Dovepress blockers or topical nitrates may be considered for those without an adequate response to lifestyle modification. Other therapies have not been demonstrated to be effective in this population. In patients with secondary RP, lifestyle modifications should also be applied; however, pharmacologic management is more likely to be necessary. In addition to calcium chan- nel blockers, there may be a role for topical nitrates, PDE5 inhibitors, endothelin antagonists, or prostaglandin derivatives (Table 4). Although additional clinical studies are necessary to validate the efficacy of these agents in RP, the clinical data, oral availability, and favorable tolerability profile suggests a trial of a PDE5 inhibitor may be appropriate in patients with severe symptoms associated with RP despite traditional vasodilator therapy. Further studies of statins, botulinum toxin, N-acetyl- cysteine are necessary to establish the role of these agents. Disclosure The author declares no conflicts of interest. References 1. Wigley FM. Raynaud’s phenomenon. N Engl J Med. 2002;347: 1001–1008. 2. Cooke JP, Marshall JM. Mechanisms of Raynaud’s disease. Vasc Med. 2005;10:293–307. 3. Bakst R, Merola JE, Franks AG Jr, Sanchez M. Raynaud’s phenom- enon: pathogenesis and management. J Am Acad Dermatol. 2008;59: 633–653. 4. Rosenkranz S, Diet F, Karasch T, Weibrauch J, Wassermann K, Erdmann E. Sildenafil improved pulmonary hypertension and peripheral blood flow in a patient with scleroderma-associated lung fibrosis and the Raynaud phenomenon [letter]. Ann Intern Med. 2003;139:871–872. 5. Fries R, Shariat K, von Wilmowsky H, Bohm M. Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation. 2005;112:2980–2985. 6. Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis. Rheumatology. 2005;44: 145–150. 7. Thompson AE, Shea B, Welch V, Fenlon D, Pope JE. Calcium-channel blockers for Raynaud’s phenomenon in systemic sclerosis. Arthritis Rheum. 2001;44:1841–1847. 8. Vinjar B, Stewart M. Oral vasodilators for primary Raynaud’s phenom- enon. Cochrane Database Syst Rev. 2008, Issue 2. Art. No.: CD006687. DOI: 10.1002/14651858.CD006687. 9. Dziadzio M, Denton CP, Smith R, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma. Arthritis Rheum. 1999;42:2646–2655. 10. Harding SE, Tingey PC, Pope J, et al. Prazosin for Raynaud’s phenome- non in progressive systemic sclerosis. Cochrane Database Syst Rev. 1998, Issue 2. Art. No.: CD000956. DOI: 10.1002/14651858.CD000956. 11. ClinicalTrials.gov database. Accessed July 15, 2009. 12. Teh LS, Manning J, Moore T, Tully MP, O’Reilly D, Jayson MI. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol. 1995;34:636–641. 13. Coppock JS, Hardman JM, Bacon PA, Woods KL, Kendall MJ. Objec- tive relief of vasospasm by glyceryl trinitrate in secondary Raynaud’s phenomenon. Postgrad Med J. 1986;62:15–18. 14. Franks AG Jr. Topical glyceryl trinitrate as adjunctive treatment in Raynaud’s disease. Lancet. 1982;1(8263):76–77. Vascular Health and Risk Management 2010:6 Treatment of Raynaud’s phenomenon 15. Hummers LK, Dugowson CE, Dechow FJ, Wise RA, Bartolucci A, Wigley FM.A multi-center, blinded, randomized, placebo-controlled study of MQX-503, a topical gel formulation of nitroglycerin, in patients with Raynaud phenomenon (RP) [abstract]. Arthritis Rheum. 2006; 54(9 Suppl):S523. 16. Chung L, Shapiro L, Fiorentino D, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud’s phenomenon. Arthritis Rheum. 2009;60:870–877. 17. Belch J, Fiorentino D, Denton C, et al. MQX-503, a novel topical nitroglyc- erin formulation, improves severity of symptoms associated with Raynaud’s phenomenon [abstract]. Arthritis Rheum. 2008;58(9 Suppl):S622. 18. Rothfield N, Shapiro L, Fiorentino D, et al. Safety and tolerability of MQX-503, a novel investigational topical formulation of nitroglycerin for the treatment of Raynaud’s phenomenon [abstract]. Arthritis Rheum. 2008;58(9 Suppl):S821. 19. Pope J, Fenlon D, Thompson A, et al. Iloprost and cisaprost for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 1998; issue 2, Art. No.: CD000953. DOI: 10.1002/ 14651858.CD000953. 20. Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. Ann Intern Med. 1994;120:199–206. 21. Yardumian DA, Isenberg DA, Rustin M, et al. Successful treatment of Raynaud’s syndrome with iloprost, a chemically stable prostacycline analogue. Br J Rheumatol. 1988;27:220–226. 22. McHugh NJ, Csuka M, Watson H, et al. Infusion of iloprost, a prosta- cyclin analogue, for treatment of Raynaud’s phenomenon in systemic sclerosis. Ann Rheum Dis. 1988;47:43–47. 23. Wigley FM, Seibold JR, Wise RA, McCloskey DA, Dole WP. Intrave- nous iloprost treatment of Raynaud’s phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol. 1992;19:1407–1414. 24. Kyle MV, Belcher G, Hazleman BL. Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud’s phenomenon. J Rheumatol. 1992;19:1403–1406. 25. Torley HI, Madhok R, Capell HA, et al. A double-blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud’s phenomenon secondary to connective tissue diseases. Ann Rheum Dis. 1991;50:800–804. 26. Kawald A, Burmester GR, Huscher D, Sunderkotter C, Riemerkasten G. Low versus high-dose iloprost therapy over 21 days in patients with secondary Raynaud’s phenomenon and systemic sclerosis: a random- ized, open, single-center study. J Rheumatol. 2008;35:1830–1837. 27. Rademaker M, Cooke ED, Almond NE, et al. Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud’s phe- nomenon in patients with systemic sclerosis: a double-blind randomised study. BMJ. 1989;298:561–564. 28. Scorza R, Caronni M, Mascagni B, et al. Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud’s phenomenon. A randomized, controlled study. Clin Exp Rheumatol. 2001;19:503–508. 29. Bettoni L, Geri A, Airo P, et al. Systemic sclerosis therapy with iloprost: a prospective observational study of 30 patients treated for a median of 3 years. Clin Rheumatol. 2002;21:244–250. 30. Hernandez FJG, Medina CO, Romero LM, et al. Iloprost for severe Raynaud’s phenomenon and ischaemic ulcers related with systemic diseases. Med Clin (Barc). 2004:122:501–504. 31. Milio G, Corrado E, Genova C, et al. Iloprost treatment in patients with Raynaud’s phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol. Rheumatology. 2006:45:999–1004. 32. Lambova SN. Therapy with iloprost in patients with severe Raynaud’s phenomenon secondary to scleroderma [abstract]. Ann Rheum Dis. 2006;65(Suppl 2):396. 33. Resende C, Castelao W, Fonseca JE, et al. Intravenous iloprost treatment of severe Raynaud’s phenomenon secondary to connective tissue diseases [abstract]. EULAR 2002. Stockholm, Sweden, June 12–15, 2002: Abstract AB0227. 34. Zulian F, Corona F, Gerloni V, et al. Safety and efficacy of iloprost for the treatment of ischemic digits in pediatric connective tissue diseases [abstract]. EULAR 2002. Stockholm, Sweden, June 12–15, 2002: Abstract FR1025. submit your manuscript | www.dovepress.com Dovepress 175