JAK抑制剂治疗斑秃的研究进展

【摘要】 斑秃是一种突然发生的局限性脱发,严重者可进展为全秃或普秃。目前认为斑秃是一种具有遗传背景的器官特异性自身免疫性疾病,毛囊免疫赦免结构的破坏是重要的发病机制。目前,斑秃的治疗方法有口服、外用、肌内或局部皮损内注射糖皮质激素、外用米诺地尔酊等,但仍有一部分患者治疗无效。近年来,国外开展了很多有关JAK抑制剂治疗斑秃的临床试验。研究显示,在采用口服JAK抑制剂治疗的患者中,约半数中重度斑秃患者在治疗后毛发几乎完全长出,疗效较明显。也有报道外用鲁索替尼治疗斑秃,但疗效不一。尽管部分患者在停药后复发或是在治疗过程中出现感染等不良反应,JAK抑制剂确实为有效治疗中重度斑秃提供了一种选择。     

JAK抑制剂治疗斑秃的现状、前景及其启示

斑秃是一种慢性、异质性炎症性疾病,确切病因未明,虽治疗方法众多,但无特效药,也无对所有患者有效的疗法,加之部分慢性、重度患者对常规治疗反应差,因此急需新型有效的治疗方法。2014年起国外应用JAK抑制剂治疗斑秃,取得确切疗效。JAK抑制剂治疗斑秃的机制主要是抑制免疫细胞产生炎症因子,还可能直接作用于毛囊上皮细胞,推动毛囊周期进入生长期,有效率可达70%～80%,尤其是对重症和激素治疗无效的患者有很好的应用前景。虽其存在价格高、有潜在感染倾向等副作用,但仍不失为重症斑秃治疗的有效和二线措施。本文主要阐述JAK抑制剂的作用机制和治疗斑秃的现状、前景以及由此引发的对斑秃发病机制的启示。     

JAK抑制剂治疗儿童重症斑秃5例

目的观察JAK抑制剂治疗5例儿童重症斑秃及合并甲改变患者的疗效。方法收集2020年1月至2022年4月于北京儿童医院就诊的5例重症斑秃患儿, 予JAK抑制剂(托法替布或巴瑞替尼)口服治疗, 采用斑秃严重程度评估工具(SALT)评估治疗12、24、36、48周秃发改善程度。对其中3例合并甲改变的重症斑秃患儿, 采用改良的甲银屑病指数评分评估治疗前后甲病的改善程度。治疗过程中同时监测不良反应。结果 5例重症斑秃患儿, 年龄2 ～ 11岁, 病程5 ～ 120个月, JAK抑制剂疗程24 ～ 48周。治疗12周, 2例患儿SALT改善率达SALT50;治疗24周, 3例达SALT95, 1例达SALT75后自行停药;治疗36周, 3例达SALT99, 开始减半量治疗;治疗48周, 4例SALT改善率分别为SALT99、SALT83、SALT31、SALT0, 其中2例为减半量治疗1 ～ 2个月出现反复并逐渐加重。3例合并甲改变的患儿, 治疗12周后手指甲严重程度指数改善率分别为67.5%、45.4%和25%, 足趾甲分别为42.5%、71.4%和5%;治疗48周, 这3例手指甲改善率分别为1...     

JAK抑制剂托法替尼治疗斑秃的研究进展

斑秃(AA)是一种由毛囊的T细胞介导的自身免疫性疾病。有研究发现酪氨酸蛋白激酶(JAK)/信号转导因子和转录激活因子(STAT)信号转导通路在AA发病中起着重要作用。托法替尼是一种作用于JAK/STAT信号通路的小分子JAK抑制剂,具有抗炎作用,能促进毛囊干细胞活化。美国食品药品监督管理局(FDA)于2012年批准托法替尼用于治疗类风湿关节炎。国外也有不少应用托法替尼治疗中、重度AA的报道。该文就JAK/STAT通路在AA发病机制中的作用、托法替尼的作用机制及临床应用作一综述。     

Janus激酶抑制剂治疗斑秃的研究进展

斑秃是一种由免疫机制介导的非瘢痕性脱发。Janus激酶抑制剂通过阻断JAK/STAT信号转导通路减少炎性因子的生成与释放,从而减轻炎性介质对毛囊的攻击,使毛发再生。部分报道已初步证实Janus激酶抑制剂治疗斑秃的有效性和安全性,因此Janus激酶抑制剂可能成为一种治疗斑秃的新型有效方法。     

Janus酪氨酸激酶抑制剂在皮肤病的应用进展

 Janus酪氨酸激酶(JAK)抑制剂可选择性抑制JAK家族,是抑制Janus酪氨酸激酶-信号转导与转录激活因子（JAK STAT）通路的一种新型药物,成为许多炎症性皮肤病的一种有前景的新治疗方式。JAK STAT通路是一种细胞内信号传导通路,引起皮肤病的许多细胞因子通过JAK STAT通路完成信号传递,使用JAK抑制剂可能是治疗这类疾病的有用策略。本文对JAK抑制剂治疗皮肤病的作用机制、疗效及不良反应进行了综述。     

Janus酪氨酸激酶抑制剂在皮肤科的应用

Janus酪氨酸激酶（JAK）-信号转导及转录激活子（STAT）途径是一种细胞内信号传导通路,是多种细胞因子如白细胞介素（IL）、干扰素（IFN）及其他分子进行细胞膜到细胞核信号传导的重要途径,依赖于JAK?STAT途径的可溶性炎症介质参与了很多炎症性疾病的发病。因此,应用JAK抑制剂是治疗这类炎症性及免疫性疾病的新手段。目前临床上已用于治疗骨髓纤维化、真性红细胞增多症、类风湿性关节炎等疾病,并且越来越多的病例报告及临床研究证实,JAK抑制剂治疗特应性皮炎、斑秃、银屑病、白癜风等皮肤疾病也取得良好疗效……     

JAK抑制剂治疗斑块型银屑病的研究进展

斑块型银屑病是一种影响患者身体健康和生活质量的慢性炎症性疾病.Janus激酶(JAK)-转录激活因子(STAT)信号通路在银屑病的发病机制中起着关键作用,JAK抑制剂具有潜在的治疗价值.目前已开发出多种JAK抑制剂,且已有多项JAK抑制剂治疗银屑病的前瞻性临床试验完成[1].本文就目前已发表的相关文献对JAK抑制剂治疗...     

斑秃合并特应性皮炎免疫学特性及治疗研究进展

目前大多数研究认为斑秃是Th1细胞介导的自身免疫性疾病,特应性皮炎是经典的Th2细胞主导的炎症性疾病。但最近的研究也显示了Th2轴在斑秃发病中的潜在作用,在斑秃患者的头皮和血清中发现Th2相关生物标志物显著升高。此外,GWAS也在斑秃中鉴定出了Th2的易感性位点(IL-4和IL-13)。同时合并FLG突变的患者更容易发展成重度斑秃。度普利尤单抗和JAK抑制剂在合并特应性皮炎的斑秃患者中的治疗效果,进一步阐明了不同细胞因子通路对斑秃表型的影响,有助于未来斑秃靶向治疗的选择。     

外用磷酸二酯酶4抑制剂软膏治疗斑秃一例附文献复习

斑秃既往治疗包括局部外用药物治疗(糖皮质激素、米诺地尔等)、系统药物治疗(口服糖皮质激素、甲氨蝶呤、环孢素等)以及物理疗法(如光化学疗法PUVA、308 nm准分子激光等)。磷酸二酯酶4(PDE-4)抑制剂通过增加细胞内环磷酸腺苷(cAMP)水平,进而调节一系列细胞因子发挥免疫调节作用。国外曾有口服PDE-4抑制剂治疗斑秃的动物模型研究和病例报道,但存在较多的不良反应。克立硼罗软膏是近年来新研发的外用磷酸二酯酶4(PDE-4)抑制剂,曾报道用于特应性皮炎、银屑病和白癜风等皮肤病的治疗,其治疗斑秃的二期临床试验正在开展,目前国内外尚无治疗斑秃的正式报道。我们报道一例外用磷酸二酯酶4抑制剂治疗斑秃的患者,取得良好治疗效果,未见明显不良反应。     

Janus kinase inhibitors: An innovative treatment for alopecia areata

Alopecia areata (AA) is a relatively common disease, but no satisfactory treatment has yet been developed. Recently, research progress has been made in the pathogenesis of AA, revealing that autoreactive cytotoxic T cells are important and that the Janus kinase (JAK) pathway is involved. Therefore, the potential of JAK inhibitors as therapeutic agents for AA is attracting attention. Several single‐arm clinical trials and retrospective studies demonstrated that oral JAK inhibitors are effective and tolerable treatments for moderate to severe AA. Although JAK inhibitors are emerging as an innovative treatment for AA, further placebo‐controlled clinical trials are required to confirm their efficacy and long‐term safety.     

Alopecia areata in children: treatment with diphencyprone

Summary We assessed the efficacy of diphencyprone (DPCP) treatment in a total of 26 children with alopecia areata (AA). Sixteen children had alopecia areata totalis (AAT) and 10 had alopecia areata localis (AAL), DPCP is an absolute contact sensitizer. Twenty-five children could be sensitized with a 2% DPCP solution, whereas one child could not be sensitized. Patients were treated, once a week for at least 3 months, for up to 1 year. Twenty-one of the 25 (84%) children showed hair regrowth to a greater or lesser extent after DPCP treatment. Eight of the 25 (32%) children showed cosmetically acceptable hair regrowth. Cosmetically acceptable regrowth at the end of the study was seen in four of the 15 (27%) children with AAT and in four of the 10 (40%) children with AAL. These results are comparable with those reported in an earlier study in children with AA. Our opinion is that DPCP is a beneficial therapeutic agent in children with severe AAT and AAL showing no spontaneous remission.     

308-nm Excimer Laser for the Treatment of Alopecia Areata in Children

Abstract:  Alopecia areata (AA) is a common skin disease which is characterized by nonscarring localized or diffused hair loss. In this study we assessed the efficacy of 308-nm Excimer laser in the treatment of alopecia areata in children. A total of 9 children with 30 recalcitrant patches alopecia areata and two children with alopecia areata totalis were enrolled in this study which included seven male and four female patients, aged between 4 and 14 years and the durations of their disease were between 7 and 25 months. All of these patients had more than one lesion of alopecia areata and at least one of them was left as a control for comparison. The lesions were treated with the 308-nm Excimer laser twice a week for a period of 12 weeks. Regrowth of hair was observed in 18 (60%) alopecia patches in the scalp, while there was no response in the control patches and over the extremities. Only four patients with scalp lesions showed a recurrence of alopecia after 6 months post laser therapy. So, 308-nm Excimer laser is considered an effective safe therapeutic option for patchy alopecia areata in children.     

The role of Janus kinase inhibitors in the treatment of alopecia areata: A systematic review

Alopecia areata (AA) is a non‐scarring alopecia, which often carries a major impact on patients' quality of life. Currently there is no single approved treatment that effectively induces permanent remission. Recently, the JAK–STAT signaling pathway has emerged as a possible therapeutic target leading to increased interest in the use of Janus kinase (JAK) inhibitors (JAKis) in the treatment of this pathology. This review of the literature summarizes information on patients with AA who underwent treatment with JAKis and discusses the current evidence on the efficacy and safety of its use. A literature search was conducted in different databases to identify clinical trials and case reports published in January 2019. Several clinical studies have shown very promising results in the treatment of AA with oral formulas of JAKis. These agents, however, need chronic administration to maintain response. Topical formulations did not show satisfactory responses. The safety profile of these agents appears to be favorable. Current evidence is promising regarding the efficacy and safety of oral JAKis. However, the data obtained are of low quality, originating predominantly from reports of clinical cases. Further studies are needed to confirm these data and to optimize its long‐term efficacy and safety.     

JAK inhibitors for alopecia areata: a systematic review and meta‐analysis

There have been a number of case reports and small clinical trials reporting promising outcomes of Janus Kinase (JAK) inhibitors tofacitinib, ruxolitinib and baricitinib for alopecia areata (AA). The majority of the literature to date is based on small volume data, with a lack of definitive evidence or guidelines. To determine the expected response of AA to JAK inhibitor therapy and factors which influence response and recurrence rates. A systematic review and meta‐analysis was performed according to PRISMA guidelines. From 30 studies and 289 cases, there were 72.4% responders, good responders 45.7% and partial responders 21.4%. Mean time to initial hair growth was 2.2 ± 6.7 months, and time to complete hair regrowth was 6.7 ± 2.2 months. All 37 recurrences occurred when treatment was ceased after 2.7 months. Oral route was significantly associated with response to treatment compared to topical therapy. No difference was found between paediatric and adult cases in proportion of responses. There is promising low‐quality evidence regarding the effectiveness of JAK inhibitors in AA. Future large‐sized randomized studies are required to confirm findings.