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Endothelial Dysfunction and Nailfold Videocapillaroscopy Pattern as Predictors of Digital Ulcers in Systemic Sclerosis: a Cohort Study and Review of the Literature

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Abstract

Raynaud’s phenomenon and digital ulcers (DUs) are frequent among systemic sclerosis (SSc) patients. Our aim was to investigate the diagnostic and predictive value for DU of endothelial dysfunction biomarkers (flow-mediated dilatation (FMD), serum levels of endothelin-1 (ET-1), and ADMA), angiogenic/angiostatic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin), and nailfold videocapillaroscopy (NVC). We compared our results with a literature review. In a cohort study of 77 SSc patients, we followed two groups of patients: (i) naïve DU patients (39) and (ii) active DU at baseline (38 patients) for 3 years. Telangiectasia (p < 0.001) and diffuse disease subset (p = 0.001) were significantly more frequent in patients with active DU at enrolment. Additionally, NVC late scleroderma pattern (AUC 0.846, 95%CI 0.760–0.932), lower values of FMD (AUC 0.754, 95%CI 0.643–0.864), increased serum levels of ET-1 (AUC 0.758, 95%CI 0.649–0.866), ADMA (AUC 0.634, 95%CI 0.511–0.757), and endoglin as well as low VEGF serum levels (AUC 0.705, 95%CI 0.579–0.830) were significantly associated to new DU events in the 3-year follow-up. Cox regression analysis showed that FMD > 9.41 % (HR 0.37, 95%CI 0.14–0.99); ET-1 >11.85 pmol/L (HR 3.81, 95%CI 1.41–10.26) and late NVC pattern (HR 2.29, 95%CI 0.97–5.38) were independent predictors of DU recurrence. When estimating the probability of occurrence of first DU in naïve DU patients, only late NVC pattern (HR 12.66, 95%CI 2.06–77.89) was an independent predictor factor. In conclusion, late scleroderma patterns in NVC are the best independent predictors of SSc patients who are at risk of developing DU. Endothelial dysfunction assessed by FMD and ET-1 was also found to be an independent predictor of DU recurrence in a 3-year follow-up.

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Abbreviations

ADMA:

Symmetric dimethylarginine

ANA:

Antinuclear antibodies

DU:

Digital ulcer

ET-1:

Endothelin-1

RP:

Raynaud’s phenomenon

FMD:

Flow-mediated dilatation

VEGF:

Vascular endothelial growth factor

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NVC:

Nailfold videocapillaroscopy

SSc:

Systemic sclerosis

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Acknowledgments

This study was partially supported by a research grant from Teaching and Research Department (Departamento de Ensino e Investigação) of Oporto Hospital Center (reference 054/10 (036-DEFI/051-CES) and from a Foundation for Science and Technology (FCT) postdoc grant SFRH/BPD/86383/2012. The authors thank the Clinical Pathology Department for their valuable technical assistance.

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Correspondence to Ivone Silva.

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Silva, I., Teixeira, A., Oliveira, J. et al. Endothelial Dysfunction and Nailfold Videocapillaroscopy Pattern as Predictors of Digital Ulcers in Systemic Sclerosis: a Cohort Study and Review of the Literature. Clinic Rev Allerg Immunol 49, 240–252 (2015). https://doi.org/10.1007/s12016-015-8500-0

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