Kawasaki disease an update of diagnosis and treatment

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
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 29:61-63,
1980


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
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 as
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;
(3) CRP 3;
(4) hematocrit 35%
(5) albumin 3.5 g/dL;
(6) age 12 months;
(7) male sex.
≥ 4/7 : high risk


ASAI
Symtomps
1.
2.
3.

4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.

Sex
Age
Days of fever
Recurrent fever
Recurrent rash
Recurrent bong da
Anemie (Hb < 10g/dL)
WBC(X 103/ mm3)
VS(mm)
VS and PLT high for a long
time(months )
Enlarge CI
Abnormal rymth
Ischemic myocady
pericarditis

0 điểm

1 điểm

Nữ
≤1
< 14
< 26
< 60
<1
-

Nam
>1
14 -15

≥ 9/23 điểm : high risk

+
26 – 30
60 – 100

2 điểm

≥ 16
+
+
+
> 30
> 100
>1

+
+
+

+
+


ĐIỀU TRỊ ASPIRIN
• AHA-2004: 80-100 mg/kg.
• Pediatrics-1995: meta-analysis.
Control

Ratio Dilated CA
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: 14.320.2%)
10.3%( 95% CI: 8.3-12.3%)

11.1%(95% CI: 8.7-13.6%)

ASA+IVIG >1g/kg

ASA+ IVIG >1g/kg lieàu duy 2.3%(95% CI: 0.5-4.2%)
nhaát
IVIG >1g/kg + ASA <80
13%(95% CI: 9-17%)
mg/kg
IVIG >1g/kg +ASA >80mg/kg 9.1% (95% CI: 6.9-11.4%)

4.4% (95% CI: 2.8-6%)
2.4%(95% CI: 0.5-4.2%)
4.8%(95% CI: 2.3-7.4%)
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 (2G/KG/D) < IVIG 1G/KG < ASA

IVIG HIGH DOSE + ASA HIGH DOSE =
IVIG HIGH DOSE + ASA LOW DOSE

IVIG HIGH DOSE + ASA HIGH DOSE
= IVIG HIGH DOSE + ASA LOW
DOSE

ASPIRIN vs IVIG
TỈ LỆ TỔN THƯƠNG MẠCH VÀNH


CORTICOID
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;
/>Kobayashi-2006


Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With
Kawasaki disease. Circulation 2006;113;2606-2612; published online May 30, 2006;
/>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.
– 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.


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
– 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%)


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


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