Early Clinical Indicators of Disease Progression in Systemic Sclerosis

Recent findings from the VEDOSS project have underscored the importance of early clinical events in predicting disease progression in very early systemic sclerosis (SSc). The project, which involves a cohort of patients demonstrating initial symptoms such as Raynaud's phenomenon and specific red flags, has shown that a significant proportion of these patients—70%—are likely to meet the 2013 ACR/EULAR SSc classification criteria within five years. However, merely fulfilling these criteria does not necessarily indicate clinically significant progression of the disease. Instead, critical early indicators such as the onset of digital ulcers, skin fibrosis, and interstitial lung disease (ILD) offer more reliable predictions regarding disease trajectory.

The research presented at the 2025 European Alliance of Associations for Rheumatology (EULAR) congress in Barcelona involved a comprehensive analysis of 442 VEDOSS patients who had not yet met the classification criteria and had no clinical endpoints at baseline. Progression was defined by the first occurrence of significant clinical events within five years, including the onset of digital ulcers, a modified Rodnan skin score (mRSS) of one or higher, or new pulmonary arterial hypertension. Notably, during the follow-up period, 51.1% of patients experienced at least one of these significant events, with cumulative progression probabilities rising from 11.1% at 12 months to 65.6% at 60 months.

Dr. Stefano Di Donato, a leading researcher in the project, emphasized that these findings validate the significance of early diagnosis and intervention, highlighting the opportunity to mitigate the impact of SSc on patients' lives. Furthermore, the study raises concerns regarding the high mortality associated with SSc, particularly due to heart and lung complications, as well as the elevated cancer risk among individuals diagnosed with the condition. The implications of early disease identification cannot be overstated, especially considering that patients with SSc are found to have a 150% higher risk of developing hematological malignancies compared to the general population.

Research conducted by Dr. Karin Gunnarsson provides additional context. An analysis of population-based healthcare registers in Sweden identified 1,720 individuals diagnosed with SSc, matched with comparable individuals from the general population. The study found that 1.6% of SSc patients developed first-time hematological malignancies, compared to 0.9% in the non-SSc group. The incidence rate was notably higher in younger patients and men. These alarming statistics indicate that early intervention in SSc cases could potentially reduce the risk of subsequent malignancies, further underscoring the importance of timely diagnosis and treatment.

In summary, the findings from the VEDOSS project and related studies suggest that early clinical events serve as robust predictors of disease progression in systemic sclerosis, offering critical insights for clinicians and patients alike. Future research should continue to explore the mechanisms behind these early indicators, aiming to establish effective intervention strategies to enhance patient outcomes and reduce the burden of this debilitating disease.