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The clinical relevance of Raynaud’s phenomenon symptom characteristics in systemic sclerosis


Raynaud’s phenomenon (RP) is a cardinal feature of systemic sclerosis (SSc) and manifests with pain, digital colour change, sensory symptoms, and impaired function. SSc-RP is exacerbated by cold exposure (RP ‘attacks’) but many patients report persistent symptoms of background digital ischaemia. The aim of our study was to examine the significance of RP with digital colour change with or without symptoms, and persistent colour change in between attacks. Patients with SSc responses were obtained from the Patient Survey of experiences of Raynaud’s Phenomenon (PASRAP). We enquired about symptoms associated with Raynaud’s attacks, and persistent symptoms in between attacks. Data were analysed as descriptive statistics with appropriate parametric/non-parametric testing. Relevant PASRAP survey question data from 747 evaluable SSc patients from across three continents were analysed. Isolated colour change was rare (29/484, 6%). Digital ulcers were more common in SSc-RP associated with other sensory symptoms (42.1% vs. 24.1%, P=0.057) and more readily treated with phosphodiesterase-type 5 inhibitors (22.5% vs. 10.3%%, P=0.124). Over one-third of patients (n=92/239, 38%) reported persistent colour change in between Raynaud’s attacks. Patients with persistent colour change were more likely to have pulmonary arterial hypertension (15.2% vs. 7.5%, P=0.057) and be treated with calcium channel blockers (54.3% vs. 39.0%, P=0.021). SSc-RP with colour change and other symptoms and/or or persistent decolourisation in between attacks were more likely to have vascular complications of SSc and be treated with vascular therapies. Future research should explore the judicious use of vascular therapies as a potential form of disease modification in SSc.

Key Points
• Isolated colour change without other symptoms is rare in SSc patients.
• SSc patients often identify persistent symptoms in between attacks of RP.
• SSc-RP with colour change and other symptoms, or persistent decolourisation, may have greater disease severity and be treated with vascular therapies.

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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.


  1. 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 

  2. Denton CP, Khanna DK (2017) Systemic sclerosis. Lancet 390:1685–1699

    Article  Google Scholar 

  3. Pauling JD, Hughes M, Pope JE (2019) Raynaud’s phenomenon - an update on diagnosis, classification and management. Clin Rheumatol 38:3317–3330

    Article  Google Scholar 

  4. Hughes M, Allanore Y, Chung L, Pauling JD, Denton CP, Matucci-Cerrinic M et al (2020) Raynaud’s phenomenon and digital ulcers in systemic sclerosis. Nat Rev Rheumatol 4:208–221

    Article  Google Scholar 

  5. Wigley FM, Flavahan NA (2016) Raynaud’s phenomenon. N Engl J Med 375:556–565

    CAS  Article  Google Scholar 

  6. Pauling JD, Saketkoo LA, Matucci-Cerinic M, Ingegnoli F, Khanna D (2018) The patient experience of Raynaud’s phenomenon in systemic sclerosis. Rheumatolology (Oxford) 58:18–26

    Article  Google Scholar 

  7. Mihai C, Landewé R, van der Heijde D, Walker UA, Constantin PI, Gherghe AM et al (2016) Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis 75:681–686

    CAS  Article  Google Scholar 

  8. Hughes M, Heal C, Henes J, Balbir-Gurman A, Distler JHW, Airò P et al (2022) Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort. Rheumatology (Oxford) 61:1141–1147

    Article  Google Scholar 

  9. Matucci-Cerinic M, Kahaleh B, Wigley FM (2013) Review: evidence that systemic sclerosis is a vascular disease. Arthritis Rheum 65:1953–1962

    CAS  Article  Google Scholar 

  10. Pauling JD, Reilly E, Smith T, Frech TM (2019) Evolving symptom characteristics of Raynaud’s phenomenon in systemic sclerosis and their association with physician and patient-reported assessments of disease severity. Arthritis Care Res (Hoboken) 71:1119–1126

    Article  Google Scholar 

  11. Pauling JD, Domsic RT, Saketkoo LA, Almeida C, Withey J, Jay H et al (2018) A multi-national qualitative research study exploring the patient experience of Raynaud’s phenomenon in systemic sclerosis. Arthritis Care Res (Hoboken) 70:1373–1384

    Article  Google Scholar 

  12. Murphy S, Lescoat A, Alore M, Hughes M, Pauling JD, Sabbagh M et al (2021) How do patients define Raynaud’s phenomenon? Differences between primary and secondary disease. Clin Rheumatol 40:1611–1616

    Article  Google Scholar 

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

    Article  Google Scholar 

  14. Hughes M, Huang S, Pauling JD, Sabbagh M, Khanna D (2021) Factors influencing patient decision-making concerning treatment escalation in Raynaud’s phenomenon secondary to systemic sclerosis. Arthritis Care Res (Hoboken) 73:1845–1852

    Article  Google Scholar 

  15. Hughes M, Khanna DK, Pauling JD (2020) Drug initiation and escalation strategies of vasodilator therapies for Raynaud’s phenomenon: can we treat to target? Rheumatology (Oxford) 59:464–466

    Article  Google Scholar 

  16. Smith V, Scirè CA, Talarico R, Airo P, Alexander T, Allanore Y et al (2019) Systemic sclerosis: state of the art on clinical practice guidelines. RMD Open 1;4(Suppl:1):e000782

    Google Scholar 

  17. Khanna D, Zhao C, Saggar R, Mathai SC, Chung LS, Coghlan JG et al (2021) Long-term outcomes in patients with connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era: meta-analyses of randomized, controlled trials and observational registries. Arthritis Rheumatol 73:837–847

    Article  Google Scholar 

  18. Hughes M, Zanatta E, Sandler RD, Avouac J, Allanore Y (2021) Improvement with time of vascular outcomes in systemic sclerosis: a systematic review and meta-analysis study. Rheumatology (Oxford) [Online ahead of print]

  19. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205

    CAS  PubMed  Google Scholar 

  20. Moinzadeh P, Riemekasten G, Siegert E, Fierlbeck G, Henes J, Blank N et al (2016) Vasoactive therapy in systemic sclerosis: real-life therapeutic practice in more than 3000 patients. J Rheumatol 43:66–74

    CAS  Article  Google Scholar 

  21. Blagojevic J, Abignano G, Avouac J, Cometi L, Frerix M, Bellando-Randone S et al (2020) Use of vasoactive/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: results from the analysis of the observational real-life DeSScipher study. Clin Rheumatol 39:27–36

    Article  Google Scholar 

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We thank the Scleroderma Foundation and Scleroderma and Raynaud’s UK for distributing the survey link to their members.


The study was funded by NIH/NIAMS K24 AR AR063120 to Dr. Dinesh Khanna.

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Correspondence to Michael Hughes.

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Ethics approval

The study was approved with exempt status by the University of Michigan IRB (Study ID: HUM00175143; OHRP IRB Registration Number(s): IRB00000246).

Conflict of interest

Michael Hughes—reports speaking fees from Actelion pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work (all <$10,000). He is a member of a Data and Safety Monitoring Board for Certa Therapeutics. Suiyuan Huang—no reported conflicts of interest or competing interests. John Pauling—reports personal fees from Boehringer Ingelheim, Astra Zenaca, Sojournix Pharma and Permeatus Inc.; grants, personal fees, and non-financial support from Janssen; all outside the submitted work (<$10,000 for all honoraria / speaker fees). Maya Sabbagh—no reported conflicts of interest or competing interests. Dinesh Khanna—consulting fees from Acceleron, Actelion, Amgen, Bayer, Boehringer Ingelheim, Chemomab, CSL Behring, Genentech/Roche, Horizon, Paracrine Cell Therapy, Mitsubishi Tanabe Pharma, Prometheus, Theraly; Dr. Khanna is Chief Medical Officer of Eicos Sciences, Inc, a subsidiary of CiviBioPharma and has stock options.

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Hughes, M., Huang, S., Pauling, J.D. et al. The clinical relevance of Raynaud’s phenomenon symptom characteristics in systemic sclerosis. Clin Rheumatol (2022).

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  • Colour change
  • Management
  • Raynaud’s phenomenon
  • Symptoms
  • Systemic sclerosis
  • Treatment