Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

Abstract

The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant.

Conclusion: The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: • Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: • This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.

Keywords: Intravenous immunoglobulin; Kawasaki disease; Meta-analysis; Risk.

Fig. 1

Literature selection for the meta-analysis

Fig. 2

Prevalence of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease among patients who received IVIG treatment ≤ 4.0 days after the onset of symptoms

Fig. 3

Hemoglobin as a predictive index for resistance to intravenous immunoglobulin therapy in Kawasaki disease

Fig. 4

Platelet count as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease

Fig. 5

Erythrocyte sedimentation rate (ESR) as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease

Fig. 6

Changes in oral mucosa as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease

Fig. 7

Conjunctival congestion as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease

Fig. 8

Cervical lymphadenopathy as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease

Fig. 9

Swelling of the extremities as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease

Fig. 10

Polymorphous rash as a predictive index for intravenous immunoglobulin resistance in Kawasaki disease