Role of Nailfold Videocapillaroscopy, VEGF in the Prognostic Evaluation of SSc

Data from this study supports nailfold videocappillaroscopy as a clinically useful tool in the longitudinal evaluation of systemic sclerosis

The presence of both giant capillaries and avascular areas, as measured by nailfold videocappillaroscopy (NVC), are associated with systemic sclerosis (SSc) disease severity, according to research published in Autoimmunity Highlights. Serum vascular endothelial growth factor (VEGF) was also identified as a potential biomarker of lung involvement in SSc. 

NVC has been used to identify microvascular manifestations of SSc, often in combination with other laboratory tests such as anti-centromere and anti-topoisomerase I antibodies to diagnose early SSc. The role of NVC in elucidating the course or prognosis of SSc disease, however, is less clear.

To study the correlations between abnormalities on NVC, capillaroscopy skin ulcer risk index (CSURI), and SSc disease severity scores, Maria De Santis, MD, of the Humanitas Research Hospital, Rozzano, Milan Italy analyzed NVC images of 44 patients diagnosed with SSc by the 2013 ACR/EULAR criteria. Study participants did not have evidence of other possibly overlapping rheumatic diseases and had NVC images taken of hand digits 2-5 bilaterally.

Forty-four patients with SSc had serum samples (including complete blood cell counts, C-reactive protein levels, creatinine concentrations, urine analyses, complement C3 and C4 levels, anti-centromere and anti-topoisomerase positivities) along with clinical information collected. Serum VEGF-A was quantitatively measured by enzyme-linked immunosorbent assay.  Study participant age, disease duration from the onset of first non-Raynaud symptom, modified Rodnan skin score (mRSS), current digit ulcers, SSc severity index, and treatment modalities were then analyzed.

Serum samples were also collected from 31 age- and sex-matched healthy participants serving as controls and from an additional 32 women with SSc in the unselected SSc group.

Two independent clinicians, blinded to patient clinical information and diagnoses, analyzed NVC mean capillary density per digit, composite number of giant capillaries, presence of neoangiogenesis, and avascular areas on 4 consecutive imaging fields over 1mm from the center of the nailfold of the second, third, fourth, and fifth digits bilaterally.  

These clinicians graded lesions as early (presence of giant capillaries), active (prevalence of giant capillaries), or late (prevalence of avascular areas) as defined by the Cutolo NVC scleroderma patterns.

Within 3 months of enrollment by NVC, the 44 SSc study participants also had the following parameters evaluated: pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography to evaluate for pulmonary hypertension, pulmonary high-resolution computed tomography (HRCT), gastroesophageal endoscopy or manometry. 

Researchers found that age and reticular pattern on HRCT was inversely correlated with the presence of giant capillaries (P=.034, r = −0.34) , and that CSURI was directly correlated with avascular areas (P=.04, r = −0.5). 

Number of digital ulcers was directly correlated to the mean capillary density  (P=.02, r = +0.4) and DLCO  (P=.02, r = +0.4), while being inversely correlated with severity index (P=.01, r = −0.4) and skin score (P=.02, r = −0.4). Notably, levels of serum VEGF were significantly higher in study participants with SSc as compared to controls (P=.03) and inversely correlated with DLCO (P=.01, r =−0.4)

“[This] data may suggest a helpful role of this simple counting score as marker of internal organ involvement,” the authors indicated. 

Summary and Clinical Applicability

The presence of giant capillaries and avascular areas on NVC appears to be related to SSc disease severity as indicated by interstitial lung disease,  higher skin score, and SSc severity index.

“Our data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation, of SSc patients,” the authors concluded.

The authors point out that while assessing Cutolo’s pattern on NVC is time-efficient, it does not allow quantitative measurements of microvasculopathy.  They suggest that analyzing mean capillary density may yield the most clinically relevant information. “[Mean capillary density] not only correlates with an important pulmonary function index (DLCO/AV), but also with SSc skin score, SSc severity index, and with the presence of digital skin ulcers,” the authors stated. 

The use of serum VEGF to assess interstitial lung disease may reduce radiation associated with HRCT evaluation.  

Limitations and Disclosures

The use of serum VEGF as a biomarker of interstitial pulmonary involvement in SSc should be confirmed in a prospective study.


De santis M, Ceribelli A, Cavaciocchi F, et al. Nailfold videocapillaroscopy and serum VEGF levels in scleroderma are associated with internal organ involvement. Auto Immun Highlights. 2016;7(1):5.