The effect of bosentan on digital ulcers (DU) was studied in two randomized placebo-controlled trials (RAPIDS-1 and RAPIDS-2). A limitation of these studies was the heterogeneous study population. More importantly, there were no endpoints that assessed changes in vasculopathy and / or perfusion. Laser Doppler imaging has been shown to effectively demonstrate blood flow restrictions in the hands of patients with Systemic Sclerosis (SSc). The relation between blood flow restriction in the hands measured by laser Doppler imaging and the extent of DU disease has not been studied. The current study will attempt to demonstrate this relation. In addition, the impact of bosentan on the blood flow in the hands, in a defined cohort of SSc-DU patients with a history of DU within the past 2 years and a clinically relevant reduction of blood flow in the hands, will be assessed.

Inclusion Criteria:

• Male and female subjects > 18 years diagnosed with SSc;
• Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to the healthy volunteers;
• Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception;
• A history of 1 or more DUs within 2 years prior to inclusion;
• No use of bosentan in the past;
• Subjects willing and able to sign informed consent.

Exclusion Criteria:

• Parenteral prostanoid treatment for DU < 3 months ago;
• Chronic treatment with PDE-5 inhibitor or ERA;
• History of bosentan use
• Irreversible significant limitation of the hand function, e.g. amputation of more than one finger;
• Other types of system- or connective tissue diseases;
• Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy;
• Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months;
• Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN);
• Moderate to severe liver function disorder;
• Pregnancy or breastfeeding;
• Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors;
• Hypersensitivity for bosentan or one of its components;
• Subjects not able to follow the protocol.