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Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular abnormalities, immunological alterations and fibrosis of the skin and visceral organs. This complex and heterogeneous condition is associated with the highest mortality among the rheumatic diseases, but to date lacks approved disease-modifying therapies. Notable advances have been in the past 5 years in the understanding of the pathogenesis, and a number of clinical trials of therapies for SSc have shown some efficacy.
This online collection of articles from Nature Reviews Rheumatology contains Reviews and News pieces authored by leaders in the field, covering the pathogenesis, diagnosis and management of SSc.
New research suggests that cytotoxic T cells are dominant in the lesional skin of patients with early diffuse cutaneous systemic sclerosis (SSc) and contribute to vasculopathy and tissue fibrosis. Could therapeutic strategies that prevent T cell activation and cytotoxicity therefore present an option to potentially halt progression of SSc?
Analysis of data from the European Scleroderma Trials and Research (EUSTAR) cohort has initially identified six subsets of systemic sclerosis (SSc), as opposed to the binary classification of limited and diffuse cutaneous SSc. We now move closer to a more actionable SSc classification for improved clinical care and trial design.
Inappropriate activation of Toll-like receptor 4 (TLR4) on resident fibroblasts, through the binding of damage-associated molecular patterns, is a potential driver of fibrosis in systemic sclerosis. New evidence suggests that targeting fibroblast-specific TLR4 or an accessory molecule MD2 could have therapeutic value.
Autologous haematopoietic stem cell transplantation (HSCT) has proved efficacious in treating patients with systemic sclerosis, but different regimens have different associated toxicities and different effects on lung function. Through comparison of different clinical trials, we can learn how to improve the safety of HSCT.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) requires accurate diagnosis and staging to identify patients with the highest risk of disease progression, who might benefit from treatment with immunosuppressants. New insights into predictors of mortality in patients with SSc-ILD should improve patient care and inform the design of future clinical trials.
The treatment of systemic sclerosis (SSc) is complex as multiple organs are frequently involved and treatment is either for overall disease modification or is organ specific. EULAR has updated its treatment recommendations for SSc, reflecting data from some new trials. However, some features of SSc are not included.
Raynaud phenomenon and digital ulcers are some of the most common and difficult to treat manifestations of systemic sclerosis. In this Review, the authors outline how to assess and treat these conditions, and also discuss unmet clinical needs.
Myofibroblasts are important mediators of wound healing but can also perpetuate fibrosis in diseases such as systemic sclerosis by evading apoptosis. Therapeutic targeting of the survival mechanisms used by these cells in fibrotic disease holds promise for the reversal of fibrosis.
A number of core pathways and mechanisms of fibrosis, outlined in this Review, are shared across different tissues and might therefore present targets for general antifibrotic strategies. Organ-specific and disease-specific differences in fibrotic diseases could also provide insights for drug development efforts.
Myeloid cells come in many shapes and sizes and are central to inflammatory processes. This Review puts myeloid cells and their inflammatory functions into the context of fibrosis and their contribution to pathology in systemic sclerosis.
Many potentially disease-modifying therapies for systemic sclerosis (SSc) are under investigation in clinical and preclinical studies. Here, Volkman and Varga review the targets and purported mechanisms of action of these therapies in the context of our evolving understanding of SSc pathophysiology.
Our ability to interrogate the genetic and epigenetic processes that underpin disease are advancing rapidly. In this Review, Radstake and colleagues highlight insights gained into the pathogenesis of systemic sclerosis from the past 4 years of genetic and epigenetic research.
The two major lung complications in systemic sclerosis, lung fibrosis and pulmonary arterial hypertension, share some pathogenic mechanisms. Strategies for managing patients with these complications have greatly advanced in the past decade, and many tools and treatments are now available.
Biomarkers are urgently needed to improve diagnosis and patient care in systemic sclerosis (SSc). Jimenez and colleagues discuss the current state of biomarkers for SSc and provide an update on how new biomarkers could make personalized medicine a reality.