Ultrasound evaluation of endothelial dysfunction in immunoglobulin-resistant children with acute Kawasaki disease

Abstract

Purpose Clinically, some children with Kawasaki disease (KD) who do not respond to the rst application of gamma globulin therapy have a longer course of disease and a higher risk of coronary artery damage. The characteristics of vascular endothelial dysfunction in intravenous immune globulin (IVIG)-resistant patients during the acute phase are not well described. We aimed to determine whether indicators that detect the situation of the endothelium are useful parameters that can accurately re ect subclinical dysfunction in resistant patients and may assist in differentiating patients with KD at a higher risk of IVIG resistance.Methods Fifty IVIG-resistant KD children, 120 IVIG-responsive KD children, 70 febrile children with acute upper respiratory infection and 100 healthy controls were recruited, and indicators re ecting endothelial in ammation, including ow-mediated dilation (FMD), were measured. Receiver operating characteristic (ROC) curve analysis was utilized to determine the threshold values of these parameters associated with IVIG resistance. Multiple logistic regression analysis was performed to determine whether FMD was an independent predictor of IVIG-resistant patients.Results Compared with normal children, febrile children and IVIG-sensitive KD patients, IVIG-resistant patients had lower FMD (P<0.05) and higher carotid artery intima-media (CIMT) (P<0.05). Laboratory data demonstrated that the percentage of neutrophils (N %) and the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum procalcitonin (PCT) were signi cantly higher in the IVIG-resistant group than in the IVIG-responsive group, while the levels of albumin (ALB) and serum sodium were signi cantly lower (P< 0.05). PCT, Na+ and FMD exhibited AUCs of 0.727, 0.653 and 0.698, respectively, in predicting IVIG resistance in KD through ROC analysis. PCT > 1.69 ng/ml, Na+ <133.2 mmol/l and FMD <5.79% were independent predictors of IVIG resistance in KD (OR, 95% CI, P< 0.05).Conclusion More severe endothelial dysfunction, especially lower FMD, was present in IVIG-resistant patients than in IVIGresponsive patients. It is a helpful diagnostic tool that provides supportive criteria to detect KD patients at a higher risk of IVIG resistance when FMD<5.79% in children. What Is KnownChildren with Kawasaki disease have declined FMD and Stiffness index (SI) values, as well as raised carotid intima media thickness (CIMT) which are related to the severity of endothelial dysfunction in later stage after the onset.What is new 1. FMD is lower and CIMT is higher in KD patients with IVIG-resistance than those without, in the acute stage. 2. FMD and PCT have a negative relationship with each other, and FMD<5.79% reminds a chance of IVIG-resistance.

Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease

“…The results confirm the existence of a process leading from acute and chronic inflammation to vascular endothelial dysfunction in humans, as shown in patients with Helicobacter pylori infection, patients with periodontal disease, patients with Kawasaki disease, patients with Bürger’s disease, and other inflammatory diseases [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ]. Vascular endothelial function may be considered a marker of vascular inflammation, although various chemical biomarkers exist for inflammation.…”

“…Inhibition of NF-kB activity suppresses interlukin-6 (IL-6), VCAM-1 and MCP-1 expression [ 89 ]. Many studies have shown that inflammation may play a role in vascular injury [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ]. The presence of angiotensin II, oxidized LDL, and inflammatory cytokines activates NADPH oxidase, which in turn induces inflammation under the condition of oxidative stress due to excess ROS.…”

“…Several lines of evidence have shown that other acute and chronic inflammatory diseases are also associated with endothelial dysfunction [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ], though the mechanisms of endothelial dysfunction in acute and chronic inflammatory diseases remain unclear. Endothelial function is impaired in various acute inflammatory diseases including acute rheumatic fever [ 104 ], systemic inflammation induced by influenza A vaccination in patients with human immunodeficiency virus infection [ 105 ], pre-eclampsia [ 106 ], acute Kawasaki disease [ 107 ], severe sepsis [ 108 ], and foot-and-mouth disease [ 109 ] and in various chronic inflammatory diseases including rheumatoid arthritis [ 110 , 111 ], juvenile idiopathic arthritis [ 112 ], systemic sclerosis [ 113 ], systemic lupus erythematosus [ 114 ], Behçet’s disease [ 115 ], rhinosinusitis [ 116 ], ankylosing spondylitis [ 117 ], multiple sclerosis [ 118 ], bowel disease [ 119 ], Takayasu disease [ 120 ], psoriasis […”