KAWASAKI DISEASE

Department of Pediatrics, National University Hospital, Singapore.

Department of Cardiology, Childrens Hospital Boston, Boston, MA.

Perceptor : dr. Ferry Mulyadi Sp.A,.M.Kes

Co-Assistant : Arum Mananti Pradita

Case Study

A 3-year-old previously healthy Hispanic girl is

brought to her pediatricians office with a
history of 6 days of fever. The fever has been
present daily and has been unremitting,
despite
administration
of
antipyretic
medications. She has been irritable with
decreased appetite. Her mother noticed an
erythematous, nonpruritic rash covering her
torso 1 day after fever onset. She has
developed red eyes in the past 2 days. She
has no siblings and attends child care.

On examination, the girl is

febrile
to
38.9C
and
tachycardic at 140 beats per
minute. Her blood pressure
while crying is 110/60 mm Hg.
Her weight is 14.5 kg. She has
conjunctival
injection
with
limbal sparing and without
exudate. Her lips appear
erythematous and cracked,
and
her
oropharynx
is
diffusely
erythematous
without exudate. She does not
have significant cervical chain
lymphadenopathy.
A
polymorphous maculopapular
rash covers her torso and

Con
tShe has a total white blood cell count of 15,600/mm3, a
hemoglobin level of 9.8 g/dL, and a platelet count of
670,000/mm3. The differential count of the white blood
cells is 81% neutrophils and 14% lymphocytes. She has
mild transaminitis with an alanine aminotransferase level
of 68 U/L; her aspartate aminotransferase level is normal.
Her C-reactive protein (CRP) level is 9.8 mg/dL and her
erythrocyte sedimentation rate (ESR) is 65 mm/hour.
There are 25 white cells per high-power field on urinalysis.

Overvie
w
Kawasaki disease (KD) is an acute febrile illness of childhood
characterized by vasculitis of medium-sized, extraparenchymal
arteries, with a predilection for coronary arteries. KD is the leading
cause of acquired heart disease in developed countries, although
rheumatic heart disease continues to dominate in the developing
world. The natural history and treatment of KD are well described,
but its etiology remains obscure, hampering efforts to identify a
specific diagnostic test and targeted treatments.

In the absence of a specific diagnostic

test, KD remains a diagnosis based on
clinical
criteria.
All
signs
and
symptoms of KD resolve following the
acute illness, but coronary artery
lesions (CALs) develop in 3% to 5% of
children treated with intravenous
immunoglobulin (IVIG), and up to 25%
of untreated children. Its prognosis is
predicated entirely on the presence
and severity of CALs, which can range
from mild dilation to giant aneurysms
(Fig 1).
Figure 1. Selective right coronary
angiogram demonstrating
multiple aneurysms in a child who
has KD.

Epidemi
KDology
was first described in 1967 by

a Japanese pediatrician, Dr
Tomisaku
Kawasaki,
as
the
mucocutaneous
lymph
node
syndrome
Since 1970,
Japan has
Risk
factors
for
poor
collected
epidemiologic
coronary artery
outcomes data
about
nearly
every 2in years
have KD
been
studied
via
nationwide surveys
several
populations.
Demographic factors, such
as young age, particularly
younger than 6 months and
older than 9 years, male
gender, Asian and Pacific
Islander race, and Hispanic
ethnicity
have
been
associated
with
poor
clinical outcomes.

Similar to prior surveys in

Japan, the most recent
survey in 20092010 found
that the incidence rate was
highest among children age
6 to 11 months and was
In
contrast
to
Japan,
higher in boys than in girls.
hospitalization rates associated
with KD in the United States have
been relatively stable over the
past decade. The rate in 1997
was 17.5 per 100,000 children
younger than age 5 years, and in
Laboratory
as
2006, 20.8parameters,
per 100,000such
children
neutrophilia,
younger than thrombocytopenia,
age 5 years. boys
hyponatremia,
than in girls. elevated CRP, and
transaminitis, have all been
associated with poor response to
IVIG and the development of
CAL. (2) Essentially, patients with
evidence of significant and
widespread inflammation are at
the highest risk.

Patho
KDs etiology remains unknown. Many aspects of KD mimic
genesi
infectious processes, such as toxin-mediated illnesses and viral
s
illnesses. Seasonal peaks have occurred in the United States
and Japan, with increased incidence in localized areas,
suggesting a transmissible vector. Researchers looked
painstakingly and unsuccessfully for an etiologic infectious
agent, including Epstein-Barr virus (EBV), adenovirus, human
coronavirus, human bocavirus, Yersinia pseudotuberculosis,
herpes viruses, and others Toxins, such as those produced by
Staphylococcus aureus and Streptococcus pyogenes, have been
postulated as the causative agents of KD because the rash can
resemble an erythroderma, similar to the toxic shock
staphylococcal
skin syndrome
Tosyndromes
date, no and
unique
agent hasscalded
been proven
to cause KD. An
alternative hypothesis posits that many infectious agents trigger
a final common pathway in genetically susceptible hosts, which is
supported by the finding that many patients diagnosed as having
KD have documented concomitant infections

Both the innate and adaptive arms of the immune system have
been evaluated in the pathogenesis of KD. The innate immune
system includes epithelial barriers and phagocytic cells that
provide protection against infection, whereas the adaptive
immune response is mediated by antigen-specific lymphocytes
stimulated by infectious agents. There is evidence that the innate
immune system plays a significant role in the pathogenesis of KD.

Clinical
Manifestatio
ns

More than 90% of children who have KD develop bilateral, nonexudative

conjunctivitis that spares the limbus (Fig 2). Anterior uveitis also may be
detected on slit-lamp examination during the acute phase of the disease.
Anterior uveitis also may be detected on slit-lamp examination during the
acute phase of the disease.

Oropharyngeal manifestations are common and include a diffusely

erythematous
oropharynx, red fissured lips, and a strawberry tongue (Fig 3).

Characteristic, although not pathognomonic, periungual

peeling from the fingers and the toes (Fig 4) begins 2 to 3
weeks after the onset of the fever

Children who have KD can have amyriad of other

signs and symptoms, including myalgias,
arthralgias, and arthritis. Neurologic involvement
can include significant irritability, likely because
of meningeal inflammation, transient facial
palsies,
and
sensorineural
hearing
loss.
Gastrointestinal complaints occur in up to 30% of
patients and include abdominal pain, vomiting,
diarrhea, acalculous distention of the gallbladder
(hydrops), and hepatomegaly.

Incompl
ete KD
A challenging subset of patients
who do not meet the classic
case definition are said to have
incomplete or atypical KD.
Children who have incomplete
KD do not have atypical
features; rather, they have
some of the classic features of
KD but not enough to meet the
case definition. Patients who
have incomplete KD are more
likely to be infants and older
children, and, as such, also are
at higher risk for CALs.

Considering
the
cardiac
consequences of failing to treat
incomplete
KD
and
the
comparative safety of IVIG
treatment, the American Heart
Association (AHA) published an
algorithm for the evaluation and
treatment
of
suspected
incomplete
KD
to
assist
clinicians (Fig 5).

Differential
Diagnosis
Because KD is a
self-limited febrile
illness, infections
dominate the list
of
differential
diagnoses (Table 2)

Evaluation for
Suspected KD
1. Laboratory Studies
o Children who have KD typically have leukocytosis with a
predominance of neutrophils and immature forms.
o Many of these children have a normocytic normochromic anemia,
with the average hematocrit at presentation being 2 SDs below the
norm for age. A sudden drop in hemoglobin concentration following
IVIG may be attributable to hemolytic anemia.
o Platelet counts usually are elevated by the end of the first week of
illness (450,000/mm3), and may evolve into significant
thrombocytosis, with platelet counts averaging 700,000/mm3 by
the third week.
o Inflammatory markers are elevated in nearly all cases of KD. The
ESR and CRP should be assessed at diagnosis. The ESR following
treatment with IVIG often is high, because the protein load from the
infusion elevates the ESR, obscuring the extent of disease activity.

o Transaminases are elevated in approximately 40% of patients with

KD, and a mild hyperbilirubinemia can occur. Plasma
gammaglutamyl
transpeptidase
levels
are
elevated
in
approximately two thirds of patients who have KD.
o Other laboratory findings, such as hypoalbuminemia and
hyponatremia, reflect more severe illness and can be associated
with capillary leak. Lipid panels in patients who have KD are
markedly altered, with decreased levels of total cholesterol, as
well as apolipoprotein A1 and high-density lipoprotein. Markers of
cardiac damage or dysfunction, such as troponins and B-type
natriuretic peptide, also may be elevated, but are not obtained

2. Cardiac
Imaging
o Echocardiography is an excellent imaging modality for evaluating coronary
artery dimensions, myocardial function, valve regurgitation, and pericardial
effusion. The procedure is noninvasive, and in experienced hands has high
sensitivity and specificity for dilation in the proximal coronary arteries.
Sedation often is required in younger children to obtain optimal images. If
the diagnosis is clear, treatment for KD should not be withheld while
waiting to schedule or obtain the results of echocardiography.
o Patients who have definite or suspected KD should undergo assessment of
each coronary artery, including the left main coronary artery, left anterior
descending artery (LAD), left circumflex coronary artery, right coronary
artery (RCA), and posterior descending coronary artery. The proximal LAD
and RCA are affected most commonly by coronary artery aneurysms.
o Although echocardiography is the preferred method of visualizing the
coronary arteries early after KD, coronary angiography is used in children
who have significant coronary artery aneurysms using techniques of
computed tomography, magnetic resonance angiography, or cardiac
catheterization.

Treat
ment
o Once the diagnosis of KD is confirmed, treatment with
highdose IVIG (2 g/kg) and high-dose ASA (80 to 100 mg/kg
per day divided into 4 doses) should be instituted promptly.
Ideally, treatment is administered within the first 7 days of
illness, and by day 10 (as defined by the first day of fever) at
the latest.
o Treatment with IVIG after day 10 of illness is reserved for
those with ongoing fever and evidence of systemic
inflammation on laboratory studies. To avoid infusion
reactions,
premedication
with
standard
dosing
of
diphenhydramine should be considered strongly. Additionally,
IVIG should be administered slowly, over 8 to 12 hours, to
avoid hemodynamic instability. IVIG can be associated with
lowgrade fevers within the first 48 hours of its administration.
Hemolytic reactions to IVIG are well described.

o Because KD is a vasculitis, corticosteroids have undergone

trials in KD. Steroids can be administered as primary
therapy when given at the time of the first dose of IVIG, or as
secondary therapy when given for IVIG resistance.
Furthermore, corticosteroids can be given in high-pulse
doses of 30 mg/kg of intravenous methylprednisolone, or in
lower doses (0.5 to 2.0 mg/kg per day) of prednisolone orally.
o The patient tolerates her IVIG infusion without complication
and defervesces within the subsequent 48 hours. Her
tachycardia resolves. The conjunctival injection improves
significantly, as does the rash. Upon discharge, she is well
appearing and prescribed ASA 40.5 mg daily. She is
scheduled
for
an
appointment
in
2
weeks
for
echocardiography and laboratory studies

Prognosis and LongTerm Managemen

The prognosis of KD
relates entirely to the
extent and severity of
cardiac disease. With
timely IVIG treatment,
the incidence of CAL in
treated
children
has
fallen to less than 5%,
and only 1% of children
develop
giant
aneurysms.

Management of children who

have significant coronary artery
disease
may
require
a
combination of beta-blockers to
decrease oxidative stress, as well
as anticoagulation therapy. These
children are followed closely with
assessment of coronary function
(eg,
exercise
stress
echocardiography in children old
enough to run on a treadmill,
dobutamine cardiac magnetic
resonance imaging for younger
children)
and
structure
(echocardiography,
coronary
angiography).

In the interim, all children with a history of

KD, even those without apparent coronary
artery
involvement,
should
undergo
assessment of risk factors, such as
hyperlipidemia and hypertension, and be
counseled regarding a healthy lifestyle and
avoidance of modifiable cardiac risk
factors, such as obesity, smoking, and a
sedentary lifestyle.

THANK
YOU