Pharmacotherapy of Systemic Sclerosis: focus on Bosentan

Systemic sclerosis is manifested by the massive deposition of collagen within various organ systems. Endothelin-1 has taken a pivotal role as not only a potent vasoconstrictor, but also as a profi brotic intermediary. Bosentan is proving to be a viable therapeutic option in alleviating manifestations of systemic sclerosis other than pulmonary hypertension. There are many reports in the literature profi ling bosentan's safety, effi cacy and tolerability in patients. In addition, it has greatly improved patients' quality of life, reduced the number of hospitalizations and increased the time to clinical worsening of the disease. The clinical indications for use of bosentan in a wide array of patients has served as a valuable asset in the medical management of systemic sclerosis. Introduction sclerosis (SSc) is a heterogeneous autoimmune disease that is manifested by the massive deposition of collagen and altered extracellular matrix turnover. Multiple vital organ systems can be involved, including the skin, blood vessels, heart, lungs and kidneys. The rate and degree of these various organ involvement and symptoms vary. Worldwide, approximately 240 per 1,000,000 people per year are affected by scleroderma. It is more commonly found in the United States 1 . 75% of patients are females typically in their fourth decade of life without a predilection in race. The diagnostic criteria classifi ed by the American College of Rheumatology was instituted due to the many different presenta- tions observed. The following criteria for diagnosis include the presence of; 1. Typical sclerodermatous skin changes; cutaneous fi brosis 2. Other skin manifestations attributable to systemic sclerosis, such as digital scars, bilateral fi nger or hand edema, abnormal skin pigmentations, Raynaud's phenomenon 3. Visceral manifestations such as pulmonary fi brosis, pulmonary hypertension, myocardial fi brosis, esophageal dysphagia or dysmotility or colonic sacculations. 2 Systemic sclerosis is typically divided into either the diffuse or limited disease form. Even though patients with the diffuse form will have thicker skin over a broader degree of their body, the limited form predisposes people to abnormalities of the systemic and pulmonary circulation. Without therapy, 50% of patients will succumb to this disease within 5 years. When treatment is provided, the 5-year survival is over 80%. The overall therapy for systemic sclerosis is focused on reducing the level of infl ammation and preventing fi brosis. Corticosteroids and DMARDS have been routinely used for symptomatic management. Many factors are involved in the pathogenesis of systemic sclerosis, including genetic, environmental and autoimmunological processes. Despite the aforementioned therapeutic options, accumulating evidence suggests that endothelin-1 in not only a potent vasoconstrictor, but also a strong profi brotic mediator integrally involved in systemic sclerosis. Although approved by the Food and Drug Administration only for scleroderma associated pulmonary hypertension, bosentan is proving to be useful in other various aspects of this disease. In the remainder of this manuscript we will focus on both the on-label and off-label use of bosentan on systemic sclerosis. It should be aforementioned that some of the currently available information regarding various manifestations of systemic sclerosis are based on small studies in abstract form.