Background/Purpose:

Digital Ulcers (DU) are a major disabling complication of Systemic Sclerosis (SSc)  interfering with personal and professional life of our patients. The aim of our study was to analyze  functional dysfunction of endothelium, capillaroscopy and angiogenesis biomarkers  in patients with SSc, with or without peripheral microvascular complications, in order to try to predict the development of digital ulcers in these patients.

Methods: This is a prospective study of a cohort of Systemic Sclerosis (SSc) and primary Raynaud Phenomenon (RP) patients attending our Raynaud’s Clinic. (n= 108 )  Demographic and epidemiological data, autoimmune serological screening, inflammatory protein screening, Flow mediated dilation (FMD) and end diastolic volume (EDV), capillaroscopy, Endothelin-1 (ET-1), ADMA, VEGF and Endoglin were analyzed and compared to a control group (n=31). Statistical calculations were performed using SPSS (v 20.0). Comparison and distribution between groups were performed using Kruskal-Wallis test. The Mann-Witney test was used to compare continuous variables wit nominal variables. A p value ≤ 0.05 was considered significant.

Results:

Flow mediated dilation (FMD) was reduced in patients with digital ulcers. The brachial artery diameter at 60 s after cuff deflation had statistical differences (P<0.001) between SSc patients with digital ulcers compared to SSc patients without DU or  primary Raynaud phenomenon (RP). End diastolic volume was significantly different between groups (P<0.001) suggesting an increase in peripheral  resistance in patients with DU. FMD was more reduced in patients with late pattern (Cutolo´s classification) in capillaroscopy and a statistical differences (P<0.001) between early and late pattern (P<0.007) was found. Endothelin-1 and ADMA were  increased  in patients with DU (P<0.001) which might explain an excessive vasoconstrictor tone in these patients in association with occlusion of distal digital circulation (avascular areas incapillaroscopy) leading to the reduced FMD in patients with DU. VEGF was increased in SSc patients without DU, we found  no difference with primary RP (P<0.168). A statistical differences (P<0.002) between patients with DU and SSc patients with no DU or with primary RP was found in VEGF. Endoglin was increased in patients with DU  (p<0,001). Patients with Cutolo´s late pattern in capillaroscopy had a increase in the angiostatic biomarker endoglin in comparison with the other groups (p<0,005).

 

Conclusion:

In our cohort, we identified patients at risk of developing DUs:  Ssc 70 positive, decreased FMD and low EDV, late pattern of Cutolo´s classification, increased ET-1, ADMA and endoglin and a reduced VEGF. Microvascular lesions  and an increase in the peripheral resistance associated to endothelial dysfunction and a impaired angiogenesis with an imbalance in favor of increased angiostatic biomarkers may be behind the underling mechanism of DU. These data may help us identify patients with high risk of developing digital ulcers and defining a correct target therapy at an early stage.

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« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/predictors-of-digital-ulcers-in-systemic-sclerosis-correlation-between-clinical-and-hemodynamic-features-capillaroscopy-endothelium-dysfunction-and-angiogenesis-biomarkers/