Review Two faces of the same coin: Raynaud phenomenon and digital ulcers in systemic sclerosis Felice Galluccio, Marco Matucci-Cerinic ⁎ Department of Biomedicine–Division of Rheumatology AOUC, Denothe centre, University of Florence, Italy abstract article info Available online 21 September 2010 Keywords: Systemic sclerosis Raynaud's phenomenon Digital ulcers Systemic sclerosis (SSc) is characterized by wide-spread fibrosis, activation of immune system with production of autoantibodies and extensive vascular damage. Raynaud's phenomenon (RP) and digital ulcers (DU) represent two faces of the same coin in SSc vasculopathy. RP, the earliest manifestation of the vascular involvement, is due to an excessive vasospasm of digital arteries, precapillary arterioles and cutaneous arteriovenous shunts, usually in response to cold exposure or other stimuli. DU are a severe complication of microvessel involvement and also of the persistent vasospasm of RP. Thus, the management of RP and DU requires a multimodal approach using a combination of pharmacological, non-pharmacological, and surgical treatments. Currently, the treatment of these complications represents a great challenge for all physicians. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241 2. First face: Raynaud's phenomenon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241 3. Second face: digital ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 4. The management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 1. Introduction Systemic sclerosis (SSc) is a severe multiorgan disease characterized by wide-spread fibrosis, activation of immune system with production of autoantibodies and extensive vascular damage [1]. The vascular involvement is clinically evident with Raynaud's phenomenon (RP) and digital ulcers (DU) that represent two faces of the same coin. In SSc, microvessels, endothelial cell injury in microvessels and in small and medium arteries [2,3] may be triggered by vasculotropic viruses, inflammatory cytokines, granzymes, endothelial cell-specific autoantibodies or elevated levels of reactive oxygen species due to oxidative stress [4]. Vascular injury leads to structural changes, loss of capillaries (well demonstrated with nailfold capillaroscopy [5]), remodelling of the vessel wall with intimal and median layers hyperplasia and adventitial fibrosis resulting in progressive luminal narrowing and eventually occlusion. This proliferative intimal vascu- lopathy is mediated by molecules that regulate mainly cell apoptosis, proliferation and vasoconstriction including an increase production of endothelin (ET), a reduction of prostacyclin release and a reduced production of nitric oxide synthase. Moreover, there is an over- expression of adhesion molecules (E-selectin, P-selectin, VCAM-1, ICAM-1) [6]. The loss of capillaries in SSc is not compensated because of defective angiogenesis and vasculogenesis [7,8]. 2. First face: Raynaud's phenomenon The earliest manifestation of the vascular involvement is RP, the clinical expression of SSc in the acral parts characterized by episodic colour changes of the digits that classically turn white (ischemia), then blue (cyanosis) and red (reperfusion). RP is essentially due to an excessive vasospasm of digital arteries, precapillary arterioles and cutaneous arteriovenous shunts, usually in response to cold exposure or other stimuli resulting in impaired oxygenation of the distal Autoimmunity Reviews 10 (2011) 241–243 ⁎ Corresponding author. Tel./fax: + 39 0557949271. E-mail address: cerinic@unifi.it (M. Matucci-Cerinic). 1568-9972/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.09.008 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev