Regular Article Digital laser doppler flowmetry may discriminate “limited” from “diffuse” systemic sclerosis Vito Grattagliano 1 , Florenzo Iannone 1 , Emanuela Praino, Alessandra De Zio, Maria Teresa Riccardi, Norma Carrozzo, Michele Covelli, Paolo Maggi, Giovanni Lapadula ⁎ DiMIMP, Rheumatology Unit, Clinica delle Malattie Infettive, University of Bari, Italy abstract article info Article history: Received 28 January 2010 Revised 11 April 2010 Accepted 14 April 2010 Available online 24 April 2010 Keywords: Videocapillaroscopy Raynaud Cold test Ischemic test Vascular tone Endothelium Objectives: To investigate skin blood flux and microvascular functional changes by laser Doppler flowmetry (LD) in patients with systemic sclerosis (SSc) at baseline and following dynamic stimulations. Methods: Skin blood flux of the dorsal hands was recorded by LD at baseline and after the cold test and the post-occlusive hyperemia test in 59 SSc patients (49 limited cutaneous, 10 diffuse cutaneous). Twenty-five patients with primary Raynaud's phenomenon (PRP), and 31 healthy donors (HD) were studied as controls. Results: After the cold test, SSc patients had a significantly higher reduction of the blood flux (-38.4% ± 28) than PRP (-21.1% ± 37) and HD (-22.1% ± 23) subjects (p b 0.05). Within the SSc group, the cold test flux was significantly reduced in limited-SSc (-399% ± 28, p b 0.05), but not in diffuse-SSc (-31.2% ± 29), whereas, the time needed to recover the basal flux after the occlusive/ischemic test was significantly longer in diffuse-SSc (18.8 s ± 21)than in limited-SSc (4.5 s ± 4, p b 0.01) or HD (2.2 s ± 2, p b 0.01) or PRP (0.4 s ± 0.7, p b 0.01). Conclusions: These data clearly indicate an impairment of vascular tone regulatory mechanisms in SSc and suggest that a peculiar pathogenic mechanism may be involved in different SSc subset. Nevertheless, it has clear that PRP and SSc-associated RP have a distinct pattern at LD evaluation, and monitoring patients with PRP could be helpful to understand whether a change in the LD pattern might predict the development of SSc. © 2010 Elsevier Inc. All rights reserved. Introduction Systemic sclerosis (SSc) is a chronic connective-tissue disease characterized by widespread damage of the small arteries and micro- vessels, and activation of the fibroblasts resulting in an abnormal remodelling of the extra-cellular matrix (ECM). There is an increased deposition of collagen and other ECM components leading to thick- ening and fibrosis of the skin, vascular walls and internal organs (Abraham and Varga, 2005). Vascular damage and extracellular matrix accumulation are the pathological hallmarks of SSc. Clinical and histological findings sug- gest a key pathogenic role of these alterations in the onset of SSc. Although late stage SSc shows a widely variable evolution, Raynaud's phenomenon (RP) is the usual symptom at onset of the disease, suggesting that microvascular alterations may be an early and key pathogenic step in the disease development (Abraham and Varga, 2005). Moreover, several studies have provided evidence that endo- thelial changes occur in the early phase of SSc, and both permeability and vasomotility alterations might be due to an imbalance consisting of an increase in the vasoconstrictor factors (endothelin-1 and thromboxane) and a relative decrease of the vasodilator factors (prostacyclin and nitric oxide) (Flavahan et al., 2003). Then, activated endothelial cells would promote adhesion and migration of the immune cells and fibroblast activation (Abraham and Varga, 2005). Microcirculatory alterations in SSc patients are both morphologic and functional, the latter being commonly regarded as vasospastic RP (Kahaleh 2004). Histology shows early capillary vessels alterations with sub-endothelial connective tissue proliferation, thinning of the media and abundant perivascular collagen deposits in the arterioles and the small arteries. Nailfold videocapillaroscopy (NVC) is a standard technique for “in vivo” assessment of morphological changes of the vascular microcircu- lation and is routinely used to define the degree of vascular damage in SSc (Cutolo and Matucci 2007). Although different attempts have been made to draw functional findings, in fact NVC provides only a static evaluation of the blood flow and no knowledge of the arteriole functions. By contrast, laser Doppler (LD) flowmetry is a non-invasive im- aging method that allows assessment of the microvasculature “in vivo” by measuring the blood flux for a limited time in a semi- quantitative way. Therefore it makes it possible to draw up a dynamic microcirculatory model for the study and follow-up of different conditions affecting the microvasculature (Anderson et al., 2002; Anderson et al., 2004; Cracowski et al., 2006; Gunawardena et al., Microvascular Research 80 (2010) 221–226 ⁎ Corresponding author. DiMIMP Rheumatology Unit, P.zza Giulio Cesare 11, 70124 Bari, Italy. Fax: +39 080 5478802. E-mail address: g.lapadula@reumbari.uniba.it (G. Lapadula). 1 The authors equally contributed to this work. 0026-2862/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.mvr.2010.04.006 Contents lists available at ScienceDirect Microvascular Research journal homepage: www.elsevier.com/locate/ymvre