Rheumatology Advance Access originally published online on March 10, 2006
Rheumatology 2006 45(7):911-912; doi:10.1093/rheumatology/kei129
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LETTER TO THE EDITOR |
Treatment of severe Raynaud's phenomenon with bosentan in a patient with systemic sclerosis
1 Department of Medicine, St Paul's Hospital, 2 University of British Columbia, 3 Capture Centre for Cardiovascular and Pulmonary Research, Vancouver, BC, Canada
SIR, Raynaud's phenomenon is characterized by recurrent episodes of vasospasm most commonly occurring in the hands and feet. It is a manifestation of the widespread vascular involvement that occurs in systemic sclerosis [1]. Digital ischaemic and necrotic lesions are a frequent complication, with an estimated frequency of 30–40% [2]. Recent studies indicate that bosentan prevents the occurrence of new digital ulcers [3] and may promote actual healing [4, 5]. The effects of bosentan on peripheral blood flow, circulating endothelial cells (CD146+), and progenitor cells (CD34+) involved in vessel repair, have not been reported.
We examined and treated a 42-yr-old woman with SCL-70-negative systemic sclerosis, early interstitial pulmonary fibrosis and an estimated pulmonary arterial pressure of 37 mmHg. Over the space of 1 yr she developed skin thickening, Raynaud's phenomenon, and then finger tip ulcers, pulp space loss and gangrene. Angiograms of the right hand showed severe vasculopathy with abrupt termination of nearly all digital arteries, the most severely affected being the index and ring fingers. The condition did not respond to calcium channel blockers, nitroglycerine or sympathetic blockade. Epoprostenol or equivalent medications were not available. She was begun on bosentan initially at 37.5 mg twice per day, her initial tolerance level, and then at 62.5 mg twice per day a month later, then 125 mg twice per day. On this regimen there was dramatic and sustained improvement, which began to occur even on the small initial doses of bosentan.
Small-vessel blood flow measured by laser Doppler fluximetry (Moore Inc, Wilmington, Delaware, USA) showed improvement (Fig. 1a, right vs left). The gangrenous areas healed within a month (Fig. 1b, right vs left). The vasodilator changes were not sustained over time, but the vessels did show increased responses to a warm and cold challenge (Fig. 2b). Circulating numbers of CD146 cells, a population of mainly endothelial cells, showed a dramatic drop over time, suggesting a reduction in vascular injury. There was a concomitant increase in circulating CD34 cells, a population of stem cells which contains endothelial progenitors or angioblasts (Fig. 2a).
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In this patient, bosentan appeared to have had a beneficial effect in healing of the gangrenous lesions of severe Raynaud's phenomenon. There was a concomitant decrease in pain and improvement in function, which was sustained. It also improved peripheral blood flow and vessel responsiveness. Our finding of a significant decrease in circulating CD146 cell levels with a concomitant rise in CD34 cell levels suggests a decrease in endothelial damage and an increase in circulating stem cells involved in vessel repair. Circulating endothelial cells have been shown to be a marker of vascular damage in scleroderma and other conditions [6–9]. Furthermore, CD34 cells contain a fraction of angioblasts which have the ability to repair damaged vasculature [10]. This case suggests that further study of the effect of bosentan in vascular healing and possibly remodelling are needed.
The author has declared no conflicts of interest.
References
- Wigley FM, Flavahan N. Raynaud's phenomenon. Rheum Dis Clin North Am 1996;22:765–81.[CrossRef][Web of Science][Medline]
- Ferri C, Valentini G, Cozzi F et al. Systemic sclerosis: demographic, clinical and serologic features and survival in 1,012 Italian patients. Medicine 2002;81:139–53.[CrossRef][Medline]
- Korn JH, Mayes M, Matucci Cerinic M et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 2004;50:3985–93.[CrossRef][Web of Science][Medline]
- Humbert M, Cabane J. Successful treatment of systemic sclerosis digital ulcers and pulmonary arterial hypertension with endothelin receptor antagonist bosentan. Rheumatology 2003;42:191–3.
[Free Full Text] - Ramos-Casals M, Brito-Zeron P, Claver NG et al. Successful treatment of severe Raynaud's phenomenon with bosentan in four patients with systemic sclerosis. Rheumatology 2004;43:1454–6.
[Free Full Text] - Dignat-George F, Sampol J. Circulating endothelial cells in vascular disorders: new insights into an old concept. Eur Haematol 2000;65:215–20.
- Clancy RM. Circulating endothelial cells and vascular injury in systemic lupus erythematosus. Curr Rheumatol Rep 2000;2:39–43.[Medline]
- Solovey A, Lin Y, Brown P et al. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med 1997;337:1584–90.
[Abstract/Free Full Text] - Del Papa N, Colombo G, Frachiolla N et al. Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis. Arthritis Rheum 2004;50:1296–304.[CrossRef][Web of Science][Medline]
- Hill JM, Zalos G, Hlacox JP et al. Circulating endothelial progenitor cells vascular function and cardiovascular risk. N Engl J Med 2003;348:593–600.
[Abstract/Free Full Text]
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