Distinct trajectories of disease severity progression in juvenile systemic sclerosis

Juvenile systemic sclerosis (JSSc) often presents with overlapping features, making phenotypic classification and disease progression difficult to define. This study investigated whether JSSc comprises latent disease severity subgroups with distinct longitudinal trajectories and examined baseline predictors of class membership.

Retrospective cohort study using prospectively collected data from 45 patients with JSSc between January 2005 and December 2024. Demographic, clinical, laboratory, and disease severity data were collected. The primary outcome was progression-free survival (PFS), defined as percentage change in the Juvenile Systemic Sclerosis Severity score (J4S) over time. A Growth Mixture Model identified latent disease severity classes with distinct longitudinal trajectories and their baseline predictors.

Thirty-eight JSSc patients (66% females), followed for ≥48 months, entered the study. PFS remained high in the fibrotic and limited cutaneous JSSc subtypes (80-100%) over the observation period, whereas the diffuse and sine scleroderma subtypes showed marked deterioration, with PFS decreasing to 54% and 25%, respectively. We identified two latent classes of disease severity: Class 1 showed low severity and good treatment response, Class 2 showed an active, progressive course with poor long-term outcomes. Baseline predictors of poor outcome were J4S >7.5, treatment initiation >9 months from disease onset, and >1.5 organs involved. Latent trajectory classes showed good concordance with JSSc clinical subtypes (κ = 0.660).

We identified two latent classes of disease severity in JSSc with clear prognostic significance. High baseline J4S, delayed treatment, and greater organ involvement predicted a more severe disease course, paving the way for precision health strategies and optimized.