Progression of patients with Raynaud's phenomenon to systemic sclerosis: a five-year analysis of the European Scleroderma Trial and Research group multicentre, longitudinal registry study for Very Early Diagnosis of Systemic Sclerosis (VEDOSS)
Progression of patients with Raynaud's phenomenon to systemic sclerosis: a five-year analysis of the European Scleroderma Trial and Research group multicentre, longitudinal registry study for Very Early Diagnosis of Systemic Sclerosis (VEDOSS)
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DOI：
10.1016/s2665-9913(21)00244-7
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发表时间：
2021-12-01
影响因子：
25.4
通讯作者：
Matucci-Cerinic, Marco
中科院分区：
文献类型：
--
作者：
Bellando-Randone, Silvia;Del Galdo, Francesco;Matucci-Cerinic, Marco
背景系统性硬化症极早期诊断的初步标准（VEDOSS）以前已被提出，以确定雷诺现象患者的体征和症状。具有VEDOSS标准的所有体征或症状的患者已经符合2013年美国风湿病学会-欧洲抗风湿联盟（ACR-EULAR）系统性硬化症的分类标准。然而，不存在满足这些标准的演变的前瞻性数据。因此，我们的目的是确定的VEDOSS标准的临床价值，以确定雷诺现象的进展，系统性sclerosis患者在5 years. Methods的VEDOSS项目是一个多中心，纵向注册研究，在42个欧洲硬皮病试验和研究组中心位于20个国家在欧洲，北美和南美。雷诺现象患者有资格入组。入选时符合1980年ACR或2013年ACR-EULAR全身性皮肤病分类标准以及其他任何ACR或EULAR其他明确结缔组织疾病分类标准的患者被排除。每年随访时记录数据，包括4个VEDOSS标准（即抗核抗体[ANA]阳性、手指肿胀、系统性硬化症特异性自身抗体和甲襞毛细血管镜检查异常）。主要终点是满足2013年ACR-EULAR系统性皮肤病分类标准（即从入组到随访的进展）。连续报告进展者比例和VEDOSS标准相互作用。根据5年时的点患病率确定不同VEDOSS标准相互作用的进展预测因素。为了研究不同VEDOSS标准及其组合的进展的中间过程，进行Kaplan-Meier分析。背景系统性硬化症（VEDOSS）的极早期诊断的初步标准先前已被提出来识别体征和症状。我们在VEDOSS数据库中登记了1150例雷诺现象患者。1150例患者中有764例（66.4%）符合VEDOSS研究入选标准。在764例患者中，553例（72.4%）至少有一次随访访视，中位随访持续时间为3.6年（IQR 1.7 - 5.8）。平均年龄为45.9岁（SD 15.0），553名参与者中有507名（91.7%）为女性，自雷诺现象发生以来的中位时间为4.0年（IQR 1.7 - 10.0）。基线时，544例雷诺现象患者中有401例（73.7%）可检测到ANA，527例患者中有208例（39.5%）系统性硬化症特异性自身抗体阳性。基线时，505例患者中有182例（36.0%）存在甲襞毛细血管镜检查异常，540例患者中有96例（17.8%）检测到手指肿胀。共进行了1885次随访。553例患者中有254例（45.9%）完成了研究进展或5年随访;其中133例达到主要终点，导致总体进展率为52.4%。在基线时没有ANA是与5年内没有进展最密切相关的因素，37例ANA阴性患者中只有4例（10.8%）进展。相反，系统性硬化症特异性自身抗体和肿胀手指的基线阳性是具有最高进展风险的组合（17例中的16例[94.1%]）。解释我们来自VEDOSS项目的结果为雷诺现象患者的分层风险方法提供了有用的工具。ANA的缺乏是一个强有力的保护因素，可以识别出患有系统性硬化症的风险非常低的患者，而雷诺现象患者中存在一个或两个VEDOSS标准，随着时间的推移，系统性硬化症的风险逐渐升高。该分层工具可用于临床管理和通知早期干预性试验。版权所有（C）2021爱思唯尔有限公司保留所有权利。
Background Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years.Methods The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR-EULAR classification criteria for systemic sderosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR-EULAR classification criteria for systemic sderosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done.Background Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in Results Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66.4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72.4%) had at least one available follow-up visit and the median duration of follow-up was 3.6 years (IQR 1.7-5.8). The mean age was 45.9 years (SD 15.0), 507 (91.7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4.0 years (IQR 1.7-10.0). At baseline, 401 (73.7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39.5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36.0%) of 505 patients and puffy fingers were detected in 96 (17.8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45.9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52.4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10.8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94.1%] of 17).Interpretation Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials. Copyright (C) 2021 Elsevier Ltd. All rights reserved.