Hibiscus score: Developing and validating a predictive tool for intravenous immunoglobulin treatment resistance in Malaysian children with Kawasaki disease

Abstract

Background

Children with intravenous immunoglobulin (IVIG) resistant Kawasaki disease (KD) are at higher risk of developing coronary artery (CA) aneurysm. Early identification of high-risk patients using a predictive tool would allow for earlier interventions to prevent cardiac complications.

Methods

Children with KD who were admitted to five selected hospitals in Malaysia between 2008 and 2018 and received 2 g/kg of IVIG within 10 days from the onset of illness were included. Predictors of IVIG resistance in KD were determined using multiple logistic regression analysis. An optimal cut-off point was set using receiver operative characteristic curve and a final multiple logistic regression analysis was performed entering these cut-off points. A new scoring system was constructed.

Results

A total of 276 patients were included. IVIG resistance occurred in 9.1 % of them. Total bilirubin [OR 7.37; 95 % CI (2.18, 24.83)], male sex [OR 0.34; 95 % CI (0.10, 1.19)], C-reactive protein (CRP) [OR 0.17; 95 % CI (0.02, 1.38)] and neutrophils [OR 0.25; 95 % CI (0.05, 1.21)] were found to be significant predictors for IVIG resistance. The findings led to the development of a new predictive tool called the Hibiscus score, which scored 1 point each for neutrophils ≥60 %, CRP ≥80 mg/L, and male sex, while total bilirubin ≥9.4 μmol/L scored 2 points. A cut-off point of ≥4 with this prediction score yielded a sensitivity of 78.9 % and specificity of 80.5 %, with area under the curve of 0.835 [95 % CI (0.752, 0.919)]. CA aneurysms occurred in 6.7 % of IVIG responders and 32 % of IVIG-resistant children (p < 0.001).

Conclusion

The findings suggest that the Hibiscus score has a higher predictive power than the existing scoring systems for IVIG resistance in children with KD in Malaysia. However, external validation is required to enable its use to guide treatment decisions.