Role of VEGF and therapeutic strategy in Kawasaki disease

微血管通透性增加是川崎病(KD)的初始阶段。我们报道了血管内皮生长因子(VEGF)可能在KD的血管渗漏中起作用。在致死性KD中，广泛记录了血管内皮生长因子阳性微血管的血浆渗漏。血管渗漏的增加会导致低蛋白血症和非心源性水肿。然后，我们比较了76名在静脉注射丙种球蛋白后5天内变得无热(IVGG反应)的患者和27名无反应(IVGG抵抗)的患者。IVGG后，两组血管内皮生长因子水平升高(P&lt；0.0001)，白蛋白水平降低(P&lt；0.00001)。然而，与IVGG反应组相比，IVGG抵抗组的血管内皮生长因子水平更高(P=0.029)，严重的低蛋白血症(P&lt；0.00001)。此外，IVGG抵抗患者在IVGG后体重增加被记录在随后发生冠状动脉瘤的患者中(P=0.003)。这些结果表明，血管渗漏可能是KD的一个重要病理特征。然后，我们研究了由IVGG联合地塞米松(DEX)组成的新方案在KD初始治疗中对临床结局和血清VEGF水平的影响。对照组46例，早期给予静脉注射2g/kg IVGG，连续4~5d，加大剂量乙酰水杨酸(对照组)治疗。两组均未发现严重不良反应。地塞米松组治疗后C反应蛋白低于对照组(P=0.033)。此外，地塞米松组首次静脉滴注地塞米松后平均发热时间为2.2d，对照组为2.8d(P=0.015)。虽然该方案不影响冠脉结局，但静脉滴注地塞米松联合地塞米松治疗川崎病是安全的，可加速全身炎症的消退。

Increased microvascular permeability is an initial step of Kawasaki disease (KD). We reported that vascular endothelial growth factor (VEGF) might play a role in the vascular leakage of KD. In fatal KD, plasma leakage was extensively documented at VEGF-positive microvessels. Increases in vascular leakage cause hypoalbuminemia and noncardiogenic edema. Then, we compared 76 patients who became afebrile within 5 days after starting intravenous gamma globulin (IVGG-responsive) with 27 patients who did not respond (IVGG-resistant). After IVGG, VEGF levels increased (P<0.0001) and albumin levels decreased (P<0.00001) in both groups. However, the IVGG-resistant group had higher VEGF levels (P=0.029) and severe hypoalbuminemia (P<0.00001) compared with the IVGG-responsive group. In addition, body weight gain after IVGG was documented in patients who subsequently developed coronary aneurysms (P=0.003) of IVGG resistant patients. These results suggest that vascular leakage may be a key feature of KD pathaphysiology.). Then, we studied the effects of a new regimen consisting of IVGG combined with dexamethasone (DEX) on clinical outcome and serum levels of VEGF in the initial treatment of KD. The control group consisted of 46 KD patients retrospectively treated earlier with 2 g/kg IVGG over 4 to 5 days plus higher dose acetylsalicylic acid (CONTROL). No serious adverse effect was noted in either group. Post-treatment C-reactive protein in the DEX group was lower than that in the CONTROL group (P=0.033). In addition, the mean duration of fever after the first IVGG infusion was 2.2 days in the DEX group and 2.8 days in the CONTROL group (P=0.015 Although this regimen did not affect coronary outcome, IVGG therapy combined with dexamethasone for the initial treatment of Kawasaki disease was safe and accelerated the resolution of systemic inflammation.