背景:Livedoid血管病变(LV)是一种罕见的,以溃疡疼痛为特征的致残疾病,网状和萎缩白色。高凝,内皮,微循环功能障碍被认为是这种难以治疗的疾病的发病机理。
目的:本研究旨在探讨内皮功能障碍的发生频率,高凝状态,LV患者的甲皱毛细血管镜特征,以阐明其病因。
方法:本病例对照研究包括16例LV患者,24患有系统性硬化症(SSc),和23个对照对象。内皮功能障碍血清标志物可溶性内皮糖蛋白,endocan,内皮素-1,脂蛋白a,纤溶酶原激活物抑制剂-1(PAI-1),可溶性血栓调节蛋白,和血管性血友病因子使用酶联免疫吸附试验进行测量。血流介导的扩张和颈动脉内膜-中膜厚度作为内皮功能障碍的标志物进行检查。和微循环的评估通过甲褶毛细管镜检查。血栓形成相关参数,包括因子V莱顿的基因多态性,凝血酶原,PAI-1基因,亚甲基四氢叶酸还原酶(MTHFR)和因子XIII突变和血清蛋白C水平,蛋白质S,抗凝血酶,同型半胱氨酸,在LV患者中研究了D-二聚体和抗磷脂抗体。
结果:LV患者的纤溶酶原激活物抑制剂-1和可溶性血栓调节蛋白水平明显高于对照组(2.3[2.05-2.79]ng/mlvs.1.89[1.43-2.33]ng/ml,p=0.007;1.15[0.88-1.4]ng/mlvs.0.76[0.56-0.9]ng/ml,分别为p=0.004)。与对照组相比,LV患者的流量介导的扩张降低了25.4%(14.77%[11.26-18.26]与19.80%[16.47-24.88],p=0.034)。毛细血管镜特征,包括后果(75%与8.7%,p<0.001),无血管区域(25%vs.0%,p=0.011)和扩张(33.2%与0%,p=0.016),LV患者明显高于对照组。LV患者有多种与血栓形成有关的生化或遗传异常,包括杂合因子VLeiden突变(6.3%),MTHFR(C677T)突变(杂合子43.8%,纯合18.8%),MTHFR(A1298C)突变(杂合子37.5%,纯合12.5%),因子XIII杂合突变(12.5%),抗凝血酶缺乏症(31.3%),蛋白S缺乏症(12.5%),高同型半胱氨酸血症(31.3%),D-二聚体升高(25%),抗β2-糖蛋白I(12.5%),狼疮抗凝抗体(6.3%),和抗心磷脂抗体(6.3%)。
结论:结论:LV患者的特征是血栓形成相关参数的增加。还表现出血管内皮和微循环功能障碍,类似于SSC。这些发现支持血栓形成的复杂相互作用,内皮功能障碍,和微循环失调在LV发病机制中的作用。因此,LV患者的治疗应个体化,基于对主要病理途径的识别。
Livedoid vasculopathy (LV) is a rare, disabling disease characterized by painful ulcers,
livedo reticularis and atrophy blanche. Hypercoagulation, endothelial, and microcirculatory dysfunction are believed to be responsible for the pathogenesis of this difficult-to-treat disease.
This study sought to investigate the frequency of endothelial dysfunction, hypercoagulability, and nailfold capillaroscopic features in LV patients to shed light on its etiology.
This case-control study included 16 patients with LV, 24 with systemic sclerosis (SSc), and 23 control subjects. Serum markers of endothelial dysfunction soluble endoglin, endocan, endothelin-1, lipoprotein a, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin, and von Willebrand factor were measured using enzyme-linked immunosorbent assays. Flow-mediated dilation and carotid intima-media thickness were examined as markers of endothelial dysfunction, and microcirculation was assessed with nailfold capillaroscopy. Thrombophilia-related parameters, including gene polymorphisms of factor V Leiden, prothrombin, PAI-1 genes, methylenetetrahydrofolate reductase (MTHFR) and factor XIII mutation and serum levels of protein C, protein S, antithrombin, homocysteine, D-dimer and antiphospholipid antibodies were investigated in LV patients.
Plasminogen activator inhibitor-1 and soluble thrombomodulin levels were significantly higher in LV patients compared to control subjects (2.3 [2.05-2.79] ng/ml vs. 1.89 [1.43-2.33] ng/ml, p = 0.007; 1.15 [0.88-1.4] ng/ml vs. 0.76 [0.56-0.9] ng/ml, p = 0.004, respectively). Flow-mediated dilation was 25.4 % lower in the LV patients compared to the control group (14.77 % [11.26-18.26] vs. 19.80 % [16.47-24.88], p = 0.034). Capillaroscopic features, including ramifications (75 % vs. 8.7 %, p < 0.001), avascular areas (25 % vs. 0 %, p = 0.011) and dilatations (33.2 % vs. 0 %, p = 0.016), were significantly higher in LV patients than in controls. LV patients had multiple biochemical or genetic abnormalities related to thrombophilia, including heterozygous factor V Leiden mutations (6.3 %), MTHFR (C677T) mutations (heterozygous 43.8 %, homozygous 18.8 %), MTHFR (A1298C) mutations (heterozygous 37.5 %, homozygous 12.5 %), factor XIII heterozygous mutation (12.5 %), antithrombin deficiency (31.3 %), protein S deficiency (12.5 %), hyperhomocysteinemia (31.3 %), D-dimer elevation (25 %), anti-β2-glycoprotein I (12.5 %), lupus anticoagulant antibodies (6.3 %), and anticardiolipin antibodies (6.3 %).
In conclusion, LV patients were characterized by an increased presence of thrombophilia-related parameters, and also exhibited vascular endothelial and microcirculatory dysfunction, resembling SSc. These findings support the complex interaction of thrombophilia, endothelial dysfunction, and microcirculation dysregulation in the pathogenesis of LV. Thus, the treatment of LV patients should be individualized, based on the identification of the predominant pathological pathways.