Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis

Abstract

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 morbimortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Selenium and Copper as Biomarkers for Pulmonary Arterial Hypertension in Systemic Sclerosis

“…Furthermore, in view of the fact that SSc-related pulmonary arterial hypertension (SSc-PAH) is the final presentation of progressive pulmonary vasculopathy, we assume that this condition may be associated with particularly depleted Se status, i.e., depressed values of total Se and SELENOP concentrations. A similar association may also apply to SSc-related skin changes, as they are associated with declining lung function [ 36 ], hypoxia and mortality risk in SSc [ 37 ]. Given the severity of the disease and the urgent need for an improved diagnosis and helpful indicators of disease risk and progression, we decided to re-evaluate different biomarkers of TE status in patients with SSc and SSc-PAH in comparison to healthy controls.…”

Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes

“…The traditional dichotomy of SSc, separating lcSSc and dcSSc, has recently been challenged as authors have highlighted there are more than two subgroups at stake and a more nuanced classification with various subsets may more accurately reflect the heterogeneity of the disease (54). Interestingly, in previous attempts to develop new classification strategies, a frequent subset characterized by modest cutaneous evolution, a high prevalence of gastro-intestinal manifestations, low mortality rate, and a high proportion of anti-centromere antibodies positive patients, has typically emerged (55)(56)(57). These new classification approaches highlight the limitations of the binary approach to disease sub-setting currently deployed (7), although a major subset of patients still responds to the "classical" image of Leroy's lcSSc.…”

“…15–17 Interestingly, in these attempts to develop new classification strategies, a frequent subgroup characterized by modest cutaneous evolution, a high prevalence of gastrointestinal manifestations, low mortality rate, and a high proportion of patients who are positive for anticentromere antibodies, has typically emerged. 18–20 These new classification approaches highlight the limitations of the binary approach to disease sub-setting currently deployed, 7 although a major subset of patients still responds to the “classical” and traditional image of LeRoy’s lcSSc. Therefore, this traditional limited cutaneous subset still deserves attention.…”

Insights into the knowledge of complex diseases: Environmental infectious/toxic agents as potential etiopathogenetic factors of systemic sclerosis

“…The same Authors found CD8 + T cell responses to the considered immunodominant viral antigens to be also significantly higher in SSc patients when compared to CD4 + T lymphocytes. Furthermore, they were connected to the disease duration, being significantly associated to a longer disease duration, as well as to the highest extent of cutaneous sclerosis assessed by modified Rodnan skin score, both connected to poorer patient outcomes [66][67][68][69][70][71].…”