Korean Circ J.  2014 Sep;44(5):328-335. 10.4070/kcj.2014.44.5.328.

Clinically Useful Predictors of Resistance to Intravenous Immunoglobulin and Prognosis of Coronary Artery Lesions in Patients with Incomplete Kawasaki Disease

• Cho KH
• Kang SJ

• KMID: 2223872
• DOI: http://doi.org/10.4070/kcj.2014.44.5.328

Abstract

BACKGROUND AND OBJECTIVES
The prevalence of incomplete Kawasaki disease (iKD) is progressively increasing. We aimed to retrospectively investigate the predictors of intravenous immunoglobulin (IVIG) resistance in iKD patients and compare them with those of IVIG resistance in complete Kawasaki disease (cKD) patients. We also compared the prognosis of coronary artery lesions (CALs) between the IVIG non-responders and responders in both iKD and cKD groups.
SUBJECTS AND METHODS
A total of 234 cKD and 77 iKD patients were treated with IVIG between February 2009 and April 2012. Among these 311 patients, we reviewed the data of 77 iKD patients and 75 age-matched cKD patients.
RESULTS
Patients with iKD having an elevated neutrophil count {percentage of segmented neutrophils (SEG%) > or =79.0} were at risk of IVIG resistance, while patients with cKD having SEG% > or =79.25 and serum total bilirubin (TB) > or =0.56 mg/dL were at risk of IVIG resistance as shown by multivariable logistic regression analysis. Fractional changes of laboratory data before and after IVIG treatment showed that Creactive protein (CRP) and N-terminal B type natriuretic peptide (NT-proBNP) levels were significantly elevated in IVIG non-responders of the iKD group, whereas erythrocyte sedimentation rate was significantly elevated in IVIG non-responders of the cKD group. Among the patients who had CALs at 10 months after the start of illness, the z scores of coronary arteries were higher in IVIG non-responders of the iKD group, when compared with IVIG non-responders of the cKD group.
CONCLUSION
Elevated SEG%, changes in CRP and NT-proBNP levels may help in early detection of IVIG resistance in patients of the iKD group, which may aid in predicting the prognosis of CALs in these patients. Further studies with a larger number of patients are warranted.

Keyword

Kawasaki disease; Immunoglobulins; Coronary arteries

MeSH Terms

Bilirubin
Blood Sedimentation
Coronary Vessels*
Humans
Immunoglobulins*
Immunoglobulins, Intravenous
Logistic Models
Mucocutaneous Lymph Node Syndrome*
Neutrophils
Prevalence
Prognosis*
Retrospective Studies
Bilirubin
Immunoglobulins
Immunoglobulins, Intravenous

Reference

1. 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. Circulation. 2004; 110:2747–2771.

2. Ghelani SJ, Sable C, Wiedermann BL, Spurney CF. Increased incidence of incomplete Kawasaki disease at a pediatric hospital after publication of the 2004 American Heart Association guidelines. Pediatr Cardiol. 2012; 33:1097–1103.

3. Sonobe T, Kiyosawa N, Tsuchiya K, et al. Prevalence of coronary artery abnormality in incomplete Kawasaki disease. Pediatr Int. 2007; 49:421–426.

4. Witt MT, Minich LL, Bohnsack JF, Young PC. Kawasaki disease: more patients are being diagnosed who do not meet American Heart Association criteria. Pediatrics. 1999; 104:e10.

5. Manlhiot C, Christie E, McCrindle BW, Rosenberg H, Chahal N, Yeung RS. Complete and incomplete Kawasaki disease: two sides of the same coin. Eur J Pediatr. 2012; 171:657–662.

6. Sudo D, Monobe Y, Yashiro M, et al. Coronary artery lesions of incomplete Kawasaki disease: a nationwide survey in Japan. Eur J Pediatr. 2012; 171:651–656.

7. Durongpisitkul K, Soongswang J, Laohaprasitiporn D, Nana A, Prachuabmoh C, Kangkagate C. Immunoglobulin failure and retreatment in Kawasaki disease. Pediatr Cardiol. 2003; 24:145–148.

8. Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008; 153:117–121.

9. Honkanen VE, McCrindle BW, Laxer RM, Feldman BM, Schneider R, Silverman ED. Clinical relevance of the risk factors for coronary artery inflammation in Kawasaki disease. Pediatr Cardiol. 2003; 24:122–126.

10. 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.

11. Sano T, Kurotobi S, Matsuzaki K, et al. Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr. 2007; 166:131–137.

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

13. McCrindle BW, Li JS, Minich LL, et al. Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements. Circulation. 2007; 116:174–179.

14. Mori M, Imagawa T, Yasui K, Kanaya A, Yokota S. Predictors of coronary artery lesions after intravenous gamma-globulin treatment in Kawasaki disease. J Pediatr. 2000; 137:177–180.

15. Fukunishi M, Kikkawa M, Hamana K, et al. Prediction of non-responsiveness to intravenous high-dose gamma-globulin therapy in patients with Kawasaki disease at onset. J Pediatr. 2000; 137:172–176.

16. Yeo Y, Kim T, Ha K, et al. Incomplete Kawasaki disease in patients younger than 1 year of age: a possible inherent risk factor. Eur J Pediatr. 2009; 168:157–162.

17. Giannouli G, Tzoumaka-Bakoula C, Kopsidas I, Papadogeorgou P, Chrousos GP, Michos A. Epidemiology and risk factors for coronary artery abnormalities in children with complete and incomplete Kawasaki disease during a 10-year period. Pediatr Cardiol. 2013; 34:1476–1481.

18. Kim HK, Oh J, Hong YM, Sohn S. Parameters to guide retreatment after initial intravenous immunoglobulin therapy in kawasaki disease. Korean Circ J. 2011; 41:379–384.

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

20. McNeal-Davidson A, Fournier A, Spigelblatt L, et al. Value of aminoterminal pro B-natriuretic peptide in diagnosing Kawasaki disease. Pediatr Int. 2012; 54:627–633.

21. Seki S, Habu Y, Kawamura T, et al. The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK)cells and NK1.1 Ag+ T cells in T helper 1 immune responses. Immunol Rev. 2000; 174:35–46.

22. Ha KS, Jang G, Lee J, et al. Incomplete clinical manifestation as a risk factor for coronary artery abnormalities in Kawasaki disease: a metaanalysis. Eur J Pediatr. 2013; 172:343–349.

23. Millar K, Manlhiot C, Yeung RS, Somji Z, McCrindle BW. Corticosteroid administration for patients with coronary artery aneurysms after Kawasaki disease may be associated with impaired regression. Int J Cardiol. 2012; 154:9–13.