The resistance of IVIG treatment in Kawasaki disease, an review of literature by Dr. Ho-Chang Kuo from Taiwan.

1. 郭和昌 醫師 高雄長庚醫院 兒童過敏免疫風濕科 長庚大學臨研所 Oct 15, 2008 Update of IVIG resistance in Kawasaki disease

2. 9th IKDS, April 10-12, 2008 Taipei, Taiwan.

5. 臨床表現特點 ( 診斷要件 ) Kuo et al. Acta Pediatr Twiwan . 2006;47(suppl):7-17.

6. Kawasaki Disease- 後天性心臟病之主因 Involved small and medial size vessel Coronary artery aneurysm

8. Pediatrics International (2008) 50 , 287–290. Increased incidence in the past 10 years in Japan

9. Pediatrics International (2008) 50 , 287–290. Age distribution of KD in Japan and CGMH-KS CGMH-KS (1999-2007)

10. Pediatrics International (2008) 50 , 287–290. CAL formation in KD in Japan 2003-2004

12. Non-Langerhans cell histiocytosis in KD Figure 3:The dermis reveals infiltration of histiocytes and multinucleate giant cells mixed with some lymphocytes (hematoxylin and eosin stain, 100X). Touton giant cells are also present (upper right corner, 400X). Figure 4: On immunohistochemical study, the histiocytes are diffuse positive for CD68 (A), but negative for S100 (B) and CD1a (C).

13. Poor response to repeat IVIG dosage and response to MP pulse Non-LCH in KD IVIG IVIG MP

14. Oct 2007, Tokyo, Japan.

17. Delay diagnosis of KD Pediatrics 2005;115;428-433. >10 days High risk of CAL J Chin Med Assoc. 2007;70:374-9. ( 北榮 , N=14/78)

18. Pediatrics 2007;120;e1434-e1440. Delayed Diagnosis of Kawasaki Disease: What Are the Risk Factors?

19. Feb 2008, Seoul, Korea

23. Infection vs. KD Pediatrics 2005;116;e760-e766. Diagnosis of KD  start IVIG Tx  stop antibiotics ?

25. Sep 2008, KL, Malaysia

26. 30/278, 10.8% IVIG responsive and resistant KD patients from 1999-2007 in CGMH-KS 17.3% 7.3% 7.8% 17.5% 15% 9.1% 13.6% 6.9% 5.12%

27. J Pediatr 2008;153:117-21. IVIG responsive and resistant KD patients in San Diego County (1998-2006)

28. J Pediatr 2008;153:117-21 Comparison between IVIG responsive and resistant KD patients

29. Eur J Pediatr (2007) 166:131–137 Risk factors to predict IVIG resistance in KD

30. Sep 2008, Xiamen, China

32. Kawasaki Disease in a Pediatric Intensive Care Unit: A Case-Control Study Pediatrics published online Sep 22, 2008;

33. J Pediatr 2008;153:365-8. Risk Factors for Nonresponse to Therapy in Kawasaki Disease

35. N Engl J Med 2007;356:663-75. MP pulse in KD

36. MP pulse in KD Wang CL et al. J Microbiol Immunol Infect. 2005. J Pediatr 2003;143:363-7

37. Sep 2008, Xiamen, China

38. May 2008, Honolulu, Hawaii

39. Kuo and Yang et al. Pediatr Allergy Immunol 2007;18:354–359. Univariate and multivariate analysis of KD patients between IVIG responsive and IVIG-resistant groups

40. Kuo and Yang et al. Pediatr Allergy Immunol 2007;18:354–359.

41. In press: Pediatr Allergy Immunol 2008

42. Eosinophil increase in acute KD and inverse correlation with IVIG resistant Kuo and Yang et al. Pediatr Allergy Immunol 2007;18:354–359.

43. In press: Pediatr Allergy Immunol 2008

44. Prognosis - role of eosinophil Kuo et al. Pediatr Allergy Immunol 2007 In press: Pediatr Allergy Immunol 2008

45. May different brands of IVIG affect the eosinophil counts in KD ? Kuo et al. Pediatr Allergy Immunol 2008;19:184-5.

47. Immune Activation Genetic Susceptibility Vasculitis Coronary artery lesions (CD40L, Skewed Th1/Th2) ( CTLA4 polymorphism ) ( NO vs NOS ) Infections, Super-Ag Kawasaki Disease vs. IVIG

48. Gender limited cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphism with intravenous Immunoglobulin resistant in Kawasaki Disease 2008 FIMSA

49. CTLA4 +49 A allele was significantly associated with the IVIG resistance in females, but not males 2008 FIMSA P=0.01 P=0.7

50. 2008 FIMSA

51. Thanks a lot for your attention and comment !!!

53. Eosinophil increase in acute KD and inverse correlation with IVIG resistant Kuo and Yang et al. Pediatr Allergy Immunol 2007;18:354–359.

54. Levels of eosinophil-related Th2 cytokines and ECP were higher in KD Control: upper respiratory track infection, student t test. <0.001 2.98±0.23 10.9±1.71 ECP (pg/ml) <0.001 2.65±0.55 5.17±0.56 IL-5 (pg/ml) 0.004 74.52±7.45 116.7±12.5 Eotaxin (pg/ml) <0.001 5.96±0.54 12.07±1.36 IL-4 (pg/ml) P value Control (N=30) KD (N=95)

55. Changes of eosinophil-related Th2 cytokine and ECP after IVIG treatment

56. Changes of eosinophils positively correlated with IL-5 but not ECP Eosinophil vs. IL-5 Eosinophil vs. ECP

57. Mann-Whitney U test Eosinophils and IL-5 after IVIG treatment were significantly higher in KD without CAL

60. CAL- timing Arch Pediatr Adolesc Med. 2006;160:686-90.

63. Pediatr Res 2008;63: 207–210.