Systemic sclerosis: hypothesis-driven treatment strategies.

We review data from controlled trials and randomised controlled trials to examine the hypothesis for the pathogenesis of systemic sclerosis. Strategies used to treat the vascular complications in systemic sclerosis have so far shown the biggest successes, especially in the management of renal crisis and pulmonary arterial hypertension. Because these drugs have improved function and quality of life and have increased survival rates, they can truly be classified as disease-modifying compounds. Immunosuppressive therapy with cyclophosphamide in particular has also shown evidence of efficacy, and randomised controlled trials of autologous stem-cell transplantation are underway. So far, strategies to reduce or control fibrosis directly (bosentan, interferon gamma, and relaxin) have been disappointing but new strategies against fibrosis based on advanced understanding of the molecular biology of systemic sclerosis hold promise. Treatments against several cardinal features of the disorder simultaneously have not yet been examined but are being considered for future trials.