eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease

Raynaud Phenomenon: Differential Diagnoses & Workup

Author: S Anita Narayanan, MD, Fellow in Rheumatology, University of Arizona College of Medicine
Coauthor(s): Jeffrey R Lisse, MD, FACP, Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine; Mayra Oberto-Medina, DO, Fellow, Section of Rheumatology, University of Arizona
Contributor Information and Disclosures

Updated: Jun 3, 2009

Differential Diagnoses

Acromegaly
Localized Fibrosing Disorders: Linear Scleroderma, Morphea, Regional Fibrosis
Acute Myelogenous Leukemia
Lung Cancer, Non-Small Cell
Antiphospholipid Antibody Syndrome and Pregnancy
Lung Cancer, Oat Cell (Small Cell)
Antithrombin Deficiency
Lymphoma, B-Cell
Arteriovenous Fistulas
Mixed Connective-Tissue Disease
Atherosclerosis
Multiple Myeloma
Buerger Disease (Thromboangiitis Obliterans)
Paroxysmal Nocturnal Hemoglobinuria
Carcinoid Lung Tumors
Peripheral Arterial Occlusive Disease
Cold Agglutinin Disease
Pheochromocytoma
Cryoglobulinemia
Polycythemia Vera
Dermatomyositis
Polymyositis
Diabetes Mellitus, Type 1
Protein C Deficiency
Diabetes Mellitus, Type 2
Protein S Deficiency
Extremity Vascular Trauma
Rheumatoid Arthritis
Frostbite
Scleroderma
Graft Versus Host Disease
Sjogren Syndrome
Heart-Lung Transplantation
Stimulants
Hemoglobinuria, Paroxysmal Cold
Systemic Lupus Erythematosus
Hepatitis B
Toxicity, Arsenic
Hepatitis C
Toxicity, Cocaine
Hypothermia
Toxicity, Cyanide
Injecting Drug Use
Toxicity, Lead

Other Problems to Be Considered

Acrocyanosis
Alfa-interferon
Antineoplastics (eg, vinca alkaloids, bleomycin, cisplatin)
Beta-adrenergic blocking drugs
Bromocriptine
Carpal Tunnel Syndrome
Chilblains
Cryoglobulinemia, mixed or type 3, associated with hepatitis B and C
Cryoglobulinemia, monoclonal or type I
Cyclosporine
Ergot alkaloids
Fabry disease
Leukemia
Livedo reticularis
Lymphoma
Mycoplasma infection with cold agglutinins
Myeloma
Oral contraceptives
Overlap syndromes
Peripheral Vascular Disease
Scleroderma, diffuse and localized (CREST syndrome)
Thoracic Outlet Syndrome
Thromboembolic disease
Vasculitis
Vibration injury
Vinyl chloride exposure
Waldenström macroglobulinemia

Workup

Laboratory Studies

  • Complete blood cell count - To evaluate for polycythemic disorders, underlying malignancies, or autoimmune disorders
  • Blood urea nitrogen - To evaluate for possible renal impairment or dehydration
  • Creatinine - To evaluate for possible renal impairment
  • Prothrombin time - To observe for any evidence of hepatic dysfunction
  • Activated partial thromboplastin time - To observe for any evidence of antiphospholipid antibody disorder or hepatic dysfunction
  • Serum glucose - To evaluate patient for diabetic disease
  • Thyroid-stimulating hormone - To observe for thyroid disorders
  • Optional laboratory tests
    • Antinuclear antibody - May be positive in autoimmune disorders and should be obtained in patients with features of these disorders
    • Serum viscosity - Elevated in hyperviscosity syndromes such as paraproteinemias
    • Serum creatine kinase - Elevated in muscle damage such as polymyositis and dermatomyositis
    • Rheumatoid factor - May be elevated in rheumatoid arthritis, other autoimmune disorders, and some forms of cryoglobulinemia (monoclonal proteins in multiple myeloma and Waldenström macroglobulinemia have an increased frequency of rheumatoid factor activity)
    • Hepatitis panel - Positive for B or C infection in many patients with cryoglobulinemia
    • Cold agglutinins - Present in Mycoplasma infections and lymphomas
    • Heavy metal screen - To observe for patients with neuropathic pain due to poisoning
    • Growth hormone - To evaluate for acromegaly
    • Serum vanillylmandelic acid - To evaluate for pheochromocytoma
    • Metanephrine - To observe for pheochromocytoma in appropriate patients
    • Catecholamines - To observe for pheochromocytoma
    • Leukocyte alkaline phosphatase - To evaluate for leukemias in appropriate patients
    • Antiphospholipid antibodies studies - Including dilute Russell viper venom studies, anticardiolipin antibodies, and anti-beta-1-glycoprotein-2 antibodies.

Imaging Studies

  • Thermography, isotope studies, and arteriography have all been used, but none has proven superior to clinical assessment in office practice.
  • A fixed, nonreversible, cyanotic lesion requires further evaluation of the vasculature.

Other Tests

  • Acid hemolysis test
  • Sucrose lysis test

Procedures

  • Serum protein electrophoresis
  • Liver or kidney biopsy
  • Measurement of digital blood pressures before and after immersion in cold water (The difference should be less than 30 mm Hg.).

More on Raynaud Phenomenon

Overview: Raynaud Phenomenon
Differential Diagnoses & Workup: Raynaud Phenomenon
Treatment & Medication: Raynaud Phenomenon
Follow-up: Raynaud Phenomenon
Multimedia: Raynaud Phenomenon
References
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References

  1. Bakst R, Merola JF, Franks AG Jr, Sanchez M. Raynaud's phenomenon: pathogenesis and management. J Am Acad Dermatol. Oct 2008;59(4):633-53. [Medline].

  2. Gayraud M. Raynaud's phenomenon. Joint Bone Spine. Jan 2007;74(1):e1-8. [Medline].

  3. 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. Feb 1996;55(2):122-7. [Medline]. [Full Text].

  4. 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. Jul 2003;48(7):1992-2000. [Medline]. [Full Text].

  5. Kirchengast M, Munter K. Endothelin-1 and endothelin receptor antagonists in cardiovascular remodeling. Proc Soc Exp Biol Med. Sep 1999;221(4):312-25. [Medline].

  6. Sakurai T, Goto K. Endothelins. Vascular actions and clinical implications. Drugs. Nov 1993;46(5):795-804. [Medline].

  7. Duprez DA. Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. J Hypertens. Jun 2006;24(6):983-91. [Medline].

  8. 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. Jan 2004;50(1):216-26. [Medline].

  9. Wigley FM, Flavahan NA. Raynaud's phenomenon. Rheum Dis Clin North Am. Nov 1996;22(4):765-81. [Medline].

  10. 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). Sep 1998;95(3):249-60. [Medline].

  11. 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. Mar 1996;134(3):399-406. [Medline].

  12. Bunker CB, Terenghi G, Springall DR, Polak JM, Dowd PM. Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon. Lancet. Dec 22-29 1990;336(8730):1530-3. [Medline].

  13. 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. Apr 2000;278(4):H1075-83. [Medline].

  14. Furspan PB, Chatterjee S, Freedman RR. Increased tyrosine phosphorylation mediates the cooling-induced contraction and increased vascular reactivity of Raynaud's disease. Arthritis Rheum. May 2004;50(5):1578-85. [Medline].

  15. 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. [Medline]. [Full Text].

  16. Herrick AL. Pathogenesis of Raynaud's phenomenon. Rheumatology (Oxford). May 2005;44(5):587-96. [Medline]. [Full Text].

  17. Suter LG, Murabito JM, Felson DT, Fraenkel L. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum. Apr 2005;52(4):1259-63. [Medline].

  18. Generali J, Cada D. Nitroglycerin (topical): Raynaud's phenomenon. Hospital Pharmacy. 2008;43:980-981. [Full Text].

  19. Al-Allaf AW, Belch J. Raynaud's phenomenon. In: Hochberg et al, eds. Practical Rheumatology. 3rd ed. Philadelphia, Pa: Mosby; 2004:467-472.

  20. Belch JJ, Newman P, Drury JK, et al. Intermittent epoprostenol (prostacyclin) infusion in patients with Raynaud's syndrome. A double-blind controlled trial. Lancet. Feb 12 1983;1(8320):313-5. [Medline].

  21. Bennett RM, O'Connell DJ. Mixed connective tisssue disease: a clinicopathologic study of 20 cases. Semin Arthritis Rheum. Aug 1980;10(1):25-51. [Medline].

  22. Challenor VF. Angiotensin converting enzyme inhibitors in Raynaud's phenomenon. Drugs. Dec 1994;48(6):864-7. [Medline].

  23. Cherniack MG. Raynaud's phenomenon of occupational origin. Arch Intern Med. Mar 1990;150(3):519-22. [Medline].

  24. [Best Evidence] Chung L, Shapiro L, Fiorentino D, Baron M, Shanahan J, Sule S, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial. Arthritis Rheum. Mar 2009;60(3):870-7. [Medline].

  25. Coffman JD, Cohen AS. Total and capillary fingertip blood flow in Raynaud's phenomenon. N Engl J Med. Jul 29 1971;285(5):259-63. [Medline].

  26. De Angelis R, Cerioni A, Del Medico P, Blasetti P. Raynaud's phenomenon in undifferentiated connective tissue disease (UCTD). Clin Rheumatol. Apr 2005;24(2):145-51. [Medline].

  27. 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. Aug 1986;37(8):565-9. [Medline].

  28. 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. Feb 1989;86(2):158-64. [Medline].

  29. Dowd PM, Martin MF, Cooke ED, et al. Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2). Br J Dermatol. Jan 1982;106(1):81-9. [Medline].

  30. 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. Dec 1999;42(12):2646-55. [Medline].

  31. Flatt AE. Digital artery sympathectomy. J Hand Surg [Am]. Nov 1980;5(6):550-6. [Medline].

  32. Freedman RR. Quantitative measurements of finger blood flow during behavioral treatments for Raynaud's disease. Psychophysiology. Jul 1989;26(4):437-41. [Medline].

  33. Freemont AJ, Hoyland J, Fielding P, Hodson N, Jayson MI. Studies of the microvascular endothelium in uninvolved skin of patients with systemic sclerosis: direct evidence for a generalized microangiopathy. Br J Dermatol. Jun 1992;126(6):561-8. [Medline].

  34. Furtado RN, Pucinelli ML, Cristo VV, Andrade LE, Sato EI. Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud's phenomenon in SLE patients. Lupus. 2002;11(1):35-41. [Medline].

  35. Gasser P, Muller P, Mauli D, Staubli C. Evaluation of reflex cold provocation by laser Doppler flowmetry in clinically healthy subjects with a history of cold hands. Angiology. May 1992;43(5):389-94. [Medline].

  36. Gerbracht DD, Steen VD, Ziegler GL, Medsger TA Jr, Rodnan GP. Evolution of primary Raynaud's phenomenon (Raynaud's disease) to connective tissue disease. Arthritis Rheum. Jan 1985;28(1):87-92. [Medline].

  37. 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. Apr 1990;29(2):89-91. [Medline].

  38. Grader-Beck T, Wigley FM. Raynaud's phenomenon in mixed connective tissue disease. Rheum Dis Clin North Am. Aug 2005;31(3):465-81, vi. [Medline].

  39. Harper FE, Maricq HR, Turner RE, Lidman RW, Leroy EC. A prospective study of Raynaud phenomenon and early connective tissue disease. A five-year report. Am J Med. Jun 1982;72(6):883-8. [Medline].

  40. Heslop J, Coggon D, Acheson ED. The prevalence of intermittent digital ischaemia (Raynaud's phenomenon) in a general practice. J R Coll Gen Pract. Feb 1983;33(247):85-9. [Medline].

  41. [Best Evidence] Ingegnoli F, Boracchi P, Gualtierotti R, Lubatti C, Meani L, Zahalkova L, et al. Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination). Arthritis Rheum. Jul 2008;58(7):2174-82. [Medline].

  42. 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. Dec 2004;50(12):3985-93. [Medline].

  43. Kyle MV, Belcher G, Hazleman BL. Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon. J Rheumatol. Sep 1992;19(9):1403-6. [Medline].

  44. Lavery JP, Lisse JR. Raynaud's Phenomenon. In: Taylor RB, ed. Difficult Diagnosis. Vol 2. Philadelphia, Pa: WB Saunders Co; 1992:386-91.

  45. Maricq HR. Wide-field capillary microscopy. Arthritis Rheum. Sep 1981;24(9):1159-65. [Medline].

  46. Maricq HR, Carpentier PH, Weinrich MC, et al. Geographic variation in the prevalence of Raynaud's phenomenon: Charleston, SC, USA, vs Tarentaise, Savoie, France. J Rheumatol. Jan 1993;20(1):70-6. [Medline].

  47. Medsger TA. Systemic sclerosis. In: Arthritis and Allied Conditions. Philadelphia, Pa: Lippincott Williams & Wilkins; 1993:1438-9.

  48. Rademaker M, Cooke ED, Almond NE, et al. Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study. BMJ. Mar 4 1989;298(6673):561-4. [Medline].

  49. Rademaker M, Meyrick Thomas RH, Kirby JD, Kovacs IB. The anti-platelet effect of nifedipine in patients with systemic sclerosis. Clin Exp Rheumatol. Jan-Feb 1992;10(1):57-62. [Medline].

  50. Ramos-Casals M, Brito-Zeron P, Nardi N, et al. Successful treatment of severe Raynaud's phenomenon with bosentan in four patients with systemic sclerosis. Rheumatology (Oxford). Nov 2004;43(11):1454-6. [Medline].

  51. Sheiner NM, Small P. Isolated Raynaud's phenomenon--a benign disorder. Ann Allergy. Feb 1987;58(2):114-7. [Medline].

  52. Wigley FM, Flavahan NA. Raynaud's phenomenon. Rheum Dis Clin North Am. Nov 1996;22(4):765-81. [Medline].

  53. Wigley FM, Wise RA, Malamet R, Scott TE. Nicardipine in the treatment of Raynaud's phenomenon. Dissociation of platelet activation from vasospasm. Arthritis Rheum. Mar 1987;30(3):281-6. [Medline].

  54. 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. Feb 1 1994;120(3):199-206. [Medline].

  55. Yamane K, Miyauchi T, Suzuki N, et al. Significance of plasma endothelin-1 levels in patients with systemic sclerosis. J Rheumatol. Oct 1992;19(10):1566-71. [Medline].

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Further Reading

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Keywords

Raynaud's phenomenon, Raynaud phenomenon, vasospasm, Raynaud disease, Raynaud’s disease, reversible ischemia of peripheral arterioles, exposure to cold, stress-related ischemia, systemic sclerosis, scleroderma, secondary Raynaud, secondary Raynaud's, vasospasm, pallor, white finger disease

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Contributor Information and Disclosures

Author

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, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

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, and Sigma Xi
Disclosure: Nothing to disclose.

Mayra Oberto-Medina, DO, Fellow, Section of Rheumatology, University of Arizona
Disclosure: Nothing to disclose.

Medical Editor

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 Research, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; 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, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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