Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection

Abstract

IntroductionKawasaki disease (KD) can be associated with concomitant viral or bacterial infections. Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. Although concomitant infection does not affect coronary outcome, it is unknown how it influences the response to IVIG treatment.MethodologyRetrospective cohort study between 2008 and 2016 in a tertiary pediatric university hospital, including 154 children, of which 59 (38%) had concomitant infection.ResultsChildren with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p = 0.04), and 48 hours after IVIG administration (111 vs 59 mg/L, p = 0.003). Nevertheless, there was no statistically significant difference in the prevalence of coronary complications (Z-score > 2.5) between children with and without concomitant infection (36% vs 39%, p = 0.68).ConclusionChildren with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment. This association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication. Accordingly, prospective studies to distinguish true IVIG resistance from infection induced persistent fever is warranted.

Association of 8p22-23-rs2254546 Genotypes with Coronary Artery Status and Resistance to Intravenous Immunoglobulin in Iranian Children with Kawasaki Disease

“…The low rate of patients with an aneurysm can be attributed to the low frequency of IVIG-resistant patients, as according to our results, 21% of the studied patients were resistant to IVIG, which is considered the main cause of aneurysm in treated patients (23). In the study by Tremoulet et al (24) in San Diego County, 38.3% of patients with KD were IVIG-resistant, which is much higher than the frequency of IVIG-resistant patients in our study, and in the study by Dionne et al (25), 24% of children were found to be IVIG-resistant, which is a little higher than the IVIG-resistance rate in our study (21%). This difference in the rates of resistance to IVIG can originate from different population characteristics, including age, serum levels of inflammatory markers, and liver enzymes, which have been suggested to affect the risk of resistance to IVIG (25).…”

“…In the study by Tremoulet et al (24) in San Diego County, 38.3% of patients with KD were IVIG-resistant, which is much higher than the frequency of IVIG-resistant patients in our study, and in the study by Dionne et al (25), 24% of children were found to be IVIG-resistant, which is a little higher than the IVIG-resistance rate in our study (21%). This difference in the rates of resistance to IVIG can originate from different population characteristics, including age, serum levels of inflammatory markers, and liver enzymes, which have been suggested to affect the risk of resistance to IVIG (25). Although concurrent infections are associated with KD, the clinical presentations, prognosis, and even response to IVIG treatment have been reported to be the same as in non-confirmed infectious patients (26).…”

The Risk Prediction of Coronary Artery Lesions through the Novel Hematological Z-Values in 4 Chronological Age Subgroups of Kawasaki Disease

“…The vascular complications and responsiveness to IVIG in KD are largely related to the extent of KD inflammation, such as the degrees of concomitant infections and other inflammatory markers [29][30][31]. It is necessary to approach KD by considering the underlying disease and other inflammatory factors along with hematological Z-values.…”

Predictors and management of intravenous immunoglobulin-resistant Kawasaki disease

“…Some of the patients who have persistent or recurrent fever more than 24 hours after completion of the initial treatment should also be assessed for concomitant infection [6] or rare hemophagocytic lymphohistiocytosis [7]. Children with KD and concomitant infection are more likely to have persistent fever after treatment and this association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication.…”