Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy

Kawasaki disease (KD), the most common cause of acquired heart disease in children in developed nations, is an acute systemic vasculitis of childhood, primarily affecting the coronary arteries. Approximately 10% to 20% of patients do not become afebrile after standard therapy with intravenous immunoglobulin (IVIG) and oral acetylsalicylic acid, and are at an increased risk for the development of coronary artery lesions (CAL) (1–6). Such patients generally receive additional treatment with IVIG (1–5), which may prevent CAL if administered promptly (6); however, not all patients respond. Other treatment options, including corticosteroids, cyclosporine, plasma exchange and infliximab, have been reported to be effective in some cases (1–5,7). Although corticosteroids are widely used, the indications and dosage for patients with KD remain controversial. Some physicians avoid corticosteroids because of the potential risk of exacerbating CAL, but no study, including the classical work by Kato et al (8), has demonstrated a significant relationship between the use of corticosteroids and CAL. Intravenous methylprednisolone pulse (IVMP) therapy rapidly resolves fever associated with refractory KD and is, thus, expected to prevent CAL. In small, open-label, randomized controlled studies performed by us (9) and Hashino et al (10), the prevalence of CAL was similar in patients with KD unresponsive to initial IVIG therapy who received IVMP and patients who received additional IVIG. In our study, IVMP induced faster resolution of fever, but caused more adverse effects, such as bradycardia, than did additional IVIG; however, the total antipyretic potency of these treatments was similar because fever recurred after the completion of IVMP therapy (9). In a double-blind, randomized controlled study, Newburger et al (11) reported that the addition of a single dose of IVMP to initial IVIG did not reduce the prevalence of CAL or the total length of the hospital stay; nonetheless, the initial period of hospitalization was shorter for all patients with KD who received IVMP, and the prevalence of CAL was significantly lower in patients unresponsive to IVIG who received IVMP, compared with patients who received placebo. These findings may reflect the prompt and short antipyretic activity of IVMP, and suggest that IVMP may prevent CAL in patients with severe KD. During the past five years, we treated KD patients who were unresponsive to additional IVIG with IVMP followed by oral prednisolone to prevent recurrent fever. We now report the extremely low prevalence of CAL among the approximately 400 patients with KD managed using this treatment regimen.