Heresi Gustavo A, Minai Omar A
Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Drugs Today (Barc). 2008 Jun;44(6):415-28. doi: 10.1358/dot.2008.44.6.1220138.
Systemic sclerosis (SSc) is a relatively rare chronic connective tissue disease characterized by varying degrees of skin fibrosis and visceral organ involvement. Pulmonary compromise, including pulmonary arterial hypertension and interstitial lung disease, is currently the leading cause of death in patients with SSc. Digital ulcers are common complications which lead to substantial morbidity and functional limitation. Until recently, treatment options for these complications were quite limited. Endothelin-1 (ET-1) is a peptide that has a role in promoting both vascular injury and the fibrotic process in SSc. Bosentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension. In patients with pulmonary hypertension secondary to SSc, bosentan therapy prevents deterioration in exercise capacity and may improve survival. No beneficial effect was found in one study in patients with interstitial lung disease and SSc. Bosentan is able to reduce the number of new digital ulcers in patients with either a history of previous ulcers or an active ulcer, without expediting the healing of existing ulcers. Bosentan therapy is contraindicated in pregnancy and causes elevated liver transaminases in up to 14% of patients. Hence, monthly pregnancy tests should be performed and hepatic function should be monitored.
系统性硬化症（SSc）是一种相对罕见的慢性结缔组织病，其特征为不同程度的皮肤纤维化和内脏器官受累。肺部损害，包括肺动脉高压和间质性肺疾病，是目前SSc患者的主要死亡原因。指端溃疡是常见的并发症，会导致严重的发病率和功能受限。直到最近，针对这些并发症的治疗选择还非常有限。内皮素-1（ET-1）是一种在SSc的血管损伤和纤维化过程中均起作用的肽。波生坦是一种双重内皮素受体拮抗剂，被批准用于治疗肺动脉高压。在继发于SSc的肺动脉高压患者中，波生坦治疗可防止运动能力恶化，并可能改善生存率。在一项针对间质性肺疾病和SSc患者的研究中未发现有益效果。波生坦能够减少有既往溃疡病史或活动性溃疡患者的新指端溃疡数量，但不会加速现有溃疡的愈合。波生坦治疗在妊娠期间禁用，并且在高达14%的患者中会导致肝转氨酶升高。因此，应每月进行妊娠试验并监测肝功能。
