Early progression of systemic sclerosis: a longitudinal cohort study on disease evolution and microvascular changes.

Objectives: This study aimed to evaluate the time from early-stage systemic sclerosis (SSc), to the onset of significant disease progression. A secondary objective was to identify early clinical features most strongly associated with disease progression. Additionally, the study examined the course of microvascular changes over time. Methods: In this prospective longitudinal cohort study (Hit Hard and Early trial, 3 years open label follow-up), we included patients who met the adjusted Very Early Diagnosis of Systemic Sclerosis criteria, with puffy fingers for less than 3 years. Disease progression was defined as skin or organ involvement. Microvascular changes were tracked through serial nailfold videocapillaroscopy, and Kaplan-Meier estimates were used to analyse time to disease progression. Baseline predictors of progression were explored with univariate logistic regression. Results: Thirty patients were included, 70% female, with a median duration of puffy fingers of 5.5 months. Anticentromere antibodies were present in 73%, and 75% showed an active nailfold capillaroscopy pattern at baseline. Over 3 years, 43% (95% CI: 25.6%-61.2%) developed clinically significant disease progression, predominantly manifesting as pitting scars, digital ulcers, and/or skin thickening. Mean capillary density declined over time, and 55% of patients with an early SSc capillaroscopy pattern progressed to an active or late pattern within 24 months. Conclusions: A large proportion of patients showed clinically relevant disease progression within 3 years. In spite of the limited sample size, the strong association between anti-ribonucleoprotein (anti-RNP) antibodies and disease progression underlines the prognostic value of this biomarker. Frequent and standardised nailfold capillaroscopy imaging provided insights into microvascular changes.