Ivig Resistent In Kawasaki Disease By Ho Chang Kuo (郭和昌)川崎症

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

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<ul><li> 1. Oct 15, 2008 Update of IVIG resistance in Kawasaki disease</li></ul> <p> 2. 9th IKDS, April 10-12, 2008 Taipei, Taiwan. 3. </p> <ul><li>Introduction</li></ul> <ul><li>Diagnosis</li></ul> <ul><li>Treatment</li></ul> <ul><li>Prognosis </li></ul> <ul><li><ul><li>CAL formation </li></ul></li></ul> <ul><li><ul><li>IVIG resistance</li></ul></li></ul> <ul><li><ul><li><ul><li>(non-responsiveness) </li></ul></li></ul></li></ul> <p>Content 4. (Kawasaki disease) </p> <ul><li> 1974 (Tomisaku Kawasaki) </li></ul> <p> 5. ( ) Kuo et al.Acta Pediatr Twiwan . 2006;47(suppl):7-17. 6. Kawasaki Disease- Involved small and medial size vesselCoronary artery aneurysm 7. </p> <ul><li>Japan: 120~150 / </li></ul> <ul><li>Korea:100-120 </li></ul> <ul><li>Taiwan: 66 </li></ul> <ul><li><ul><li>1976 </li></ul></li></ul> <ul><li>Hong Kong: 25 </li></ul> <ul><li>USA: 10 </li></ul> <ul><li>Australian: 4 </li></ul> <ul><li>European: 3 </li></ul> <ul><li>Male/female ratio: 1.4 </li></ul> <ul><li>85% &lt; 5y/o </li></ul> <ul><li>50% = 5 days </li></ul> <ul><li>&lt; 4 diagnostic criteria, with CAL </li></ul> <ul><li>About 15% </li></ul> <ul><li><ul><li>Nippon Rinsho.2008 ;66:321-5. </li></ul></li></ul> <ul><li> 6y/o </li></ul> <ul><li> 6m/o</li></ul> <ul><li><ul><li>(35% vs.12%, p=0.025) </li></ul></li></ul> <ul><li><ul><li><ul><li>Pediatr Infect Dis J2006; 25:241-4. </li></ul></li></ul></li></ul> <p>Incomplete or atypical KD 16. </p> <ul><li>ESR&gt;40 or CRP &gt;30 </li></ul> <ul><li> ( 3) : </li></ul> <ul><li> (&lt; 3) </li></ul> <ul><li> (WBC&gt;10/HPF) </li></ul> <ul><li> (&gt;15000) </li></ul> <ul><li>(anemia by age) </li></ul> <ul><li>(45 ,7 days) </li></ul> <p>Circulation2004;110;2747-2771. Incomplete or atypical KD 17. Delay diagnosis of KD Pediatrics2005;115;428-433. &gt;10 days High risk of CAL J Chin Med Assoc.2007;70:374-9.( , N=14/78) 18. Pediatrics2007;120;e1434-e1440. Delayed Diagnosis of Kawasaki Disease:What Are the Risk Factors? 19. Feb 2008, Seoul, Korea 20. History of IVIG in KD </p> <ul><li>1981: Imback: IVIG in ITP( Lancet ) </li></ul> <ul><li>1983: Furusho: IVIG in 40 Japanese patients with KD( Lancet ) </li></ul> <ul><li>1986: US Multicenter KD Study Group: 168 KD patients, 400mg/kg x 4 d reduces CAA from 20% to 3-5 % ( NEJM ) </li></ul> <ul><li>1991: US Multicenter KD Study Group: 549 US patients, single infusion of 2 g/kg superiors to400mg/kg x 4d in reducing fever and inflammatory markers( NEJM ) </li></ul> <p> 21. </p> <ul><li>High dose IVIG (2gm/kg) </li></ul> <ul><li>Aspirin(80-100 mg/kg) in acute stage </li></ul> <ul><li>Aspirin (3-5 mg/kg) after fever subside</li></ul> <ul><li><ul><li>Normal ESR, Plt and 2D echo</li></ul></li></ul> <ul><li>Aspirin:(should receive an annual influenza vaccine) </li></ul> <ul><li><ul><li> (80~100mg/kg/day) Nelson textbook </li></ul></li></ul> <ul><li><ul><li><ul><li>Circulation1993; 87:1776-80. </li></ul></li></ul></li></ul> <ul><li><ul><li> (30~50mg/kg/day) </li></ul></li></ul> <ul><li><ul><li><ul><li>Prog Clin Biol Res1987; 250:401-13. </li></ul></li></ul></li></ul> <ul><li><ul><li>Hsieh KS et al. 1993~2003 162 KD </li></ul></li></ul> <ul><li><ul><li><ul><li>Pediatrics2004; 114;689-93.</li></ul></li></ul></li></ul> <p>Treatment Q2: standard Tx for KD 22. </p> <ul><li>Day 4 </li></ul> <ul><li><ul><li>Early IVIG treatment for KD: the nationwide surveys in Japan.</li></ul></li></ul> <ul><li><ul><li><ul><li>J Pediatr2005;146:149-50. </li></ul></li></ul></li></ul> <ul><li>Day 5 </li></ul> <ul><li><ul><li>15,940 KD patients in Japan </li></ul></li></ul> <ul><li><ul><li><ul><li>Pediatr Infect Dis J.2008;27:155-160. </li></ul></li></ul></li></ul> <p>Treatment-IVIG timing 23. Infection vs. KD Pediatrics2005;116;e760-e766. Diagnosis of KD start IVIG Tx stop antibiotics ? 24. </p> <ul><li> 7.8%~38% </li></ul> <ul><li><ul><li>Pediatr Cardiol.2003; Pediatr Infect Dis J.1998 </li></ul></li></ul> <ul><li><ul><li>Pediatr . 2008 Jul;153(1):117-21. </li></ul></li></ul> <ul><li>Our hospital: 10.8% (30/278) </li></ul> <ul><li>3-4% non-response to 2nd dose IVIG </li></ul> <ul><li><ul><li>4/278 (1.4 % in our hospital) </li></ul></li></ul> <ul><li>20% in Japan </li></ul> <ul><li><ul><li>Nippon Rinsho . 2008;66:332-7. </li></ul></li></ul> <ul><li>Recurrent KD: 6.89 per 1000/years </li></ul> <ul><li><ul><li>Acta Paediatr.2001;90:40-4 . </li></ul></li></ul> <ul><li>2/278 (0.72% in our hospital)</li></ul> <p>Initial IVIG treatment failure 25. Sep 2008, KL, Malaysia 26. 30/278, 10.8% IVIG responsive and resistant KD patientsfrom 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 patientsin 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) 166:131137 Risk factors to predict IVIG resistance in KD 30. Sep 2008, Xiamen, China 31. Taiwan 1996-2002 Pediatrics. 2004 Dec;114(6):e678-82. </p> <ul><li>Recurrence: 1.3%(94/7305) of these children </li></ul> <ul><li><ul><li>The median (range) of the interval between the first attack of KD and the second attack was 145 (9-1891) days.</li></ul></li></ul> <ul><li><ul><li>85% (80/94) of the second attack occurred within 2 years following the first episode</li></ul></li></ul> <ul><li>coronary artery aneurysm in 7.3%(536/7305)</li></ul> <p> 32. Kawasaki Disease in a Pediatric Intensive Care Unit: A Case-Control Study Pediatricspublished online Sep 22, 2008; 33. J Pediatr 2008;153:365-8. Risk Factors for Nonresponse to Therapyin Kawasaki Disease 34. </p> <ul><li>Methylpredinsolone pulse </li></ul> <ul><li>Cyclosporin </li></ul> <ul><li>Cyclophosphamide </li></ul> <ul><li>Methotrexate </li></ul> <ul><li><ul><li>Scand J Rheumatol 2005;34:136-9. </li></ul></li></ul> <ul><li>Plasma exchange </li></ul> <ul><li><ul><li>Eur J Pediatr.2004;163:263264. </li></ul></li></ul> <ul><li>Pentoxifylline (inhibit TNF mRNA) </li></ul> <ul><li><ul><li>Eur J Pediatr.1994;153:663667. </li></ul></li></ul> <ul><li>Abciximab </li></ul> <ul><li>Enbrel</li></ul> <ul><li>Ulinastatin </li></ul> <ul><li><ul><li>trypsin inhibitor </li></ul></li></ul> <p>Other Treatment 35. N Engl J Med2007;356:663-75. MP pulse in KD 36. MP pulse in KDWang CL et al. J Microbiol Immunol Infect. 2005. J Pediatr2003;143:363-7 37. Sep 2008, Xiamen, China 38. May 2008, Honolulu, Hawaii 39. Kuo and Yang et al.Pediatr Allergy Immunol2007;18:354359. Univariate and multivariate analysis of KD patients between IVIG responsive and IVIG-resistant groups 40. Kuo and Yang et al.Pediatr Allergy Immunol2007;18:354359. 41. In press:Pediatr Allergy Immunol 2008 42. Eosinophil increase in acute KD and inverse correlation with IVIG resistantKuo and Yang et al.Pediatr Allergy Immunol2007;18:354359. 43. In press:Pediatr Allergy Immunol 2008 44. Prognosis - role of eosinophil Kuo et al.Pediatr Allergy Immunol2007 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. 46. </p> <ul><li>Male gender </li></ul> <ul><li>Recurrent KD </li></ul> <ul><li>IVIG before day 4 </li></ul> <ul><li>IVIG after day 10 </li></ul> <ul><li>IVIG dose</li></ul>