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Cyclosporin A Treatment for Kawasaki Disease Refractory to Initial and Additional Intravenous Immunoglobulin

Suzuki, Hiroyuki MD, PhD*; Terai, Masaru MD, PhD; Hamada, Hiromichi MD, PhD; Honda, Takafumi MD; Suenaga, Tomohiro MD*; Takeuchi, Takashi MD*; Yoshikawa, Norishige MD, PhD*; Shibuta, Shoichi MD; Miyawaki, Masakazu MD, PhD; Oishi, Ko MD§; Yamaga, Hironobu MD; Aoyagi, Noriyuki MD; Iwahashi, Seiji MD**; Miyashita, Ritsuko MD††; Onouchi, Yoshihiro MD, PhD‡‡; Sasago, Kumiko PhD§§; Suzuki, Yoichi MD, PhD§§; Hata, Akira MD, PhD§§

The Pediatric Infectious Disease Journal: October 2011 - Volume 30 - Issue 10 - p 871-876
doi: 10.1097/INF.0b013e318220c3cf
Original Studies

Background: There are still no definite treatments for refractory Kawasaki disease (KD). In this pilot study, we evaluated the use of cyclosporin A (CyA) treatment in patients with refractory KD.

Methods: We prospectively collected clinical data of CyA treatment (4–8 mg/kg/d, oral administration) for refractory KD patients using the same protocol among several hospitals. Refractory KD is defined as the persistence or recurrence of fever (37.5°C or more of an axillary temperature) at the end of the second intravenous immunoglobulin (2 g/kg) following the initial one.

Results: Subjects were enrolled out of 329 KD patients who were admitted to our 8 hospitals between January 2008 and June 2010. Among a total of 28 patients of refractory KD treated with CyA, 18 (64.3%) responded promptly to be afebrile within 3 days and had decreased C-reactive protein levels, the other 4 became afebrile within 4 to 5 days. However, 6 patients (21.4%) failed to become afebrile within 5 days after the start of CyA and/or high fever returned after becoming afebrile within 5 days. Although hyperkalemia developed in 9 patients at 3 to 7 days after the start of CyA treatment, there were no serious adverse effects such as arrhythmias. Four patients (1.2%), 2 before and the other 2 after the start of CyA treatment, developed coronary arterial lesions.

Conclusion: CyA treatment is considered safe and well tolerated, and a promising option for patients with refractory KD. Further investigations will be needed to clarify optimal dose, safety, and timing of CyA treatment.

From the *Department of Pediatrics, Wakayama Medical University, Wakayama, Japan; †Department of Pediatrics, Tokyo Women's Medical University Yachio Medical Center, Yachio, Japan; ‡Department of Pediatrics, Social Insurance Kinan Hospital, Tanabe, Japan; §Department of Pediatrics, Hashimoto Municipal Hospital, Hashimoto, Japan; ¶Department of Pediatrics, Naga Hospital, Kinokawa, Japan; ∥Department of Pediatrics, Wakayama Rosai Hospital, Wakayama, Japan; **Department of Pediatrics, Hidaka General Hospital, Gobo, Japan; ††Department of Pediatrics, Izumiotsu Municipal Hospital, Izumiotsu, Japan; ‡‡Laboratory of Cardiovascular Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan; and §§Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.

Accepted for publication April 20, 2011.

Supported by the Ministry of Health, Labour and Welfare, Japan (2008–2010) through a Grant-in-Aid.

The authors do not have a commercial or other conflict of interest.

Address for correspondence: Hiroyuki Suzuki, MD, PhD, Department of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.