Endothelial Dysfunction and Nailfold Videocapillaroscopy Pattern as Predictors of Digital Ulcers in Systemic Sclerosis: a Cohort Study and Review of the Literature Ivone Silva 1,2 & Andreia Teixeira 3 & José Oliveira 4 & Isabel Almeida 2 & Rui Almeida 1 & Artur Águas 5,6 & Carlos Vasconcelos 2,5,6 # Springer Science+Business Media New York 2015 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 endo- thelial 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 fac- tor. 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. Keywords Digital ulcer . Endothelin-1 . Capillaroscopy . Flow-mediated dilatation . Endothelin-1 . VEGF 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 Electronic supplementary material The online version of this article (doi:10.1007/s12016-015-8500-0) contains supplementary material, which is available to authorized users. * Ivone Silva heitor.ivone@gmail.com 1 Angiology and Vascular Surgery Service and Clinical Immunology Unit, Centro Hospitalar do Porto, Praça da Revista o Tripeiro, n° 42, hab 23, 4150-789 Porto, Portugal 2 Clinical Immunology Unit, Porto, Portugal 3 CINTESIS - Center for Research in Health Technologies and Information Systems Porto, Porto, Portugal 4 Clinical Pathology Department, Centro Hospitalar do Porto (CHP), Porto, Portugal 5 Abel Salazar Biomedical Health Institute, Porto, Portugal 6 Multidisciplinary Unit for Biomedical Investigation (UMIB), University of Porto, Porto, Portugal Clinic Rev Allerg Immunol DOI 10.1007/s12016-015-8500-0