Outcome measures and monitoring framework in juvenile systemic sclerosis: bridging routine care and clinical trials

Juvenile systemic sclerosis (jSSc) is an orphan multisystem autoimmune disease that can cause significant morbidity during childhood and can lead to significant worsening of quality of life. The pathophysiological features are identical with adult-onset systemic sclerosis (SSc), jSSc exhibits a distinct clinical phenotype characterized by a significantly higher prevalence of diffuse cutaneous involvement, frequent overlap syndromes, distinct autoantibody profiles, and different long-term survival trajectories. Historically, the evaluation of jSSc has relied heavily on the extrapolation of adult outcome measures, which fail to account for developmental physiology, somatic growth, and pediatric-specific feasibility constraints. This review provides a comprehensive overview of indicators of disease activity and severity which might be used in daily clinical practice and adapted as outcome measures in future clinical trials. It includes global outcome measures, organ-specific outcomes (including skin, pulmonary, cardiac, gastrointestinal, musculoskeletal, renal, and vascular involvement), patient-reported outcome measures (PROMs), and clinician-reported outcomes (ClinROs). The performance of adult indices within pediatric cohorts are evaluated, if applicable. Additionally, we analyze severity scores like the Juvenile Systemic Sclerosis Severity Score (J4S) alongside modern consensus metrics derived from the international Hamburg symposia. We emphasize the integration of pediatric-adapted clinical assessments, quantitative imaging, and patient and physician related outcomes. The development of outcome measure in jSSc requires a paradigm shift from static severity scores to dynamic, multi-dimensional indicators capable of differentiating reversible inflammatory activity from potential permanent damage accrual. Validating pediatric-specific thresholds for physiological and cutaneous change remains an urgent priority. Over the next decade, the integration of artificial intelligence (AI)-driven quantitative imaging, decentralized home-based digital health tools, and molecular biomarkers probably will gain an essential role to optimize clinical trial readiness and personalize therapeutic strategies for children with systemic sclerosis. Not applicable.