Yonsei Med J.  2008 Oct;49(5):714-718. 10.3349/ymj.2008.49.5.714.

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

• Lee TJ
• Kim KH
• Chun JK
• Kim DS

• KMID: 2158188
• DOI: http://doi.org/10.3349/ymj.2008.49.5.714

Abstract

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 (38.6degrees C vs. 37.0degrees 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.

Keyword

Kawasaki disease; methotrexate; resistance to immunoglobulin

MeSH Terms

Child
Child, Preschool
Drug Resistance
Female
Humans
Immunoglobulins, Intravenous/*therapeutic use
Infant
Male
Methotrexate/administration & dosage/*therapeutic use
Mucocutaneous Lymph Node Syndrome/*drug therapy
Treatment Outcome

Figure

• 

  Fig. 1 Changes in the maximum body temperature attained each day after treatment with MTX. The starting day of MTX was defined as day 1. The upper and lower ends of each box indicate the first and third quartiles, and the line inside the box represents the median value. The upper fence of a whisker corresponds with the largest value within 1.5 times the interquartile range above the third quartile and the lower fence of a whisker is the smallest value within 1.5 times the interquartile below the first quartile. Values beyond the fences are marked with circles. MTX, methotrexate. *p < 0.001.

• 

  Fig. 2 Changes in the serum level of CRP after treatment with MTX. Compared with the pretreatment phase, the reduction in serum levels of CRP on day 7 was significantly greater with MTX administration (p < 0.001). The upper and lower ends of a box show the first and third quartiles, and the line inside the box the median value. The upper fence of a whisker represents the largest value within 1.5 times the interquartile range above the third quartile and the lower fence of a whisker the smallest value within 1.5 times the interquartile below the first quartile. Values beyond the fences are marked with circles. CRP, C-reactive protein; MTX, methotrexate.

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