New findings highlight risks and therapeutic targets in systemic sclerosis

Primary cardiac involvement (pCI) is a major contributor to morbidity and mortality in people with systemic sclerosis, and early cardiac manifestations may be under-recognised, particularly when there is no systematic screening in routine practice. At the EULAR 2026 Congress in London, Shirkhan Amikishiyev presented the baseline prevalence and clinical correlates of pCI in the SOLAR registry, summarising incident pCI during follow-up in 372 patients. At baseline, pCI was present in 6.5% - a small number that may partly reflect real-world reporting practices and the likelihood that subclinical disease is under-captured in a registry setting. Associated factors included older age, diffuse cutaneous subtype, myositis, pulmonary arterial hypertension, overlap syndrome, and hypertension - clustering with a higher-risk clinical profile. Among those who were pCI-negative at baseline, around 2% developed incident pCI. This emergence of new cases during follow-up suggests that a single baseline assessment may miss evolving cardiac involvement, supporting the need for structured and repeated cardiac evaluation in systemic sclerosis, especially in patients with multi-system disease.

A poster at the Congress also looked at ideas around progression and prognosis. Although the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) approach has improved early identification of systemic sclerosis in people with Raynaud's phenomenon, current prognostic models rely on individual clinical or serological features - failing to capture complex, multidimensional interactions between demographics, immunological profiles, inflammatory burden, and early subclinical organ involvement. Vincenzo Venerito and colleagues used an unsupervised machine-learning technique to identify distinct clinical phenotypes among 238 VEDOSS patients - with the aim of evaluating differences in rate and timing of progression. The approach identified three distinct clusters. The first was younger patients with earlier Raynaud's onset, minimal clinical and subclinical organ involvement, low inflammatory markers, and low prevalence of autoantibodies. This cluster had the lowest risk of progression to definite systemic sclerosis (21.4%) and the longest disease-free time period. Cluster 2 were a more intermediate age at Raynaud's onset, with prominent vasculopathic and cutaneous features, and the highest prevalence of anti-centromere antibodies; this group had intermediate risk of progression (39.4%) and a relatively indolent disease course. Cluster 3 included older patients with later onset, higher inflammatory burden, early cardiopulmonary and gastrointestinal involvement, higher prevalence of anti-topoisomerase I antibodies, and evidence of subclinical organ dysfunction. This third cluster had the highest risk (58.0%) and a significantly shorter time to progression. Such phenotypic stratification could be useful to improve early prognostic accuracy, enabling personalised monitoring intensity, as well as risk-adapted therapeutic strategies in people with very early disease.

Presenting the work, Astrid Hofman said "Overall, PDE4B expression emerges as a shared feature across tissues in systemic sclerosis, supporting its relevance as a potential therapeutic target."

Source:

European Alliance of Associations for Rheumatology, EULAR

Journal references:

• Amikishiyev S, et al. Primary Cardiac Involvement in Early Systemic Sclerosis: Baseline Profile of the patients in the SOLAR Registry. Presented at EULAR 2026; OP0215. Ann Rheum Dis 2026; DOI: 10.1136/annrheumdis-2026-eular.B.2918.
• Venerito V, et al. Multidimensional Approach to Predict disease Progression and prognosis in patients with Very Early Diagnosis Of Systemic Sclerosis (MAPPing VEDOSS). Presented at EULAR 2026; POS0325. Ann Rheum Dis 2026; DOI: 10.1136/annrheumdis-2026-eular.B.4080.
• Hofman A, et al. Single-Cell Profiling Identifies PDE4B as a Disease-Relevant Target in Systemic Sclerosis Across Tissues and Cell Subsets. Presented at EULAR 2026; OP0309. Ann Rheum Dis 2026; DOI: 10.1136/annrheumdis-2026-eular.B.1248.