Korean Circ J.  2010 May;40(5):239-242. 10.4070/kcj.2010.40.5.239.

Predicting Factors for Refractory Kawasaki Disease

• Do YS
• Kim KW
• Chun JK
• Cha BH
• Namgoong M
• Lee HY

• KMID: 1456369
• DOI: http://doi.org/10.4070/kcj.2010.40.5.239

Abstract

BACKGROUND AND OBJECTIVES
About 10-15% of Kawasaki disease (KD) is refractory to intravenous immunoglobulin (IVIG) therapy. This study was designed to investigate the predicting factors for refractory KD.
SUBJECTS AND METHODS
We reviewed retrospectively the clinical records of 77 patients with typical KD admitted at Wonju Christian Hospital from January, 2005, to December, 2008. The variance of laboratory and demographic parameters between the IVIG-responsive group and IVIG-resistant group were analyzed. Thirteen patients with urinary tract infections were randomly collected as a febrile control group.
RESULTS
Among 77 patients diagnosed with complete KD, 13 patients (16.9%) were IVIG-resistant. The febrile period and hospital days were significantly longer in the IVIG-resistant group than IVIG-responsive group (p<0.001, p=0.002). Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group (p=0.025). The Kobayashi score could differentiate these two groups (p=0.015). Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group (p=0.032). Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients (p=0.038).
CONCLUSION
The percentage of neutrophils and lymphocytes in patients with KD, in addition to known risk factors for refractory KD, may help predict IVIG-resistance in patients with KD.

Keyword

Mucocutaneous Lymph Node Syndrome; Risk factors; Coronary arteries

MeSH Terms

Coronary Vessels
Dilatation
Humans
Immunoglobulins
Lymphocytes
Mucocutaneous Lymph Node Syndrome
Neutrophils
Retrospective Studies
Risk Factors
Sodium
Urinary Tract Infections
Immunoglobulins
Sodium

Reference

1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi. 1967; 16:178–222. PMID: 6062087.

2. Nakamura Y, Yashiro M, Uehara R, Oki I, Kayaba K, Yanagawa H. Increasing incidence of Kawasaki disease in Japan: nationwide survey. Pediatr Int. 2008; 50:287–290. PMID: 18533938.

3. Burns JC, Glode MP. Kawasaki syndrome. Lancet. 2004; 364:533–544. PMID: 15302199.

4. Moon SY, Kim NS, Lee HB, Lee H. Comparative study about the therapeutic effect between single and five-day administration of gammaglobulin in Kawasaki disease. Korean Circ J. 1994; 24:77–85.

5. Freeman AF, Shulman ST. Refractory Kawasaki disease. Pediatr Infect Dis J. 2004; 23:463–464. PMID: 15131473.

6. Dominguez SR, Friedman K, Seewald R, Anderson MS, Willis L, Glode MP. Kawasaki disease in a pediatric intensive care unit: a case-control study. Pediatrics. 2008; 122:e786–e790. PMID: 18809597.

7. Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006; 113:2606–2612. PMID: 16735679.

8. Ashouri N, Takahashi M, Dorey F, Mason W. Risk factors for nonresponse to therapy in Kawasaki disease. J Pediatr. 2008; 153:365–368. PMID: 18534243.

9. Uehara R, Belay ED, Maddox RA, et al. Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J. 2008; 27:155–160. PMID: 18174868.

10. Harada T, Ito S, Shiga K, et al. A report of two cases of Kawasaki disease treated with plasma exchange. Ther Apher Dial. 2008; 12:176–179. PMID: 18387169.

11. Popper SJ, Shimizu C, Shike H, et al. Gene-expression patterns reveal underlying biological processes in Kawasaki disease. Genome Biol. 2007; 8:R261. PMID: 18067656.

12. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int. 2005; 47:232–234. PMID: 15771703.

13. Cha S, Yoon M, Ahn Y, Han M, Yoon KL. Risk factors for failure of initial intravenous immunoglobulin treatment in Kawasaki disease. J Korean Med Sci. 2008; 23:718–722. PMID: 18756064.

14. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004; 114:1708–1733. PMID: 15574639.

15. Ahn SY, Kim DS. Treatment of intravenous immunoglobulin-resistant Kawasaki disease with methotrexate. Scand J Rheumatol. 2005; 34:136–139. PMID: 16095010.

16. Yun SW. Diagnostic value of serum cardiac troponin T, troponin I and CK-MB in acute Kawasaki disease. Korean Circ J. 2004; 34:582–592.

17. Hamamichi Y, Ichida F, Yu X, et al. Neutrophils and mononuclear cells express vascular endothelial growth factor in acute Kawasaki disease: its possible role in progression of coronary artery lesions. Pediatr Res. 2001; 49:74–80. PMID: 11134495.

18. Inoue Y, Kato M, Kobayashi T, Shinohara M, Sone K, Morikawa A. Increased circulating granulocyte colony-stimulating factor in acute Kawasaki disease. Pediatr Int. 1999; 41:330–333. PMID: 10365591.

19. Tsujimoto H, Takeshita S, Nakatani K, Kawamura Y, Tokutomi T, Sekine I. Intravenous immunoglobulin therapy induces neutrophil apoptosis in Kawasaki disease. Clin Immunol. 2002; 103:161–168. PMID: 12027421.

20. Yi QJ, Li CR, Yang XQ. Effect of intravenous immunoglobulin on inhibiting peripheral blood lymphocyte apoptosis in acute Kawasaki disease. Acta Paediatr. 2001; 90:623–627. PMID: 11440093.

21. Koga M, Hasegawa S, Furukawa S. No increase in soluble Fas and Fas ligand in Kawasaki disease: comment on the article by Nozawa et al. Arthritis Rheum. 1998; 41:568–570. PMID: 9506592.

22. Sundel RP, Baker AL, Fulton DR, Newburger JW. Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. J Pediatr. 2003; 142:611–616. PMID: 12838187.

23. Chun JK, Kang DW, Yoo BW, Shin JS, Kim DS. Programmed death-1 (PD-1) gene polymorphisms lodged in the genetic predispositions of Kawasaki Disease. Eur J Pediatr. 2010; 169:181–185. PMID: 19468750.

24. Matsubara T, Ichiyama T, Furukawa S. Immunological profile of peripheral blood lymphocytes and monocytes/macrophages in Kawasaki disease. Clin Exp Immunol. 2005; 141:381–387. PMID: 16045726.

25. Lang BA, Yeung RS, Oen KG, et al. Corticosteroid treatment of refractory Kawasaki disease. J Rheumatol. 2006; 33:803–809. PMID: 16583481.

26. Oishi T, Fujieda M, Shiraishi T, et al. Infliximab treatment for refractory Kawasaki disease with coronary artery aneurysm. Circ J. 2008; 72:850–852. PMID: 18441471.

27. Kim NY, Choi DY, Jung MJ, Jeon IS. A case of refractory Kawasaki disease complicated by peripheral ischemia. Pediatr Cardiol. 2008; 29:1110–1114. PMID: 18481137.

28. Lee SY, Gwon HC, Park SW, et al. Acute myocardial infarction in young patient probably due to Kawasaki disease. Korean Circ J. 2001; 31:119–124.

29. Egami K, Muta H, Ishii M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006; 149:237–240. PMID: 16887442.

30. Dalla Pozza R, Bechtold S, Urschel S, Kozlik-Feldmann R, Netz H. Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease. J Pediatr. 2007; 151:239–243. PMID: 17719930.