State-of-the-art technologies provide new insights linking skin and blood vessel abnormalities in SSc-related disorders

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Objective: A key unanswered question in systemic sclerosis (SSc) is how microvascular abnormality and fibrosis inter-relate. Our aim was to use state-of-the-art non-invasive imaging methods to gain new insights into pathophysiology, comparing patients with different subtypes of SSc, including early dcSSc, not only to healthy controls but also to patients with causes of Raynaud's phenomenon not progressing to fibrosis. Methods: Laser Doppler imaging, nailfold capillaroscopy, spectroscopy, and ultrasound measured (respectively) perfusion, microvascular structure, oxygenation/oxidative stress, and skin thickening in the hands of 265 subjects: 31 patients with primary Raynaud’s phenomenon (PRP), 35 with undifferentiated connective tissue disease (UCTD), 93 with limited cutaneous SSc (lcSSc), 46 with diffuse cutaneous SSc (dcSSc, including 27 ‘early’) and 60 healthy controls. Results: Mean perfusion was reduced in SSc groups compared to controls (lcSSc 172 perfusion units [standard deviation 157], late-dcSSc 90 [145], early-dcSSc 68 [137] vs. controls 211 [146]; p=0.0002) as was finger-oxygenation (lcSSc 12.1 [13.6] arbitrary units [AU], late-dcSSc 12.2 [8.4], early-dcSSc 11.1 [11.3] vs controls 14.9 [10.5]; p=0.0049). Oxidative stress was increased at the hand-dorsum in SSc groups (p=0.0007). Perfusion positively correlated with oxygenation (r=0.23, p<0.001), and capillary density negatively with skin thickness (r=-0.26, p<0.001). Conclusion: Our findings lend support to the hypothesis that in SSc, particularly early dcSSc, (but not in PRP or UCTD), reduced perfusion (together with structural microvascular abnormality) associates with reduced oxygenation, with oxidative stress and with skin thickening/fibrosis, most likely driving a vicious cycle which ultimately results in irreversible tissue injury. Findings in skin may mirror alterations in internal organs.
Original languageEnglish
Article number104006
JournalMicrovascular Research
Early online date19 Apr 2020
Publication statusPublished - 1 Jul 2020


  • Hypoxia
  • Imaging
  • Laser Doppler
  • Nailfold capillaroscopy
  • Oxidative stress
  • Raynaud's phenomenon
  • Spectroscopy
  • Systemic sclerosis


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