Progression of patients with Raynaud's phenomenon to systemic sclerosis: a five-year analysis of the European Scleroderma Trial and Research group multicentre, longitudinal registry study for Very Early Diagnosis of Systemic Sclerosis (VEDOSS)

Background:Vasculopathy is already evident in early systemic sclerosis (SSc); Raynaud’s phenomenon and typical nailfoldcapillaroscopic findings are part of the criteria of very early diagnosis of SSc (VEDOSs) (1). As not all early SSc patients have alterations in their nailfoldcapillaries, there is need for other diagnostic tools. Photoacoustics(PA) and high-frequency ultrasound (HFUS) might be able to fulfill this need (2). The former can measure the oxygen saturation of hemoglobin by using short pulsed laser light while the latter can provide high-resolution images that allow measuring skin thickening distal from DIP joint, which could be used to determine skin involvement early.Objectives:We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud’s phenomenon (PR) by measuring the oxygenation (by PA) of the fingertip and skin thickening (by HFUS).Methods:In our cross-sectional study, we compared measurements of the third finger in (early)SSc patients with individuals with PR and healthy volunteers. Smoking and beta-blockage were exclusion criteria. The level of oxygenation (by PA) and skin thickness (by HFUS) were compared between groups. Nailfoldcapillaroscopy was performed on all subjects and analyzed for the pattern.Results:Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR and 9 healthy controls.We found a significant difference in median (IQR) oxygen saturation between earlySSc patients 75.9% (IQR 75.1%-86.6%) and subjects with PR 94.1% (IQR 93.1%-94.5%) (p=0.0002) using the Wilcoxon rank-sum test (figure 1).Figure 1.Boxplot of saturation (%) per group.Measurements of skin thickening also showed a significant difference in early SSc patients compared to subjects with PR, respectively 0.5mm (IQR 0.4mm-0.5mm) vs. 0.3mm (IQR 0.3mm-0.3mm), P=0.0002 (figure 2).Figure 2.Boxplot of skin thickness (mm) per group.Conclusion:Our results demonstrate that photoacoustic and high-frequency ultrasound can distinguish between (early)SSc and PR in both oxygenation saturation and skin thickening. In a larger prognostic study we want to determine the value of photoacoustic and high frequency ultrasound in diagnosing earlySSc.References:[1]Minier T, Guiducci S, Bellando-Randone S, Bruni C, Lepri G, Czirjak L, et al. Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Annals of the rheumatic diseases. 2014;73(12):2087-93.[2]Wang LV, Yao J. A practical guide to photoacoustic tomography in the life sciences. Nature methods. 2016;13(8):627-38Disclosure of Interests:Brigit Kersten: None declared, Khalid Daoudi: None declared, C.H.M. van den Ende: None declared, FHJ van den Hoogen Consultant of: AbbVie, Actelion, Biogen, BMS, Celltrion, Corbus, Eli-Lilly, Mundipharma, Pfizer, Sanofi-Genzyme, Speakers bureau: Amgen, Boehringer-Ingelheim, Novartis, CL de Korte: None declared, Madelon Vonk Grant/research support from: Janssen and Ferrer, Consultant of: Boehringer Ingelheim, Janssen and GSK, Speakers bureau: Boehringer Ingelheim, BMS and Roche

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Ascorbic Acid does not Improve Endothelium-Dependent Flow-mediated Dilatation of the Brachial Artery in Patients with Raynaud’s Phenomenon Secondary to Systemic Sclerosis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.1.3 ◽

2003 ◽

Vol 73 (1) ◽

pp. 3-7 ◽

Cited By ~ 22

Author(s):

M. E. Mavrikakis ◽

J. P. Lekakis ◽

M. Papamichael ◽

K. S. Stamatelopoulos ◽

Ch. C. Kostopoulos ◽

...

Keyword(s):

Ascorbic Acid ◽

Smooth Muscle ◽

Systemic Sclerosis ◽

Endothelial Dysfunction ◽

Brachial Artery ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Water Soluble ◽

Placebo Administration ◽

Flow Mediated Dilatation

Previous studies have shown that patients with Raynaud’s phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud’s phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud’s phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud’s phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 ± 2.2% to 2.2 ± 2.5%, ns) or placebo administration (1.2 ± 1,9% to 1.7 ± 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 ± 7.4% vs 17 ± 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud’s phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.

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