Highlights & Basics
- Raynaud phenomenon (RP) is common, affecting between 3% and 5% of the population.
- The diagnosis is made clinically: digits turn white (pallor) then blue with deoxygenation and/or red with reperfusion; pallor is well demarcated.
- Primary RP often needs no pharmacologic treatment. Keeping warm, smoking cessation, regular exercise, and avoiding stress are recommended.
- Secondary RP can be severe, especially when associated with scleroderma. Other connective tissue diseases, malignancy, and atherosclerosis may also be the underlying cause.
- In secondary RP, calcium-channel blockers, angiotensin receptor antagonists, ACE inhibitors, SSRIs, systemic and topical nitrates, phosphodiesterase-5 inhibitors, and prostacyclins are potential treatment options.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Citations
Brand FN, Larson MG, Kannel WB, et al. The occurrence of Raynaud's phenomenon in a general population: the Framingham Study. Vasc Med. 1997;2:296-230.[Abstract]
Fernández-Codina A, Walker KM, Pope JE, et al. Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheumatol. 2018 Nov;70(11):1820-8.[Abstract][Full Text]
1. Herrick A. Pathogenesis of Raynaud's phenomenon. Rheumatology (Oxford). 2005;44:587-596.[Abstract][Full Text]
2. White CR, Haidekker MA, Stevens HY, et al. Extracellular signal-regulated kinase activation and endothelin-1 production in human endothelial cells exposed to vibration. J Physiol. 2004;555(Pt 2):565-572.[Abstract][Full Text]
3. Garner R, Kumari R, Lanyon P, et al. Prevalence, risk factors and associations of primary Raynaud's phenomenon: systematic review and meta-analysis of observational studies. BMJ Open. 2015 Mar 16;5(3):e006389.[Abstract][Full Text]
4. Belch J, Carlizza A, Carpentier PH, et al. ESVM guidelines - the diagnosis and management of Raynaud's phenomenon. Vasa. 2017 Oct;46(6):413-23.[Abstract][Full Text]
5. Brand FN, Larson MG, Kannel WB, et al. The occurrence of Raynaud's phenomenon in a general population: the Framingham Study. Vasc Med. 1997;2:296-230.[Abstract]
6. Maricq HR, Carpentier PH, Weinrich MC, et al. Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison. J Rheumatol. 1997 May;24(5):879-89.[Abstract]
7. Flavahan NA, Flavahan S, Liu Q, et al. Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum. 2000;43:1886-1890.[Abstract][Full Text]
8. Wigley FM. Raynaud's phenomenon. Curr Opin Rheumatol. 1993;5:773-784.[Abstract]
9. Pistorius MA, Planchon B, Schott JJ, et al. Heredity and genetic aspects of Raynaud's disease. J Mal Vasc. 2006;31:10-15.[Abstract]
10. Smyth AE, Hughes AE, Bruce IN, et al. A case-control study of candidate vasoactive mediator genes in primary Raynaud's phenomenon. Rheumatology (Oxford). 1999;38:1094-1098.[Abstract][Full Text]
11. Freedman RR, Mayes MD. Familial aggregation of primary Raynaud's disease. Arthritis Rheum. 1996;39:1189-1191.[Abstract]
12. Eliasson K, Danielson M, Hylander B, et al. Raynaud's phenomenon caused by beta-receptor blocking drugs. Improvement after treatment with a combined alpha- and beta-blocker. Acta Med Scand. 1984;215:333-339.[Abstract]
13. Brotzu G, Falchi S, Mannu B, et al. The importance of presynaptic beta receptors in Raynaud's phenomenon. J Vasc Surg. 1989;9:767.[Abstract]
14. Herrick A. Treatment of Raynaud's phenomenon: new insights and developments. Curr Rheumatol Rep. 2003;5:168-174.[Abstract]
15. Pope JE, Al-Bishri J, Al-Azem H, et al. The temporal relationship of Raynaud's phenomenon and features of connective tissue disease in rheumatoid arthritis. J Rheumatol. 2008;35:2329-2333.[Abstract]
16. Lalani S, Pope J, de Leon F, et al. Clinical features and prognosis of late-onset systemic lupus erythematosus: results from the 1000 faces of lupus study. J Rheumatol. 2010;37:38-44.[Abstract]
17. Ramos-Casals M, Anaya JM, García-Carrasco M, et al. Cutaneous vasculitis in primary Sjögren syndrome: classification and clinical significance of 52 patients. Medicine (Baltimore). 2004;83:96-106.[Abstract]
18. García-Carrasco M, Sisó A, Ramos-Casals M, et al. Raynaud's phenomenon in primary Sjögren's syndrome. Prevalence and clinical characteristics in a series of 320 patients. J Rheumatol. 2002;29:726-730.[Abstract]
19. Parodi A, Caproni M, Marzano AV, et al. Dermatomyositis in 132 patients with different clinical subtypes: cutaneous signs, constitutional symptoms and circulating antibodies. Acta Derm Venereol. 2002;82:48-51.[Abstract]
20. Grader-Beck T, Wigley FM. Raynaud's phenomenon in mixed connective tissue disease. Rheum Dis Clin North Am. 2005;31:465-481.[Abstract]
21. Hong P, Pope JE, Ouimet JM, et al. Erectile dysfunction associated with scleroderma: a case-control study of men with scleroderma and rheumatoid arthritis. J Rheumatol. 2004;31:508-513.[Abstract]
22. Taylor W. Hand-arm vibration syndrome: a new clinical classification and an updated British standard guide for hand transmitted vibration. Br J Ind Med. 1988;45:281-282.[Abstract]
23. Harada N, Mahbub MH. Diagnosis of vascular injuries caused by hand-transmitted vibration. Int Arch Occup Environ Health. 2008;81:507-518.[Abstract]
24. Małecki R, Zdrojowy K, Adamiec R. Thromboangiitis obliterans in the 21st century - a new face of disease. Atherosclerosis. 2009;206:328-334.[Abstract]
25. Paraskevas KI, Liapis CD, Briana DD, et al. Thromboangiitis obliterans (Buerger's disease): searching for a therapeutic strategy. Angiology. 2007;58:75-84.[Abstract]
26. Suter LG, Murabito JM, Felson DT, et al. Smoking, alcohol consumption, and Raynaud's phenomenon in middle age. Am J Med. 2007;120:264-267.[Abstract]
27. Moore TL, Roberts C, Murray AK, et al. Reliability of dermoscopy in the assessment of patients with Raynaud's phenomenon. Rheumatology (Oxford). 2010;49:542-547.[Abstract]
28. Boin F, Wigley FM. Understanding, assessing and treating Raynaud's phenomenon. Curr Opin Rheumatol. 2005;17:752-760.[Abstract]
29. Baron M, Bell M, Bookman A, et al. Office capillaroscopy in systemic sclerosis. Clin Rheumatol. 2006;26:1268-1274.[Abstract]
30. Ko GD, Berbrayer D. Effect of ceramic-impregnated "thermoflow" gloves on patients with Raynaud's syndrome: randomized, placebo-controlled study. Altern Med Rev. 2002;7:328-335.[Abstract][Full Text]
31. Huisstede BM, Hoogvliet P, Paulis WD, et al. Effectiveness of interventions for secondary Raynaud's phenomenon: a systematic review. Arch Phys Med Rehabil. 2011;92:1166-1180.[Abstract]
32. Ennis H, Hughes M, Anderson ME, et al. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2016 Feb 25;2:CD002069.[Abstract][Full Text]
33. Rirash F, Tingey PC, Harding SE, et al. Calcium channel blockers for primary and secondary Raynaud's phenomenon. Cochrane Database Syst Rev. 2017 Dec 13;12:CD000467.[Abstract][Full Text]
34. Roustit M, Blaise S, Allanore Y, et al. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials. Ann Rheum Dis. 2013;72:1696-1699.[Abstract]
35. Teh LS, Manning J, Moore T, et al. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud's phenomenon. Br J Rheumatol. 1995;34:636-641.[Abstract]
36. Franks AG Jr. Topical glyceryl trinitrate as adjunctive treatment in Raynaud's disease. Lancet. 1982;1:76-77.[Abstract]
37. 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.[Abstract][Full Text]
38. Hummers LK, Dugowson CE, Dechow FJ, et al. A multi-centre, blinded, randomised, 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.[Abstract]
39. Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. Rheumatology (Oxford). 2005;44:145-150.[Abstract][Full Text]
40. Challenor VF, Waller DG, Hayward RA, et al. Vibrotactile sensation and response to nifedipine dose titration in primary Raynaud's phenomenon. Angiology. 1989;40:122-128.[Abstract]
41. Raynaud's Treatment Study Investigators. Comparison of sustained-release nifedipine and temperature biofeedback for treatment of primary Raynaud phenomenon: results from a randomized clinical trial with 1-year follow-up. Arch Intern Med. 2000;160:1101-1108.[Abstract][Full Text]
42. Sarkozi J, Bookman AA, Mahon W, et al. Nifedipine in the treatment of idiopathic Raynaud's syndrome. J Rheumatol. 1986;13:331-336.[Abstract]
43. Corbin DO, Wood DA, Macintyre CC, et al. A randomized double blind cross-over trial of nifedipine in the treatment of primary Raynaud's phenomenon. Eur Heart J. 1986;7:165-170.[Abstract]
44. Gjorup T, Kelbaek H, Hartling OJ, et al. Controlled double-blind trial of the clinical effect of nifedipine in the treatment of idiopathic Raynaud's phenomenon. Am Heart J. 1986;111:742-745.[Abstract]
45. Waller DG, Challenor VF, Francis DA, et al. Clinical and rheological effects of nifedipine in Raynaud's phenomenon. Br J Clin Pharmacol. 1986;22:449-454.[Abstract][Full Text]
46. Stewart M, Morling JR. Oral vasodilators for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2012;(7):CD006687.[Abstract][Full Text]
47. French Cooperative Multicenter Group for Raynaud Phenomenon. Controlled multicenter double-blind trial of nicardipine in the treatment of primary Raynaud phenomenon. Am Heart J. 1991;122:352-355.[Abstract]
48. Wollersheim H, Thien T. Double-blind placebo-controlled crossover study of oral nicardipine in the treatment of Raynaud's phenomenon. J Cardiovasc Pharmacol. 1991;18:813-818.[Abstract]
49. La Civita L, Pitaro N, Rossi M, et al. Amlodipine in the treatment of Raynaud's phenomenon. A double-blind placebo-controlled crossover study. Clin Drug Invest. 1997;13:126-131.[Abstract]
50. Rhedda A, McCans J, Willan AR, et al. A double blind controlled crossover randomized trial of diltiazem in Raynaud's phenomenon. J Rheumatol. 1985;12:724-727.[Abstract]
51. 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.[Abstract][Full Text]
52. Wood HM, Ernst ME. Renin-angiotensin system mediators and Raynaud's phenomenon. Ann Pharmacother. 2006;40:1998-2002.[Abstract]
53. Coleiro B, Marshall SE, Denton CP, et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford). 2001;40:1038-1043.[Abstract][Full Text]
54. Wollersheim H, Thien T, Fennis J, et al. Double-blind, placebo-controlled study of prazosin in Raynaud's phenomenon. Clin Pharmacol Ther. 1986;40:219-225.[Abstract]
55. Rustin MH, Almond NE, Beacham JA, et al. The effect of captopril on cutaneous blood flow in patients with primary Raynaud's phenomenon. Br J Dermatol. 1987;117:751.[Abstract]
56. Gliddon AE, Doré CJ, Black CM, et al. Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril. Arthritis Rheum. 2007;56:3837-3846.[Abstract][Full Text]
57. Davinroy M, Mosnier M. Double-blind clinical evaluation of naftidrofuryl in Raynaud's phenomenon [in French]. Sem Hop Paris. 1993;69:1322-1326.
58. Herrick AL, van den Hoogen F, Gabrielli A, et al. Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis. Arthritis Rheum. 2011;63:775-782.[Abstract][Full Text]
59. Fries R, Shariat K, von Wilmowsky H, et al. Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005;112:2980-2985.[Abstract][Full Text]
60. 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 (Oxford). 2010;49:2420-2428.[Abstract]
61. Caglayan E, Axmann S, Hellmich M, et al. Vardenafil for the treatment of Raynaud phenomenon: a randomized, double-blind, placebo-controlled crossover study. Arch Intern Med. 2012;172:1182-1184.[Abstract]
62. De LaVega AJ, Derk CT. Phosphodiesterase-5 inhibitors for the treatment of Raynaud's: a novel indication. Expert Opin Investig Drugs. 2009;18:23-29.[Abstract]
63. Lee EY, Park JK, Lee W, et al. Head-to-head comparison of udenafil vs amlodipine in the treatment of secondary Raynaud's phenomenon: a double-blind, randomized, cross-over study. Rheumatology (Oxford). 2014;53:658-664.[Abstract]
64. 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 (Oxford). 2010;49:2420-2428.[Abstract]
65. Fries R, Shariat K, von Wilmowsky H, et al. Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005;112:2980-2985.[Abstract][Full Text]
66. 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.[Abstract]
67. Varga J. New hope for systemic sclerosis patients with digital ulcers. Curr Rheumatol Rep. 2005;7:127.[Abstract]
68. 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.[Abstract][Full Text]
69. Seibold JR, Matucci-Cerinic M, Denton CP, et al. Bosentan reduces the number of new digital ulcers in patients with systemic sclerosis. Ann Rheum Dis. 2006;65(suppl II):90.
70. Wigley FM, Seibold JR, Wise RA, et al. Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol. 1992;19:1407-1414.[Abstract]
71. Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med. 1994;120:199-206.[Abstract]
72. Wasserman A, Brahn E. Systemic sclerosis: bilateral improvement of Raynaud's phenomenon with unilateral digital sympathectomy. Semin Arthritis Rheum. 2010;40:137-146.[Abstract]
73. Challenor VF, Waller DG, Hayward RA, et al. Vibrotactile sensation and response to nifedipine dose titration in primary Raynaud's phenomenon. Angiology. 1989;40:122-128.[Abstract]
74. Belch JJ, Shaw B, O'Dowd A, et al. Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double blind study. J Thromb Haemost. 1985;54:490.[Abstract]
75. DiGiacomo RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud's: a double-blind, controlled, prospective study. Am J Med. 1989;68:158-164.[Abstract]
76. DiGiacomo RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud's: a double-blind, controlled, prospective study. Am J Med. 1989;68:158-164.[Abstract]
77. Muir AH, Robb R, McLaren M, et al. The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo controlled trial. Vasc Med. 2002;7:265-267.[Abstract]
78. Bredie SJ, Jong MC. No significant effect of ginkgo biloba special extract EGb 761 in the treatment of primary Raynaud phenomenon: a randomized controlled trial. J Cardiovasc Pharmacol. 2012;59:215-221.[Abstract]
79. Muir AH, Robb R, McLaren M, et al. The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo controlled trial. Vasc Med. 2002;7:265-267.[Abstract]
80. Appiah R, Hiller S, Caspary L, et al. Treatment of primary Raynaud's syndrome with traditional Chinese acupuncture. J Intern Med. 1997;241:119.[Abstract]
81. Appiah R, Hiller S, Caspary L, et al. Treatment of primary Raynaud's syndrome with traditional Chinese acupuncture. J Intern Med. 1997;241:119.[Abstract]
82. Al-Awami M, Schillinger M, Maca T, et al. Low-level laser therapy treatment of primary and secondary Raynaud's phenomenon. Vasa. 2004;33:25-29.[Abstract]
83. Al-Awami M, Schillinger M, Maca T, et al. Low-level laser therapy treatment of primary and secondary Raynaud's phenomenon. Vasa. 2004;33:25-29.[Abstract]
84. Ko GD, Berbrayer D. Effect of ceramic-impregnated "thermoflow" gloves on patients with Raynaud's syndrome: randomized, placebo-controlled study. Altern Med Rev. 2002;7:328-335.[Abstract][Full Text]
85. Malenfant D, Catton M, Pope JE. The efficacy of complementary and alternative medicine in the treatment of Raynaud's phenomenon: a literature review and meta-analysis. Rheumatology (Oxford). 2009;48:791-795.[Abstract]
86. Hélou J, Moutran R, Maatouk I, et al. Raynaud's phenomenon and vitamin D. Rheumatol Int. 2013;33:751-755.[Abstract]
87. Fernández-Codina A, Walker KM, Pope JE, et al. Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheumatol. 2018 Nov;70(11):1820-8.[Abstract][Full Text]
88. Pope JE, Black C, Matucci-Cerinic M, et al. Functional correlates of reduction of digital ulcers by bosentan therapy in patients with systemic sclerosis (SSc). Arthritis Rheum. 2006;54(suppl):S740.[Full Text]
89. Bello RJ, Cooney CM, Melamed E, et al. The therapeutic efficacy of botulinum toxin in treating scleroderma-associated Raynaud's phenomenon: a randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol. 2017;69:1661-1669.[Abstract]
90. Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud's phenomenon: a review. Semin Arthritis Rheum. 2012;41:599-603.[Abstract]
91. Neumeister MW, Chambers CB, Herron MS, et al. Botox therapy for ischemic digits. Plast Reconstr Surg. 2009;124:191-201.[Abstract]
92. Jenkins SN, Neyman KM, Veledar E, et al. A pilot study evaluating the efficacy of botulinum toxin A in the treatment of Raynaud phenomenon. J Am Acad Dermatol. 2013;69:834-835.[Abstract][Full Text]
93. Kim DC, Lee CE. NXCL-4950, a novel composite applicable to peripheral skin, is capable of increasing skin temperature by enhancing capillary circulation. Clin Exp Dermatol. 2013;38:244-250.[Abstract]
94. Pope J, Fenlon D, Thompson A, et al. Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 1998;(2):CD000954.[Abstract][Full Text]
95. Fava A, Wung PK, Wigley FM, et al. Efficacy of Rho kinase inhibitor fasudil in secondary Raynaud's phenomenon. Arthritis Care Res (Hoboken). 2012;64:925-929.[Abstract]
96. Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76:1327-1339.[Abstract][Full Text]
97. Denton CP, Hughes M, Gak N, et al. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford). 2016 Oct;55(10):1906-10.[Abstract][Full Text]
98. Spencer-Green G. Outcomes in primary Raynaud phenomenon: a meta-analysis of the frequency, rates, and predictors of transition to secondary diseases. Arch Intern Med. 1998;158:595-600.[Abstract][Full Text]
99. Spencer-Green G. Outcomes in primary Raynaud phenomenon: a meta-analysis of the frequency, rates, and predictors of transition to secondary diseases. Arch Intern Med. 1998;158:595-600.[Abstract][Full Text]
100. Khanna D, Denton C, Merkel PA, et al. Macitentan in systemic sclerosis associated with ischemic digital ulcers: results from two large randomized controlled trials. JAMA. In press.
101. Black C, Denton CP, Furst DE, et al. Bosentan reduces the number of new digital ulcers in patients with systemic sclerosis: open-label extension to a double-blind trial. Ann Rheum Dis. 2006;65(suppl II):384.
Key Articles
Referenced Articles
Sign in to access our clinical decision support tools