Raynaud's phenomenon and other features of scleroderma, including pulmonary hypertension.

Longitudinal studies of large cohorts of patients with Raynaud's Phenomenon have addressed the predictors of developing a secondary disease. New insights have been reported into the pathogenesis of Raynaud's phenomenon and the consequences of ischemia. Studies have suggested that more than one defect may cause Raynaud's phenomenon, including increased alpha-2 sympathetic receptor activity on vessels, endothelial dysfunction, deficiency of calcitonin gene related peptide protein--containing nerves or some central thermoregulatory defect. The vasoconstricting and profibrotic cytokine endothelin-1 was found to be elevated in scleroderma but did not correlate with disease subset or with evidence of pulmonary hypertension. Oxidant stress is thought to be increased in scleroderma, causing tissue damage and provoking fibrosis. Treatment with infusion of prostacyclin for primary pulmonary hypertension was approved, paving the way for studies of secondary forms of pulmonary hypertension. Oral prostanoids are being tested for the treatment of Raynaud's phenomenon.