Systemic sclerosis is characterized by autoimmunity, vasculopathy and different degrees of inflammatory fibrosis. The link between these three features is still not fully elucidated as well as the heterogeneity of the disease. Mortality and morbidity are high. For the treatment of Raynaud's phenomenon and its complications vasoactive therapies such as ACE inhibitors, prostanoids, endothelin receptor blockers, or PDE-V inhibitors are used in patients with vascular complications. The role of calcium channel blockers to prevent disease complications is still a matter of debate. However; manifestations such as digital ulcers or PAH represent already existing structural changes and therefore, these therapies are prescribed at a late stage and, at least for PAH, despite existing knowledge about best therapeutic effects in early disease processes. Therefore, predictors are needed to identify those patients with high risk of vascular complications. Several observational studies have elucidated risk factors for vascular complications such as decreases in lung function, high concentrations of anti-angiotensin, anti-endothelin receptor antibodies, and high NT-proBNP values to predict PAH. Initiatives are ongoing to treat early PAH with lower mean pulmonary arterial pressure and hopefully, more drugs are available based on pathophysiologic concepts.
Compared to Systemic Lupus Erythematodes (SLE) or Mixed Connective Tissue Disease (MCTD), systemic sclerosis is more resistant to immunosuppressive therapies. On the other hand, primary Sjoegren's syndrome and primary antiphospholipid antibody syndrome are other related autoimmune diseases with poor response to immunosuppressant. Recent studies on autologous stem cell transplantation serve as proof of concept for immunosuppressive effects. In addition, several immunosuppressants, combination therapies, and biologic agents have shown efficacy mostly in small observational studies. In comparison to SLE, more intensive therapies are needed. However; they can reduce signs of fibrosis and can improve skin sclerosis, lung function parameters and HR-CT findings.
There are several novel therapeutic concepts with promising results in pilot studies. Nevertheless, some disease manifestations such as arthritis, contractures, severe gastrointestinal involvement, or calcinoses remain therapeutic problems. Systemic sclerosis has still a need for effective therapies with impact on morbidity and mortality. Therefore, centres of excellence, registries, multidisciplinary cooperations, and clinical trials are needed. Initiatives such as the European Scleroderma Trial and Research Network (EUSTAR) or DeSscipher are important to understand the disease and the natural course.
Disclosure of Interest None declared