Renert-Yuval Yael, Guttman-Yassky Emma
Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adv Ther. 2017 Jul;34(7):1594-1609. doi: 10.1007/s12325-017-0542-7. Epub 2017 Jun 23.
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use. The pathogenesis of AA is not yet fully understood, but recent investigations of the immune activation in AA skin reveal Th1/IFN-γ, as well as Th2, PDE4, IL-23, and IL-9 upregulations. Tissue analyses of both animal models and human lesions following broad-acting and cytokine-specific therapeutics (such as JAK inhibitors and ustekinumab, respectively) provide another opportunity for important insights into the pathogenesis of AA. As reviewed in this paper, numerous novel therapeutics are undergoing clinical trials for AA, emphasizing the potential transformation of the clinical practice of AA, which is currently lacking. Dermatologists are already familiar with the revolution in disease management of psoriasis, stemming from better understanding of immune dysregulations, and atopic dermatitis will soon follow a similar path. In light of these recent developments, the therapeutic arena of AA treatments is finally getting more exciting. AA will join the lengthening list of dermatologic diseases with mechanism-targeted drugs, thus changing the face of AA.
斑秃（AA）是一种常见的炎症性脱发原因，对于广泛病例缺乏美国食品药品监督管理局（FDA）批准的治疗方法，这些病例的自发毛发生长率极低且会导致严重的心理困扰。目前针对严重病例的治疗方法包括广泛的免疫抑制剂，但这些药物会产生显著的副作用，无法长期使用，停药后会迅速脱发。由于严重病例中疾病的范围，局部接触致敏剂和皮损内治疗的用途有限。AA的发病机制尚未完全了解，但最近对AA皮肤免疫激活的研究揭示了Th1/干扰素-γ以及Th2、磷酸二酯酶4（PDE4）、白细胞介素-23（IL-23）和白细胞介素-9（IL-9）的上调。在使用广泛作用的治疗药物和细胞因子特异性治疗药物（分别如JAK抑制剂和乌司奴单抗）后，对动物模型和人类皮损进行的组织分析为深入了解AA的发病机制提供了另一个重要机会。如本文所述，许多新型治疗药物正在进行AA的临床试验，这突出了目前缺乏的AA临床实践的潜在转变。皮肤科医生已经熟悉了银屑病疾病管理的革命，这源于对免疫失调的更好理解，特应性皮炎很快也将走上类似的道路。鉴于这些最新进展，AA治疗领域终于变得更加令人兴奋。AA将加入越来越多有机制靶向药物的皮肤病名单，从而改变AA的面貌。
