Defining the risk of first intravenous immunoglobulin unresponsiveness in non-Asian patients with Kawasaki disease

Abstract

About 10-20% of patients with Kawasaki disease (KD) are unresponsive to intravenous immunoglobulin (IVIg) and are at increased risk of coronary artery abnormalities (CAAs). Early identification is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Japanese populations. We investigated the accuracy of 3 Japanese scoring systems and studied factors associated with IVIg unresponsiveness in a large multiethnic French population of children with KD to build a new scoring system. Children admitted for KD between 2011-2014 in 65 centers were enrolled. Factors associated with second line-treatment; i.e. unresponsiveness to initial IVIg treatment, were analyzed by multivariate regression analysis. The performance of our score and the Kobayashi, Egami and Sano scores were compared in our population and in ethnic subgroups. Overall, 465 children were reported by 84 physicians; 425 were classified with KD (55% European Caucasian, 12% North African/ Middle Eastern, 10% African/Afro-Caribbean, 3% Asian and 11% mixed). Eighty patients (23%) needed second-line treatment. Japanese scores had poor performance in our whole population (sensitivity 14-61%). On multivariate regression analysis, predictors of secondary treatment after initial IVIG were hepatomegaly, ALT level ≥30 IU/L, lymphocyte count <2400/mm 3 and time to treatment <5 days. The best sensitivity (77%) and specificity (60%) of this model was with 1 point per variable and cutoff ≥2 points. The sensitivity remained good in our 3 main ethnic subgroups (74-88%). We identified predictors of IVIg resistance and built a new score with good sensitivity and acceptable specificity in a non-Asian population. Kawasaki disease (KD) is the leading cause of acquired heart disease in childhood in developed countries 1. The level of coronary artery involvement mainly determines the prognosis of this systemic vasculitis affecting predominantly young children, although pericarditis, myocarditis and valvular dysfunction are not uncommon 1,2. Occasionally, KD can be complicated during the acute phase by shock syndrome 3 , macrophage activation syndrome 4 , or myocardial infarction 1. Although the mortality rate is relatively low during the acute phase, sudden death due to myocardial ischemia could occur many years later in children or adults with coronary artery sequelae 1. The efficacy of early treatment with intravenous immunoglobulin (IVIg) is well established 5,6 and has reduced the prevalence of coronary artery abnormalities (CAAs) from 26-30% to 2.5-5% at 1 month after disease onset 6,7. However, 30% to 40% of KD patients develop coronary dilatations within the first days of the disease 8. In addition,

How useful are Kawasaki disease risk scoring systems to the Turkish population?

“…Low performance was observed in all patients in whom Japanese risk scores were administered (sensitivity=14%–61%). Therefore, a new risk scoring with better sensitivity and acceptable specificity was applied in a non-Asian country with IVIG resistance ( 47 ).…”

Delineating phenotypes of Kawasaki disease and SARS-CoV-2-related inflammatory multisystem syndrome: a French study and literature review

“…We aimed to define boundaries between KD and PIMS/MIS-C by comparing their clinical and biological characteristics. We used cases from our historic KD database (KD-HIS), the largest in France, implemented before the SARS-CoV-2 pandemic [ 28 ]. We also constituted a cohort of children with severe forms of KD requiring admission to an ICU (KD-ICU), the largest reported to our knowledge.…”

Revised recommendations of the Italian Society of Pediatrics about the general management of Kawasaki disease

“…It is believed that IVIG-resistant KD reflects severity of the underlying inflammation, explaining the increased incidence of CAA in this subset of patients. Severe anemia at disease onset, early development of CAA, and signs of MAS or septic shock should be considered in predicting the risk of IVIG non-responsiveness [ 37 ]. The identification of patients with KD having a higher propensity to be IVIG-refractory is challenging: many efforts have been made to discriminate which patients might not respond to IVIG in order to undertake a more aggressive treatment combined with IVIG, but different scores useful in the Eastern Asiatic populations have been unsuccessful in the Caucasians [ 21 , 38 – 40 ].…”