SAT0340 A REDUCED NUMBER OF CAPILLARIES AND AN INCREASED NUMBER OF MEGACAPILLARIES PREDICT THE DEVELOPMENT OF SYSTEMIC SCLEROSIS IN RAYNAUD’S PHENOMENON PATIENTS AT RISK

Background:Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc) is a condition characterised by Raynaud’s phenomenon and either SSc marker autoantibodies or typical capillaroscopic findings or both, unsatisfying classification criteria for SSc and evolving into definite SSc in about 30-50% of cases (1,2). Recently, we developed a weighted score based on a baseline IF-ANA titer ≥1:320, marker autoantibody positivity and presence of avascular areas at videocapillaroscopy identifying patients who will evolve with a 91.3% sensitivity and a 73.2% specificity (3).Objectives:To improve the predictivity of the score assessing the role of marker autoantibody ELISA titer and further capillaroscopic items.Methods:The 102 UCTD-risk-SSc patients investigated for the development of the previous score were reassessed for anti-Scl-70 and anti-centromere antibody titers detected by ELISA and for the mean number of capillaries observed in the same capillaroscopic field (Cs) and the total number of giant capillaries (GC) by videocapillaroscopy (4). Each patient was evaluated every 6 months to assess disease progression. Risk prediction was assessed by Cox regression analyses. The predictive value of the score was determined by receiver operating curve (ROC) analysis.Results:Table 1 shows the resulting predictive variables in multivariate Cox analysis and their relative weight in a 10-point scale. No increase in the predictivity was detected by adding the anti-Scl-70 and anti-centromere antibody ELISA titers. However, a mean number of Cs≤5/mm and GC>5 improved the score. At ROC analysis (Figure 1) a score >3.25 predicted evolution to SSc with a sensitivity of 93.5% and a 75% specificity (AUC=0.91).Table 1.Indipendent predictive variables in multivariate regression analysis and the resulting weighted prediction model *VariableβHR95% CIPWeightAnti-Scl70Cs≤5/mm2.95531.909319.216.754.87-75.762.07-22.00<0.0010.0013.252ANA ≥ 1:3201.74025.701.42-22.850.012ACA1.67405.331.51-1.900.011.75GC>51.00492.731.44-5.170.0021*β: regression coefficients; HR: hazard ratio; 95% CI: 95% confidence interval; Cs: Capillaries; ANA: anti-nuclear antibodies; ACA: anti-centromere antibodies; GC: giant capillariesConclusion:Assessing the mean number of capillaries/mm and the total number of giant capillaries instead of avascular areas at videocapillaroscopy, resulted in improving the sensitivity and specificity of the score recently developed to predict the evolution of UCTD-risk-SSc into definite SSc.References:[1]Valentini G. Autoimmun Rev 2015;[2]Valentini G. et al. Arthritis Care Res (Hoboken). 2014;[3]Riccardi A. et al. Autoimmun Rev. 2019;[4]Sambataro et al. Arthritis Research & Therapy 2014, 16:462.Disclosure of Interests:Antonella Riccardi: None declared, Antonella Marcoccia: None declared, SERENA FASANO: None declared, Tiziana Guastafierro: None declared, Rosaria Irace: None declared, Valentina Messiniti: None declared, Francesco Bondanini: None declared, Alessandro Sanduzzi: None declared, Marialuisa Bocchino: None declared, Aldo Ciani: None declared, Michele D’Alto: None declared, Paola Argiento: None declared, Giovanni Maria De Matteis: None declared, Alberto Spanò: None declared, Gabriele Valentini Grant/research support from: BMS, MSD, NOVARTIS, LILLY, PFIZER, ABBVIE, CELGENE

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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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Faculty Opinions recommendation of Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1129797.586876 ◽

2008 ◽

Author(s):

Margitta Worm

Keyword(s):

Systemic Sclerosis ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Digital Ulcers

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Factors influencing patient decision‐making concerning treatment escalation in Raynaud’s phenomenon secondary to systemic sclerosis

Arthritis Care & Research ◽

10.1002/acr.24710 ◽

2021 ◽

Author(s):

Michael Hughes ◽

Suiyuan Huang ◽

John D Pauling ◽

Maya Sabbagh ◽

Dinesh Khanna

Keyword(s):

Decision Making ◽

Systemic Sclerosis ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Patient Decision Making ◽

Factors Influencing ◽

Patient Decision ◽

Treatment Escalation

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OP0252 CIRCULATING COLLAGEN TURNOVER MARKERS ARE SPECIFICALLY CHANGED IN VERY EARLY SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5683 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 159.1-159

Author(s):

R. Dobrota ◽

S. Jordan ◽

P. Juhl ◽

B. Maurer ◽

M. O. Becker ◽

...

Keyword(s):

Systemic Sclerosis ◽

Roc Analysis ◽

Cox Regression ◽

Classification Criteria ◽

Full Time ◽

Research Support ◽

Type Iii ◽

Turnover Markers ◽

Full Time Employee

Background:Timely diagnosis of patients with very early systemic sclerosis (veSSc) is essential for their personalized and optimal management. We hypothesise that changes in serum-based extracellular matrix (ECM) turnover biomarkers are already detectable in patients with veSSc, even before occurrence of specific clinical signs.Objectives:To investigate circulating ECM turnover markers as potential biomarkers for veSSc.Methods:Patients with veSSc, n=42, defined as presence of Raynaud’s syndrome and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, who did not meet any classification criteria for SSc, were compared to healthy controls (HC, n=29). Longitudinal assessment, data and sera collection were conducted by EUSTAR standards. ECM-degradation (BGM, C3M, C4M, C6M) and ECM-formation biomarkers (PRO-C3, PRO-C4, PRO-C5) were measured in serum using ELISA assays. The statistical analyses included Mann-Whitney U, Spearman correlation and ROC analysis. Using Kaplan-Meier plots and univariable Cox regression, we explored if biomarkers can predict progression towards definite SSc (fulfillment of ACR/EULAR criteria or minimum two points increase in the criteria score) during the longitudinal follow-up.Results:Compared to HC, veSSc patients showed a deregulated turnover of type III and IV collagen, with higher degradation (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, Figure 1a, resulting in lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was also higher in veSSc (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower than in HC (p=0.002). In the ROC analysis, biomarkers of type III and IV collagen distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001 (Figure 1b).Median follow up was 4.5 years (range 0.5-7.9 years), mean age was 50±2.2 years, 88% female gender, 24% with puffy fingers, 92% were ANA positive, 64% had an abnormal capillaroscopy, none had organ involvement or skin fibrosis. 14/42 veSSc patients fulfilled the ACR/EULAR classification criteria at follow-up (time to fulfilment of criteria ranged between 0.5 and 6.8 years from inclusion) and in addition, 18/42 veSSc patients gained at least two classification criteria-points. This resulted in 14, respectively 18 progressors for the longitudinal analysis. However, in univariable Cox regression, the baseline levels of the markers did not predict progression over time.Conclusion:ECM turnover is already altered in veSSc patients compared to HC. Biomarkes of type III and IV collagen distinguished between veSSc patients and HC, which may indicate them as potential biomarkers for the detection of veSSc in addition to the established immunological and capillaroscopic criteria.Disclosure of Interests:Rucsandra Dobrota: None declared, Suzana Jordan: None declared, Pernille Juhl Employee of: Nordic Bioscience, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Mike O. Becker: None declared, Carina Mihai: None declared, Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Full time employee at Nordic Bioscience A/S., Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Anne Sofie Siebuhr Employee of: Nordic Bioscience, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

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