Skin ulcers in systemic sclerosis: Determinants of presence and predictive factors of healing Stefano Alivernini, MD, a Maria De Santis, MD, a Barbara Tolusso, BS, a Alice Mannocci, MS, b Silvia Laura Bosello, MD, a Giusy Peluso, MD, a Michela Pinnelli, MD, a Graziella D’Antona, MD, a Giuseppe LaTorre, MD, b and Gianfranco Ferraccioli, MD a Rome, Italy Background: Skin ulcers are common vascular complications of systemic sclerosis (SSc). Objective: The aim of the study was to identify clinical, biologic, and imaging parameters that constitute risk factors for the occurrence and persistence of skin ulcers. Methods: One hundred thirty Italian SSc patients were examined at entry and after 20 months of follow-up. Results: The diffuse SSc phenotype with avascular areas on capillaroscopy, thrombophilia, and systemic inflammation as defined by interleukin 6 plasma levels, represented the major risk factors for ulcer development. Infection was associated with a risk of poor or no healing, and cardiopulmonary involvement was a major comorbid factor in patients with ulcers. The presence of infection and avascular areas represented the main determinants for ulcer healing. Limitations: Our data should be confirmed with a longer follow-up period since skin ulcers represent a frequent vascular complication in scleroderma patients. Conclusion: Aggressive therapies aiming at improving angiogenesis and controlling infection and the course of the disease appear to be crucial to obtain ulcer healing. ( J Am Acad Dermatol 2009;60:426-35.) INTRODUCTION Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive thickening and fibrosis of the skin and internal organs, and by diffuse damage of the microvascular system, includ- ing arterioles and small and medium-sized arteries in the peripheral circulation. 1 The most common manifestation of vascular ab- normalities in SSc is Raynaud’s phenomenon (RP). Blood vessels have abnormal reactivity to stimuli, which leads to digital ischemia with the development of long-term complications such as digital ulcers and necrosis. 1 Digital ulcers are much more common in patients with SSc-associated RP than in patients with Raynaud’s From the Division of Rheumatology, a and the Institute of Hygiene, b Catholic University of the Sacred Heart. Funding sources: ASRALES foundation. Conflicts of interest: None declared. Accepted for publication November 3, 2008. Reprint requests: Gianfranco Ferraccioli, MD, Division of Rheumatology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy. E-mail: gf.ferraccioli@rm.unicatt.it. 0190-9622/$36.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2008.11.025 Abbreviations used: ACA: anti-centromere antibody CI: confidence interval CRP: C-reactive protein dSSc: diffuse systemic sclerosis ELISA: enzyme-linked immunosorbent assay ESR: erythrocyte sedimentation rate HDL: high-density lipoprotein HGF: hepatocyte growth factor HRCT: high-resolution computed tomography IL: interleukin lSSc: limited systemic sclerosis NCEP ATP III: National Cholesterol Education Program Adult Treatment Panel III OR: odds ratio QTc: Q-T interval corrected for heart rate RF: rheumatoid factor RP: Raynaud phenomenon SD: standard deviation sTNF-RI/RII: soluble tumor necrosis factor receptor I/II TLCO: total lung carbon monoxide capacity TNF-RI/II: tumor necrosis factor receptor I/II 426