Diagnostic Considerations

Anatomic syndromes that may be confused with Raynaud phenomenon include the following:

Miscellaneous circulatory syndromes that may be confused with Raynaud phenomenon include the following:

Peripheral Vascular Disease
Thromboangiitis obliterans
Vasculitis
Thromboembolic disease

Vasospastic syndromes that may be confused with Raynaud phenomenon include the following:

Livedo reticularis
Acrocyanosis
Chilblains

Other problems to be considered in the differential diagnosis of Raynaud phenomenon include the following:

Cryoglobulinemia, mixed or type 3, associated with hepatitis B and C
Cryoglobulinemia, monoclonal or type I
Dermatomyositis
Fabry disease
Leukemia
Lymphoma
Mycoplasma infection with cold agglutinins
Myeloma
Scleroderma, diffuse and localized (CREST syndrome)
Systemic Lupus Erythematosus (SLE)
Vibration injury ^[29]
Vinyl chloride exposure
Waldenström macroglobulinemia

Drugs to be considered in the differential diagnosis of Raynaud phenomenon include the following:

Alfa-interferon
Antineoplastics (eg, vinca alkaloids, bleomycin, cisplatin)
Beta-adrenergic blocking drugs
Bromocriptine
Cocaine
Cyclosporine
Ergot alkaloids
Oral contraceptives

Differential Diagnoses

Workup

Wigley FM, Flavahan NA. Raynaud's Phenomenon. N Engl J Med. 2016 Aug 11. 375 (6):556-65. [QxMD MEDLINE Link].
Bakst R, Merola JF, Franks AG Jr, Sanchez M. Raynaud's phenomenon: pathogenesis and management. J Am Acad Dermatol. 2008 Oct. 59(4):633-53. [QxMD MEDLINE Link].
Curtiss P, Svigos K, Schwager Z, Lo Sicco K, Franks AG Jr. Part I: Epidemiology, Pathophysiology, and Clinical Considerations of Primary and Secondary Raynaud's Phenomenon. J Am Acad Dermatol. 2022 Jul 6. [QxMD MEDLINE Link].
Herrick AL. The pathogenesis, diagnosis and treatment of Raynaud phenomenon. Nat Rev Rheumatol. 2012 Aug. 8(8):469-79. [QxMD MEDLINE Link].
Herrick AL, Illingworth K, Blann A, Hay CR, Hollis S, Jayson MI. Von Willebrand factor, thrombomodulin, thromboxane, beta-thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis. Ann Rheum Dis. 1996 Feb. 55(2):122-7. [QxMD MEDLINE Link]. [Full Text].
Rajagopalan S, Pfenninger D, Kehrer C, Chakrabarti A, Somers E, Pavlic R. Increased asymmetric dimethylarginine and endothelin 1 levels in secondary Raynaud's phenomenon: implications for vascular dysfunction and progression of disease. Arthritis Rheum. 2003 Jul. 48(7):1992-2000. [QxMD MEDLINE Link]. [Full Text].
Sakurai T, Goto K. Endothelins. Vascular actions and clinical implications. Drugs. 1993 Nov. 46(5):795-804. [QxMD MEDLINE Link].
Duprez DA. Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. J Hypertens. 2006 Jun. 24(6):983-91. [QxMD MEDLINE Link].
Kawaguchi Y, Takagi K, Hara M, et al. Angiotensin II in the lesional skin of systemic sclerosis patients contributes to tissue fibrosis via angiotensin II type 1 receptors. Arthritis Rheum. 2004 Jan. 50(1):216-26. [QxMD MEDLINE Link].
Hughes M, Herrick AL. Raynaud's phenomenon. Best Pract Res Clin Rheumatol. 2016 Feb. 30 (1):112-32. [QxMD MEDLINE Link].
Edwards CM, Marshall JM, Pugh M. Lack of habituation of the pattern of cardiovascular response evoked by sound in subjects with primary Raynaud's disease. Clin Sci (Lond). 1998 Sep. 95(3):249-60. [QxMD MEDLINE Link].
Bunker CB, Goldsmith PC, Leslie TA, Hayes N, Foreman JC, Dowd PM. Calcitonin gene-related peptide, endothelin-1, the cutaneous microvasculature and Raynaud's phenomenon. Br J Dermatol. 1996 Mar. 134(3):399-406. [QxMD MEDLINE Link].
Bunker CB, Terenghi G, Springall DR, Polak JM, Dowd PM. Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon. Lancet. 1990 Dec 22-29. 336(8730):1530-3. [QxMD MEDLINE Link].
Chotani MA, Flavahan S, Mitra S, Daunt D, Flavahan NA. Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol. 2000 Apr. 278(4):H1075-83. [QxMD MEDLINE Link].
Furspan PB, Chatterjee S, Freedman RR. Increased tyrosine phosphorylation mediates the cooling-induced contraction and increased vascular reactivity of Raynaud's disease. Arthritis Rheum. 2004 May. 50(5):1578-85. [QxMD MEDLINE Link].
Lau CS, McLaren M, Saniabadi A, Belch JJ. Increased whole blood platelet aggregation in patients with Raynaud's phenomenon with or without systemic sclerosis. Scand J Rheumatol. 1993. 22(3):97-101. [QxMD MEDLINE Link]. [Full Text].
Herrick AL. Pathogenesis of Raynaud's phenomenon. Rheumatology (Oxford). 2005 May. 44(5):587-96. [QxMD MEDLINE Link]. [Full Text].
Ascherman DP, Zang Y, Fernandez I, Clark ES, Khan WN, Martinez L, et al. An Autoimmune Basis for Raynaud's Phenomenon: Murine Model and Human Disease. Arthritis Rheumatol. 2018 Sep. 70 (9):1489-1499. [QxMD MEDLINE Link].
Stjernbrandt A, Pettersson H, Lundström R, Liljelind I, Nilsson T, Wahlström J. Incidence, remission, and persistence of Raynaud's phenomenon in the general population of northern Sweden: a prospective study. BMC Rheumatol. 2022 Jul 21. 6 (1):41. [QxMD MEDLINE Link]. [Full Text].
Khouri C, Blaise S, Carpentier P, Villier C, Cracowski JL, Roustit M. Drug-induced Raynaud's phenomenon: beyond β-adrenoceptor blockers. Br J Clin Pharmacol. 2016 Jul. 82 (1):6-16. [QxMD MEDLINE Link].
Kim H, Jones AJ, Labadzhyan A, Placencio-Hickok VR, Wallace DJ, Gong J, et al. Raynaud's Phenomenon From PD-1 Immune Checkpoint Inhibition. JCO Oncol Pract. 2020 Oct. 16 (10):701-702. [QxMD MEDLINE Link].
Umair HM, Sandler RD, Alunno A, Matucci-Cerinic M, Hughes M. Association between central nervous system stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon: A scoping review. Semin Arthritis Rheum. 2021 Sep 16. 51 (6):1200-1204. [QxMD MEDLINE Link].
Deshayes S, Auboire L, Jaussaud R, Lidove O, Parienti JJ, Triclin N, et al. Prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in Fabry disease: a cross-sectional study. Medicine (Baltimore). 2015 May. 94 (20):e780. [QxMD MEDLINE Link].
Aqodad Z, Bachir H, Alaoui H, Hamaz S, Serraj K Sr. Raynaud's Phenomenon: Beware of Cancers!. Cureus. 2021 Mar 20. 13 (3):e14009. [QxMD MEDLINE Link]. [Full Text].
Abdulle AE, Arends S, van Goor H, Brouwer E, van Roon AM, Westra J, et al. Low body weight and involuntary weight loss are associated with Raynaud's phenomenon in both men and women. Scand J Rheumatol. 2021 Mar. 50 (2):153-160. [QxMD MEDLINE Link].
Suter LG, Murabito JM, Felson DT, Fraenkel L. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum. 2005 Apr. 52(4):1259-63. [QxMD MEDLINE Link].
Nietert PJ, Shaftman SR, Silver RM, Wolf BJ, Egan BM, Hunt KJ, et al. Raynaud phenomenon and mortality: 20+ years of follow-up of the Charleston Heart Study cohort. Clin Epidemiol. 2015. 7:161-8. [QxMD MEDLINE Link]. [Full Text].
Mueller M, Gschwandtner ME, Gamper J, Giurgea GA, Charwat-Resl S, Kiener HP, et al. Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon. Circulation. 2016 Feb 2. 133 (5):509-17. [QxMD MEDLINE Link].
Shen SC, House RA. Hand-arm vibration syndrome: What family physicians should know. Can Fam Physician. 2017 Mar. 63 (3):206-210. [QxMD MEDLINE Link]. [Full Text].
Nilsson T, Wahlström J, Burström L. Hand-arm vibration and the risk of vascular and neurological diseases-A systematic review and meta-analysis. PLoS One. 2017. 12 (7):e0180795. [QxMD MEDLINE Link]. [Full Text].
Purdie GL, Purdie DJ, Harrison AA. Raynaud's Phenomenon in Medical Laboratory Workers Who Work with Solvents. J Rheumatol. 2011 Sep. 38(9):1940-6. [QxMD MEDLINE Link].
Coulombe J, Powell J, Hatami A, McCuaig C, Renet S, Marcoux D. Diseases of abnormal sensitivity to cold in children on psychostimulant drugs. J Cutan Med Surg. 2014 Oct. 18(5):1-4. [QxMD MEDLINE Link].
Smith V, et al; EULAR Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium Group on Capillaroscopy. Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis. Autoimmun Rev. 2020 Mar. 19 (3):102458. [QxMD MEDLINE Link]. [Full Text].
Piotto DG, Hilário MO, Carvalho NS, Len CA, Andrade LE, Terreri MT. Prospective nailfold capillaroscopy evaluation of Raynaud's phenomenon in children and adolescents. Acta Reumatol Port. 2013 Apr-Jun. 38(2):114-21. [QxMD MEDLINE Link].
Smitaman E, Pereira BP, Huang BK, Zakhary MM, Fliszar E, Resnick DL. Abnormal Bone Marrow Signal Intensity in the Phalanges of the Foot as a Manifestation of Raynaud Phenomenon: A Report of Six Patients. AJR Am J Roentgenol. 2016 Aug 30. 1-5. [QxMD MEDLINE Link].
Quarta S, Galea N, Gigante A, Romaniello A, Rosato E, Carbone I. The cardiac magnetic resonance in the diagnosis of cardiac Raynaud phenomenon in a patient with systemic sclerosis: case report and review of literature. Expert Rev Clin Immunol. 2016. 12 (3):251-5. [QxMD MEDLINE Link].
Hughes M, Snapir A, Wilkinson J, Snapir D, Wigley FM, Herrick AL. Prediction and impact of attacks of Raynaud's phenomenon, as judged by patient perception. Rheumatology (Oxford). 2015 Aug. 54 (8):1443-7. [QxMD MEDLINE Link].
Curtiss P, Svigos K, Schwager Z, Lo Sicco K, Franks AG Jr. Part II: The Treatment of Primary and Secondary Raynaud's Phenomenon. J Am Acad Dermatol. 2022 Jul 6. [QxMD MEDLINE Link].
Generali J, Cada D. Nitroglycerin (topical): Raynaud's phenomenon. Hospital Pharmacy. 2008. 43:980-981. [Full Text].
Qiu O, Chan T, Luen M, Cruz JE, Hermes-DeSantis ER. Use of nitroglycerin ointment to treat primary and secondary Raynaud's phenomenon: a systematic literature review. Rheumatol Int. 2018 Aug 22. [QxMD MEDLINE Link].
Huisstede BM, Hoogvliet P, Paulis WD, et al. Effectiveness of Interventions for Secondary Raynaud's Phenomenon: A Systematic Review. Arch Phys Med Rehabil. 2011 Jul. 92(7):1166-80. [QxMD MEDLINE Link].
Goodfield MJ, Hume A, Rowell NR. The acute effects of cigarette smoking on cutaneous blood flow in smoking and non-smoking subjects with and without Raynaud's phenomenon. Br J Rheumatol. 1990 Apr. 29(2):89-91. [QxMD MEDLINE Link].
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 Jul. 48(7):791-5. [QxMD MEDLINE Link].
Zhou F, Huang E, Zheng E, Deng J. The use of acupuncture in patients with Raynaud's syndrome: a systematic review and meta-analysis of randomized controlled trials. Acupunct Med. 2022 May 24. 9645284221076504. [QxMD MEDLINE Link]. [Full Text].
Schlager O, Gschwandtner ME, Mlekusch I, Herberg K, Frohner T, Schillinger M, et al. Auricular electroacupuncture reduces frequency and severity of Raynaud attacks. Wien Klin Wochenschr. 2011 Feb. 123(3-4):112-6. [QxMD MEDLINE Link].
Belch JJ, Shaw B, O'Dowd A, Saniabadi A, Leiberman P, Sturrock RD, et al. Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double blind study. Thromb Haemost. 1985 Aug 30. 54 (2):490-4. [QxMD MEDLINE Link].
Evening Primrose. 2021 May 17. [QxMD MEDLINE Link]. [Full Text].
Choi WS, Choi CJ, Kim KS, Lee JH, Song CH, Chung JH, et al. To compare the efficacy and safety of nifedipine sustained release with Ginkgo biloba extract to treat patients with primary Raynaud's phenomenon in South Korea; Korean Raynaud study (KOARA study). Clin Rheumatol. 2009 May. 28 (5):553-9. [QxMD MEDLINE Link].
Muir AH, Robb R, McLaren M, Daly F, Belch JJ. The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo-controlled trial. Vasc Med. 2002. 7 (4):265-7. [QxMD MEDLINE Link].
Curtiss P, Cobos G, Lo Sicco K, Franks AG Jr. The Frisbee maneuver: A novel method to abort acute attacks of the Raynaud phenomenon. J Am Acad Dermatol. 2018 Mar. 78 (3):e61. [QxMD MEDLINE Link]. [Full Text].
Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2016 Feb 25. 2:CD002069. [QxMD MEDLINE Link].
Zhu JL, Black SM, Chen HW, Jacobe HT. Emerging treatments for scleroderma/systemic sclerosis. Fac Rev. 2021. 10:43. [QxMD MEDLINE Link]. [Full Text].
Levien TL. Advances in the treatment of Raynaud's phenomenon. Vasc Health Risk Manag. 2010 Mar 24. 6:167-77. [QxMD MEDLINE Link]. [Full Text].
Cutolo M, Ruaro B, Pizzorni C, Ravera F, Smith V, Zampogna G, et al. Longterm treatment with endothelin receptor antagonist bosentan and iloprost improves fingertip blood perfusion in systemic sclerosis. J Rheumatol. 2014 May. 41 (5):881-6. [QxMD MEDLINE Link].
Kamata Y, Minota S. Effects of phosphodiesterase type 5 inhibitors on Raynaud's phenomenon. Rheumatol Int. 2014 Nov. 34 (11):1623-6. [QxMD MEDLINE Link].
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 Dec. 42(12):2646-55. [QxMD MEDLINE Link].
Żebryk P, Puszczewicz MJ. Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic review. Arch Med Sci. 2016 Aug 1. 12 (4):864-70. [QxMD MEDLINE Link]. [Full Text].
Motegi SI, Uehara A, Yamada K, Sekiguchi A, Fujiwara C, Toki S, et al. Efficacy of Botulinum Toxin B Injection for Raynaud's Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis. Acta Derm Venereol. 2017 Jul 6. 97 (7):843-850. [QxMD MEDLINE Link]. [Full Text].
Dhaliwal K, Griffin M, Denton CP, Butler PEM. The novel use of botulinum toxin A for the treatment of Raynaud's phenomenon in the toes. BMJ Case Rep. 2018 Mar 9. 2018:[QxMD MEDLINE Link].
Nagarajan M, McArthur P. Targeted high concentration botulinum toxin A injections in patients with Raynaud's phenomenon: a retrospective single-centre experience. Rheumatol Int. 2021 May. 41 (5):943-949. [QxMD MEDLINE Link].
Motegi SI, Uehara A, Yamada K, Sekiguchi A, Fujiwara C, Toki S, et al. Efficacy of Botulinum Toxin B Injection for Raynaud's Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis. Acta Derm Venereol. 2017 Jul 6. 97 (7):843-850. [QxMD MEDLINE Link].
Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford). 2001 Sep. 40(9):1038-43. [QxMD MEDLINE Link]. [Full Text].
Destors JM, Gauthier E, Lelong S, Boissel JP. Failure of a pure anti-platelet drug to decrease the number of attacks more than placebo in patients with Raynaud's phenomenon. Angiology. 1986 Aug. 37 (8):565-9. [QxMD MEDLINE Link].
Gliddon AE, Dore 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 Nov. 56(11):3837-46. [QxMD MEDLINE Link].
Merritt WH. Role and rationale for extended periarterial sympathectomy in the management of severe Raynaud syndrome: techniques and results. Hand Clin. 2015 Feb. 31 (1):101-20. [QxMD MEDLINE Link].
DiGiacomo RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud's phenomenon: a double-blind, controlled, prospective study. Am J Med. 1989 Feb. 86(2):158-64. [QxMD MEDLINE Link].
Roquelaure Y, Ha C, Le Manac'h AP, Bodin J, Bodere A, Bosseau C, et al. Risk factors for Raynaud's phenomenon in the workforce. Arthritis Care Res (Hoboken). 2012 Jun. 64 (6):898-904. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

A 9-year-old with Raynaud phenomenon. Notice the discoloration of the fingers.
Photo of a patient with Raynaud phenomenon that resulted from working with a jackhammer. Courtesy of the CDC.
Raynaud phenomenon showing demarcation of color difference.

of 3

Author

Heather Hansen-Dispenza, MD Rheumatology Fellow, University of Arizona College of Medicine

Heather Hansen-Dispenza, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

S Anita Narayanan, MD Fellow in Rheumatology, University of Arizona College of Medicine

S Anita Narayanan, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association

Disclosure: Nothing to disclose.

Mayra Oberto-Medina, DO Fellow, Department of Rheumatology, University of Arizona

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Lewis Katz School of Medicine at Temple University

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Jeffrey R Lisse, MD, FACP Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine

Jeffrey R Lisse, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, American Geriatrics Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Received consulting fee from Genentech for consulting; Received consulting fee from Centacor for consulting; Received consulting fee from Novartis for review panel membership.

John Varga, MD Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University

John Varga, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Central Society for Clinical and Translational Research, Society for Investigative Dermatology

Disclosure: Nothing to disclose.