Predict of coronary artery lesions (CAL) in Kawasaki disease (KD)

1. Heidelberg, Germany Predict CAL formation in Kawasaki disease 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 June 30, 2010

3. 9th IKDS, April 10-12, 2008 Taipei, Taiwan.

5. 『 虛空有盡，我願無窮 ，我今生做不完的事，願在未來的無量生中繼續推動， 我個人無法完成的事，勸請大家共同推動 』 -- 聖嚴法師 做儍事！

9. 臨床表現特點 ( 診斷要件 ) Q1: Diagnostic criteria Kuo et al. Acta Pediatr Twiwan . 2006;47(suppl):7-17.

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

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

13. Pediatrics International (2008) 50 , 287–290. Age distribution of KD in Japan and CGMH-KS CGMH-KS (1999-2007) N=278 90% <5y/o 56% <1 y/o

14. CAL formation rate in CGMH-KS Liang and Kuo et al. Am Heart J 2009;157:584-8. (SCI IF:4.285) 88/325=27.1% 36/325=11.1%

15. CAL formation in other countries Pediatrics. 2009 Mar;123(3):e401-5.

16. Circulation 2008;118;e110-e112

17. 南靖土樓

19. 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). Kuo et al. BMJ Case Reports 2009 [doi:10.1136/bcr.11.2008.1227]

22. 排除其他類似之臨床疾患 In press “ 護理雜誌 ”

23. 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) 醫師心中要有川崎病，才能確診

24. 廈門環島路夜景 Treatment

27. High dose aspirin in KD 2010 6 th ASPR, Taipei.

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

33. 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%

34. In press “ Acta Paediatrica ” (SCI IF: 1.768)

35. Serum Albumin Level Predicts Initial IVIG Treatment Failure in KD In press “ Acta Paediatrica ” (SCI IF: 1.768)

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

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

39. Poor response to repeat IVIG dosage and response to MP pulse Kuo et al. BMJ Case Reports 2009 [doi:10.1136/bcr.11.2008.1227] IVIG IVIG MP

40. Prognosis- CAL formation in our study Pediatr Allergy Immunol 2009: 20: 266–272.

41. Pediatr Allergy Immunol 2009: 20: 266–272.

42. Pediatr Allergy Immunol 2009: 20: 266–272.

43. Pediatr Allergy Immunol 2009: 20: 266–272.

44. Genetic study in CAL formation of KD

45. CTLA4 +49/-318 showed no association with susceptibility

49. High-Throughput Customized SNP Profiling DNA extraction by kit (1~2 mg DNA) DNA of cord (3~5 ml cord blood ) Hybridization by Illumina array chip (250 ng DNA) DNA QC by PicoGreen (Invitrogen) Analysis (BeadStudio) Combination and calculation (UVA, MVA, MDR) Illumina array chip

54. P = 9.71*10 -7 PDE2A interact with CYFIP2 in the susceptibility of KD

55. High risk group had lower TGFβ in KD patients P = 0.007 No significant difference in other cytokines studied: IFNγ, IL-2, IL-4, IL-5, IL-6 and IL-10 Plasma TGF-beta1 levels (pg/ml) Low risk group High risk group N=32 N=88 Mann-Whitney U test

56. High risk group didn’t have correlation with CAL and IVIG resistance P=0.42 P=0.86 CAL IVIG resistance

59. LOC100133214 (HCG-8) - similar to PAMP6501 HCG8 : HLA complex group 8

61. P = 3.36*10 -6 IL2RA interact with LOC100133214 in CAL formation of KD

62. KD patients carry high risk group genotypes had higher inflammatory cytokines IL-2, P = 0.008 IFNγ, P = 0.03 IL-6, P = 0.01 Low risk group High risk group Low risk group High risk group Low risk group High risk group Plasma IL-2 levels (pg/ml) Plasma IFNγ levels (pg/ml) Plasma IL-6 levels (pg/ml) N=120, 38 in high risk group 82 in low risk group Mann-Whitney U test

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

69. 我們在川崎症的研究報告