Cyclosporine

一、共识基本信息与背景 制定机构：中国医师协会皮肤科医师分会、中国中西医结合学会皮肤性病学分会。 通信作者：史玉玲、王刚、顾军。 发布年份：2024年。二、引言与流行病学 定义：EP是银屑病的一种少见且严重的亚型，以全身弥漫性潮红、浸润肿胀、大量糠状鳞屑为特征，常伴系统症状，易复发。 患病率：占银屑病患者的1%~2%。1984年我国银屑病患病率为0.123%，2012年升至约0.47%，但EP所占比例未更新。 国际数据：美国为1%~2.25%；荷兰每10万人中0.9例；亚洲人群好发，平均发病年龄53.7岁，男性多于女性。 性别比例：国外男:女=(1.2~3.3):1，我国为(1.6~4.93):1。 发病背景：多数EP发生于斑块状银屑病或泛发性脓疱型银屑病人群，少数以EP为首发表现。三、病因及发病机制 诱因： 最常见：银屑病治疗不规范（尤其长期外用或系统使用强效糖皮质激素后不规则停药或减量）。 其他：感染、某些药物（β受体阻滞剂、锂剂、抗疟药、NSAIDs、四环素类、安非他酮等）、妊娠、精神情绪因素。 遗传机制： 中国EP患者中常见HLA-C和HLA-DRB1基因变异。 常见等位基因：HLA-C*01:02（34.4%）、HLA-C*0702（18.0%）；HLA-DRB1*0901（20.7%）、HLA-DRB1*0803（13.8%）。 免疫机制： 核心通路：IL-23/Th17轴，IL-23促进Th17产生IL-17，诱导疾病进展。 近年观点：同时涉及Th1和Th2通路，Th1持续分泌IL-2、IFN-γ可能与斑块状银屑病转型为EP有关。 其他可能机制：细胞间黏附分子与配体相互作用、TWEAK因子等。四、临床表现 皮肤表现： 急性进展：鲜红色皮损，浸润肿胀明显，掌跖角化，手套/袜套样脱屑，周期性复发-缓解。 稳定期：暗红色皮损，浸润肿胀减轻，脱屑减少，可伴色素沉着。 全身弥漫性潮红、浸润、肿胀、大量糠状脱屑。 两种转归模式： 甲损害：油滴状甲、甲增厚、甲分离、点状凹陷（常见）。 眼部受累：约14%患者，包括结膜水肿、睑外翻、眼睑肿胀、闭合不全、前葡萄膜炎、角膜溃疡等。 类型转化： 斑块状银屑病可转为EP（病情加重）。 EP治疗好转后可再现斑块状皮损。 脓疱型银屑病好转过程中可先表现为EP，再转为斑块状。 关节病型银屑病可与EP同时出现。 全身表现： 贫血、低蛋白血症、水电解质紊乱、多脏器功能异常、继发感染。 体温调节异常：环境适应差，可体温过低或过高。 高热需警惕感染（尤其金黄色葡萄球菌脓毒症），可致感染性休克、急性肾衰竭、心衰、ARDS。 体温过低可致低血压、心动过缓、室颤。 消化道及其他：肝脾肿大、肝功能异常、脂肪泻；可伴代谢性疾病（肥胖、糖尿病、血脂异常等），但与EP相关性数据不足。五、辅助检查（一）组织病理 表皮角化不全、颗粒层变薄或消失、棘层肥厚、表皮突延长、细胞间水肿、海绵形成。 真皮上部水肿、血管扩张充血，早期中性粒细胞和淋巴细胞浸润，后期以淋巴细胞为主。（二）实验室检查 血常规异常：白细胞、中性粒细胞、嗜酸性粒细胞比例升高。 炎症指标：CRP升高、ESR增快、总IgE升高。 血生化异常：肝肾功能、血糖、血脂异常，水电解质紊乱，低蛋白血症，高乳酸血症。 感染排查：高热者需做创面/血培养、降钙素原、G试验、GM试验、病毒抗体及载量、高通量测序、胸部CT。 关节受累：关节超声、类风湿因子、抗CCP抗体、HLA-B27。 危重监测：氧饱和度、动脉血气、中心静脉压。 鉴别诊断相关：肿瘤标志物、腹部超声、自身免疫抗体。 生物制剂治疗后：需关注淋巴瘤发生风险。六、诊断及鉴别诊断（一）诊断标准（专家建议） 典型临床表现：弥漫性潮红/暗红色，片状或糠状鳞屑，炎症浸润明显。 皮损面积≥体表面积75%~90%。 有银屑病史和/或组织病理符合银屑病特征。（二）鉴别诊断（需排除其他原因引起的红皮病） 继发于其他皮肤病：特应性皮炎、接触性皮炎、嗜酸性粒细胞增多性皮炎、副银屑病、毛发红糠疹、扁平苔藓、落叶型天疱疮等。 感染诱发：葡萄球菌性烫伤样皮肤综合征、HIV、乙肝病毒感染、挪威疥。 药物性红皮病：抗癫痫药（卡马西平、苯妥英钠）、镇静安眠药、青霉素、别嘌醇等；可急性起病，伴全身症状。 自身免疫性疾病：皮肌炎、皮肤型红斑狼疮、移植物抗宿主病、种痘反应。 肿瘤相关性：皮肤T细胞淋巴瘤（如蕈样肉芽肿、Sézary综合征）、霍奇金淋巴瘤、淋巴细胞白血病、实体器官恶性肿瘤晚期。 先天性红皮病：大疱/非大疱性先天性鱼鳞病样红皮病、Netherton综合征、Omenn综合征等。 特发性红皮病：约30%病因不明，应谨慎诊断。七、病情严重程度评估 轻、中、重度分级标准（符合以下至少2条为中重度，1条为轻度）： 体温≥37.3℃； 50%以上皮损肿胀或下肢水肿； 浅表淋巴结肿大（可触及或超声发现）。 其他评估工具：PGA、BSA、DLQI。八、治疗方案（一）治疗原则 控制稳定病情、减缓进展、减轻症状。 兼顾皮肤屏障修复。 个体化治疗，避免诱因，减少不良反应，预防并发症。 目前无法根治，需与患者充分沟通。（二）一般治疗 监测生命体征，去除诱因，停用诱发药物。 支持治疗：营养支持、维持水电解质平衡、纠正低蛋白血症、贫血、预防体温过低。 抗感染（尤其金黄色葡萄球菌）。（三）基础治疗（皮肤护理） 清洁：清水沐浴，水温35~37℃，时间≤15min，每天1次。 保湿：选用经临床验证产品。 湿包护理：内层湿性敷料+外层干性敷料。 封包护理：封闭式包裹，增强药物吸收。（四）局部治疗 轻度EP单用局部药；中度联合物理/系统治疗；重度以系统为主。 急性期避免维A酸类、维生素D3衍生物，推荐润肤剂或屏障保护剂。 稳定期可酌情使用钙调磷酸酶抑制剂，避免大剂量强效糖皮质激素。（五）系统治疗1. 传统系统药物 阿维A： 起始剂量0.2~0.4 mg/(kg·d)，每1~2周增加10 mg/d。 控制后每2~4周减10 mg，至10 mg/d维持≥3个月。 低白蛋白会降低疗效。 甲氨蝶呤： 推荐剂量7.5~15 mg/周，最高≤25 mg/周。 控制后维持1~2个月，每4周减2.5 mg。 低白蛋白时毒性风险增加。 环孢素： 剂量3~5 mg/(kg·d)，急性期从较大剂量开始。 控制后每2周减0.5 mg/(kg·d)，维持剂量0.5~3.5 mg/(kg·d)。 停药后易复发，可联合阿维A。 其他：吗替麦考酚酯仅个案有效。一般不推荐系统糖皮质激素，除非危及生命且排除感染。2. 生物制剂（推荐用于急性期） TNF-α抑制剂：依那西普、英夫利西单抗、阿达木单抗有效。英夫利西单抗为2010年美国指南一线推荐。 IL-17A抑制剂：司库奇尤单抗（快速应答）、依奇珠单抗（日本获批）、布罗利尤单抗（日本获批）。 IL-12/23p40抑制剂：乌司奴单抗，对顽固性EP、TNF抑制剂失败者有效，CARD14突变者反应更佳。 IL-23p19抑制剂：古塞奇尤单抗、替瑞奇珠单抗、瑞莎珠单抗（日本获批）。3. 小分子靶向药物 阿普米司特（PDE4抑制剂）：个案报道，适用于合并多种共病或无法监测者。 氘可来昔替尼（TYK2抑制剂）：日本获批用于成人EP，Ⅲ期研究显示52周疗效良好。（六）物理治疗 窄谱中波紫外线：适用于病情相对稳定者。 水疗： 温水浴：36~40℃，15~20min，每天1次。 淀粉浴/麦麸浴：水温36~37℃，15~20min，每天1~2次。 高锰酸钾浴：1:8000，36~40℃，15~20min，每天1次。（七）传统中医疗法 辨证：热毒伤阴证。 治则：清热解毒、养阴凉血。 方药：清营汤合生脉饮加减。（八）特殊人群治疗1. 妊娠期 推荐：生物制剂、环孢素、糖皮质激素（避免孕早期3个月）。 TNF-α抑制剂可用于早中期；培塞利珠单抗胎盘穿透少，但未获批银屑病适应证。 哺乳期可用阿达木单抗、英夫利西单抗、依那西普。 婴儿出生后6个月内不宜接种活疫苗。 不因病情终止妊娠，需医患共同决策。2. 婴幼儿和儿童 1岁以内：静脉注射丙种球蛋白。 ≥1岁：优先环孢素（避免长期）。 阿维A慎用（骨骼损伤风险）。 MTX：2岁以下不推荐；13岁以下按体重；13岁以上同成人。 生物制剂多为超适应证使用，仅有个案报道。3. 老年患者 优选：生物制剂（安全性与年轻无显著差异）。 次选：MTX（按肌酐清除率调整）、阿维A（监测肝功能和血脂）、环孢素（排查高血压、肝肾功能、电解质等）。 注意感染风险。（九）并发症治疗 早期住院，营养支持，补液，纠正低蛋白血症，控制感染。 监测重要脏器功能，多学科会诊。 危重者入ICU。 系统糖皮质激素仅在危及生命且其他治疗无效或禁忌时谨慎使用，尽快减量停用。九、预后 稳定型EP：症状轻，治疗后皮损控制快，预后良好。 急性进展型EP：易复发，迁延不愈，可伴发热及多系统并发症，预后较差。 转型表现：脓疱型银屑病治疗中先转为EP再转为斑块状，视为病情好转。 目前缺乏EP病死率等循证数据。十、共识形成方法与局限性 方法：基于国内外指南、注册临床研究数据、专家经验，全体专家一致同意。 局限性：诊疗进展快，需定期更新。共识仅代表专家组建议，供临床参考。总结（供医学生记忆要点） 项目 核心内容 定义 银屑病严重亚型，全身潮红、脱屑、系统症状 诱因 不规范用药（尤其激素）、感染、药物、情绪 诊断 典型皮损+面积≥75%~90%+银屑病史/病理 分级 体温≥37.3℃、水肿≥50%、淋巴结肿大（≥2条为中重度） 治疗核心 传统药物（阿维A、MTX、环孢素）+ 生物制剂（IL-17、IL-23等抑制剂）+ 小分子药物（TYK2抑制剂） 特殊人群 妊娠优选TNF-α抑制剂；儿童不推荐MTX<2岁；老年优选生物制剂 禁忌 避免系统糖皮质激素（除非危及生命）；急性期避免维A酸类外用药

WILMINGTON, Del.--(BUSINESS WIRE)--Incyte (Nasdaq:INCY) today announced final 24-week data from the Phase 3 TRuE-AD4 study evaluating the efficacy and safety of Opzelura® (ruxolitinib) cream in adults with moderate atopic dermatitis (AD) who had an inadequate response, intolerance or contraindication to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). These data were presented (Abstract ID: P0851) today at the 2026 European Academy of Dermatology and Venereology (EADV) Symposium, being held May 7–9, 2026, in Athens, Greece. As previously reported, the TRuE-AD4 study met both of its co-primary endpoints at Week 8, with a statistically significantly higher proportion of patients on Opzelura versus vehicle cream achieving EASI75 (≥75% improvement in Eczema Area and Severity Index score from baseline) and, separately, IGA-TS (Investigator's Global Assessment Treatment Success, defined as an IGA score of 0 [clear] or 1 [almost clear] with at least a two-point improvement from baseline).1 Patients who achieved an EASI50 response at Week 8 continued double-blind treatment, as needed, through Week 24. Most patients (84.3%) in the Opzelura treatment group completed treatment through Week 24. Among those patients, 84.3% achieved EASI75 and 70.6% achieved IGA-TS at Week 24, similar to the frequencies at Week 8 (83.5% and 74.4%, respectively). Mean affected body surface area (BSA) remained low (2.5% at Weeks 8 and 24) and itch relief (NRS4; ≥4-point improvement in Itch Numeric Rating Scale) remained high (74.3% at Week 8 and 64.7% at Week 24) with Opzelura treatment. As-needed treatment with Opzelura was well tolerated, with few application site reactions (1.7%) and no new safety signals up to 24 weeks. The most common treatment-emergent adverse events were upper respiratory tract infection (10.6%) and nasopharyngitis (6.3%). “We are pleased to share these results, which demonstrate sustained disease control over 24 weeks in adults with moderate AD and further reinforce the well-tolerated safety profile of Opzelura,” said Pablo J. Cagnoni, M.D., President and Global Head of Research and Development, Incyte. “We look forward to continuing to work with EU regulatory authorities to bring this differentiated, nonsteroidal treatment option to European adults with moderate AD who have progressed on standard topical therapies.” More information regarding the EADV Symposium can be found at: https://eadv.org/symposium/. About TRuE-AD4 TRuE-AD4 (NCT06238817) is a randomized, double-blind, vehicle-controlled Phase 3b study designed to evaluate the efficacy and safety of Opzelura® (ruxolitinib) cream in adults with moderate atopic dermatitis (AD). The study enrolled 241 patients (≥18 years old) who met the specific inclusion criteria, including an IGA (Investigator's Global Assessment) score of 3 and an EASI (Eczema Area and Severity Index) score greater than 7 at both screening and Day 1, and who have AD on 10% to 20% of their Body Surface Area (BSA; excluding scalp). Patients also had to have a documented history of inadequate response, intolerance or contraindication to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs) within the 12 months prior to the screening visit. Patients were randomized 2:1 to receive Opzelura applied twice daily (BID) or vehicle (non-medicated cream) BID. At Week 8, patients who achieved EASI50 continued double-blind, BID treatment, applied as needed for an additional 16 weeks. Patients for whom EASI50 was not achieved at two consecutive visits ≥1 week apart were eligible to enter the escape arm at Week 8 or later, in which open-label Opzelura cream was applied as needed. The co-primary endpoints of TRuE-AD4 were the proportion of patients achieving IGA Treatment Success (IGA-TS), defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a two-point improvement from baseline, and EASI75, defined as ≥75% improvement in EASI score, at Week 8. Secondary endpoints included the proportion of patients with a ≥4-point improvement in NRS4 (≥4-point improvement in Itch Numeric Rating Scale) score at various time points. Other efficacy measures included the proportion of patients who achieved IGA-TS, NRS4, EASI75, a negative change from baseline in the affected body surface area (%BSA), change from baseline in the skin pain NRS score, EASI50 and more, measured at various time points. The study also tracked the frequency, duration and severity of adverse events associated with the use of Opzelura. For more information on the study, visit https://www.clinicaltrials.gov/study/NCT06238817. About Atopic Dermatitis AD – the most common type of eczema – is a chronic, recurring, inflammatory and highly pruritic skin condition that affects up to 25% of children and up to 12% of adults worldwide, with an estimated prevalence of 4.4% - 7.1% of adults in Europe.2,3 Signs and symptoms include irritated and itchy skin that can cause red lesions that may ooze and crust.4 About Opzelura® (ruxolitinib) Cream Opzelura® (ruxolitinib) cream, a novel cream formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, approved by the U.S. FDA for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older, is the first and only treatment for repigmentation approved for use in the United States. Opzelura is also approved in the U.S. for the topical short-term and non-continuous chronic treatment of mild to moderate AD in non-immunocompromised patients 2 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Use of Opzelura in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants, such as azathioprine or cyclosporine, is not recommended. In Europe, Opzelura (ruxolitinib) cream 15mg/g is approved for the treatment of nonsegmental vitiligo with facial involvement in adults and adolescents from 12 years of age. Incyte has worldwide rights for the development and commercialization of Opzelura. Opzelura is a registered trademark of Incyte. For more information, see the Opzelura SmPC. About Incyte® Incyte is redefining what’s possible in biopharmaceutical innovation. Through deep scientific expertise and a relentless focus on patients, we have built an established portfolio of first-in-class medicines and an extensive portfolio of next-generation medicines across our key franchises: Hematology, Oncology and Inflammation and Autoimmunity. To learn more, visit Incyte.com and Investor.Incyte.com. Follow us on social media: LinkedIn, X and Instagram. Incyte Forward-Looking Statements Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the TRuE-AD4 study, anticipated discussions between Incyte and EU regulatory authorities, whether and when Opzelura might be approved or commercially available in Europe for adults with moderate AD and the potential for Opzelura to offer an effective nonsteroidal topical treatment option that can help delay or prevent progression to systemic therapy in appropriate adult patients, contain predictions, estimates, and other forward-looking statements. These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including risks and uncertainties regarding research and development of products and product candidates, the sufficiency of clinical trial data to meet applicable regulatory standards or warrant continued development, the ability to enroll sufficient numbers of subjects in clinical trials, determinations made by the FDA, EMA and other regulatory authorities, the efficacy or safety of Incyte’s products, the acceptance of Incyte’s products in the marketplace, market competition, sales, marketing, manufacturing and distribution requirements, and other risks detailed from time to time in our reports filed with the U.S. Securities and Exchange Commission, including our annual report on Form 10-K and our quarterly report on Form 10-Q for the quarter ended March 31, 2026. Incyte disclaims any intent or obligation to update these forward-looking statements. __________________________ 1 Carrascosa JM, et al. Efficacy and safety of ruxolitinib cream in adults with moderate atopic dermatitis: results from TRuE-AD4, a phase 3b, randomized, double-blind, vehicle-controlled study. Presented at: 15th Georg RAJKA International Symposium on Atopic Dermatitis; October 24–26, 2025; Melbourne, Australia. 2 Global Atopic Dermatitis Atlas. Global report on atopic dermatitis 2022. Available at: https://www.eczemacouncil.org/assets/docs/global-report-on-atopic-dermatitis-2022.pdf. Accessed April 2026 3 Eckert L, Gupta S, Gadkari A, et al. Burden of illness in adults with atopic dermatitis: Analysis of national health and wellness survey data from France, Germany, Italy, Spain, and the United Kingdom. J Am Acad Dermatol. 4 Boguniewicz M, Fonacier L, Guttman-Yassky E, et al. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120(1):10-22.e2. Link to source (https://pubmed.ncbi.nlm.nih.gov/29273118/)