and IL-13 and is the first biologic to be approved for the treatment of moderate-to-severe AD in adult patients. Other biologics in current trials for AD are targeting the IL-31 receptor, IL-13, and the common p40 subunit of IL-12/IL-23.
特应性皮炎(AD)是一种常见的慢性瘙痒性炎症性皮肤病,影响患者和照护者的生活质量,已成为全球性健康问题。人们越来越认识到,AD 不仅是儿童的疾病,也是成年人的疾病,其病程可能从儿童时期持续或复发,也可能出现新发病例。除了已确立的特应性合并症外,还报道了与许多非特应性合并症相关的关联。AD 的特征是免疫失调和表皮屏障功能障碍。AD 非皮损部位既有终末角质形成细胞分化缺陷,又有免疫异常,以及循环中多种免疫和炎症激活标志物,这表明疾病具有全身性,并具有重要的转化意义。尽管 AD 主要与 2 型免疫反应相关,但已报道其他细胞因子通路(包括 T1、T22 和 T17/IL-23)的激活,这提示了潜在的治疗靶点,并为使用新型生物制剂治疗提供了依据。度普利尤单抗是一种靶向 IL-4Rα 亚基的全人源单克隆抗体,可阻断 IL-4 和 IL-13 的信号传导,是首个获批用于治疗成人中重度 AD 的生物制剂。目前 AD 临床试验中的其他生物制剂则针对 IL-31 受体、IL-13 和 IL-12/IL-23 的共同 p40 亚基。