Use of intravenous epoprostenol as a treatment for the digital vasculopathy associated with the scleroderma spectrum of diseases

Abstract

ORIGINAL RESEARCH ARTICLE cations adversely affect the quality of life of patients and, in the extreme, can affect the integrity and viability of any digit. The pathophysiology of scleroderma spectrum digital vasculopathy (including RP) is poorly understood, but is likely multifactorial. However, studies have suggested that an overproduction of the vasoconstrictor endothelin-1 (1), and/or an underproduction of the vasodilators nitric oxide and prostacyclin by endothelial cells of peripheral blood vessels are important contributing factors (2). Management options for scleroderma spectrum digital vasculopathy include first-line therapy such as dihydropyridine-type calcium channel receptor antagonists. For severe or refractory cases of SSc-related vasculopathy, phosphodiesterase-5 inhibitors (PDE-5i), nitroglycerin ointment, and other vasodilators have been used. In cases where digits are at imminent risk of necrosis, prostanoids have been utilized (3-14). For example, a multicenter, placebo-controlled, double-blind study of iloprost observed a mean reduction in weekly RP attacks of 39% (compared with 22% in the placebo arm, p = 0.005) (12). There were also statistically significant improvements in RP clinical scores and degree of digital ulcer healing. Although much of the healing of pre-existing ulcers occurred in the first few weeks of the study, the effect of the iloprost

Raynaud's phenomenon and digital ulcers: advances in evaluation and management

“…Intravenous prostanoid therapy is well established for the treatment of severe Raynaud's phenomenon and digital ulceration. Recent reports have described different protocols [44,50,51 ] in a retrospective single-centre study of 47 patients compared a continuous 48-h infusion with 3-5 h/day outpatient infusions (0.5-2.0 ng/kg/min) for 2 days: costs were comparable, but the outpatient infusions were less well tolerated. An interesting recent development is the suggestion that i.v.…”

“…Intravenous prostanoid therapy is well established for the treatment of severe Raynaud's phenomenon and digital ulceration. Recent reports have described different protocols [44,50,51 ▪ ], and a systematic review of i.v. iloprost highlighted the lack of consensus between experts regarding the optimal regime [52].…”

Digital ulcers: should debridement be a standard of care in systemic sclerosis?

“…iloprost) reduce the development of new DUs and are associated with improved DU healing. 24,25 Although approved in the EU and UK for the treatment of DU and severe RP, IV prostanoids are not yet approved for these indications in the US, but Phase III clinical trials are currently ongoing. There is some evidence that phosphodiesterase type-5 inhibitors may facilitate improved DU healing; however, the authors of a recent randomised, placebo-controlled trial of sildenafil found no difference (in part due to the unexpectedly high healing rate in the placebo arm).…”

Raynaud’s phenomenon

“…69,70 Prescribing practice varies internationally: IV iloprost has been most studied and is most widely used, and in varying regimes, 71 but is not available in the United States, IV epoprostenol is another option. 72 Cruz et al 73 have recently reviewed the use of IV epoprostenol. A major disadvantage of IV prostanoids is the need for hospitalisation, as well as systemic vasodilatory side-effects.…”