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Raynaud’s phenomenon—an update on diagnosis, classification and management

Clinical Rheumatology volume 38, pages 3317–3330 (2019)Cite this article

Abstract

Raynaud’s phenomenon (RP) is used to describe a symptom complex caused by digital vascular compromise. RP is a clinical diagnosis. The typically episodic nature of RP has resulted in a reliance upon patient self-report for diagnosis. The term ‘primary RP’ is generally applied when no underlying pathology can be demonstrated. Whilst ‘primary RP’ is currently considered a distinct disorder, there is evidence that the term may comprise several entities that include a functional vasospastic disorder, a physiologically appropriate thermoregulatory response, subclinical atherosclerosis and ‘cold intolerance’. Optimal management may differ depending on cause. The term ‘secondary RP’ encompasses a broad range of rheumatological, haematological, endocrinological and vascular pathology. RP can range from relatively benign but intrusive vasospasm, to the progressive obliterative microangiopathy of systemic sclerosis (SSc), in which severe digital ischaemia can threaten tissue viability. SSc has formed the focus of much of the research into RP but, consistent with most medical symptom complexes, the aetiopathogenesis of RP varies greatly dependent on cause. Vasospasm within the digital macro- and microvasculature occurs in SSc, but digital ischaemia is further compounded by a progressive obliterative microangiopathy. Recent work exploring the patient experience of SSc-RP is challenging the ‘episodic’ paradigm of ‘Raynaud’s’, with important implications for clinical trials utilising diary-based patient-reported outcome instruments for assessing Raynaud’s symptoms. This review shall examine the causes, pathogenesis, clinical features, classification and management of RP. A practical approach to the evaluation and management of RP is outlined, highlighting important knowledge gaps and unmet research needs where applicable.

Key Points
• Raynaud’s phenomenon is a symptom complex related to digital vascular compromise secondary to broad-ranging pathology.
• Raynaud’s phenomenon, as currently classified, likely encompasses a number of aetiopathogenic processes.
• Raynaud’s phenomenon causes significant disease-related morbidity in autoimmune rheumatic diseases such as systemic sclerosis.

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References

  1. Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD (2011) Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int 31:1409–1417

    Article  PubMed  Google Scholar 

  2. Barlow T (1862 and 1874). On local asphyxia and symmetrical gangrene of the extremities, and new research on the nature and treatment of local asphyxia of the extremities. Selected monographs. London: New Sydenham Society

  3. Allen E, Brown G (1932) Raynaud’s disease: a critical review of minimal requisites for diagnosis. Am J M Sc 183:187–200

    Article  Google Scholar 

  4. Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y, Guiducci S, Hesselstrand R, Hummers LK, Duong C, Kahaleh B, Macgregor A, Matucci-Cerinic M, Wollheim FA, Mayes MD, Gershwin ME (2014) International consensus criteria for the diagnosis of Raynaud’s phenomenon. J Autoimmun 48-49:60–65

    Article  PubMed  Google Scholar 

  5. Maricq HR, Carpentier PH, Weinrich MC, Keil JE, Palesch Y, Biro C et al (1997) Geographic variation in the prevalence of Raynaud’s phenomenon: a 5 region comparison. J Rheumatol 24:879–889

    CAS  PubMed  Google Scholar 

  6. LeRoy EC, Medsger TA (1992) Raynaud’s phenomenon: a proposal for classification. Clin Exp Rheumatol 10:485–488

    CAS  PubMed  Google Scholar 

  7. Brennan P, Silman A, Black C, Bernstein R, Coppock J, Maddison P, et al. (1993) Validity and reliability of three methods used in the diagnosis of Raynaud’s phenomenon. The UK Scleroderma Study Group. Br J Rheumatol 32:357–361

  8. Garner R, Kumari R, Lanyon P, Doherty M, Zhang W (2015) Prevalence, risk factors and associations of primary Raynaud’s phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 5:e006389–e006389

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hutchinson J (1901) Raynaud’s phenomenon. Med Press Circ 128:403–405

    Google Scholar 

  10. Hadler N (1998) “Primary Raynaud’s” is not a disease or even a disorder; it’s a trait. J Rheumatol 25:2291–2294

    CAS  PubMed  Google Scholar 

  11. Allen E, Brown G (1932) Raynaud’s disease: a clinical study of one hundred and forty-seven cases. J Am Med Assoc 99:1472–1478

    Article  Google Scholar 

  12. Bayle O, Consoli SM, Baudin M, Vayssairat M, Fiessinger JN, Housset E (1990) Idiopathic and secondary Raynaud’s phenomenon. A comparative psychosomatic approach. Presse Med 19:741–745

    CAS  PubMed  Google Scholar 

  13. Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (1998) Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain 32:21–26

    Article  Google Scholar 

  14. Wolfe F, Petri M, Alarcon G, Goldman J, Chakravarty E, Katz R et al (2009) Fibromyalgia, systemic lupus erythematosus (SLE), and evaluation of SLE activity. J Rheumatol 36:82–88

    Article  PubMed  PubMed Central  Google Scholar 

  15. Scolnik M, Vasta B, Hart DJ, Shipley JA, McHugh NJ, Pauling JD (2016) Symptoms of Raynaud’s phenomenon (RP) in fibromyalgia syndrome are similar to those reported in primary RP despite differences in objective assessment of digital microvascular function and morphology. Rheumatol Int 36:1371–1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nietert PJ, Shaftman SR, Silver RM, Wolf BJ, Egan BM, Hunt KJ, Smith EA (2015) Raynaud phenomenon and mortality: 20+ years of follow-up of the Charleston Heart Study cohort. Clin Epidemiol 7:161–168

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pizzorni C, Sulli A, Smith V, Ruaro B, Trombetta AC, Cutolo M, Paolino S (2017) Primary Raynaud’s phenomenon and nailfold videocapillaroscopy: age-related changes in capillary morphology. Clin Rheumatol 36:1637–1642

    Article  PubMed  Google Scholar 

  18. Spencer-Green G (1998) Outcomes in primary Raynaud phenomenon: a meta-analysis of the frequency, rates, and predictors of transition to secondary diseases. Arch Intern Med 158:595–600

    Article  CAS  PubMed  Google Scholar 

  19. Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR scleroderma trials and research group database. Ann Rheum Dis 2007:754–763

    Article  Google Scholar 

  20. Delisle VC, Hudson M, Baron M, Thombs BD, And The Canadian Scleroderma Research Group A (2014) Sex and time to diagnosis in systemic sclerosis: an updated analysis of 1,129 patients from the Canadian scleroderma research group registry. Clin Exp Rheumatol 32:S-10–S-14

    Google Scholar 

  21. Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR, Rich É, Grodzicky T, Raymond Y, Senécal JL (2008) Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum 58:3902–3912

    Article  PubMed  Google Scholar 

  22. Schneeberger D, Tyndall A, Kay J, Søndergaard KH, Carreira PE, Morgiel E et al (2012) Systemic sclerosis without antinuclear antibodies or Raynaud’s phenomenon: a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database. Rheumatology (Oxford) 52:560–567

    Article  CAS  Google Scholar 

  23. Fiorentino DF, Kuo K, Chung L, Zaba L, Li S, Casciola-Rosen L (2015) Distinctive cutaneous and systemic features associated with antitranscriptional intermediary factor-1γ antibodies in adults with dermatomyositis. J Am Acad Dermatol 72:449–455

    Article  PubMed  PubMed Central  Google Scholar 

  24. Carpintero MF, Martinez L, Fernandez I, Romero ACG, Mejia C, Zang YJ, Hoffman RW, Greidinger EL (2015) Diagnosis and risk stratification in patients with anti-RNP autoimmunity. Lupus 24:1057–1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Arroyo-Ávila M, Santiago-Casas Y, McGwin G, Cantor RS, Petri M, Ramsey-Goldman R, Reveille JD, Kimberly RP, Alarcón GS, Vilá LM, Brown EE (2015) Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. Clin Rheumatol 34:1217–1223

    Article  PubMed  PubMed Central  Google Scholar 

  26. Nakano M, Ohuchi Y, Hasegawa H, Kuroda T, Ito S, Gejyo F (2000) Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus. J Rheumatol 27:1403–1407

    CAS  PubMed  Google Scholar 

  27. Kuramoto N, Ohmura K, Ikari K, Yano K, Furu M, Yamakawa N, Hashimoto M, Ito H, Fujii T, Murakami K, Nakashima R, Imura Y, Yukawa N, Yoshifuji H, Taniguchi A, Momohara S, Yamanaka H, Matsuda F, Mimori T, Terao C (2017) Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis. Sci Rep 7:6911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lee K-E, Kang J-H, Lee J-W, Wen L, Park D-J, Kim T-J, Park YW, Lee SS (2015) Anti-centromere antibody-positive Sjögren’s syndrome: a distinct clinical subgroup? Int J Rheum Dis 18:776–782

    Article  CAS  PubMed  Google Scholar 

  29. Tsukamoto M, Suzuki K, Takeuchi T (2018) Clinical and immunological features of anti-centromere antibody-positive primary Sjögren’s syndrome. Rheumatol Ther 5:499–505

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hebbar M, Lassalle P, Delneste Y, Hatron PY, Devulder B, Tonnel AB, Janin A (1997) Assessment of anti-endothelial cell antibodies in systemic sclerosis and Sjögren’s syndrome. Ann Rheum Dis 56:230–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li M-T, Ai J, Tian Z, Fang Q, Zheng W-J, Zeng X-J, Zeng XF (2010) Prevalence of anti-endothelial cell antibodies in patients with pulmonary arterial hypertension associated with connective tissue diseases. Chin Med Sci J 25:27–31

    Article  PubMed  Google Scholar 

  32. Riemekasten G, Philippe A, Näther M, Slowinski T, Müller DN, Heidecke H et al (2011) Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis 70:530–536

    Article  CAS  PubMed  Google Scholar 

  33. Shah AA, Montagne J, Oh S-Y, Wigley FM, Casciola-Rosen L (2015) Pilot study to determine whether transient receptor potential melastatin type 8 (TRPM8) antibodies are detected in scleroderma. Clin Exp Rheumatol 33:S123–S126

    PubMed  Google Scholar 

  34. Maricq HR, Weinrich MC (1998) Diagnosis of Raynaud’s phenomenon assisted by color charts. J Rheumatol 15:454–459

    Google Scholar 

  35. Wollersheim H, Thien T (1990) The diagnostic value of clinical signs and symptoms in patients with Raynaud’s phenomenon. A cross-sectional study. Neth J Med 37:171–182

    CAS  PubMed  Google Scholar 

  36. Ingegnoli F, Gualtierotti R, Orenti A, Schioppo T, Marfia G, Campanella R et al (2015) Uniphasic blanching of the fingers, abnormal capillaroscopy in nonsymptomatic digits, and autoantibodies: expanding options to increase the level of suspicion of connective tissue diseases beyond the classification of Raynaud’s phenomenon. J Immunol Res 2015:371960

    Article  PubMed  PubMed Central  Google Scholar 

  37. Pauling JD, Reilly E, Smith T, Frech TM. Evolving symptoms of Raynaud’s phenomenon in systemic sclerosis are associated with physician and patient-reported assessments of disease severity. Arthritis Care Res (Hoboken) 2018. doi:https://doi.org/10.1002/acr.23729.

  38. Pauling JD, Domsic RT, Saketkoo LA, Almeida C, Withey J, Jay H, Frech TM, Ingegnoli F, Dures E, Robson J, McHugh NJ, Herrick AL, Matucci-Cerinic M, Khanna D, Hewlett S (2018) A multi-national qualitative research study exploring the patient experience of Raynaud’s phenomenon in systemic sclerosis. Arthritis Care Res 70:1373–1384

    Article  Google Scholar 

  39. Pauling JD, Saketkoo LA, Domsic RT (2018) Patient perceptions of the Raynaud’s condition score diary provide insight into its performance in clinical trials of Raynaud’s phenomenon: comment on the article by Denton et al. Arthritis Rheum 70:973–974

    Article  Google Scholar 

  40. Pauling JD, Saketkoo LA, Matucci-Cerinic M, Ingegnoli F, Khanna D (2019) The patient experience of Raynaud’s phenomenon in systemic sclerosis. Rheumatology (Oxford) 58:18–26

    Article  Google Scholar 

  41. Pauling JD, Frech TM, Hughes M, Gordon JK, Domsic RT, Anderson ME, Ingegnoli F, McHugh NJ, Johnson SR, Hudson M, Boin F, Ong VH, Matucci-Cerinic M, Altorok N, Scolnik M, Nikpour M, Shah A, Pope JE, Khanna D, Herrick AL (2018) Patient-reported outcome instruments for assessing Raynaud’s phenomenon in systemic sclerosis: a SCTC vascular working group report. J Scleroderma Relat Disord 3:249–252

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pauling JD, Shipley JA, Hart DJ, McGrogan A, McHugh NJ (2015) Use of laser speckle contrast imaging to assess digital microvascular function in primary Raynaud phenomenon and systemic sclerosis: a comparison using the Raynaud condition score diary. J Rheumatol 42:1163–1168

    Article  CAS  PubMed  Google Scholar 

  43. Wilkinson JD, Leggett SA, Marjanovic EJ, Moore TL, Allen J, Anderson ME, Britton J, Buch MH, del Galdo F, Denton CP, Dinsdale G, Griffiths B, Hall F, Howell K, MacDonald A, McHugh NJ, Manning JB, Pauling JD, Roberts C, Shipley JA, Herrick AL, Murray AK (2018) A multicenter study of the validity and reliability of responses to hand cold challenge as measured by laser speckle contrast imaging and thermography: outcome measures for systemic sclerosis-related Raynaud’s phenomenon. Arthritis Rheum 70:903–911

    Article  Google Scholar 

  44. Pauling JD, Reilly EE, Smith T, Frech TM (2019) Factors influencing Raynaud’s condition score diary outcomes in systemic sclerosis. J Rheumatol. https://doi.org/10.3899/jrheum.180818

  45. Hughes M, Snapir A, Wilkinson J, Snapir D, Wigley FM, Herrick AL (2015) Prediction and impact of attacks of Raynaud’s phenomenon, as judged by patient perception. Rheumatol 54:1443–1447

  46. Watson HR, Robb R, Belcher G, Belch JJ (1999) Seasonal variation of Raynaud’s phenomenon secondary to systemic sclerosis. J Rheumatol 26:1734–1737

    CAS  PubMed  Google Scholar 

  47. Freedman RR, Ianni P (1983) Role of cold and emotional stress in Raynaud’s disease and scleroderma. Br Med J (Clin Res Ed) 287:1499–1502

    Article  CAS  Google Scholar 

  48. Sandqvist G, Wollmer P, Scheja A, Wildt M, Hesselstrand R (2018) Raynaud’s phenomenon and its impact on activities in daily life during one year of follow-up in early systemic sclerosis. Scand J Rheumatol 47:206–209

    Article  CAS  PubMed  Google Scholar 

  49. Pauling J, Nagaraja V, Khanna D Insight into the contrasting findings of therapeutic trials of digital ischaemic manifestations of systemic sclerosis. Curr Treat Opinions in Rheum 5:85–103

  50. Chikura B, Moore T, Manning J, Vail A, Herrick AL (2010) Thumb involvement in Raynaud’s phenomenon as an indicator of underlying connective tissue disease. J Rheumatol 37:783–786

    Article  PubMed  Google Scholar 

  51. Bassel M, Hudson M, Taillefer SS, Schieir O, Baron M, Thombs BD (2011) Frequency and impact of symptoms experienced by patients with systemic sclerosis: results from a Canadian National Survey. Rheumatology (Oxford) 50:762–767

    Article  Google Scholar 

  52. Frantz C, Avouac J, Distler O, Amrouche F, Godard D, Kennedy AT, Connolly K, Varga J, Matucci-Cerinic M, Allanore Y (2016) Impaired quality of life in systemic sclerosis and patient perception of the disease: a large international survey. Semin Arthritis Rheum 46:115–123

    Article  PubMed  Google Scholar 

  53. Kwakkenbos L, Sanchez TA, Turner KA, Mouthon L, Carrier M-E, Hudson M et al (2018) The association of sociodemographic and disease variables with hand function: a scleroderma patient-centered intervention network cohort study. Clin Exp Rheumatol 36:88–94

    PubMed  Google Scholar 

  54. Merkel PA, Herlyn K, Martin RW, Anderson JJ, Mayes MD, Bell P, Korn JH, Simms RW, Csuka ME, Medsger TA Jr, Rothfield NF, Ellman MH, Collier DH, Weinstein A, Furst DE, Jiménez SA, White B, Seibold JR, Wigley FM, for the Scleroderma Clinical Trials Consortium (2002) Measuring disease activity and functional status in patients with scleroderma and Raynaud’s phenomenon. Arthritis Rheum 46:2410–2420

    Article  PubMed  Google Scholar 

  55. Herrick AL (2012) The pathogenesis, diagnosis and treatment of Raynaud phenomenon. Nat Rev Rheumatol 8:469–479

    Article  CAS  PubMed  Google Scholar 

  56. Giurgea G-A, Mlekusch W, Charwat-Resl S, Mueller M, Hammer A, Gschwandtner ME et al (2015) Relationship of age and body mass index to skin temperature and skin perfusion in primary Raynaud’s phenomenon. Arthritis Rheumatol (Hoboken, NJ) 67:238–242

    Article  Google Scholar 

  57. Munir S, Freidin MB, Brain S, Williams FMK (2018) Association of Raynaud’s phenomenon with a polymorphism in the NOS1 gene. PLoS One 2018;13:e0196279

  58. Wigley FM (2002) Raynaud’s phenomenon. N Engl J Med 347:1001–1008

    Article  PubMed  Google Scholar 

  59. Hughes M, Baker A, Farrington S, Pauling JD (2019) Patient organisation-led initiatives can play an important role in raising awareness about Raynaud’s phenomenon and encourage earlier healthcare utilisation for high-risk groups. Ann Rheum Dis 78:439–441

    Article  PubMed  Google Scholar 

  60. Freedman RR, Mayes MD (1996) Familial aggregation of primary Raynaud’s disease. Arthritis Rheum 39:1189–1191

    Article  CAS  PubMed  Google Scholar 

  61. Frech T, Khanna D, Markewitz B, Mineau G, Pimentel R, Sawitzke A (2010) Heritability of vasculopathy, autoimmune disease, and fibrosis: a population-based study of systemic sclerosis. Arthritis Rheum 62:2109–2116

    PubMed  PubMed Central  Google Scholar 

  62. Pauling JD, Salazar G, Lu H, Betteridge ZE, Assassi S, Mayes MD, McHugh NJ (2018) Presence of anti-eukaryotic initiation factor-2B, anti-RuvBL1/2 and anti-synthetase antibodies in patients with anti-nuclear antibody negative systemic sclerosis. Rheumatology (Oxford) 57:712–717

    Article  CAS  Google Scholar 

  63. Hughes M, Ong VH, Anderson ME, Hall F, Moinzadeh P, Griffiths B, Baildam E, Denton CP, Herrick AL (2015) Consensus best practice pathway of the UK scleroderma study group: digital vasculopathy in systemic sclerosis. Rheumatology (Oxford) 54:2015–2024

    Article  CAS  Google Scholar 

  64. Cutolo M, Smith V (2013) State of the art on nailfold capillaroscopy: a reliable diagnostic tool and putative biomarker in rheumatology? Rheumatology (Oxford) 52:1933–1940

    Article  Google Scholar 

  65. Smith V, Beeckman S, Herrick AL, Decuman S, Deschepper E, De Keyser F et al (2016) An EULAR study group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases. Rheumatology (Oxford) 55:883–890

    Article  Google Scholar 

  66. Kubo S, Smith V, Cutolo M, Tanaka Y (2018) The role of nailfold videocapillaroscopy in patients with systemic sclerosis. Immunol Med 4:113–119

    Article  Google Scholar 

  67. Cutolo M, Melsens K, Wijnant S, Ingegnoli F, Thevissen K, De Keyser F et al (2018) Nailfold capillaroscopy in systemic lupus erythematosus: a systematic review and critical appraisal. Autoimmun Rev 7:344–352

    Article  Google Scholar 

  68. Corominas H, Ortiz-Santamaría V, Castellví I, Moreno M, Morlà R, Clavaguera T et al (2016) Nailfold capillaroscopic findings in primary Sjögren’s syndrome with and without Raynaud’s phenomenon and/or positive anti-SSA/Ro and anti-SSB/La antibodies. Rheumatol Int 36:365–369

    Article  CAS  PubMed  Google Scholar 

  69. Bukhari M, Herrick AL, Moore T, Manning J, Jayson MI (1996) Increased nailfold capillary dimensions in primary Raynaud’s phenomenon and systemic sclerosis. Br J Rheumatol 35:1127–1131

    Article  CAS  PubMed  Google Scholar 

  70. Sebastiani M, Triantafyllias K, Manfredi A, González-Gay MA, Palmou-Fontana N, Cassone G, Drott U, Delbrück C, Rojas-Serrano J, Bertolazzi C, Nuño L, Giannini M, Iannone F, Vicente EF, Castañeda S, Selva-O’Callaghan A, Trallero Araguas E, Emmi G, Iuliano A, Bauhammer J, Miehle N, Parisi S, Cavagna L, Codullo V, Montecucco C, Lopez-Longo FJ, Martínez-Barrio J, Nieto-González JC, Vichi S, Confalonieri M, Tomietto P, Bergner R, Sulli A, Bonella F, Furini F, Scirè CA, Bortoluzzi A, Specker C, Barsotti S, Neri R, Mosca M, Caproni M, Weinmann-Menke J, Schwarting A, Smith V, Cutolo M, The American and European Network of Antisynthetase Syndrome Collaborative Group (2019) Nailfold capillaroscopy characteristics of antisynthetase syndrome and possible clinical associations: results of a multicenter international study. J Rheumatol 46:279–284

    Article  CAS  PubMed  Google Scholar 

  71. Hughes M, Moore T, O’Leary N, Tracey A, Ennis H, Dinsdale G, Murray A, Roberts C, Herrick AL (2015) A study comparing videocapillaroscopy and dermoscopy in the assessment of nailfold capillaries in patients with systemic sclerosis-spectrum disorders. Rheumatol 54:1435–1442

    Article  Google Scholar 

  72. Pauling JD, Flower V, Shipley JA, Harris ND, McHugh NJ (2011) Influence of the cold challenge on the discriminatory capacity of the digital distal-dorsal difference in the thermographic assessment of Raynaud’s phenomenon. Microvasc Res 82:364–368

    Article  CAS  PubMed  Google Scholar 

  73. Pauling JD (2018) The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis. Expert Rev Clin Immunol 14:431–442

    Article  CAS  PubMed  Google Scholar 

  74. Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, Black CM (1999) Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum 42:2646–2655

    Article  CAS  PubMed  Google Scholar 

  75. Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, Black CM (2001) Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 40:1038–1043

    Article  CAS  Google Scholar 

  76. Pauling JD, Shipley JA, Harris ND, McHugh NJ (2012) Use of infrared thermography as an endpoint in therapeutic trials of Raynaud’s phenomenon and systemic sclerosis. Clin Exp Rheumatol 30:S103–S115

    PubMed  Google Scholar 

  77. Wilkinson JD, Leggett SA, Marjanovic EJ, Moore TL, Allen J, Anderson ME, Britton J, Buch MH, del Galdo F, Denton CP, Dinsdale G, Griffiths B, Hall F, Howell K, MacDonald A, McHugh NJ, Manning JB, Pauling JD, Roberts C, Shipley JA, Herrick AL, Murray AK (2018) A multicenter study of the validity and reliability of responses to hand cold challenge as measured by laser speckle contrast imaging and thermography. Arthritis Rheum 70:903–911

    Article  Google Scholar 

  78. Daniels J, Pauling JD, Eccleston C (2018) Behaviour change interventions for the management of Raynaud’s phenomenon: a systematic literature review. BMJ Open 2018;8:e024528

  79. Denton C, Hughes M, Gak N, Vila J, Buch MH, Chakravarty K et al (2016) BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford) 55:1906–1910

    Article  Google Scholar 

  80. Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y et al (2016) Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 76:1327–1339

    Article  PubMed  Google Scholar 

  81. Fernández-Codina A, Walker KM, Pope JE, Scleroderma Algorithm Group (2018) Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheum 70:1820–1828

    Article  CAS  Google Scholar 

  82. Rirash F, Tingey PC, Harding SE, Maxwell LJ, Tanjong Ghogomu E, Wells GA et al (2017) Calcium channel blockers for primary and secondary Raynaud’s phenomenon. Cochrane Database Syst Rev 12:CD000467

    PubMed  Google Scholar 

  83. Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski J-L (2013) Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomised trials. Ann Rheum Dis 72:1696–1699

    Article  CAS  PubMed  Google Scholar 

  84. Denton CP, Hachulla É, Riemekasten G, Schwarting A, Frenoux J-M, Frey A, le Brun FO, Herrick AL, on behalf of the Raynaud Study Investigators (2017) Efficacy and safety of selexipag in adults with Raynaud’s phenomenon secondary to systemic sclerosis. Arthritis Rheum 69:2370–2379

    Article  CAS  Google Scholar 

  85. Moinzadeh P, Riemekasten G, Siegert E, Fierlbeck G, Henes J, Blank N, Melchers I, Mueller-Ladner U, Frerix M, Kreuter A, Tigges C, Lahner N, Susok L, Guenther C, Zeidler G, Pfeiffer C, Worm M, Karrer S, Aberer E, Bretterklieber A, Genth E, Simon JC, Distler JHW, Hein R, Schneider M, Seitz CS, Herink C, Steinbrink K, Sárdy M, Varga R, Mensing H, Mensing C, Lehmann P, Neeck G, Fiehn C, Weber M, Goebeler M, Burkhardt H, Buslau M, Ahmadi-Simab K, Himsel A, Juche A, Koetter I, Kuhn A, Sticherling M, Hellmich M, Kuhr K, Krieg T, Ehrchen J, Sunderkoetter C, Hunzelmann N, The German Network for Systemic Scleroderma (2016) Vasoactive therapy in systemic sclerosis: real-life therapeutic practice in more than 3000 patients. J Rheumatol 43:66–74

    Article  CAS  PubMed  Google Scholar 

  86. Iorio ML, Masden DL, Higgins JP (2012) Botulinum toxin a treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum 41:599–603

    Article  CAS  PubMed  Google Scholar 

  87. Momeni A, Sorice SC, Valenzuela A, Fiorentino DF, Chung L, Chang J (2015) Surgical treatment of systemic sclerosis-is it justified to offer peripheral sympathectomy earlier in the disease process? Microsurgery 35:441–446

    Article  PubMed  Google Scholar 

  88. Bello RJ, Cooney CM, Melamed E, Follmar K, Yenokyan G, Leatherman G, Shah AA, Wigley FM, Hummers LK, Lifchez SD (2017) The therapeutic efficacy of botulinum toxin in treating scleroderma-associated Raynaud’s phenomenon: a randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheum 69:1661–1669

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Royal National Hospital for Rheumatic Diseases (at Royal United Hospitals), Upper Borough Walls, Bath, BA1 1RL, UK

    John D Pauling

  2. Department of Pharmacy and Pharmacology, University of Bath, Bath, UK

    John D Pauling

  3. Department of Rheumatology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    Michael Hughes

  4. University of Western Ontario, London, ON, Canada

    Janet E Pope

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JDP, MH and JEP conceived the idea for the manuscript, developed the search strategy and selection criteria. All authors contributed to the iterative drafting of the final manuscript.

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Correspondence to John D Pauling.

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Conflict of interest

Dr Pauling has undertaken consultancy work and received speaker honoraria from Actelion pharmaceuticals. Dr Hughes has received speaker honoraria from Actelion pharmaceuticals. Dr Pope has undertaken consultancy work for AbbVie, Actelion, Baxter, Bayer, BMS, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB.

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Pauling, J.D., Hughes, M. & Pope, J.E. Raynaud’s phenomenon—an update on diagnosis, classification and management. Clin Rheumatol 38, 3317–3330 (2019). https://doi.org/10.1007/s10067-019-04745-5

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Keywords

  • Assessment
  • Classification
  • Management
  • Pathogenesis
  • Raynaud’s phenomenon
  • Systemic sclerosis