Low occurrence of digital ulcers in scleroderma patients treated with bosentan for pulmonary arterial hypertension: a retrospective case–control study

Abstract

Digital ulcers (DU) are one of the most common and debilitating manifestations of vasculopathy in systemic sclerosis (SSc). Their prevention is important in order to improve patients' outcome and as a result of the economic impact they have on society. Randomised controlled studies have demonstrated that bosentan, an endothelin receptor antagonist, reduces the appearance of new DU. The aim of this retrospective study was to evaluate the occurrence of DU in a group of patients receiving long-term bosentan treatment for pulmonary arterial hypertension associated with SSc (PAH-SSc). Patients with PAH-SSc and treated with bosentan for at least 6 months (n = 30) were evaluated. Thirty patients with SSc not treated with bosentan, but matched for sex, age, disease duration and cutaneous form of SSc, were considered as a control group. The occurrence of DU, defined as loss of tissue of varying degrees in the epidermis, dermis and subcutaneous tissue, was determined in the bosentan-treated and untreated groups. Mean duration of bosentan treatment was 3.6 years. DU were detected in six patients in the bosentan-treated group (20.0 %) and 16 patients (53.3 %) in the untreated group (p = 0.0015). There were no significant differences in demographic or clinical characteristics between patients with or without DU at study end. The occurrence of DU in patients with PAH-SSc receiving long-term bosentan treatment was significantly lower than in untreated patients. The results from this long-term observational study provide valuable information on management of patients with PAH-SSc.

The Role of Endothelin-1 and Endothelin Receptor Antagonists in Inflammatory Response and Sepsis

“…Despite having side effects such as increases in liver transaminase content, headache, peripheral oedema, dizziness, nasal congestion and nausea, bosentan therapy is generally regarded as beneficial (Montani et al 2013 ; Motte et al 2006 ). Bosentan also has been found to exert a positive therapeutic influence on the treatment of systemic sclerosis (scleroderma) and other disorders (Cozzi et al 2013 ) (Table 3 ).…”

Beneficial effects of long-term treatment with bosentan on the development of pulmonary arterial hypertension in patients with systemic sclerosis

“…These findings are in agreement with those reported in a long-term observational study showing the low occurrence of digital ulcers in patients with systemic sclerosis receiving bosentan for PAH. 9 Increased ET-1 activity inhibits nitric oxide synthesis, which has been found to be impaired in patients with systemic sclerosis. 10 Bosentan improves exercise-induced and flow-mediated pulmonary vasodilatation and thus restores endothelial function by increasing nitric oxide production.…”

Update on Systemic Sclerosis

“…First-line treatment and prevention strategy of chronic ulcers are calcium channel blockers [48] with addition of PDE5i for second-line treatment [24•]. ERAs have been shown to help in prevention of new digital ulcers [71], but most studies do not demonstrate efficacy in healing ulcers [49]; thus, they are usually considered third-line therapy. In active ischemia, there is not a consensus on first-line therapy, but IV prostaglandins should be considered for treatment as randomized controlled trials have shown efficacy in healing digital ulcers [51,52].…”