Gaining the upper hand on scleroderma digital ulcers

Vasculopathy of the small blood vessels is one of the cardinal features of systemic sclerosis (SSc). The anatomical alterations of the microcirculation and small blood vessels associated with Raynaud phenomenon, the most common vascular manifestation of SSc, in combination with endothelial dysregulation and altered coagulation and fibrinolysis can lead to digital ulcers (DU)1,2. DU are a severe manifestation of SSc-associated vasculopathy, affecting up to half of patients with SSc, and are associated with a more fulminant SSc disease course1,3. Current treatment options for DU remain inadequate, and DU continue to cause a large degree of pain and disability for patients with SSc1. Two randomized controlled trials (RCT) have supported the use of intravenous iloprost in the treatment of active DU4,5, and current treatment recommendations suggest that phosphodiesterase 5 inhibitors may be efficacious in the treatment of DU6. The success of endothelin receptor antagonists (ERA) in the treatment of pulmonary arterial hypertension, another severe vasculopathic manifestation of SSc, triggered interest in their use for the treatment of DU. The RAPIDS-1 and RAPIDS-2 RCT evaluated the effect of bosentan on DU prevention and healing. In both studies, bosentan reduced the number of new DU, and the treatment effects appeared to be most pronounced in those patients with > 4 DU at baseline7,8. In these trials, the diagnosis of new DU and assessment of DU healing were … Address correspondence to Assoc. Prof. M. Nikpour, Departments of Rheumatology and Medicine, The University of Melbourne at St Vincent’s, Hospital (Melbourne), 41 Victoria Parade, Fitzroy VIC, 3065, Australia. E-mail: m.nikpour{at}unimelb.edu.au