Systemic sclerosis (SSc) is an autoimmune and chronic disease characterized by endothelial dysfunction, immune system dysregulation and fibrosis of skin and internal organs. Gastrointestinal involvement, chronic inflammation, malnutrition, steroid therapy and physical inactivity contribute to the development of sarcopenia among SSc patients. Sarcopenia is quite common in SSc patients with a prevalence of 22.5%, and negatively impacts on morbidity, mortality, rehospitalization rates and healthcare costs. It is known that malnutrition delays digital ulcers (DUs) healing in SSc. Digital ulcers related to SSc are recorded in up-to 50% of patients representing the most important vascular complication that lead to severe reduction the patient's quality of life and relevant disability. Ischemia related to Raynaud phenomenon and impaired angiogenesis are the pathogenic mechanisms of DUs in SSc. In SSc an imbalance between angiogenic and angiostatic factors exists that alters vascular recovery. Impaired angiogenesis is a feature of DUs and several studies showed low serum levels of vascular endothelial growth factor (VEGF) in SSc patients with active DUs. Skeletal muscle is the largest organ in the body and has been identified as a secretor of myokines which participate not only in the regulation of energy homeostasis and nutrient metabolism but also in angiogenesis, as it is the case for VEGF. In skeletal muscle, VEGF plays an essential role not only in angiogenesis, but also in maintenance of the capillary bed. With this project we aim to demonstrate, for the first time, that sarcopenia can be a possible risk factor of DU development in SSc patients. In particular, we speculate that SSc-associated sarcopenia may concur to impaired neoangiogenesis together with the classically recognized factors.
