Skip to main content

The association of Raynaud’s syndrome with rheumatoid arthritis—a meta-analysis


Rheumatoid arthritis (RA) has traditionally been included among the diseases associated with Raynaud’s syndrome (RS). The prevalence of RS in patients with RA is not well defined. The objective of this paper was to assess the prevalence of RS in patients with RA—a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and RA. The studies provided sufficient data to estimate the prevalence of RS in patients with RA. A forest plot was determined by the revealed prevalences. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger’s method). A meta-regression was conducted by the year of publication. Twenty-eight eligible studies, contributing data on 3,730 subjects, were included in this meta-analysis. For RA, a pooled prevalence of 12.3% and 95% CI = 0.093–0.157 were obtained. A mixture model analysis found five latent classes. Statistically and graphically, publication bias was present (p = 0.031). In the meta-regression, the estimated prevalence decreased within the observation period (1977–2010) from 11.2% to 9.4%. Despite some heterogeneity, there is a possible indication of an association for RS and patients with RA.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Tobon GJ, Youinou P, Saraux A (2010) The environment, geo-epidemiology, and autoimmune disease: rheumatoid arthritis. Autoimmun Rev 9(5):A288–A292. doi:10.1016/j.autrev.2009.11.019

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Feigenbaum SL, Masi AT, Kaplan SB (1979) Prognosis in rheumatoid arthritis. A longitudinal study of newly diagnosed younger adult patients. Am J Med 66(3):377–384

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Meyer MF, Schmidt O, Hellmich B, Schatz H, Klein HH, Braun J (2007) Microvascular dysfunction in rheumatoid arthritis assessed by laser Doppler anemometry: relationship to soluble adhesion molecules and extraarticular manifestations. Rheumatol Int 28(2):145–152. doi:10.1007/s00296-007-0397-3

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Pope JE, Al-Bishri J, Al-Azem H, Ouimet JM (2008) The temporal relationship of Raynaud's phenomenon and features of connective tissue disease in rheumatoid arthritis. J Rheumatol 35(12):2329–2333

    PubMed  Article  Google Scholar 

  5. 5.

    Block JA, Sequeira W (2001) Raynaud's phenomenon. Lancet 357(9273):2042–2048. doi:10.1016/S0140-6736(00)05118-7

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Heidrich H (2010) Functional vascular diseases: Raynaud's syndrome, acrocyanosis and erythromelalgia. Vasa 39(1):33–41. doi:10.1024/0301-1526/a000003

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Fraenkel L (2002) Raynaud's phenomenon: epidemiology and risk factors. Curr Rheumatol Rep 4(2):123–128

    PubMed  Article  Google Scholar 

  8. 8.

    Belch JJ (1991) Raynaud's phenomenon: its relevance to scleroderma. Ann Rheum Dis 50(Suppl 4):839–845

    PubMed  Article  Google Scholar 

  9. 9.

    Lekakis J, Mavrikakis M, Emmanuel M, Prassopoulos V, Papazoglou S, Papamichael C, Moulopoulou D, Kostamis P, Stamatelopoulos S, Moulopoulos S (1998) Cold-induced coronary Raynaud's phenomenon in patients with systemic sclerosis. Clin Exp Rheumatol 16(2):135–140

    PubMed  CAS  Google Scholar 

  10. 10.

    Mathews JL, Ward JR, Samuelson CO, Knibbe WP (1983) Spontaneous nasal septal perforation in patients with rheumatoid arthritis. Clin Rheumatol 2(1):13–18

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Mourao AF, Amaral M, Caetano-Lopes J, Isenberg D (2009) An analysis of joint replacement in patients with systemic lupus erythematosus. Lupus 18(14):1298–1302. doi:10.1177/0961203309345795

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Schlattmann P (2009) Medical applications of finite mixture models. Springer, Berlin

    Google Scholar 

  14. 14.

    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    PubMed  CAS  Google Scholar 

  15. 15.

    Meta-Analysis with R [program]. 1.5–0 Version, 2010

  16. 16.

    Meta-analysis [program]. 2.16 version, 2009

  17. 17.

    Finite Mixture Models and metaanalysis tools - based on C.A.MAN [program]. 0.64 version, 2008

  18. 18.

    Weinrich MC, Maricq HR, Keil JE, McGregor AR, Diat F (1990) Prevalence of Raynaud phenomenon in the adult population of South Carolina. J Clin Epidemiol 43(12):1343–1349

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    De Angelis R, Salaffi F, Grassi W (2006) Raynaud's phenomenon: prevalence in an Italian population sample. Clin Rheumatol 25(4):506–510. doi:10.1007/s10067-005-0077-1

    PubMed  Article  Google Scholar 

  20. 20.

    Suter LG, Murabito JM, Felson DT, Fraenkel L (2005) The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum 52(4):1259–1263. doi:10.1002/art.20988

    PubMed  Article  Google Scholar 

  21. 21.

    McEntegart A, Capell HA, Creran D, Rumley A, Woodward M, Lowe GD (2001) Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis. Rheumatol Oxf 40(6):640–644

    Article  CAS  Google Scholar 

  22. 22.

    Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, Garcia-Porrua C, Llorca J, Gonzalez-Gay MA (2004) Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor alpha antibody. Arthritis Rheum 51(3):447–450. doi:10.1002/art.20407

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Herrick AL (2005) Pathogenesis of Raynaud's phenomenon. Rheumatol Oxf 44(5):587–596. doi:10.1093/rheumatology/keh552

    Article  CAS  Google Scholar 

  24. 24.

    Carroll GJ, Withers K, Bayliss CE (1981) The prevalence of Raynaud's syndrome in rheumatoid arthritis. Ann Rheum Dis 40(6):567–570

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Schlattmann P, Höhne J, Plümper M, Heidrich H (2008) The association of Raynaud's phenomenon/syndrome with scleroderma and Sjögren's syndrome—a meta-analysis. Vasa 37(Supplement/73):26–32

    Article  Google Scholar 

  26. 26.

    Fischer M, Mielke H, Glaefke S, Deicher H (1984) Generalized vasculopathy and finger blood flow abnormalities in rheumatoid arthritis. J Rheumatol 11(1):33–37

    PubMed  CAS  Google Scholar 

  27. 27.

    Chung MS, Gong HS, Baek GH (1999) Prevalence of Raynaud's phenomenon in patients with idiopathic carpal tunnel syndrome. J Bone Joint Surg Br 81(6):1017–1019

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Maricq HR, Carpentier PH, Weinrich MC, Keil JE, Palesch Y, Biro C, Vionnet-Fuasset M, Jiguet M, Valter I (1997) Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison. J Rheumatol 24(5):879–889

    PubMed  CAS  Google Scholar 

  29. 29.

    Rossol M, Pierer M, Arnold S, Keysser G, Burkhardt H, Baerwald C, Wagner U (2009) Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis. Arthritis Res Ther 11(3):R91. doi:10.1186/ar2733

    PubMed  Article  Google Scholar 

  30. 30.

    Calguneri M, Ureten K, Akif Ozturk M, Onat AM, Ertenli I, Kiraz S, Akdogan A (2006) Extra-articular manifestations of rheumatoid arthritis: results of a university hospital of 526 patients in Turkey. Clin Exp Rheumatol 24(3):305–308

    PubMed  CAS  Google Scholar 

  31. 31.

    Alexiou I, Germenis A, Koutroumpas A, Kontogianni A, Theodoridou K, Sakkas LI (2008) Anti-cyclic citrullinated peptide-2 (CCP2) autoantibodies and extra-articular manifestations in Greek patients with rheumatoid arthritis. Clin Rheumatol 27(4):511–513. doi:10.1007/s10067-007-0800-1

    PubMed  Article  Google Scholar 

  32. 32.

    Hong P, Pope JE, Ouimet JM, Rullan E, Seibold JR (2004) Erectile dysfunction associated with scleroderma: a case–control study of men with scleroderma and rheumatoid arthritis. J Rheumatol 31(3):508–513

    PubMed  Google Scholar 

  33. 33.

    Wagner U, Pierer M, Kaltenhauser S, Wilke B, Seidel W, Arnold S, Hantzschel H (2003) Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements. Eur J Immunol 33(1):79–84. doi:10.1002/immu.200390010

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Zimmermann C, Steiner G, Skriner K, Hassfeld W, Petera P, Smolen JS (1998) The concurrence of rheumatoid arthritis and limited systemic sclerosis: clinical and serologic characteristics of an overlap syndrome. Arthritis Rheum 41(11):1938–1945. doi:10.1002/1529-0131(199811)41:11<1938::AID-ART7>3.0.CO;2-X

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Tishler M, Aharon A, Ehrenfeld M, Avni I, Bendet E, Bombardieri S, Yaron M, Shoenfeld Y (1994) Sjogren's syndrome in Israel: primary versus secondary disease. Clin Rheumatol 13(3):438–441

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Pal B, Gibson C, Passmore J, Griffiths ID, Dick WC (1989) A study of headaches and migraine in Sjogren's syndrome and other rheumatic disorders. Ann Rheum Dis 48(4):312–316

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Calderon J, Rodriguez-Valverde V, Sanchez Andrade S, Riestra JL, Gomez-Reyno J (1984) Clinical profiles of patients with antibodies to nuclear ribonucleoprotein. Clin Rheumatol 3(4):483–492

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Nishikai M, Asaba G, Homma M (1977) Rheumatoid esophageal disease. Am J Gastroenterol 67(1):29–33

    PubMed  CAS  Google Scholar 

  39. 39.

    Moutsopoulos HM, Webber BL, Vlagopoulos TP, Chused TM, Decker JL (1979) Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis. Am J Med 66(5):733–736

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Youinou P, Le Goff P, Colaco CB, Thivolet J, Tater D, Viac J, Shipley M (1985) Antikeratin antibodies in serum and synovial fluid show specificity for rheumatoid arthritis in a study of connective tissue diseases. Ann Rheum Dis 44(7):450–454

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Hantzschel H, Seidel W, Otto W, Arnold S, Fischer H, Kruger W, Gruber G, Treutler H, Lasek G, Sack G et al (1986) Diagnostic and prognostic significance of so-called rheumatoid vasculitis—2. Z Gesamte Inn Med 41(6):162–166

    PubMed  CAS  Google Scholar 

  42. 42.

    Janssens X, Herman L, Mielants H, Verbruggen G, Veys EM (1987) Disease manifestations of progressive systemic sclerosis: sensitivity and specificity. Clin Rheumatol 6(4):532–538

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Drosos AA, Lanchbury JS, Panayi GS, Moutsopoulos HM (1992) Rheumatoid arthritis in Greek and British patients. A comparative clinical, radiologic, and serologic study. Arthritis Rheum 35(7):745–748

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Grassi W, Blasetti P, Core P, Cervini C (1994) Raynaud's phenomenon in rheumatoid arthritis. Br J Rheumatol 33(2):139–141

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Nishimura S, Nishiya K, Hisakawa N, Chikazawa H, Ookubo S, Nakatani K, Hashimoto K (1996) Positivity for antinuclear antibody in patients with advanced rheumatoid arthritis. Acta Med Okayama 50(5):261–265

    PubMed  CAS  Google Scholar 

  46. 46.

    Saraux A, Allain J, Guedes C, Baron D, Youinou P, Le Goff P (1996) Raynaud's phenomenon in rheumatoid arthritis. Br J Rheumatol 35(8):752–754

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Saraux A, Bendaoud B, Guedes C, Le Goff P, Youinou P (1998) Antiphospholipid antibodies and Raynaud's phenomenon in rheumatoid arthritis. Clin Exp Rheumatol 16(3):351

    PubMed  CAS  Google Scholar 

  48. 48.

    Hernandez-Molina G, Avila-Casado C, Cardenas-Velazquez F, Hernandez-Hernandez C, Calderillo ML, Marroquin V, Soto-Abraham V, Recillas-Gispert C, Sanchez-Guerrero J (2010) Similarities and differences between primary and secondary Sjogren's syndrome. J Rheumatol 37(4):800–808. doi:10.3899/jrheum.090866

    PubMed  Article  Google Scholar 

  49. 49.

    Tansey RJ, Wragg EA, Herrick AL (2010) Raynaud's phenomenon and hand function in patients with rheumatoid arthritis. J Rheumatol 37(6):1358–1359. doi:10.3899/jrheum.091006

    PubMed  Article  Google Scholar 

Download references



Author information



Corresponding author

Correspondence to Peter Hartmann.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hartmann, P., Mohokum, M. & Schlattmann, P. The association of Raynaud’s syndrome with rheumatoid arthritis—a meta-analysis. Clin Rheumatol 30, 1013 (2011).

Download citation


  • Meta-analysis
  • Prevalence
  • Raynaud’s phenomenon
  • Raynaud’s syndrome
  • Rheumatism
  • Rheumoid arthritis