In systemic sclerosis (SSc), the natural history of microvascular damage progresses from capillary dilation to capillary loss and reactive angiogenesis, as detectable by nailfold videocapillaroscopy (NVC) . The process is systemic and determines multiple clinical manifestations, from the early appearance of Raynaud's phenomenon, trough formation of digital ulcers (DUs), until severe organ involvement, impairing patient's quality of life or leading to main death causes, including interstitial lung disease and pulmonary arterial hypertension (PAH), hearth involvement, scleroderma renal crisis [2,3]. Although microvascular and macrovascular abnormalities frequently coexist in disease such as diabetes mellitus and other vascular diseases, the possible association between microvascular failure and macrovasculopathy in SSc patients has not been deeply investigated. However, significant correlations seem to exist between increased Intima-Media Thickness (IMT) of periferic small-caliber arteries (macrocirculation) and altered peripheral BP (LASCA) at the level of hand microvessels (microcirculation) in SSc patients.
SiIn addition, sgnificant capillary loss, observed at NVC, is peculiar of the ”Late” scleroderma pattern of microangiopathy and is mainly preceded by progressive capillary enlargement, microhemorrhages and their collapse, leeding to presence of large avascular areas . The importance of capillary loss was already demonstrated by a simple and reliable prognostic index, capable to predict digital trophic lesion development in SSc-related microvascular disease, when evaluated as part of the semi-quantitative NVC scoring . Moreover, microvascular function and its alterations in SSc, can be reliably assessed by laser-doppler flowmetry (LDF) and laser speckled contrast analysis (LASCA), evaluating blood perfusion at fingertips or at larger body areas [6–9].
The most frequently used drugs for treatment of complications in SSc patients, approved with evidence grade Ia, are vasoactive drugs. In particular, for severe RP and for prevention of DUs onset and treatment of PAH, both intravenous prostanoid iloprost (ILO), and the dual endothelin-1 receptor antagonist (ERA) BOSE are used, respectively . Bosentan seems to block pathogenic activities of Endothelin-1, the endothelial derived mediator determining both vasoconstriction and also the fibrosis genes induction [11–14].
Previous long-term follow up studies, showed that treatment with BOSE in combination with ILO interferes with progression of nailfold microvascular damage, evaluated through both capillary number semi-quantitative scoring at NVC and fingertip blood perfusion (FBP) at LDF [15,16].
In particular, an open label, prospective study of 4 follow up years showed that long-term treatment with BOSE added to ILO infusions administered quarterly in SSc patients, exerts a remodelling effect on structural and functional microvascular alterations and on stabilization of lung function, compared to ILO mono-therapy .
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Disclosure of Interest M. Cutolo Grant/research support from: actelion, italfarmaco