Increased Intrarenal Arterial Stiffness May Predict the Occurrence of New Digital Ulcers in Systemic Sclerosis EDOARDO ROSATO, BIAGIO BARBANO, ANTONIETTA GIGANTE, ILENIA MOLINARO, SILVIA QUARTA, SIMONETTA PISARRI, ANTONIO AMOROSO, ROSARIO CIANCI, AND FELICE SALSANO Objective. Patients with systemic sclerosis (SSc; scleroderma) are at high risk for the development of ischemic digital ulcers (DUs), which occur in 35– 60% of SSc patients. The aim of this study was to assess the correlation between intrarenal arterial stiffness and DUs in SSc patients and to evaluate the prognostic value of Doppler indices to predict new DU occurrence. Methods. Seventy unselected, consecutive patients with SSc (58 women and 12 men, mean  SD age 49.5  13.8 years) were enrolled. In all patients, Doppler ultrasound examination was performed. The following Doppler indices of intrarenal stiffness were measured: peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D). Results. In total, 30 (42%) of 70 patients experienced new DUs. RI, S/D, and PI were significantly higher in SSc patients with new DUs than in SSc patients without new DUs. The receiver operating characteristic (ROC) curves demonstrated a good accuracy of new DU prediction for RI (0.94, P < 0.0001), S/D (0.92, P < 0.0001), and PI (0.88, P < 0.0001). Conversely, the ROC curve showed no performance for PSV (0.58, P > 0.05) and EDV (0.28, P > 0.05). Using a cutoff value of 0.70 for RI and 3.25 for S/D, the positive predictive value was 90.6% and 92.9%, respectively. Conclusion. We can conclude that Doppler indices of intrarenal stiffness are reliable markers of new DU occurrence. Doppler indices could be used in association with the capillaroscopic and clinical findings or serologic tests for the identification of patients at high risk of developing DUs. INTRODUCTION Systemic sclerosis (SSc; scleroderma) is an autoimmune disease characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Endothelial dys- function, microvascular damage, and macrovascular damage are the hallmarks of SSc (1,2). Patients with SSc are at high risk for the development of ischemic digital ulcers (DUs), which occur in 35– 60% of SSc patients (3). The early detection of patients with a high risk of developing DUs could allow a preventive treatment of these complications, with a reduction of morbidity and social costs. The capillaroscopic skin ulcer risk index (CSURI) may represent a novel tool with the ability to predict the development of DUs in SSc patients (4). Chronic renal vasculopathy is frequent in SSc pa- tients, while scleroderma renal crisis (SRC) has been reported in 10% of SSc patients. Increased arterial stiffness is known to be associated with sclerodermic kidney dysfunction. It is known that Doppler renal ul- trasound is a useful and noninvasive diagnostic tool to evaluate intrarenal arterial stiffness. In SSc patients, renal Doppler ultrasound is especially useful in both subclinical renal damage and SRC (5). Rosato et al dem- onstrated that intrarenal hemodynamic parameters cor- relate with glomerular filtration rate (GFR) and digital microvascular damage in SSc (6). Moreover, the indices are also useful in monitoring SRC and evaluating the response to specific drugs (7). The aim of this study was to asses a correlation between intrarenal arterial stiff- ness and DUs in SSc patients and to evaluate the prog- nostic value of Doppler indices to predict new DU oc- currence. SUBJECTS AND METHODS Subjects. Enrolled in this study were 70 consecutive patients with SSc (58 women and 12 men, mean  SD ages Edoardo Rosato, MD, PhD, Biagio Barbano, MD, Antonietta Gigante, MD, Ilenia Molinaro, MD, Silvia Quarta, MD, Simonetta Pisarri, MD, Antonio Amoroso, MD, Rosario Cianci, MD, Felice Salsano, MD: Sapienza Univer- sity of Rome, Rome, Italy. Address correspondence to Edoardo Rosato, MD, PhD, Sapienza University of Rome, Department of Clinical Med- icine, Clinical Immunology Unit, Viale dell’Universita ` 37, 00185 Rome, Italy. E-mail: edoardo.rosato@uniromal.it. Submitted for publication June 3, 2013; accepted in re- vised form February 4, 2014. Arthritis Care & Research Vol. 66, No. 9, September 2014, pp 1380 –1385 DOI 10.1002/acr.22309 © 2014, American College of Rheumatology ORIGINAL ARTICLE 1380