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Detection of microvascular changes in systemic sclerosis and other rheumatic diseases

Abstract

Morphological and functional analysis of the microcirculation are objective outcome measures that are recommended for use in the presence of clinical signs of altered peripheral blood flow (such as Raynaud phenomenon), which can occur in systemic sclerosis (SSc) and other autoimmune rheumatic diseases. Several advanced non-invasive tools are available for monitoring the microcirculation, including nailfold videocapillaroscopy, which is the best-studied and most commonly used method for distinguishing and quantifying microvascular morphological alterations in SSc. Nailfold videocapillaroscopy can also be used alongside laser Doppler techniques to assist in the early diagnosis and follow-up of patients with dermatomyositis or mixed connective tissue disease. Power Doppler ultrasonography, which has been used for many years to evaluate the vascularity of synovial tissue in rheumatoid arthritis, is another promising tool for the analysis of skin and nailbed capillary perfusion in other autoimmune rheumatic diseases. Other emerging methods include raster-scanning optoacoustic mesoscopy, which offers non-invasive high-resolution 3D visualization of capillaries and has been tested in psoriatic arthritis and SSc. The principle functions and operative characteristics of several non-invasive tools for analysing microvascular changes are outlined in this Review, and the clinical roles of validated or tested imaging methods are discussed for autoimmune rheumatic diseases.

Key points

  • Careful detection of the microvasculature can be performed using a variety of advanced imaging methods, which have also enabled new insights into the pathophysiology of several autoimmune rheumatic diseases.

  • Nailfold videocapillaroscopy is the gold standard method for distinguishing between primary and secondary Raynaud phenomenon, through the identification of a ‘scleroderma’ pattern, and for quantifying differences in microvascular morphology.

  • The presence of a ‘scleroderma-like’ nailfold videocapillaroscopy pattern supports the diagnosis of autoimmune rheumatic diseases such as dermatomyositis, mixed connective tissue disease and antisynthetase syndrome.

  • Several non-invasive methods, including laser Doppler techniques, enable the detection and quantification of characteristic alterations in peripheral blood perfusion in a number of autoimmune rheumatic diseases.

  • Imaging of the microcirculation is recommended at least twice a year for patients with persistent Raynaud phenomenon, and also for the follow-up of patients with selected autoimmune rheumatic diseases.

  • Almost all the most common techniques for morphological and functional microvascular evaluation can be used in combinations and managed by rheumatologists, bringing diagnostic power to the rheumatologist’s imaging armamentarium.

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Fig. 1: Direct optical imaging of microvascular morphology.
Fig. 2: Optoacoustic imaging of microvascular morphology.
Fig. 3: Imaging of microvascular function.
Fig. 4: Alternative imaging tools for assessing peripheral blood flow.
Fig. 5: Nailfold capillaroscopic patterns in rheumatic diseases other than systemic sclerosis.
Fig. 6: Combined microvascular morphology and functional blood flow analysis.

References

  1. Murray, A. K. et al. Noninvasive imaging techniques in the assessment of scleroderma spectrum disorders. Arthritis Rheum. 15, 1103–1111 (2009).

    Article  Google Scholar 

  2. Cutolo, M., Sulli, A. & Smith, V. Assessing microvascular changes in systemic sclerosis diagnosis and management. Nat. Rev. Rheumatol. 6, 578–587 (2010).

    PubMed  Article  Google Scholar 

  3. Ingegnoli, F. et al. An international survey on non-invasive techniques to assess the microcirculation in patients with Raynaud’s phenomenon (SUNSHINE survey). Rheumatol. Int. 37, 1879–1890 (2017).

    PubMed  Article  Google Scholar 

  4. Cutolo, M., Grassi, W. & Matucci Cerinic, M. Raynaud’s phenomenon and the role of capillaroscopy. Arthritis Rheum. 48, 3023–3030 (2003).

    PubMed  Article  Google Scholar 

  5. Herrick, A. L., Dinsdale, G. & Murray, A. New perspectives in the imaging of Raynaud’s phenomenon. Eur. J. Rheumatol. 7 (Suppl. 3), 212–221 (2020).

    Article  Google Scholar 

  6. Cutolo, M., Soldano, S. & Smith, V. Pathophysiology of systemic sclerosis: current understanding and new insights. Expert Rev. Clin. Immunol. 15, 753–764 (2019).

    CAS  PubMed  Article  Google Scholar 

  7. Cutolo, M., Sulli, A., Pizzorni, C. & Accardo, S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J. Rheumatol. 27, 155–160 (2000).

    CAS  PubMed  Google Scholar 

  8. Lonzetti, L. S. et al. Updating the American College of Rheumatology preliminary classification criteria for systemic sclerosis: addition of severe nailfold capillaroscopy abnormalities markedly increases the sensitivity for limited scleroderma. Arthritis Rheum. 44, 735–736 (2001).

    CAS  PubMed  Article  Google Scholar 

  9. Hudson, M. et al. Improving the sensitivity of the American College of Rheumatology classification criteria for systemic sclerosis. Clin. Exp. Rheumatol. 25, 754–757 (2007).

    CAS  PubMed  Google Scholar 

  10. Koenig, M. et al. 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 (2008).

    PubMed  Article  Google Scholar 

  11. Van den Hoogen, F. et al. 2013 classification criteria for systemic sclerosis. Arthritis Rheum. 65, 2737–2747 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  12. Cutolo, M. & Sulli, A. Optimized treatment algorithms for digital vasculopathy in SSc. Nat. Rev. Rheumatol. 11, 569–571 (2015).

    CAS  PubMed  Article  Google Scholar 

  13. Maricq, H. R., Weinberger, A. B. & LeRoy, E. C. Early detection of scleroderma-spectrum disorders by in vivo capillary microscopy. J. Rheumatol. 9, 289–291 (1982).

    CAS  PubMed  Google Scholar 

  14. Cracowski, J. L. & Roustit, M. Human skin microcirculation. Compr. Physiol. 10, 1105–1154 (2020).

    PubMed  Article  Google Scholar 

  15. Anderson, M. E. et al. Computerized nailfold video capillaroscopy — a new tool for assessment of Raynaud’s phenomenon. J. Rheumatol. 32, 841–848 (2005).

    PubMed  Google Scholar 

  16. Herrick, A. L. The pathogenesis, diagnosis and treatment of Raynaud phenomenon. Nat. Rev. Rheumatol. 8, 469–479 (2012).

    CAS  PubMed  Article  Google Scholar 

  17. Smith, V. et al. Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud’s phenomenon and systemic sclerosis. Autoimmun. Rev. 19, 102458 (2020).

    PubMed  Article  Google Scholar 

  18. Cutolo, M., Paolino, S. & Smith, V. Nailfold capillaroscopy in rheumatology: ready for the daily use but with care in terminology. Clin. Rheumatol. 38, 2293–2297 (2019).

    PubMed  Article  Google Scholar 

  19. Sulli, A., Secchi, M. E., Pizzorni, C. & Cutolo, M. Scoring the nailfold microvascular changes during the capillaroscopic analysis in systemic sclerosis patients. Ann. Rheum. Dis. 67, 885–887 (2008).

    CAS  PubMed  Article  Google Scholar 

  20. Smith, V. et al. Fast track algorithm: how to differentiate a “scleroderma pattern” from a “non-scleroderma pattern”. Autoimmun. Rev. 18, 102394 (2019).

    PubMed  Article  Google Scholar 

  21. Murray, A. K. et al. Preliminary clinical evaluation of semi-automated nailfold capillaroscopy in the assessment of patients with Raynaud’s phenomenon. Microcirculation 18, 440–447 (2011).

    PubMed  Article  Google Scholar 

  22. Gronenschild, E. H. et al. Semi-automatic assessment of skin capillary density: proof of principle and validation. Microvasc. Res. 90, 192–198 (2013).

    CAS  PubMed  Article  Google Scholar 

  23. Berks, M. A. et al. An automated system for detecting and measuring nailfold capillaries. Med. Image Comput. Comput. Assist. Interv. 17, 658–665 (2014).

    PubMed  PubMed Central  Google Scholar 

  24. Cheng, C., Lee, C. W. & Daskalakis, C. A reproducible computerized method for quantitation of capillary density using nailfold capillaroscopy. J. Vis. Exp. 27, e53088 (2015).

    Google Scholar 

  25. Cutolo, M. et al. Automated assessment of absolute nailfold capillary number on videocapillaroscopic images: proof of principle and validation in systemic sclerosis. Microcirculation 25, e12447 (2018).

    PubMed  Article  CAS  Google Scholar 

  26. Emrani, Z., Karbalaie, A., Fatemi, A., Etehadtavakol, M. & Björn-Erlandsson, E. Capillary density: an important parameter in nailfold capillaroscopy. Microvasc. Res. 10, 7–18 (2017).

    Article  Google Scholar 

  27. Herrick, A. L., Berks, M. & Taylor, C. Quantitative nailfold capillaroscopy — update and possible next steps. Rheumatology 60, 2054–2065 (2021).

    PubMed  Article  Google Scholar 

  28. Dinsdale, G. et al. The assessment of nailfold capillaries: comparison of dermoscopy and nailfold videocapillaroscopy. Rheumatology 5, 1115–1116 (2018).

    Article  Google Scholar 

  29. Hughes, M. et al. A study comparing videocapillaroscopy and dermoscopy in the assessment of nailfold capillaries in patients with systemic sclerosis-spectrum disorders. Rheumatology 54, 1435–1442 (2015).

    PubMed  Article  Google Scholar 

  30. Radic, M. et al. Consensus-based evaluation of dermatoscopy versus nailfold videocapillaroscopy in Raynaud’s phenomenon linking USA and Europe: a European League Against Rheumatism study group on microcirculation in rheumatic diseases project. Clin. Exp. Rheumatol. 38 (Suppl. 125), 132–136 (2020).

    PubMed  Google Scholar 

  31. Berks, M. et al. Comparison between low cost USB nailfold capillaroscopy and videocapillaroscopy: a pilot study. Rheumatology 60, 3862–3867 (2021).

    PubMed  Article  Google Scholar 

  32. Masthoff, M. et al. Multispectral optoacoustic tomography of systemic sclerosis. J. Biophotonics 11, e201800155 (2018).

    PubMed  Article  CAS  Google Scholar 

  33. Nitkunanantharajah, S. et al. Three-dimensional optoacoustic imaging of nailfold capillaries in systemic sclerosis and its potential for disease differentiation using deep learning. Sci. Rep. 10, 16444 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Daoudi, K. et al. Photoacoustic and high-frequency ultrasound imaging of systemic sclerosis patients. Arthritis Res. Ther. 23, 22 (2021).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. Abignano, G. et al. Virtual skin biopsy by optical coherence tomography: the first quantitative imaging biomarker for scleroderma. Ann. Rheum. Dis. 72, 1845–1851 (2013).

    PubMed  Article  Google Scholar 

  36. Abignano, G., Laws, P., Del Galdo, F., Marzo-Ortega, H. & McGonagle, D. Three-dimensional nail imaging by optical coherence tomography: a novel biomarker of response to therapy for nail disease in psoriasis and psoriatic arthritis. Clin. Exp. Dermatol. 44, 462–465 (2019).

    CAS  PubMed  Article  Google Scholar 

  37. Abignano, G. & Del Galdo, F. Biomarkers as an opportunity to stratify for outcome in systemic sclerosis. Eur. J. Rheumatol. 7 (Suppl. 3), 193–202 (2020).

    Google Scholar 

  38. Ranjbar, M. et al. Evaluation of choroidal substructure perfusion in patients affected by systemic sclerosis: an optical coherence tomography angiography study. Scand. J. Rheumatol. 49, 141–145 (2020).

    CAS  PubMed  Article  Google Scholar 

  39. Rommel, F., Prangel, D., Prasuhn, M., Grisanti, S. & Ranjbar, M. Correlation of retinal and choroidal microvascular impairment in systemic sclerosis. Orphanet J. Rare Dis. 16, 27–32 (2021).

    PubMed  PubMed Central  Article  Google Scholar 

  40. Clark, S. et al. Comparison of thermography and laser Doppler imaging in the assessment of Raynaud’s phenomenon. Microvasc. Res. 66, 73–76 (2003).

    PubMed  Article  Google Scholar 

  41. Chojnowski, M. Infrared thermal imaging in connective tissue diseases. Reumatologia 5, 38–43 (2017).

    Google Scholar 

  42. Pauling, J. D., Shipley, J. A., Harris, N. D. & McHugh, N. J. Use of infrared thermography as an endpoint in therapeutic trials of Raynaud’s phenomenon and systemic sclerosis. Clin. Exp. Rheumatol. 30 (Suppl. 71), 103–115 (2012).

    Google Scholar 

  43. Hughes, M. et al. Thermographic abnormalities are associated with future digital ulcers and death in patients with systemic sclerosis. J. Rheumatol. 43, 1519–1522 (2016).

    PubMed  Article  Google Scholar 

  44. Murray, A. K., Herrick, A. L. & King, T. A. Laser Doppler imaging: a developing technique for application in the rheumatic diseases. Rheumatology 43, 1210–1218 (2004).

    CAS  PubMed  Article  Google Scholar 

  45. Cutolo, M. et al. Peripheral blood perfusion correlates with microvascular abnormalities in systemic sclerosis: a laser-Doppler and nailfold videocapillaroscopy study. J. Rheumatol. 37, 1174–1180 (2010).

    PubMed  Article  Google Scholar 

  46. Melsens, K., Paolino, S., Vanhaecke, A., Cutolo, M. & Smith, V. The preliminary validation of laser Doppler flowmetry in systemic sclerosis in accordance with the OMERACT filter: a systematic review. Semin. Arthritis Rheum. 50, 321–328 (2020).

    PubMed  Article  Google Scholar 

  47. Sulli, A., Ruaro, B. & Cutolo, M. Evaluation of blood perfusion by laser speckle contrast analysis in different areas of hands and face in patients with systemic sclerosis. Ann. Rheum. Dis. 73, 2059–2061 (2014).

    CAS  PubMed  Article  Google Scholar 

  48. Ruaro, B. et al. Laser speckle contrast analysis: a new method to evaluate peripheral blood perfusion in systemic sclerosis patients. Ann. Rheum. Dis. 73, 1181–1185 (2014).

    PubMed  Article  Google Scholar 

  49. Cutolo, M. et al. Is laser speckle contrast analysis (LASCA) the new kid on the block in systemic sclerosis? A systematic literature review and pilot study to evaluate reliability of LASCA to measure peripheral blood perfusion in scleroderma patients. Autoimmun. Rev. 17, 775–780 (2018).

    PubMed  Article  Google Scholar 

  50. Pauling, J. D., Shipley, J. A., Hart, D. J., McGrogan, A. & McHugh, N. J. 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 (2015).

    CAS  PubMed  Article  Google Scholar 

  51. Lambrecht, V. et al. Reliability of the quantitative assessment of peripheral blood perfusion by laser speckle contrast analysis in a systemic sclerosis cohort. Ann. Rheum. Dis. 75, 1263–1264 (2016).

    PubMed  Article  Google Scholar 

  52. Ruaro, B., Paolino, S., Pizzorni, C., Cutolo, M. & Sulli, A. Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis. Reumatismo 69, 134–136 (2017).

    CAS  PubMed  Article  Google Scholar 

  53. Gigante, A., Villa, A. & Rosato, E. Laser speckle contrast analysis predicts major vascular complications and mortality of patients with systemic sclerosis. Rheumatology 60, 1850–1857 (2021).

    PubMed  Article  Google Scholar 

  54. Iagnocco, A. et al. Power Doppler ultrasound monitoring of response to anti-tumour necrosis factor alpha treatment in patients with rheumatoid arthritis. Rheumatology 54, 1890–1896 (2015).

    CAS  PubMed  Article  Google Scholar 

  55. Lee, S. I., Lee, S. Y. & Yoo, W. H. The usefulness of power Doppler ultrasonography in differentiating primary and secondary Raynaud’s phenomenon. Clin. Rheumatol. 25, 814–818 (2006).

    PubMed  Article  Google Scholar 

  56. Schioppo, T. et al. Evidence of macro- and micro-angiopathy in scleroderma: an integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy. Microvasc. Res. 12, 125–130 (2019).

    Article  Google Scholar 

  57. Eisenbrey, J. R., Stanczak, M., Forsberg, F., Mendoza-Ballesteros, F. A. & Lyshchik, A. Photoacoustic oxygenation quantification in patients with Raynaud’s: first-in-human results. Ultrasound Med. Biol. 44, 2081–2088 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  58. Werner, S. G. et al. Indocyanine green-enhanced fluorescence optical imaging in patients with early and very early arthritis: a comparative study with magnetic resonance imaging. Arthritis Rheum. 65, 3036–3044 (2013).

    CAS  PubMed  Article  Google Scholar 

  59. Fischer, T. et al. Detection of rheumatoid arthritis using non-specific contrast enhanced fluorescence imaging. Acad. Radiol. 17, 375–378 (2010).

    PubMed  Article  Google Scholar 

  60. Friedrich, S. et al. Disturbed microcirculation in the hands of patients with systemic sclerosis detected by fluorescence optical imaging: a pilot study. Arthritis Res. Ther. 19, 87–92 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  61. Deschepper, E. et al. An EULAR study group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases. Rheumatology 55, 883–890 (2016).

    PubMed  Article  Google Scholar 

  62. Cutolo, M. et al. Reliability of simple capillaroscopic definitions in describing capillary morphology in rheumatic diseases. Rheumatology 57, 757–759 (2018).

    PubMed  Article  Google Scholar 

  63. Cutolo, M., Pizzorni, C. & Sulli, A. Identification of transition from primary Raynaud’s phenomenon to secondary Raynaud’s phenomenon by nailfold videocapillaroscopy. Arthritis Rheum. 56, 2102–2103 (2007).

    PubMed  Article  Google Scholar 

  64. Smith, V. et al. May capillaroscopy be a candidate tool in future algorithms for SSc-ILD: are we looking for the holy grail? A systematic review. Autoimmun. Rev. 19, 102619 (2020).

    PubMed  Article  Google Scholar 

  65. Sulli, A. et al. Progression of nailfold capillaroscopic patterns and correlation with organ involvement in systemic sclerosis: a 12 year study. Rheumatology 59, 1051–1058 (2020).

    CAS  PubMed  Article  Google Scholar 

  66. Smith, V. et al. Nailfold capillaroscopy: construction of a simple scoring modality as a clinical prognostic index for digital trophic lesions. Ann. Rheum. Dis. 70, 180–183 (2011).

    PubMed  Article  Google Scholar 

  67. Smith, V. E. et al. Do worsening scleroderma capillaroscopic patterns predict future severe organ involvement? A pilot study. Ann. Rheum. Dis. 71, 1636–1639 (2012).

    PubMed  Article  Google Scholar 

  68. Trombetta, A. C. et al. Quantitative alterations of capillary diameter have a predictive value for development of the capillaroscopic systemic sclerosis pattern. J. Rheumatol. 43, 599–606 (2016).

    PubMed  Article  Google Scholar 

  69. Cutolo, M. et al. Nailfold videocapillaroscopic features and other clinical risk factors for digital ulcers in systemic sclerosis: a multicenter, prospective cohort study. Arthritis Rheumatol. 6, 527–539 (2016).

    Google Scholar 

  70. Sulli, A. et al. Timing of transition between capillaroscopic patterns in systemic sclerosis. Arthritis Rheum. 64, 821–825 (2012).

    PubMed  Article  Google Scholar 

  71. Caetano, J., Paula, F. S., Amaral, M., Oliveira, S. & Alves, J. D. Nailfold videocapillaroscopy changes are associated with the presence and severity of systemic sclerosis-related interstitial lung disease. J. Clin. Rheumatol. 25, e12–e15 (2019).

    PubMed  Article  Google Scholar 

  72. Gheorghiu, A. M. et al. Capillary loss reflects disease activity and prognosis in patients with systemic sclerosis. Exp. Ther. Med. 20, 3438–3443 (2020).

    PubMed  PubMed Central  Google Scholar 

  73. Berks, M. et al. Automated structure and flow measurement — a promising tool in nailfold capillaroscopy. Microvasc. Res. 118, 173–177 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  74. Sternbersky, J., Tichy, M. & Zapletalova, J. Infrared thermography and capillaroscopy in the diagnosis of Raynaud’s phenomenon. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc. Czech Repub. 165, 90–98 (2021).

    PubMed  Article  Google Scholar 

  75. Pavlov-Dolijanovic, S. et al. Relationship between 99mTc-pertechnetate hand perfusion scintigraphy and nailfold capillaroscopy in systemic sclerosis patients: a pilot study. Arch. Rheumatol. 35, 321–327 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  76. Pauling, J. D. & Christopher-Stine, L. The aetiopathogenic significance, clinical relevance and therapeutic implications of vasculopathy in idiopathic inflammatory myopathy. Rheumatology 60, 1593–1607 (2021).

    PubMed  Article  Google Scholar 

  77. Bertolazzi, C., Cutolo, M., Smith, V. & Gutierrez, M. State of the art on nailfold capillaroscopy in dermatomyositis and polymyositis. Semin. Arthritis Rheum. 47, 432–444 (2017).

    PubMed  Article  Google Scholar 

  78. Miossi, R., de Souza, F. H. C. & Shinjo, S. K. Nailfold capillary changes in adult new-onset dermatomyositis: a prospective cross-sectional study. Clin. Rheumatol. 38, 2319–2326 (2019).

    PubMed  Article  Google Scholar 

  79. Pizzorni, C. et al. Long-term follow-up of nailfold videocapillaroscopic changes in dermatomyositis versus systemic sclerosis patients. Clin. Rheumatol. 37, 2723–2729 (2018).

    CAS  PubMed  Article  Google Scholar 

  80. Cavagna, L. et al. Clinical spectrum time course in anti Jo-1 positive antisynthetase syndrome: results from an international retrospective multicenter study. Medicine 94, e1144 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. Cassone, G. et al. Nailfold videocapillaroscopy in antisynthetase syndrome. Reumatismo 70, 257–258 (2018).

    CAS  PubMed  Article  Google Scholar 

  82. Sebastiani, M. et al. Nailfold capillaroscopy characteristics of antisynthetase syndrome and possible clinical associations: results of a multicenter international study. J. Rheumatol. 46, 279–284 (2019).

    CAS  PubMed  Article  Google Scholar 

  83. Candela, M. et al. Nailfold capillary microscopy in patients with antiphospholipid syndrome. Recenti Prog. Med. 89, 444–449 (1998).

    CAS  PubMed  Google Scholar 

  84. Pyrpasopoulou, A., Triantafyllou, A., Anyfanti, P., Douma, S. & Aslanidis, S. Capillaroscopy as a screening test for clinical antiphospholipid syndrome. Eur. J. Intern. Med. 22, e158–e159 (2011).

    PubMed  Article  Google Scholar 

  85. Aslanidis, S. et al. Association of capillaroscopic microhaemorrhages with clinical and immunological antiphospholipid syndrome. Clin. Exp. Rheumatol. 29, 307–309 (2011).

    CAS  PubMed  Google Scholar 

  86. Sulli, A., Pizzorni, C. & Cutolo, M. Nailfold videocapillaroscopy abnormalities in patients with antiphospholipid antibodies. J. Rheumatol. 27, 1574–1576 (2000).

    CAS  PubMed  Google Scholar 

  87. Bernardino, V., Rodrigues, A., Lladó, A. & Panarra, A. Nailfold capillaroscopy and autoimmune connective tissue diseases in patients from a Portuguese nailfold capillaroscopy clinic. Rheumatol. Int. 40, 295–301 (2020).

    PubMed  Article  Google Scholar 

  88. Nagy, Y. & Czirjak, L. Nailfold digital capillaroscopy in 447 patients with connective tissue disease and Raynaud’s disease. J. Eur. Acad. Dermatol. Venereol. 18, 62–68 (2004).

    CAS  PubMed  Article  Google Scholar 

  89. Paolino, S. et al. Long-term follow-up of nailfold videocapillaroscopic microvascular parameters in mixed connective tissue disease versus systemic sclerosis patients: a retrospective cohort study. Clin. Exp. Rheumatol. 37 (Suppl. 119), 102–107 (2019).

    PubMed  Google Scholar 

  90. Cutolo, M. et al. Nailfold capillaroscopy in systemic lupus erythematosus: a systematic review and critical appraisal. Autoimmun. Rev. 17, 344–352 (2018).

    PubMed  Article  Google Scholar 

  91. Schonenberg-Meinema, D. et al. Capillaroscopy in childhood-onset systemic lupus erythematosus: a first systematic review. Clin. Exp. Rheumatol. 38, 350–354 (2020).

    PubMed  Google Scholar 

  92. Schonenberg-Meinema, D. et al. Nailfold capillary abnormalities in childhood-onset systemic lupus erythematosus: a cross-sectional study compared with healthy controls. Lupus 30, 818–827 (2021).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Ruaro, B. et al. Peripheral blood perfusion in patients with systemic lupus erythematosus and in primary Raynaud’s phenomenon. Eur. J. Rheumatol. 8, 7–11 (2021).

    PubMed  Article  Google Scholar 

  94. Capobianco, K. G., Xavier, R. M., Bredemeier, M., Restelli, V. G. & Brenol, J. C. Nailfold capillaroscopic findings in primary Sjögren’s syndrome: clinical and serological correlations. Clin. Exp. Rheumatol. 23, 789–794 (2005).

    CAS  PubMed  Google Scholar 

  95. Szabo, N. et al. Functional and morphological evaluation of hand microcirculation with nailfold capillaroscopy and laser Doppler imaging in Raynaud’s and Sjögren’s syndrome and poly/dermatomyositis. Scand. J. Rheumatol. 37, 23–29 (2008).

    CAS  PubMed  Article  Google Scholar 

  96. Melsens, K. et al. Nailfold capillaroscopy in Sjögren’s syndrome: a systematic literature review and standardised interpretation. Clin. Exp. Rheumatol. 38 (Suppl. 126), 150–157 (2020).

    PubMed  Google Scholar 

  97. Hendriks, A. G. et al. Whole field laser Doppler imaging of the microcirculation in psoriasis and clinically unaffected skin. J. Dermatolog. Treat. 25, 18–21 (2014).

    CAS  PubMed  Article  Google Scholar 

  98. Hendriks, A. G. et al. Clearing of psoriasis documented by laser Doppler perfusion imaging contrasts remaining elevation of dermal expression levels of CD31. Skin Res. Technol. 21, 340–345 (2015).

    CAS  PubMed  Article  Google Scholar 

  99. Cutolo, M. et al. Longterm effects of endothelin receptor antagonism on microvascular damage evaluated by nailfold capillaroscopic analysis in systemic sclerosis. J. Rheumatol. 40, 40–45 (2013).

    CAS  PubMed  Article  Google Scholar 

  100. Cutolo, M. et al. Longterm treatment with endothelin receptor antagonist bosentan and iloprost improves fingertip blood perfusion in systemic sclerosis. J. Rheumatol. 41, 881–386 (2014).

    CAS  PubMed  Article  Google Scholar 

  101. Bellando-Randone, S. et al. Combination therapy with bosentan and sildenafil improves Raynaud’s phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis. Clin. Rheumatol. 35, 127–132 (2016).

    CAS  PubMed  Article  Google Scholar 

  102. Trombetta, A. C. et al. Effects of longterm treatment with bosentan and iloprost on nailfold absolute capillary number, fingertip blood perfusion, and clinical status in systemic sclerosis. J. Rheumatol. 43, 2033–2041 (2016).

    CAS  PubMed  Article  Google Scholar 

  103. Smith, V. et al. Stabilization of microcirculation in patients with early systemic sclerosis with diffuse skin involvement following rituximab treatment: an open-label study. J. Rheumatol. 43, 995–996 (2016).

    PubMed  Article  CAS  Google Scholar 

  104. Rotondo, C. et al. Evidence for increase in finger blood flow, evaluated by laser Doppler flowmetry, following iloprost infusion in patients with systemic sclerosis: a week-long observational longitudinal study. Scand. J. Rheumatol. 47, 311–318 (2018).

    CAS  PubMed  Article  Google Scholar 

  105. Ruaro, B. et al. Short-term follow-up of digital ulcers by laser speckle contrast analysis in systemic sclerosis patients. Microvas. Res. 101, 82–85 (2015).

    Article  Google Scholar 

  106. Gaillard-Bigot, F. et al. Abnormal amplitude and kinetics of digital postocclusive reactive hyperemia in systemic sclerosis. Microvasc. Res. 94, 90–95 (2014).

    CAS  PubMed  Article  Google Scholar 

  107. Roustit, M. et al. On-demand sildenafil as a treatment for Raynaud phenomenon: a series of n-of-1 trials. Ann. Intern. Med. 169, 694–703 (2018).

    PubMed  Article  Google Scholar 

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Acknowledgements

The authors thank C. Pizzorni, A. Sulli and S. Paolino for their continuous support and S. De Gregorio and E. Gotelli for their involvement in figure definition. M.C. and V.S. are members of and/or chair the EULAR Study Group on Microcirculation in Rheumatic Diseases, which makes the dissemination of research projects on this topic possible.

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M.C. researched data for the article and wrote the article. V.S. reviewed and/or edited the manuscript before submission.

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Correspondence to Maurizio Cutolo.

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V.S. is a senior clinical investigator of the Research Foundation Flanders, Belgium (FWO; 1.8.029.20 N). The FWO was not involved in the study design, collection, analysis and interpretation of data, writing of the report or in the decision to submit the manuscript for publication.

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Nature Reviews Rheumatology thanks S. Lambova, J.-L. Cracowski and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Telangiectasias

Also named spider veins, these are small, dilated blood vessels that can occur near the surface of the skin or mucous membranes.

Proximal–distal gradient

In healthy individuals, perfusion is typically high in the distal fingertips and low in the dorsum of the hands.

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Cutolo, M., Smith, V. Detection of microvascular changes in systemic sclerosis and other rheumatic diseases. Nat Rev Rheumatol 17, 665–677 (2021). https://doi.org/10.1038/s41584-021-00685-0

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