Nailfold videocapillaroscopy and serum VEGF levels in scleroderma are associated with internal organ involvement

Abstract

PurposeNailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases.MethodsWe studied 44 patients with SSc who were evaluated within 3 months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X-ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls.ResultsGiant capillaries were inversely correlated with age (p = 0.034, r = −0.34) and to the extent of reticular pattern at HRCT (p = 0.04, r = −0.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p = 0.006, r = +0.4) and severity index (p = 0.004, r = +0.5). The mean capillary density was directly correlated to the ulcer number (p = 0.02, r = +0.4) and to DLCO/alveolar volume (p = 0.02, r = +0.4) and inversely correlated with severity index (p = 0.01, r = −0.4) and skin score (p = 0.02, r = −0.4). Serum VEGF levels were higher in the SSc population vs controls (p = 0.03) and inversely correlated with DLCO (p = 0.01, r =−0.4) and directly with ground-glass and reticular pattern at HRCT (p = 0.04, r = +0.4 for both).ConclusionsOur data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation of SSc patients. Of note, serum VEGF levels may act as a biomarker of interstitial lung involvement.

The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

“…A 20-year prospective study following the disease course of patients with RP, noted transition on nailfold capillaroscopy (NC) from giant capillaries to capillary loss occurring in close temporal relationship to the emergence of clinical features that led to a diagnosis of definite SSc (usually defined by the emergence of cutaneous fibrosis) [20]. A number of studies have also identified a positive and progressive association between the severity of microangiopathy on NC and the extent of skin fibrosis [21][22][23][24][25]. Indeed, 'early' changes are more frequently identified in limited cutaneous SSc (lcSSc) [23,26] whereas 'late' changes are more prevalent in diffuse cutaneous SSc (dcSSc) [19,25].…”

“…In view of the characteristic microvascular manifestations of SSc, VEGF-A pathways have attracted interest as potentially important drivers of disease pathogenesis. In view of the pronounced capillary drop out found in SSc, the authors of early studies were surprised to identify high levels of circulating serum VEGF-A in both early [9] and established SSc [22,54], although serum VEGF-A was noted to be comparatively lower in SSc patients with DU [9,55]. VEGF associations with systemic organ manifestations of SSc have been less extensively studied and are notably varied.…”

“…Commercially available VEGF-A ELISAs are unable to differentiate between these isoforms. Thus, aforementioned studies [9,22,54,60,61] likely detected pan-VEGF-A (representing co-detection of VEGF-Axxxa and VEGF-Axxxb soluble isoforms). Subsequent studies used isoform VEGF-A165b specific detection methods to confirm an association between VEGF-A165b and the 'late' avascular patterns on NC [14].…”

Clinical associations of vascular endothelial growth factor in patients with systemic sclerosis

“…Аналогичная взаимосвязь -обратная корреляция между концентрацией VEGF в крови и ДЛСО у больных ССД -получена и в работе M. De Santis и соавт. [27].…”

Potential biomarkers in patients with systemic sclerosis

“…However, paradoxically a deficit of angiogenesis in the skin of these patients has been reported with development of avascular areas in the skin and in the internal organs, leading to digital ulcers, skin and organ fibrosis. 1 The detection of vascular endothelial growth factor (VEGF) in the circulation of SSc patients has given conflicting results, while in some studies VEGF and other pro-angiogenic mediators, such as fibroblast growth factor (FGF)-2 and interleukin (IL)-8, have been shown to be up-regulated; [2][3][4] in others the levels of VEGF were similar to those of healthy controls. 5 Among the antiangiogenic mediators, endostatin (ES), by inhibiting VEGF, is one of the main anti-angiogenic molecules in physiological and pathological conditions.…”