Optimal management of digital ulcers in systemic sclerosis

Shawn Abraham, Virginia Steen, Shawn Abraham, Virginia Steen

Abstract

Raynaud's phenomenon and digital ulcerations are two common clinical features seen in patients with systemic sclerosis. They are painful and lead to significant morbidity and altered hand function within this patient population. While currently there are no US Food and Drug Administration (FDA)-approved medications for the treatment of digital ulcerations in the United States, clinical trials have supported the use of pharmacologic and nonpharmacologic modalities in facilitating healing of existing digital ulcers and preventing formation of new ulcers. This article reviews the published data on these therapeutic options.

Keywords: Raynaud’s phenomenon; digital ulcers; scleroderma; systemic sclerosis; treatment.

References

    1. Denton CP, Korn JH. Digital ulceration and critical digital ischaemia in scleroderma. Scleroderma Care Res. 2003;1:12–16.
    1. Baron M. Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis. Clin Rheumatol. 2014;33(2):207–214.
    1. Sunderkotter C, Hergott I, Bruckner C, et al. Comparison of patients with and without digital ulcers in systemic sclerosis: detection of possible risk factors. Br J Dermatol. 2009;160:835–843.
    1. Hachulla E, Clerson P, Launay D, et al. Natural history of ischemic digital ulcers in systemic sclerosis: a single-center retrospective longitudinal study. J Rheumatol. 2007;34:2423–2430.
    1. Steen V, Denton CP, Pope JE, Matucci-Cerinic M. Digital ulcers: overt vascular disease in systemic sclerosis. Rheumatology. 2009;48:19–24.
    1. Ferri C, Sebastiani M, Lo Monaco, et al. Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients’ population and review of the literature. Autoimmun Rev. 2014;13(10):1026–1034. doi: 10.1016/j.autrev.2014.08.029.
    1. Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis. Rheumatology. 2005;44:145–150.
    1. Botzoris V, Drosos AA. Management of Raynaud’s phenomenon and digital ulcers in systemic sclerosis. Joint Bone Spine. 2011;78(4):341–346.
    1. Hughes J, Lockhart J, Joyce A. Do calcium antagonists contribute to gastro-oesophageal reflux disease and concomitant noncardiac chest pain. Br J Clin Pharmacol. 2007;64(1):83–89.
    1. Gore J, Silver R. Oral sildenafil for the treatment of Raynaud’s phenomenon and digital ulcers secondary to systemic sclerosis. Ann Rheum Dis. 2005;64(9):1387.
    1. Kumar K, Griffiths B, Allen J. Thermographic and symptomatic effect of a single dose of sildenafil citrate on Raynaud’s phenomenon in patients with systemic sclerosis: a potential treatment. J Rheumatol. 2006;33(9):1918–1919.
    1. Fries R, Shariat K, Von Wilmowsky H, Bohm M. Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation. 2005;112(19):2980–2985.
    1. Brueckner CS, Becker MO, Kroencke T, et al. Effect of sildenafil on digital ulcers in systemic sclerosis: analysis from a single centre pilot study. Ann Rheum Dis. 2010;69(8):1475–1478.
    1. Caglayan E, Huntgeburth M, Karasch T, et al. Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud’s disease. Arch Intern Med. 2006;166(2):231–233.
    1. Carlino G. Treatment of Raynaud’s phenomenon with tadalafil, a phosphodiesterase-5 inhibitor (abstract) Ann Rheum Dis. 2005;64:258.
    1. Schiopu E, Hsu VM, Impens AJ, et al. Randomized placebo-controlled crossover trial of tadalafil in Raynaud’s phenomenon secondary to systemic sclerosis. J Rheumatol. 2009;36(10):2264–2268.
    1. Rosato E, Letizia C, Proietti M, et al. Plasma adrenomedullin and endothelin-1 levels are reduced and Raynaud’s phenomenon improved by daily tadalafil administration in male patients with systemic sclerosis. J Biol Regul Homeost Agents. 2009;23(1):23–29.
    1. Shenoy PD, Kumar S, Jha LK, et al. Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy: a double blind randomized cross over trial. Rheumatology. 2010;49(12):2420–2428.
    1. Agarwal V, Ghosh P, Sharma A, et al. Efficacy of tadalafil in Raynaud’s phenomenon secondary to systemic sclerosis: a double blind randomized placebo controlled parallel group multicenter study. Arthritis Rheum. 2010;62:S872.
    1. Lee EY, Park JK, Lee W, et al. Head-to-head comparison of udenafil versus amlodipine in the treatment of secondary Raynaud’s phenomenon: a double-blind, randomized, cross-over study. Rheumatology (Oxford) 2014;53(4):658–664.
    1. Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomised trials. Ann Rheum Dis. 2013;72(10):1696–1699.
    1. Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusions in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med. 1994;120:199–206.
    1. Badesch D, Tapson V, McGoon M, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to scleroderma spectrum of disease. Ann Intern Med. 2000;132:425–434.
    1. Wigley FM, Korn JH, Csuka ME, et al. Oral iloprost treatment in patients with Raynaud phenomenon secondary to systemic sclerosis: a multi-center, placebo-controlled, double-blind study. Arthritis Rheum. 1998;41:670–677.
    1. Shah AA, Schiopu E, Hummers LK, et al. Retrospective look at the recurrence of digital ulcers in patients with scleroderma after discontinuation of oral treprostinil. Arthritis Rheum. 2015;66:S848.
    1. Garcia de la Pena-Lefebvre P, Rodriguez Rubio S, Valero Expositio M, et al. Long term experience of bosentan for treating ulcers and healed ulcers in systemic sclerosis patients. Rheumatology (Oxford) 2008;47:464–466.
    1. 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;50:3985–3993.
    1. Seibold JR, Denton CP, Furst DE, et al. Bosentan prevents occurrence but does not speed healing of digital ulcers in patients with systemic sclerosis (SSc) Arthritis Rheum. 2005;52:4057.
    1. Anderson ME, Moore TL, Hollis S, Jayson MIV, King TA, Herrick AL. Digital vascular response to topical glyceryl trinitrate, as measured by laser Doppler imaging, in primary Raynaud’s phenomenon and systemic sclerosis. Rheumatology. 2002;41(3):324–328.
    1. Chung L, Shapiro L, Fiorentino D, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud’s phenomenon: a randomized controlled trial. Arthritis Rheum. 2009;60:870–877.
    1. Hummers LK, Dugowson CE, Dechow F, et al. A multi-centre, blinded, randomized, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon. Ann Rheum Dis. 2013;72:1962–1967.
    1. Teh LS, Manning J, Moore T, Tully MP, O’Reilly D, Jayson MIV. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol. 1995;34:636–641.
    1. Sambo P, Amico D, Giacomelli R, et al. Intravenous N-acetylcysteine for treatment of Raynaud’s phenomenon secondary to systemic sclerosis: a pilot study. J Rheumatol. 2001;28(10):2257–2262.
    1. Rosato E, Borghese F, Pisarri S, et al. The treatment with N-acetylcysteine of Raynaud’s phenomenon and ischemic ulcers therapy in sclerodermic patients: a prospective observational study of 50 patients. Clin Rheumatol. 2009;28(12):1379–1384.
    1. Dziadzio M, Denton CP, Smith R, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum. 1999;42:2646–2655.
    1. Pope J, Fenlon D, Thompson A, et al. Prazosin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 2000;(2):CD000956.
    1. Coleiro B, Marshall SE, Denton CP, et al. Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology. 2001;40:1038–1043.
    1. Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol. 2008;35:1801–1808.
    1. Fiori G, Galluccio F, Braschi F, et al. Vitamin E gel reduces time of healing of digital ulcers in systemic sclerosis. Clin Exp Rheumatol. 2009;27(3):51–54.
    1. Moran ME. Scleroderma and evidence based non-pharmaceutical treatment modalities for digital ulcers: a systematic review. J Wound Care. 2014;23(10):510–516.
    1. Matsumoto Y, Ueyama T, Endo M, et al. Endoscopic thoracic sympathectomy for Raynaud’s phenomenon. J Vasc Surg. 2002;36(1):57–61.
    1. Wasserman A, Brahn E. Systemic sclerosis: bilateral improvement of Raynaud’s phenomenon with unilateral digital sympathectomy. Semin Arthritis Rheum. 2010;40:137–146.
    1. Ruch DS, Holden M, Smith BP, et al. Periarterial sympathectomy for treatment of chronic digital ischemia. J Rheumatol. 2003;30(8):1788–1792.
    1. Momeni A, Sorice S, Valenzuela A. Surgical treatment of systemic sclerosis – is it justified to offer peripheral sympathectomy earlier in the disease process? Microsurgery. 2015 Jan 14; doi: 10.1002/micr.22379. Epub.
    1. Uppal L, Dhaliwal K, Butler PE. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud’s syndrome associated with scleroderma. J Hand Surg. 2014;39:876–880.
    1. Iorio M, Masden D, Higgins J. Botulinum toxin a treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum. 2012;41:599–603.
    1. Granel B, Daumas A, Jouve E, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase 1 trial. Ann Rheum Dis. 2014 Aug 11; doi: 10.1136/annrheumdis-2014-205681. Epub.
    1. Del Bene MD, Pozzi MR, Rovati L, et al. Autologous fat grafting for scleroderma-induced digital ulcers. An effective technique in patients with systemic sclerosis. Handchir Mikrochir Plast Chir. 2014;46:242–247.
    1. Taylor MH, McFadden JA, Bolster MB, et al. Ulnar artery involvement in systemic sclerosis (scleroderma) J Rheumatol. 2002;29(1):102–106.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren