BACKGROUND Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival. METHODS From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes. RESULTS A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1-6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2-5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5. CONCLUSIONS Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

中文翻译：

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皮肤增厚的早期轨迹与系统性硬化症的严重程度和死亡率有关。

背景技术系统性硬化症（SSc）是一种严重且高度异质的疾病。改良的Rodnan皮肤评分（mRSS）是广泛用于评估皮肤厚度范围和程度的工具。这项研究的目的是在没有任何先验假设的情况下，确定具有早期相似皮肤增厚轨迹的患者类别，并研究他们与器官受累和生存的关系。方法从法国SSc全国队列中，纳入入选时病程少于2年且随访的前4年内可获得至少2 mRSS的患者。基于潜在的类别混合模型，确定了具有相似mRSS轨迹的患者类别。比较获得的各类别的临床特征和生存率。结果共有198例患者符合纳入标准，共有641例mRSS。中位疾病持续时间和随访时间分别为0.8年（四分位间距0.4； 1.2）和6.3（3.8； 8.9）岁。患者之间mRSS的个体轨迹高度异质。依次评估了具有1-6个潜在类别的轨迹的模型，而5类模型代表了最适合数据的模型。每个类别的特征都是mRSS的独特全局轨迹。中位疾病持续时间在各班之间无显着差异。与第一类（低基线mRSS，无随时间的显着变化）相比，随着时间的推移发生显着变化（2-5类）的基线器官受累更为频繁。使用Cox回归，我们观察到从1级到5级的死亡风险逐渐增加。结论基于皮肤增厚轨迹的临床表型的早期鉴定可以预测SSc的病死率。这项研究表明，mRSS轨迹的表征对于临床实践和未来的试验设计可能至关重要。