Prognostic Impact of Vascular Leakage in Acute Kawasaki Disease

Abstract

Background-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. However, the prognostic impact of vascular leakage in KD remains unclear. Methods and Results-We compared 76 patients who became afebrile within 5 days after starting intravenous gamma globulin (IVGG) (2 g/kg over 5 days) (IVGG-responsive) with 27 patients who did not respond (IVGG-resistant). Baseline levels of serum VEGF and albumin were similar between the groups. After IVGG, VEGF levels increased (PϽ0.0001) and albumin levels decreased (PϽ0.00001) in both groups. However, the IVGG-resistant group had higher VEGF levels (Pϭ0.029) and severe hypoalbuminemia (PϽ0.00001) compared with the IVGG-responsive group. Coronary aneurysms were documented in 12 patients from the IVGG-resistant group but not in the IVGG-responsive group. Then IVGG-resistant patients were divided into 2 subgroups according to the presence (nϭ12) or absence (nϭ15) of coronary aneurysms. There was no difference between subgroups in age, sex, laboratory data including albumin, and retreated doses of IVGG. However, body weight gain after IVGG was documented in patients who subsequently developed coronary aneurysms (Pϭ0.003) but not in those who did not (Pϭ0.967). Conclusions-These

Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells

“…KD is an especially interesting model of vasculitis syndromes because it is usually responsive to treatment with high doses of ␥-globulin within a few days, allowing easy follow-up of patients. 48,49 Indeed we found a high expression of MRP8 and MRP14 in neutrophils attaching to the affected vessels and a strong deposition of both molecules at the endothelial surface of the vessels within the inflamed tissue. Furthermore, the rapid decrease of initially high serum concentrations of MRP8/MRP14, in association with the clinical response to treatment, indicates a functional role for these S100 proteins in systemic vasculitis.…”

Immunoglobulin Resistance in Kawasaki Disease

“…7 In patients in the present study, arthritis was seen in the acute phase of Kawasaki disease prior to any immunoglobulin therapy, all in male gender, usually involving large joints, and was both oligoarticular and polyarticular (one child also had cervical arthritis). This may be explained by the fact that a higher degree of ''leaky'' vessels 45 would lead to more joint effusions and edema in children with immunoglobulin-resistant Kawasaki disease. Furthermore, involvement of bradytrophic cartilage within joints may represent worse inflammation that may be less responsive to immunoglobulin.…”

The IL-10 (-627 A/C) Promoter Polymorphism May Be Associated With Coronary Aneurysms and Low Serum Albumin in Korean Children With Kawasaki Disease

“…Increases in vascular permeability have been associated with hypoalbuminemia and noncardiogenic edema (39), and endothelial permeability has been associated with inflammatory mediators, such as IL-10 and vascular endothelial growth factor (40 -43). Thus, our findings that KD children harboring the risk (-627C) allele at the IL-10 polymorphism showed significantly lower albumin levels may form a functional connection between IL-10 and early coronary artery aneurysm.…”