IL-17A单抗治疗儿童泛发性脓疱型银屑病一例并文献复习

传统药物如甲氨蝶呤,阿维A和环孢菌素A等治疗儿童泛发性脓疱型银屑病（GPP）受到限制,目前没有针对青少年GPP的标准化诊疗指南,本文报道IL-17A单抗成功治疗儿童脓疱型银屑病一例并进行文献复习。     

司库奇尤单抗治疗重度斑块状银屑病发生大疱性类天疱疮一例

司库奇尤单抗是一种靶向白介素-17A(IL-17A)的重组全人源单克隆抗体,目前被批准用于治疗中重度银屑病,虽然其表现出良好的安全性和耐受性,但国际上仍有报道关于在使用司库奇尤单抗的过程中诱发多种自身免疫性疾病的案例,如系统性红斑狼疮、大疱性类天疱疮等。本文报道一例在应用司库奇尤单抗治疗重度斑块状银屑病的过程中发生大疱性类天疱疮的病例。     

白细胞介素17A在银屑病发病及治疗中的研究进展

【摘要】 近十余年来的基础和临床研究发现并确立了Th17/白细胞介素17A（IL-17A）在银屑病发病中的核心地位。IL-17A不仅能影响角质形成细胞的增殖活性和细胞功能，对银屑病免疫病理环境中的免疫细胞和相关细胞因子也有很重要的调控作用。近年来针对IL-17A通路的单抗如司库奇尤单抗、ixekizumab、brodalumab等在国内外陆续上市，在临床应用中展现出了显著的疗效。本文介绍IL-17A在银屑病发病机制中的作用以及靶向IL-17A及其受体IL-17RA生物治疗的最新进展。     

白细胞介素-17抑制剂治疗银屑病的效能及应用

银屑病是一种慢性复发性炎症性疾病,发病机制与免疫异常密切相关。近年来,银屑病的免疫机制研究进展迅速,推动了生物制剂的开发与临床应用。肿瘤坏死因子(TNF)-α抑制剂、白细胞介素(IL)-12/23抑制剂、IL-17抑制剂等相继问世,极大地改变了银屑病的治疗。选择性拮抗IL-17A及IL-17A受体的生物制剂,如司库奇尤单抗、依奇珠单抗及柏达鲁单抗,已应用于临床,并显示出卓越的疗效和良好的安全性,为银屑病的治疗提供了新选择。     

免疫检查点抑制剂帕博利珠单抗诱发银屑病一例并文献复习

报道1例57岁男性肺癌患者应用帕博利珠单抗后诱发银屑病并复习相关文献。临床表现为斑块型银屑病合并掌跖脓疱病和严重甲受累,既往无银屑病史或家族史。组织病理符合银屑病。经阿维A联合窄谱UVB治疗后病情控制。回顾文献,共有25例免疫检查点抑制剂诱发银屑病的报道。大多数患者为老年男性,以肺癌和黑素瘤为主,最常报道的诱发药物为纳武利尤单抗和帕博利珠单抗,从首次用药到出现皮损的中位时间为9周,临床表现以斑块型银屑病为主,组织病理特点与经典银屑病类似,所有患者经外用药、光疗和/或系统治疗后皮损改善,大部分患者无需停用免疫检查点抑制剂。     

阿维A对脓疱性银屑病患者外周血 IL-8水平的影响

目的 　探讨脓疱性银屑病患者经阿维A治疗前后外周血中白介素8（IL-8）水平的变化。方法 用双抗体夹心法（ELISA） 检测患者治疗前、后外周血白介素（IL-8）的水平并与正常人进行比较,进一步评价IL-8与脓疱性银屑病病情的相关性。结果 阿维A在改善脓疱性银屑病患者病情的同时,外周血IL-8的水平（治疗前96.84 ± 14.68 pg/ml,治疗后57.07 ± 12.02 pg/ml）显著下降,差异有统计学意义（P均 < 0.05）。结论 阿维A下调IL-8水平可能是其治疗脓疱性银屑病的作用机制之一。     

白芍总苷对银屑病患者皮损中IL-17A表达的影响

目的:评价白芍总苷对轻、中度寻常型银屑病患者皮损区IL- 17A表达的影响.方法:免疫组化法检测30例寻常型银屑病患者经白芍总苷治疗前后及健康对照组皮损中IL- 17A的表达.结果:寻常型银屑病患者皮损中IL- 17A的表达较健康对照组显著升高,白芍总苷治疗后皮损中IL-17A表达较治疗前显著降低(P＜0.05);治疗前、后患者皮损中IL- 17A的表达与银屑病面积和严重程度(P ASI)评分呈正相关.结论:白芍总苷可能部分通过调节寻常型银屑病皮损中IL- 17A的表达发挥治疗作用.     

司库奇尤单抗治疗七例银屑病疗效评价

目的：评价司库奇尤单抗治疗银屑病的疗效和安全性。方法：选取中重度斑块状银屑病患者及泛发性脓疱型银屑病患者，给予司库奇尤单抗,300 mg/次，0～4周每周一次，后每4周一次，并分别于治疗前、1周后、4周后、8周后记录斑块状银屑病患者的银屑病皮损面积和严重度指数(PASI)、泛发性银屑病患者银屑病症状量表(PSS)评分。结果：共治疗6例斑块状银屑病和1例脓疱型银屑病患者，所选的患者均接受至少8周的司库奇尤单抗治疗，起效时间为（1.6±0.73)天；治疗4周时，6例斑块状银屑病患者中全部达到PASI 75，3例达到PASI 90；脓疱型患者PSS评分为2。治疗8周时6例斑块状银屑病患者均达到PASI 100；脓疱型患者PSS评分为0。所有患者治疗期间均未出现严重的药物不良反应。结论：司库奇尤单抗治疗中重度银屑病起效迅速，疗效显著，不良反应少。     

阿维A联合百癣夏塔热胶囊治疗银屑病疗效观察及对Th17细胞的影响

目的:评价阿维A联用百癣夏塔热胶囊治疗寻常型银屑病临床疗效及银屑病与Th17细胞的相关性.方法:将就诊于我院的124例银屑病患者随机分为治疗组和对照组.治疗组使用阿维A联合百癣夏塔热胶囊进行治疗,对照组单独使用阿维A治疗;并对所有患者治疗前后血清IL-17、IL-22、IL-23的水平进行检测.结果:治疗组有效率96.3%,明显高于对照组.经过8周治疗,治疗组与对照组血清IL-17、IL-22、IL-23水平较治疗前均有所改善,但治疗组的改善程度明显优于对照组.对两组患者血清中IL-17、IL-22、IL-23水平有显著性差异(P<0.05).结论:Th17细胞与银屑病存在相关性.阿维A 联合百癣夏塔热胶囊治疗寻常型银屑病疗效显著,并能有效降低患者血清中Th17细胞相关因子(IL-17、IL-22、IL-23)水平.     

白细胞介素17A单克隆抗体在非银屑病性皮肤病中的应用

白细胞介素（IL）-17在多种疾病的发病机制中起着重要作用。近年来，靶向IL-17家族成员IL-17A的单克隆抗体已经应用于多种皮肤病的治疗。该文对司库奇尤单抗、依奇珠单抗等靶向IL-17A的药物在化脓性汗腺炎、毛发红糠疹、白塞综合征、人乳头瘤病毒感染、SAPHO综合征、扁平苔藓、坏疽性脓皮病和酒渣鼻等非银屑病性皮肤病中的治疗情况作一综述。     

Anti-IL-17 Medications Used in the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review

Our ability to successfully treat patients with moderate to severe psoriasis has improved significantly over the last several years with the development of more targeted therapies. IL-17A, a member of the IL-17 family of interleukins, is involved in regulating the innate and adaptive immune systems and has been identified as a key cytokine involved in the pathogenesis of psoriasis and psoriatic arthritis. In this review, we summarize our understanding of IL-17 and its role in psoriasis and psoriatic arthritis, as well as key findings from clinical trials using anti-IL-17 medications for the treatment of the aforementioned diseases. Secukinumab, ixekizumab, and brodalumab are three anti-IL-17 medications used for treating psoriasis, of which only secukinumab is FDA approved; ixekizumab and brodalumab remain under clinical development. Results from clinical trials show that these three medications are highly effective in treating psoriasis and appear to be as safe as other biologic treatments that are FDA approved.     

Epidemiological survey of patients with pustular psoriasis in the Japanese Society for Psoriasis Research from 2017 to 2020

The Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with pustular psoriasis in Japan since 2017. This study aimed to conduct a recent epidemiological analysis of patients with pustular psoriasis who were enrolled in the JSPR from 2017 to 2020. A total of 291 patients from 131 medical institutions were enrolled, of which 47.4% (138 cases) were males and 52.6% (153 cases) were females. The mean ± standard deviation (SD) age of the patients was 57.4 ± 20.3 years (males, 61.2 ± 17.3 years; females, 54.1 ± 22.1 years). The mean ± SD age of the patients at disease onset was 48.5 ± 22.5 years (males, 50.8 ± 20.6 years; females, 46.4 ± 24.0 years). The types of pustular psoriasis observed included the von Zumbusch type (59.8%), annular pustular psoriasis (8.2%), impetigo herpetiformis (6.5%), and acrodermatitis continua of Hallopeau (4.8%), of which, the majority of the patients with impetigo herpetiformis were female. Among the patients, 58.4% were treated with oral medications and 44.0% were treated with biologics. The most common oral medication prescribed was etretinate (52.4%), followed by corticosteroids (24.7%) and cyclosporin (22.9%). The most common biologics used were IL-17 inhibitors (ixekizumab [28.1%] and secukinumab [22.7%]), followed by tumor necrosis factor (TNF) inhibitors (infliximab [15.6%]) and IL-23 inhibitors (guselkumab [14.8%] and risankizumab [10.2%]). This survey thus provides new and significant information regarding the recent perspective of pustular psoriasis, such as patient characteristics and treatment trends, in Japan.     

Successful treatment with interleukin‐17A antagonists of generalized pustular psoriasis in patients without IL36RN mutations

Generalized pustular psoriasis (GPP) is a potentially life‐threatening disease that can be attributed to mutations in IL36RN in a subgroup of patients. In small trials, interleukin (IL)‐17A and IL‐17RA antagonists have been shown to be effective in patients with generalized pustular psoriasis in Japan. We identified seven patients who received the IL‐17A antagonists secukinumab (six cases) or ixekizumab (one case) in two dermatological centers. All patients showed a good or excellent clinical response. Anti‐IL‐17A therapy was well tolerated and ongoing in all patients after an average therapy duration of 12.9 months. Analysis of IL36RN mutation status was performed in six patients, one patient carried a heterozygous mutation, while the other five patients did not show a mutation in IL36RN. This is the first report of a successful treatment of GPP patients without IL36RN mutations responding to anti‐IL‐17A therapy.     

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis,erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week,open‐label,phase 3 study (UNCOVER‐J)

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.     

抗白细胞介素17生物制剂治疗银屑病的疗效和安全性

银屑病是一种多基因遗传和环境相互作用下,主要由细胞免疫异常介导的慢性炎症性增生性皮肤病,其确切的发病机制尚未完全清楚.目前认为,白细胞介素17细胞因子对角质形成细胞的增生及异常激活十分重要,是银屑病发病机制中的关键环节.新研发的3种针对白细胞介素17通路的生物制剂已应用于银屑病的临床治疗或试验,包括直接拮抗白细胞介素17A的苏金单抗(secukinumab)、ixekizumab及通过拮抗白细胞介素17RA,从而抑制白细胞介素17下游信号分子通路的brodalumab.其治疗寻常性银屑病及关节病性银屑病的有效性和安全性在临床试验中得到肯定,给银屑病患者带来新的治疗选择,但其安全性仍需长远评价.     

A case of erythrodermic psoriasis successfully treated with ixekizumab

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. International guidelines on EP treatment are lacking, with most of the biologic drugs being used basing on case reports or small case series. Ixekizumab, a fully human anti‐interleukin (IL)‐17A monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. However, two studies conducted on eight Japanese EP patients have showed ixekizumab as an efficacious and well tolerated therapy up to 24 and 52 weeks, respectively. To date, no case reports on Caucasian patients have been described. We report the case of a 66‐year‐old Caucasian female with EP successfully treated with ixekizumab, reaching PASI 100 after only 6 weeks of therapy and still maintaining this response at week 24. Our case report suggests ixekizumab as a highly efficacious treatment in EP, presenting also a very rapid action which leads to complete resolution of the disease after 6 weeks. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of the new biologics in EP.     

白细胞介素17A及其受体拮抗剂治疗银屑病的不良反应

【摘要】 白细胞介素17A在银屑病的发生发展中具有关键作用。目前,有多种白细胞介素17A及其受体拮抗剂在多个国家上市并应用于银屑病的治疗,取得了明确疗效。然而,该类生物制剂在临床试验阶段及上市后,仍然有多项不良反应报道,包括上呼吸道感染、念珠菌感染、中性粒细胞减少和炎症性肠病等,严重者甚至可危及生命。本文综述3种白细胞介素17A及其受体拮抗剂司库奇尤单抗、ixekizumab和brodalumab的临床安全性。     

Systematic review on rapidity of onset of action for interleukin-17 and interleukin-23 inhibitors for psoriasis

Several novel biologics are available or in development for moderate-to-severe plaque psoriasis. These drugs may differ in time until Psoriasis Area and Severity Index (PASI) response is obtained. In this systematic review, we examined the time to onset of action for interleukin (IL)-17 and IL-23 agents in the treatment of psoriasis. The primary objective was the weighted mean time needed for 25% and 50% of patients with psoriasis to achieve PASI90. The medical databases PubMed, Web of Science and EMBASE were searched using the following terms: psoriasis AND (ixekizumab OR secukinumab OR brodalumab OR risankizumab OR guselkumab OR tildrakizumab). A total of 27 studies were included for data extraction and qualitative synthesis, and 26 of these were quantitatively analysed. The shortest time to 25% and 50% of patients to achieved PASI90 were seen with brodalumab 210 mg every 2 weeks (Q2W; 3.5 weeks and 6.2 weeks, respectively) followed by ixekizumab 80 mg Q2W (4.1 and 7.4 weeks, respectively) and ixekizumab 80 mg Q4W (4.6 and 8.1 weeks, respectively) dosages. In conclusion, clinical trials yielded shorter time to onset of action in studies assessing approved dosing ranges of IL-17 inhibitors compared with studies assessing IL-23 inhibitors.     

Serum and tissue levels of IL-17 in different clinical subtypes of psoriasis

Serum IL-17 levels and IL-17 mRNA expression have been reported to be higher in psoriatic skin than normal skin. There are very limited data in the literature about difference in the levels of this cytokine in various clinical disease subtypes. We aimed to evaluate whether there is a difference in the level of this cytokine according to clinical subtypes of psoriasis. 70 psoriasis patients (30 plaque psoriasis, 20 guttate psoriasis, and 20 pustular psoriasis) and 50 age- and sex-matched healthy volunteers were included in the study. Serum IL-17 levels were determined by ELISA. Skin biopsies obtained from lesions and non-lesional skin area of 12 patients and healthy individuals (n = 5) were analyzed by quantitative PCR (qPCR) to measure the mRNA levels of IL-17. Statistically, the serum IL-17 levels did not exhibit any difference between the patients and control groups. However, analysis of each subgroup revealed that the IL-17 levels were significantly higher in pustular psoriasis group (10.09 ± 12.6 pg/ml) than controls (4.4 ± 4.1 pg/ml) (p = 0.02). In addition, the IL-17 levels of plaque psoriasis patients with PASI score ≥10 (11.30 ± 6.0 pg/ml) were significantly higher than that of patients with PASI score <10 (3.39 ± 2.6 pg/ml) and controls (p < 0.001). The Pearson correlation analysis showed a positive correlation between the serum IL-17 levels and PASI. Lesional skin samples of psoriasis patients showed significantly higher levels of IL-17 mRNA compared with perilesional skin samples (p = 0.017). Also, in the pustular psoriasis, IL-17 mRNA levels were found to be distinctively high in comparison with other clinical subtypes and healthy controls. Our results indicate that IL-17 and Th17 cells have an important role in pustular psoriasis and severe psoriasis.     

Biologic therapy for acrodermatitis continua of Hallopeau: Successful treatment with secukinumab and review of the literature

Acrodermatitis continua of Hallopeau (ACH) is a rare pustular psoriasis variant refractory to many conventional treatments. We report the successful treatment with secukinumab of a patient with a long history of ACH with marked onychodystrophy with frank pustulosis on the nail bed and with accompanying arthritis. Blockade of the IL‐17 receptor A has shown promise in the treatment of psoriatic erythroderma and generalized pustular psoriasis not responsive to conventional treatment. A rapid response was observed in our patient, in both skin lesions and arthritic symptoms, underlining the ability of secukinumab to improve symptoms beyond those of plaque psoriasis.