DR Dr Najib Advani SpA(K),MMed(Paed)

1979 : Doctor, University of Indonesia

1989 : Pediatrician, University of Indonesia
1997 : Cardiology fellow, SCH, Rotterdam, Holland
1997- 98 : Cardiology fellow, RCH, Melbourne, Australia
1999 : Master of Medicine in Paediatrics, University of Melbourne
1999 : Consultant in Pediatric Cardiology
1994 - present: teaching staff at Department of Child Health University of Indonesia
2014 : PhD in Kawasaki Disease
Kawasaki disease:
(Head) ASEAN countries Kawasaki disease Registry
Member of International Kawasaki Disease Genetic Studies
Member of International KD Climate Studies
International Faculty for International KD Symposium IX, Taipei, 2008
International Faculty for International KD Symposium X, Kyoto 2012
 Kawasaki disease
what should we know ?

Dr dr Najib Advani SpA(K), MMed (Paed)

Dept of Childhealth University of Indonesia
Jakarta
advanin@cbn.net.id

HP 0813 15 15 9500
Dr Kawasaki , 87 th birthday, 6-02-2012,
Kyoto, Japan
 First described by Tomisaku Kawasaki in 1967 in
Japan.
Complication : coronary artery aneurysm in 20
40% of patients
Etiology : unknown
Systemic vasculitis
Kawasaki Disease
Newly born in Kalimantan, 4th May 2006, healthy and cute
Age 1 month, got Kawasaki Disease
Delayed diagnosis
Developed coronary aneurysm
 EPIDEMIOLOGY

The commonest acquired heart disease in

children in developed countries
Japan : highest in the world, > 200,000 children
Worldwide: estimated 1000,000 Kawasaki cases
Asia esp Japan and Korea : 100-200/ year
per 100,000 children below 5 yr
Male to female : 1.6 : 1 (Indonesia, Advani 2014)
Indonesia
- Estimated incidence 5000 per year, diagnosed
100/yr (Advani 2006, Advani et al 2008)
- 667 cases reported 2003-2013
71 % below 5 yr, youngest 33 days
old, oldest 16 yr (Advani 2014)
Distribusi pasien PK menurut usia
n=667 (2003-2013). Advani 2014
 Total pasien per bulan 2003-2012 n=598 (Advani
2014)
70

60

50

40

30

20

10

0
Jan Feb Mar Apr Mei Juni Juli Agustus Sept Okt Nov Des
Distribusi pasien baru PK pertahun (n=598)
Advani 2014
 CLINICAL MANIFESTATIONS
ACUTE PHASE (First 10 days)
Conjunctivitis, bilateral, non exudative
Changes in mouth and lips : strawberry tongue, red oral
cavity, erythema and cracked lips
Changes in the hands and feet : erythema and edema
Polymorphous exanthem
Fever (remittent), not responsive to antibiotics, may
persist for 1-2 / 3-4 wks
Cervical lymphadenopathy, unilateral (>1.5 cm)
Other associated findings (acute phase)

Sterile pyuria (60 %)

Liver dysfunction (40%)
Arthritis of large joints (30%)
Aseptic meningitis (25%)
Abdominal pain with diarrhea
Hydrops of gallbladder with jaundice (10%)
CNS symptoms (irritable, lethargic, semicoma)
BCG scar : redness and crust
 My HEART
Clinical manifestations of KD
M ucosal changes : erythema
H and and foot changes: erythema,
edema
E ye changes : conjunctivitis
A denopathy : unilateral
R ash : polymorph exanthem
T emperature : remittent
Cardiovascular findings during acute phase

Tachycardia
Murmur / gallop
Cardiomegaly
Pericardial effusion
LV dysfunction
ECG changes : PR interval >, low QRS voltage
ST depression/elevation
BCG
Subacute phase (day 11-25)
Desquamation: tips of fingers and toes
Rash, fever, lymphadenopathy disappear
Significant cardiovascular changes : coronary
aneurysm, pericardial eff, myocard infarct
Thrombocytosis, peaking at 2 weeks />
Convalescent phase (day > 25)
Lasts till ESR and platelet count return to
normal. Deep transverse grooves (Beaus
line) : finger nails and toenails
DIAGNOSTIC CRITERIA FOR KD

1. Remittent fever for 5 days/more

2. Bilateral conjunctival injection (no exudate)
3. Changes in the mouth and lips : strawberry tongue,
diffuse reddening of oral cavity, erythema and cracking of
lips.
4. Changes in the hands and feet : erythema and edema
5. Polymorphous exanthem
6. Unilateral cervical lymphadenopathy (>1.5 cm)
 Diagnostic criteria
Fever plus 4 of the 5 other criteria allows for
diagnosis
Fever plus fewer than 4 of 5 other criteria can
be diagnosed as KD if coronary artery disease
is detected (incomplete KD)
Other possible diagnoses should be excluded
Incomplete KD should be suspected in all
children with unexplained fever 5 days + 2-3
diagnostic criteria

The risk of coronary aneurysm is the same either

in complete or incomplete KD
Not all of the clinical features may present at a
single point in time -> watchful waiting is
sometimes necessary before a diagnosis can be
made
KD should be considered in DD/ of every child
with fever of at least several days duration,
rash, and nonpurulent conjunctivitis
Laboratory test : not pathognomonic
Leukocytosis with a shift to the left
Mild to moderate anemia
CRP, ESR during acute phase
Thrombocytosis : subacute phase may
> 1,000,000 sometimes 2,000,000/mm3
Pyuria (due to urethritis)
Liver enzyme increase, hypoalbuminemia
 ECG
Low voltage QRS
ST elevation/depression
QTc >
Wide and deep Q wave : myocard infarct
ST depression and sinus tachycardia at acute stage of KD before IVIG
Three days post IVIG, normal ECG
Echocardiography
Mandatory
Detect coronary artery aneurysm and cardiac
dysfunction
May reveal coronary artery changes, depressed
LV function, regurgitation tricuspid, mitral,
aortic and pericardial effusion
N coronary size : Z score
Newberger et al Circulation 2004 ;110 :2747-71
Aortic insufficiency in acute Kawasaki Disease
 RV

Pericardial effusion in acute KD

Mitral insufficiency in acute Kawasaki Disease
 Giant aneurysm of LAD

Normal LAD

Normal vs giant aneurysm of Left Coronary Artery (LCA, LAD)

Normal RCA

Giant aneurysm of RCA

Normal vs giant aneurysm of Right Coronary Artery (RCA)

Thrombus in LAD
 Thrombus

Thrombus in LAD (Left Anterior Descending)

Catheterization
Selective
Large or multiple aneurysm
Sign of ischemia clinically or in ECG
Suggest stenosis
Kurva dan tabel kesintasan untuk aneurisme
RCA (Advani 2014)

Log-rank test
p < 0,001

Ukuran koroner Rerata (bulan), 95% IK Median (bulan), min-maks

Kecil 12,64 (6,07-19,22) 2,5 (0,03-82,1)

Sedang 44,76 (20,31-69,21) 36,77 (0,77-92,83)

Raksasa 64,08 (39,70-88,45)

Kurva dan tabel kesintasan untuk aneurisme
LMCA (Advani 2014)

Log-rank test
p = 0,008

Ukuran koroner Rerata (bulan),95%IK Median (bulan), min-maks

Kecil 8,55 (4,99-12,1) 1,1 (0-82,1)

Sedang 30,22 (3,56-56,87) 2,97 (0,87-92,83)
Kurva dan tabel kesintasan untuk aneurisme LAD
(Advani 2014)

Log-rank test
p = 0,011

Ukuran koroner Rerata (bulan), 95% IK Median (bulan), min-maks

Kecil 19,68 (10,29-29,06) 3,27 (0,00-82,10)

Sedang 44,86 (23,95-65,77) 66,03 (0,47-78,43)

Raksasa 67,35 (53,63-81,07)

 DIFFERENTIAL DIAGNOSIS

Measles
Stevens Johnson syndrome
Staphylococcal scalded skin syndrome
Drug reaction
Scarlet fever
Exanthema subitum
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Should avoid :
Over diagnosis
Actually not Kawasaki but diagnosed as Kawasaki
Under diagnosis
Actually Kawasaki but undiagnosed

Need to have a good knowledge on DD/ of KD

 Management
All KD patients should be hospitalized, consult pediatric cardiologist if possible

IGIV 2 g/kgBW single dose within 10-12 hours

Aspirin 80-100 mg/kgBW/day, orally divided into 4 doses till 2-3 days after fever
subsides, then
3-5 mg/kgBW/day single dose untill no aneurysms detected by echocardiography ,
at least for 6 weeks

Fever persists >36-48 hours after completion of IVIG -> repeat IVIG if necessary
(reevaluate diagnosis, no other source of fever)

Newburger JW, dkk. Pediatrics. 2004;114:1708-33.

Dummer KB, dkk. Pediatr Cardiol. 2004;19:129-35.
 Invasive treatment

Coronary Artery Bypass Graft (CABG) for

obstructive lesion
Baloon angioplasty : not successful
Stent placement : in older children
Cardiac transplantation : last choice
 Outcome

Without coronary aneurysms

Total recovery

Myocarditis, pericardial effusion

Improve within 1 month

With coronary aneurysms

Outcome depends on diameter of aneurysms

Advani, thesis, 2014

Belay ED, Pediatr Infect Dis J. 2006;25:245-249.
Kato H, dkk. Circulation. 1996;94:1379-85..
 Outcome

Small aneurysm (< 5 mm)

Mostly regress within 2 years

Moderate aneurysms (5-8 mm)

Mostly regress within 5 years

Giant aneurysms (>8mm)

Unlikely to regress thrombosis or stenosis may follow

years later

Regressed aneurysms intimal thickening and endothelial dysfunction

atherosclerotic lesion long-term follow up needed?

Advani, thesis, 2014

Belay ED, Pediatr Infect Dis J. 2006;25:245-249.
Kato H, dkk. Circulation. 1996;94:1379-85..
Course and complications
Self limiting
IVIG : clinical improvement within 24 hours and reduce
incidence of Coronary Aneurysm (C.A)
Arterial remodeling or revascularization may occur
C. A infarct
Mortality 1-5 % decreasing
Advani 2013 : mortality 0% (667 cases observed for max 126
months)
Persisting C.A ischaemic heart disease at young adult age
Regressed C.A intimal thickening & endothel dysfunction
premature atherosclerosis
Lifelong monitoring needed ?
 Conclusion
KD is a vasculitis of unknown etiology
Diagnosis of KD is based on clinical findings, lab tests are not
specific but may support the diagnosis
KD should be considered in DD/ of every child with fever of at
least several days duration, rash, and nonpurulent
conjunctivitis
All patients with KD must be hospitalized and consulted to a
pediatric cardiologist who is familiar with KD
IVIG 2 g/kg BW for 10-12 hours is the treatment of choice,
best given on day 5-7 to 10.
Coronary aneurysm occurs in 15-25% of untreated cases
Outcome depends on the diameter of coronary aneurysms
ARIGATO
 Thank You HARIGATO

Dr Kawasaki
Mrs Kawasaki
 I need more attention

You might have met me but did not recognise

Born in 1967, I am not young anymore,
Never had a broken heart, but
Have broken many hearts
I do love kids and babies,
Yet their moms and dads detest me
In Japan, Taiwan and the States I am the best
In Indonesia, sadly I am just the rest
O, how I envy a lady, a local diva,
Who bears the same name with me
People know more about her
Even many of us here ?
I realise being just a KD (Kawasaki Disease)
And not a KD (Kris Dayanti)
Give me more attention please
Dont let me blow up the coronary arteries
(NA 2005)
 Prevalence of CAA, IVIG & ASA doses
1629 KD patients from 6 studies, blinded echo readings
Prevalence of coronary artery aneurysm in
convalescent stage vs IVIG dose
ASA (aspirin) alone 14.7%
ASA + < 1 g/kg IVIG 8.6%
ASA + 1-1.2 g/kg IVIG 7.0%
ASA + 1.6 g/kg IVIG 3.7%
ASA + 2 g/kg IVIG 2.6%
Terai, Shulman J Pediatr 1997; 131: 888-93