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.

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

  • 1. Oct 15, 2008 Update of IVIG resistance in Kawasaki disease

2. 9th IKDS, April 10-12, 2008 Taipei, Taiwan. 3.

  • Introduction
  • Diagnosis
  • Treatment
  • Prognosis
    • CAL formation
    • IVIG resistance
      • (non-responsiveness)

Content 4. (Kawasaki disease)

  • 1974 (Tomisaku Kawasaki)

5. ( ) Kuo et al.Acta Pediatr Twiwan . 2006;47(suppl):7-17. 6. Kawasaki Disease- Involved small and medial size vesselCoronary artery aneurysm 7.

  • Japan: 120~150 /
  • Korea:100-120
  • Taiwan: 66
    • 1976
  • Hong Kong: 25
  • USA: 10
  • Australian: 4
  • European: 3
  • Male/female ratio: 1.4
  • 85% < 5y/o
  • 50% = 5 days
  • < 4 diagnostic criteria, with CAL
  • About 15%
    • Nippon Rinsho.2008 ;66:321-5.
  • 6y/o
  • 6m/o
    • (35% vs.12%, p=0.025)
      • Pediatr Infect Dis J2006; 25:241-4.

Incomplete or atypical KD 16.

  • ESR>40 or CRP >30
  • ( 3) :
  • (< 3)
  • (WBC>10/HPF)
  • (>15000)
  • (anemia by age)
  • (45 ,7 days)

Circulation2004;110;2747-2771. Incomplete or atypical KD 17. Delay diagnosis of KD Pediatrics2005;115;428-433. >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

  • 1981: Imback: IVIG in ITP( Lancet )
  • 1983: Furusho: IVIG in 40 Japanese patients with KD( Lancet )
  • 1986: US Multicenter KD Study Group: 168 KD patients, 400mg/kg x 4 d reduces CAA from 20% to 3-5 % ( NEJM )
  • 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 )

21.

  • High dose IVIG (2gm/kg)
  • Aspirin(80-100 mg/kg) in acute stage
  • Aspirin (3-5 mg/kg) after fever subside
    • Normal ESR, Plt and 2D echo
  • Aspirin:(should receive an annual influenza vaccine)
    • (80~100mg/kg/day) Nelson textbook
      • Circulation1993; 87:1776-80.
    • (30~50mg/kg/day)
      • Prog Clin Biol Res1987; 250:401-13.
    • Hsieh KS et al. 1993~2003 162 KD
      • Pediatrics2004; 114;689-93.

Treatment Q2: standard Tx for KD 22.

  • Day 4
    • Early IVIG treatment for KD: the nationwide surveys in Japan.
      • J Pediatr2005;146:149-50.
  • Day 5
    • 15,940 KD patients in Japan
      • Pediatr Infect Dis J.2008;27:155-160.

Treatment-IVIG timing 23. Infection vs. KD Pediatrics2005;116;e760-e766. Diagnosis of KD start IVIG Tx stop antibiotics ? 24.

  • 7.8%~38%
    • Pediatr Cardiol.2003; Pediatr Infect Dis J.1998
    • Pediatr . 2008 Jul;153(1):117-21.
  • Our hospital: 10.8% (30/278)
  • 3-4% non-response to 2nd dose IVIG
    • 4/278 (1.4 % in our hospital)
  • 20% in Japan
    • Nippon Rinsho . 2008;66:332-7.
  • Recurrent KD: 6.89 per 1000/years
    • Acta Paediatr.2001;90:40-4 .
  • 2/278 (0.72% in our hospital)

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.

  • Recurrence: 1.3%(94/7305) of these children
    • The median (range) of the interval between the first attack of KD and the second attack was 145 (9-1891) days.
    • 85% (80/94) of the second attack occurred within 2 years following the first episode
  • coronary artery aneurysm in 7.3%(536/7305)

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.

  • Methylpredinsolone pulse
  • Cyclosporin
  • Cyclophosphamide
  • Methotrexate
    • Scand J Rheumatol 2005;34:136-9.
  • Plasma exchange
    • Eur J Pediatr.2004;163:263264.
  • Pentoxifylline (inhibit TNF mRNA)
    • Eur J Pediatr.1994;153:663667.
  • Abciximab
  • Enbrel
  • Ulinastatin
    • trypsin inhibitor

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.

  • Male gender
  • Recurrent KD
  • IVIG before day 4
  • IVIG after day 10
  • IVIG dose