Inclusion Criteria:  Adult patients fulfilling ACR/EULAR classification criteria for SSc Presence of RP with or without DU Failure of at least one standard of care treatment (CCB or iloprost) for at least three months RCS > 4 Possibility to obtain venous access (either through a peripherally or centrally inserted catheter)  Exclusion Criteria:  Significant anemia (<8 g/dL) Clinically relevant hemorrhagic diathesis or coagulopathy Diabetes mellitus Serious acute or chronic kidney (eGFR<30 ml/min/1.73m2) or liver failure Hypotension with systolic blood pressure <100 mmHg Chronic viral infections (HIV, Hepatitis B, C) Epilepsia, psychosis, dementia, or other relevant neurologic condition precluding the conduct of plasmapheresis Malignant disease or any other condition with life expectancy <12 months Known history of alcohol or drug abuse Long-term serious tobacco abuse with documented severe vascular disease (Fontaine >III). Severe hyperlipoproteinemia, defined as a significant elevation of Lp(a) or LDL cholesterol despite standard doses of medical therapy