Demographic and Treatment Variability of Refractory Kawasaki Disease: A Multicenter Analysis From 2005 to 2009

Abstract

Objective: Approximately 10% to 15% of Kawasaki disease (KD) is refractory to treatment with initial intravenous immunoglobulin (IVIG). However, there is no consensus on pharmacologic treatment of refractory KD (rKD). Demographic characteristics of patients with rKD and regional variability in their treatment in the United States have not been reported on a large scale. The goal of this study was to describe the demographic and treatment variability in rKD by using a large multi-institutional database. Methods: Data were obtained for patients with KD from January 2005 to June 2009 by using the Pediatric Health Information System. Patients who received a single dose of IVIG were labeled as having standard KD (sKD) and those who required additional medications were labeled as having rKD. Results: Of the 5633 patients studied, 4818 (85.5%) received 1 dose of IVIG (sKD) and 815 (14.5%) received >1 medication (rKD). Median age was 30 months (interquartile range: 14-53) and 30 months (interquartile range: 15-54) for rKD and sKD patients, respectively (P= .438). No significant change was noted in the gender or ethnic distribution of patients between rKD and sKD groups. Seasonal distribution of rKD was comparable to sKD. IVIG was the most common (64.5%) initial medication chosen to treat rKD, followed by methylprednisolone (27.1%) and infliximab (8.3%); however, there was significant regional variability. Of patients with rKD, 81% required only 1 additional medication (after the initial IVIG) for treatment. Conclusions: Patients with rKD have similar age, gender, ethnic, and seasonal distribution as sKD patients. IVIG is the most common initial medication chosen to treat rKD; however, there is regional variation.

Prediction of unresponsiveness to second intravenous immunoglobulin treatment in patients with Kawasaki disease refractory to initial treatment

“…IVIG was the second-line drug of choice in 64.5% of the patients unresponsive to initial IVIG treatment in a previous investigation of 5,633 patients in the United States10). A nationwide survey in Japan showed that second-line treatment with additional IVIG was performed in 44.1% of hospitals and that it was combined with other drugs in 26% of hospitals11).…”

“…Despite the significant level of unresponsiveness to first-line treatment in patients with KD, the best second-line treatment remains unknown. The administration of a second IVIG dose is currently the most common therapeutic strategy in unresponsive cases1011). Although the rate of unresponsiveness to second-line treatment with IVIG has been reported as 22%–49% 121314151617), no studies have reported on the prediction of unresponsiveness to second-line IVIG treatment.…”

Use of corticosteroids during acute phase of Kawasaki disease

“…The best second line therapeutic methods for patients unresponsive to initial IVIG treatment is still uncertain. In an investigation of 5633 patients with Kawasaki disease in the United States, methylprednisolone was used as the second line therapy in 196 patients (27.1%) among the 722 patients unresponsive to initial IVIG [20] . IVIG was the second line drug of choice in 466 patients (64.5%) in this investigation.…”

High‐dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease

“…In these patients with refractory KD, a second IVIG infusion is often administered, a cumulative dose of 4 g/kg. There is substantial practice variability in the treatment of refractory KD in the absence of clear consensus guidelines or definitive clinical trials . Recently Ebato and colleagues have proposed a strategy for the effective prevention of coronary artery aneurysm in refractory KD.…”

“…There is substantial practice variability in the treatment of refractory KD in the absence of clear consensus guidelines or definitive clinical trials. 4 Recently Ebato and colleagues 5 have proposed a strategy for the effective prevention of coronary artery aneurysm in refractory KD. This study utilized an algorithmic approach that included infliximab or plasma exchange for patients resistant to IVIG and pulse steroids.…”