Kawasaki disease an update of diagnosis and treatment

Kawasaki Disease:An Update of diagnosis and treatment... Phases of Disease• Acute 1-2 weeks from onset – Febrile, irritable, toxic appearing – Oral changes, rash, edema/erythema of feet

Kawasaki Disease:

An Update of diagnosis and

treatment

What is Kawasaki Disease?

• Idiopathic multisystem disease

characterized by vasculitis of small & medium blood vessels, including

coronary arteries

Diagnostic Criteria

• Fever for at least 5 days

• At least 4 of the following 5 features:

1 Changes in the extremities

 Edema, erythema, desquamation

2 Polymorphous exanthem, usually truncal

Atypical or Incomplete

Kawasaki Disease

• Present with < 4 of 5 diagnostic criteria

• Compatible laboratory findings

• Still develop coronary artery aneurysms

• No other explanation for the illness

• More common in children < 1 year of age

• 2004 AHA guidelines offer new evaluation and treatment algorithm

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)

• AHA classify coronary

abnormal

• 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;

Abnormal coronary

artery

Diameter of CA /BSA

Coronary Artery Involvement in Children With Kawasaki Disease:

Risk Factors

Harada et al – risk score

(1) white blood cell count 12 000/mm3; (2) platelet count 350 000/mm3;

< 26

< 60

< 1 - - - -

 16 + + +

> 30

> 100

>1

+ +

 9/23 điểm : high risk

ĐIỀU TRỊ ASPIRIN

• AHA-2004: 80-100 mg/kg.

• Pediatrics-1995: meta-analysis.

after 30 days (n=2547) After 60 days (n=4151)ASA 22.8% ( 95% CI: 20.6-25%) 17.1%(95% CI: 13.6-20.7%)

ASA+IVIG 1g/kg 17.3%(95% CI:

14.3-20.2%) 11.1%(95% CI: 8.7-13.6%)ASA+IVIG >1g/kg 10.3%( 95% CI: 8.3-12.3%) 4.4% (95% CI: 2.8-6%)

ASA+ IVIG >1g/kg lieàu duy

nhaát 2.3%(95% CI: 0.5-4.2%) 2.4%(95% CI: 0.5-4.2%)IVIG >1g/kg + ASA <80

mg/kg 13%(95% CI: 9-17%) 4.8%(95% CI: 2.3-7.4%)IVIG >1g/kg +ASA >80mg/kg 9.1% (95% CI: 6.9-11.4%) 4%(95% CI: 2.-6.1%)

Dilated CA in 30 days Dilated CA in 60 days

IVIG (2G/KG/D) < IVIG 1G/KG < ASA

IVIG HIGH DOSE + ASA HIGH DOSE =

IVIG HIGH DOSE + ASA LOW DOSE

IVIG (2G/KG/D) < IVIG 1G/KG < ASA

IVIG HIGH DOSE + ASA HIGH DOSE

= IVIG HIGH DOSE + ASA LOW DOSE

ASPIRIN vs IVIG

TỈ LỆ TỔN THƯƠNG MẠCH VÀNH

1 Initial CORTICOID vs ASPIRIN.

2 Initial CORTICOID+ ASPIRIN+ IVIG vs

ASPIRIN+IVIG.

3 Resistance IVIG.

IVIG+ASPIRIN vs IVIG+ASPIRIN+ METHYPREDNISOLON

Randomized Trial of Pulsed Corticosteroid Therapy for Primary Treatment of Kawasaki

Disease N Engl J Med 2007;356:663-75

- 30 mg/kg over 2 to 3 hours

- IVIG 2g/kg.

- Aspirin 80-100mg/kg.

Effect and result

• Response with IVIG : 90 %

• No response with IVIG : 10 %

Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With

Kawasaki disease Circulation 2006;113;2606-2612; published online May 30, 2006;

http://circ.ahajournals.org/cgi/content/full/113/22/2606

Kobayashi-2006

Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With

Kawasaki disease Circulation 2006;113;2606-2612; published online May 30, 2006;

http://circ.ahajournals.org/cgi/content/full/113/22/2606

TIÊN ĐÓAN TỔN THƯƠNG MẠCH VÀNH

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

KHÁNG IVIG

AHA-2004 recommends

1.Steroid treatment berestricted to children in whom 2 infusions of IVIG have been

ineffective in alleviating fever and acute

inflammation (evidence level C)

2.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.

Acute Kawasaki Disease: Conclusion

for Treatment ( AHA 2004)

• IVIG: 2g/kg as one-time dose

Japanese

– Mechanism of action is unclear

– Significant reduction in CAA in pts

treated with IVIG plus aspirin vs aspirin alone (15-25%3-5%)

Acute Kawasaki Disease:

Treatment

• IVIG

– 70-90% defervesce & show symptom

resolution within 2-3 days of treatment – Retreat those with failure of response to

2/3 respond to a second course

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

Acute Kawasaki Disease:

– Due to potential risk of Reye syndrome

instruct parents about symptoms of influenza

or varicella

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