Kawasaki Disease: An Update of diagnosis and treatment

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Kawasaki DiseaseAn Update of diagnosis and
treatment
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What is Kawasaki Disease?

• Idiopathic multisystem disease characterized by
  vasculitis of small medium blood vessels,
  including coronary arteries

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Diagnostic Criteria

• Fever for at least 5 days
• At least 4 of the following 5 features
• Changes in the extremities
• Edema, erythema, desquamation
• 2. Polymorphous exanthem, usually truncal
• 3. Conjunctival injection
• 4. Erythema/or fissuring of lips and oral cavity
• 5. Cervical lymphadenopathy
• Illness not explained by other known disease
  process

Modified from Centers for Disease Control.
Kawasaki Disease. MMWR 2961-63, 1980
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Atypical or Incomplete Kawasaki Disease

• Present with lt 4 of 5 diagnostic criteria
• Compatible laboratory findings
• Still develop coronary artery aneurysms
• No other explanation for the illness
• More common in children lt 1 year of age
• 2004 AHA guidelines offer new evaluation and
  treatment algorithm

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Phases of Disease

• Acute (1-2 weeks from onset)
• Febrile, irritable, toxic appearing
• Oral changes, rash, edema/erythema of feet
• Subacute (2-8 weeks from onset)
• Desquamation, may have persistent arthritis or
  arthralgias
• Gradual improvement even without treatment
• Convalescent (Months to years later)

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• AHA classify coronary arteries aneurysms
• Small (5 mm internal diameter),
• medium (5 to 8 mm internal
• diameter),
• or giant (8 mm internal diameter).

• The Japanese Ministry of Health Classify coronary
  arteries asabnormal
• the internal lumen diameter is 3 mm in children 5
  years old or 4 mm in children 5 years old
• the internal diameter of a segment measures 1.5
  times that of an adjacent segment

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Abnormal coronary artery
Diameter of CA /BSA
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Coronary Artery Involvement in Children With
Kawasaki Disease Risk Factors
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Harada et al risk score
(1) white blood cell count 12 000/mm3 (2) platelet count 350 000/mm3 (3) CRP 3 (4) hematocrit 35 (5) albumin 3.5 g/dL (6) age 12 months (7) male sex.
? 4/7 high risk
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ASAI
Symtomps 0 di?m 1 di?m 2 di?m
Sex Age Days of fever Recurrent fever Recurrent rash Recurrent bong da Anemie (Hb lt 10g/dL) WBC(X 103/ mm3) VS(mm) VS and PLT high for a long time(months ) Enlarge CI Abnormal rymth Ischemic myocady pericarditis N? ? 1 lt 14 - - - - lt 26 lt 60 lt 1 - - - - Nam gt 1 14 -15 26 30 60 100 ? 16 gt 30 gt 100 gt1
? 9/23 di?m high risk
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ÐI?U TR? ASPIRIN

• AHA-2004 80-100 mg/kg.
• Pediatrics-1995 meta-analysis.

Control Ratio Dilated CA Ratio Dilated CA
after 30 days (n2547) After 60 days (n4151)
ASA 22.8 ( 95 CI 20.6-25) 17.1(95 CI 13.6-20.7)
ASAIVIG 1g/kg 17.3(95 CI 14.3-20.2) 11.1(95 CI 8.7-13.6)
ASAIVIG gt1g/kg 10.3( 95 CI 8.3-12.3) 4.4 (95 CI 2.8-6)
ASA IVIG gt1g/kg lieàu duy nhaát 2.3(95 CI 0.5-4.2) 2.4(95 CI 0.5-4.2)
IVIG gt1g/kg ASA lt80 mg/kg 13(95 CI 9-17) 4.8(95 CI 2.3-7.4)
IVIG gt1g/kg ASA gt80mg/kg 9.1 (95 CI 6.9-11.4) 4(95 CI 2.-6.1)
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Dilated CA in 30 days Dilated CA in 60 days
IVIG (2G/KG/D) lt IVIG 1G/KG lt ASA IVIG HIGH DOSE ASA HIGH DOSE IVIG HIGH DOSE ASA LOW DOSE IVIG (2G/KG/D) lt IVIG 1G/KG lt ASA IVIG HIGH DOSE ASA HIGH DOSE IVIG HIGH DOSE ASA LOW DOSE
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ASPIRIN vs IVIG
T? L? T?N THUONG M?CH VÀNH
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CORTICOID

1. Initial CORTICOID vs ASPIRIN.
2. Initial CORTICOID ASPIRIN IVIG vs
   ASPIRINIVIG.
3. Resistance IVIG.

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IVIGASPIRIN vs IVIGASPIRIN METHYPREDNISOLON
Randomized Trial of Pulsed Corticosteroid Therapy
for Primary Treatment of Kawasaki Disease. N Engl
J Med 2007356663-75.
- 30 mg/kg over 2 to 3 hours - IVIG 2g/kg. -
Aspirin 80-100mg/kg.
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Effect and result

• Response with IVIG 90
• No response with IVIG 10

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Prediction of Intravenous Immunoglobulin
Unresponsiveness in Patients With Kawasaki
disease. Circulation 20061132606-2612
published online May 30, 2006
http//circ.ahajournals.org/cgi/content/full/113/2
2/2606.
Kobayashi-2006
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Prediction of Intravenous Immunoglobulin
Unresponsiveness in Patients With Kawasaki
disease. Circulation 20061132606-2612
published online May 30, 2006
http//circ.ahajournals.org/cgi/content/full/113/2
2/2606.
TIÊN ÐÓAN T?N THUONG M?CH VÀNH
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ANTI IVIG

• IVIG ONLY 2 g/kg (evidence level C).
• STEROID ONLY.
• PULSE STEROID IVIG Hashino et al RCT.
• 17 patients who did not respond to an initial
  infusion of 2 g/kg IVIG plus aspirin followed by
  an additional IVIG infusion of 1 g/kg.
• Randomized to receive either a single additional
  dose of IVIG (1 g/kg) or pulse steroid therapy.
• RESULT
• Patients in the steroidgroup had a shorter
  duration of fever and lower medical costs.
• No significant difference in the incidence of
  coronary arteryaneurysms was noted between the 2
  groups, but power to detect a difference was
  limited.

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KHÁNG IVIG

• AHA-2004 recommends
• Steroid treatment berestricted to children in
  whom 2 infusions of IVIG have been ineffective in
  alleviating fever and acute inflammation
  (evidence level C).
• The most commonly used steroid regimen is
  intravenous pulse methylprednisolone, 30 mg/kg
  for 2 to 3 hours, administered once daily for 1
  to 3 days.

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Acute Kawasaki Disease Conclusion for Treatment
( AHA 2004)

• IVIG 2g/kg as one-time dose
• Beneficial effect 1st reported by Japanese
• Mechanism of action is unclear
• Significant reduction in CAA in pts treated with
  IVIG plus aspirin vs. aspirin alone (15-25?3-5)

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Acute Kawasaki Disease Treatment

• IVIG
• 70-90 defervesce show symptom resolution
  within 2-3 days of treatment
• Retreat those with failure of response to 1st
  dose or recurrent symptoms ? Up to 2/3 respond to
  a second course

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Acute Kawasaki Disease Treatment

• Aspirin
• High dose (80-100 mg/kg/day) until afebrile x 48
  hrs /or decrease in acute phase reactants
• Need high doses in acute phase due to
  malabsorption of ASA
• Dosage of ASA in acute phase does not seem to
  affect subsequent incidence of CAA

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Acute Kawasaki Disease Treatment

• Aspirin
• Decrease to low dose (3-5 mg/kg/day) for 6-8
  weeks or until platelet levels normalize (
  evidence level C).
• No evidence /effect on CAA when used alone
• Due to potential risk of Reye syndrome instruct
  parents about symptoms of influenza or varicella

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• In case of persistent or recrudescent
  fever   Repeat dose of IVIG 2 g/kg as single
  infusion consider IV methylprednisolone 30 mg/kg
  once a day may be repeated as necessary up to a
  total of three doses