No abstract

The efficacy and safety, including arrhythmia and sudden death, 1 2 of intravenous methylprednisolone pulse (IVMP) therapy in patients with Kawasaki disease (KD) are uncertain. We conducted a control study in KD patients with persistent or recurrent fever (>37.5˚C) 48 hours after a single infusion of initial intravenous immunoglobulin (IVIG) 2 g/kg. At enrolment (day 1), the subjects were randomised to receive IVMP (30 mg/kg/day of methylprednisolone for three days), or additional IVIG (2 g/kg). Heparin was also continuously infused (15-20 units/kg/h) in the IVMP group. The study was halted prematurely because of adverse effects of IVMP when 22 patients were recruited; they accounted for 13% of KD patients treated with initial IVIG. The antipyretic effect of IVMP was superior to that of additional IVIG on day 2 (p = 0.02, repeated measures analysis), but not on day 3 and later (fig 1). The fraction of febrile patients was significantly lower in the IVMP group until day 3 (1/11 v 8/11, p , 0.001, Fisher exact test), but not on day 4 and later (6/11 v 6/11). Coronary artery dimensions and the prevalence of coronary artery lesions (2/11 v 3/11) were similar in the two groups. Regarding adverse effects, sinus bradycardia and hyperglycaemia occurred more often in the IVMP group (table 1). Hypertension occurred in 91% of the IVMP group, but the fraction did not differ significantly, probably due to the small sample size. All of the adverse effects were transient. There were no convulsions, gastrointestinal symptoms, infection, malignant arrhythmia, or sudden death in any subjects. KD patients refractory to initial IVIG should be treated with additional IVIG, 3 4 because IVMP induced faster but temporary resolution of fever and more adverse effects. Further investigations with steroid therapy are necessary to determine the indication and the appropriate dose in KD.

This study aimed to determine the effects of intravenous methylprednisolone pulse (IVMP) therapy on cytokine levels in patients with acute Kawasaki disease (KD) unresponsive to initial intravenous immunoglobulin (IVIG) therapy. Fifteen KD patients unresponsive to initial IVIG, 2 g/kg/day, were randomized to receive IVMP (n = 7), 30 mg/kg/day for 3 days or additional IVIG (n = 8), 2 g/kg/day, and plasma cytokine levels were compared. The fraction of febrile patients was significantly lower in the IVMP group than in the additional IVIG group on day 2 (0/7 vs. 3/8, p = 0.03), but not on day 4 and later (3/7 vs. 4/8, p = 1.00) because of recurrent fever. The prevalence of coronary lesions was similar between the two groups (2/7 vs. 2/8, p = 1.00). The ratios of plasma levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 to those at enrollment (defined as day 1) were significantly lower in the IVMP group on day 4 (0.50 +/- 0.27 vs. 1.01 +/- 0.46, 0.53 +/- 0.39 vs. 0.93 +/- 0.44, p = 0.02 and 0.045, respectively), but not on day 7 (0.54 +/- 0.34 vs. 0.88 +/- 0.39, 0.76 +/- 0.39 vs. 0.61 +/- 0.17, p = 0.07 and 0.83, respectively). The ratios of interleukin-2 receptor, interleukin-6, and vascular endothelial cell growth factor to those at enrollment did not differ significantly between the two groups. In conclusion, for KD patients unresponsive to initial IVIG, IVMP suppresses cytokine levels faster, but subsequently similarly, compared with additional IVIG.

In KD patients unresponsive to additional IVIG, IVMP promptly induced defervescence, and subsequent oral prednisolone suppressed recurrence of fever. IVMP followed by prednisolone therapy may prevent CAL, without severe adverse effects.