Systemic sclerosis is a rare connective tissue disease characterized by autoimmune features with vascular manifestations, causing fibrosis of the skin and internal organs. EULAR (European Union of Rheumatology Associations) focuses on systemic sclerosis as the rheumatic disease with the highest morbidity and mortality. New data presented at EULAR 2026 Congress highlights important complications and offers hope for potential new treatment strategies.
Primary cardiac lesions (pCI) are a major cause of morbidity and mortality in patients with systemic sclerosis, and early cardiac symptoms may be underrecognized, especially if systematic screening is not performed in routine clinical practice. At the EULAR 2026 Congress in London, Shirkhan Amikishiyev presented the baseline prevalence and clinical correlates of pCI in the SOLAR registry and summarized pCI incidents during follow-up of 372 patients. At baseline, pCI was present at 6.5%. This small number may partially reflect real-world reporting practices and the possibility that subclinical disease is not adequately captured in registry settings. Associated factors include older age, diffuse skin subtype, myositis, pulmonary arterial hypertension, overlap syndrome, and hypertension, clustering with a high-risk clinical profile. Of those who were pCI negative at baseline, approximately 2% developed pCI. The emergence of new cases during follow-up suggests that a single baseline assessment may miss ongoing cardiac pathology and supports the need for structured and repeated cardiac evaluations in patients with systemic sclerosis, especially multisystem disease.
Congressional posters also featured ideas about 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 characteristics and fail to capture the complex, multidimensional interactions between demographics, immunological profile, inflammatory burden, and early subclinical organ involvement. Vincenzo Venerito and colleagues used unsupervised machine learning techniques to identify distinct clinical phenotypes among 238 VEDOSS patients, aiming to assess differences in the rate and timing of progression. This approach identified three distinct clusters. The first was younger patients with earlier onset of Raynaud’s disease, minimal clinical and subclinical organ involvement, lower inflammatory markers, and lower prevalence of autoantibodies. This cluster had the lowest risk of progression to overt systemic sclerosis (21.4%) and the longest disease-free interval. Cluster 2 was a more intermediate age of Raynaud’s onset, had prominent vasculopathy and cutaneous features, and had the highest prevalence of anticentromere antibodies. This group had an intermediate risk of progression (39.4%) and a relatively indolent course of disease. Cluster 3 included older patients with late onset, high inflammatory burden, early cardiopulmonary and gastrointestinal compromise, high prevalence of anti-topoisomerase I antibodies, and evidence of subclinical organ damage. This third cluster had the highest risk (58.0%) and had a significantly shorter time to progression. Such phenotypic stratification may help improve early prognostic accuracy and allow for personalized monitoring intensity and risk-adapted treatment strategies for people with very early-stage disease.
Systemic sclerosis is an immunofibrotic disease. A key item on the research agenda in the 2023 EULAR recommendations is expanding the treatment portfolio to improve clinical outcomes in systemic sclerosis. 1 Recently, selective inhibition of PDE4B was shown to be effective in progressive fibrotic interstitial lung disease, suggesting that fibroimmunomodulatory effects may be a promising strategy against systemic sclerosis. Until now, cell type-specific expression patterns across affected tissues in systemic sclerosis have not been systematically investigated. However, the oral abstract presentation on Friday, June 5th, provided new insights. For the lung, two single-cell RNA-seq datasets were merged. One used interstitial lung disease with systemic sclerosis (SSc-ILD) samples and the other used idiopathic pulmonary fibrosis (IPF) samples, as well as lung samples from healthy controls. Single-cell RNA-seq was also performed on peripheral blood mononuclear cells (PBMCs) from patients with early active disease and age-matched controls. Differential expression analysis showed increased PDE4B expression in several cell types including both CD8+ and CD4+ T cells in SSc-ILD and IPF compared to controls, with further upregulation in SSc-ILD compared to IPF. In PBMCs, expression was significantly increased in B cells, CD8+ T cells, and monocytes of systemic sclerosis patients. As another target organ for systemic sclerosis, single-cell RNA-seq data from the skin was analyzed and revealed upregulation of PDE4B in both myeloid and lymphoid populations in patients with systemic sclerosis. Immunohistochemistry confirmed increased expression of PDE4B protein in the skin.
Astrid Hoffmann, who presented the work, said:Overall, PDE4B expression appears as a common feature across tissues in systemic sclerosis, supporting its relevance as a potential therapeutic target.. ”
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European Union of Rheumatology Associations, EULAR
References:
- Amicsiyev S, et al. Primary cardiac involvement in early systemic sclerosis: Baseline profile of 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. A multidimensional approach to predicting disease progression and prognosis in very early diagnosed patients with systemic sclerosis (MAPPing VEDOSS). Presented at EULAR 2026. POS0325. Ann Rheumdis 2026; DOI: 10.1136/annrheumdis-2026-eular.B.4080.
- Hoffman 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.
