Low-dose Methotrexate Therapy for Intravenous Immunoglobulin-resistant Kawasaki Disease

PURPOSE The aim of this study was to evaluate the efficacy of low-dose oral methotrexate (MTX) as a treatment for patients with Kawasaki disease (KD) which was resistant to intravenous immunoglobulin (IVIG). PATIENTS AND METHODS The patients who had persistent or recrudescent fever after treatment with IVIG were subsequently treated with low-dose oral MTX [10mg/body surface area (BSA)] once weekly. RESULTS Seventeen patients developed persistent or recrudescent fever after treatment of KD with IVIG and were consequently given MTX. The proportion of children with coronary artery lesions (CALs) was 76%. The median value of maximum body temperatures decreased significantly within 24 hours of MTX therapy (38.6 degrees C vs. 37.0 degrees C, p < 0.001). The median CRP (C-reactive protein) level was found to be significantly lower 1 week after administering the first dose of MTX (8.9mg/dL vs. 1.2mg/dL, p < 0.001). The median duration of fever before MTX treatment was shorter in CALs (-) group than in CALs (+) group (7 days vs. 10 days, p = 0.023). No adverse effects of MTX were observed. CONCLUSION MTX treatment for IVIG-resistant KD resulted in quick resolution of fever and rapid improvement of inflammation markers without causing any adverse effects. MTX therapy should further be assessed in a multicenter, placebo-blinded trial to evaluate whether it also improves coronary artery outcome.