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. 2020 Jun;5(2):159-164.
doi: 10.1177/2397198319876738. Epub 2019 Sep 19.

Combination therapy with bosentan and sildenafil for refractory digital ulcers and Raynaud's phenomenon in a 30-year-old woman with systemic sclerosis: Case report and literature review

Jan-Gerd Rademacher  1 , Chris Wincup  2   3 , Björn Tampe  1 , Peter Korsten  1
Affiliations

Combination therapy with bosentan and sildenafil for refractory digital ulcers and Raynaud's phenomenon in a 30-year-old woman with systemic sclerosis: Case report and literature review

Jan-Gerd Rademacher et al. J Scleroderma Relat Disord. 2020 Jun.

Abstract

Background: Systemic sclerosis is a rare autoimmune disease characterized by skin and organ fibrosis, and vasculopathy. Raynaud's phenomenon is almost universally present in systemic sclerosis and can be the most debilitating symptom. Raynaud's phenomenon may lead to the development of digital ulcers, potentially complicated by infection, tissue necrosis, and auto-amputation. Recommended treatments have variable efficacy.

Methods: We report the case of a 30-year-old woman with diffuse systemic sclerosis suffering from severe Raynaud's phenomenon and digital ulcers with digital tissue necrosis who was treated with combination therapy of an endothelin receptor antagonist and phosphodiesterase 5 inhibitor. In addition, we reviewed the literature on the topic.

Results: Previous therapy with calcium-channel blockers, intravenous iloprost, and bosentan had all failed to control symptoms. We added sildenafil in combination with bosentan and observed a rapid and sustained treatment effect. Raynaud's phenomenon severity, number of attacks, and attack duration decreased within 2 weeks of initiating treatment. Furthermore, this resulted in the healing of established digital ulcers.

Conclusion: Our case report suggests that combination therapy may be a feasible treatment for the most severely affected and refractory patients. In our literature review, we found one retrospective study and three additional cases with similarly encouraging results.

Keywords: Raynaud’s phenomenon; digital ulcers; endothelin receptor antagonists; phosphodiesterase inhibitors; systemic sclerosis.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Clinical images of the patient’s digits: (a) there is marked tissue necrosis with digital ulcers and (b) 12 weeks following treatment initiation, there is improved DU healing.
Figure 2.
Figure 2.
Effect of bosentan and sildenafil on Raynaud’s attack frequency, duration, and intensity. (a) The maximum number of attacks decreased from more than 25 per day to 3 after 4 weeks of treatment. (b) The maximum duration of attacks decreased from 30 min to a maximum of 2 min within the first weeks of treatment and was sustained. (c) The Raynaud’s Condition Score (RCS) ranging from 0 to 10 (10 being the most intense score) decreased from 10 to 3 after 4 weeks.
See this image and copyright information in PMC

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