Kawasaki disease is a vasculitic disease in
which medium-sized arteries throughout the
body become inflamed.
It typically affects young children from 1
to 5 years old, but can sometimes affect teenagers
and even adults.
It is usually a self-limited condition, with
fever and manifestations of acute inflammation
for at least five days, lasting for an average
of 12 days without therapy, and it’s not
very responsive to treatment with paracetamol
or ibuprofen.
The most frequent and characteristic signs
and symptoms, included in the diagnostic criteria,
can be remembered with the mnemonic CRASH.
First off, they may typically present with
bilateral bulbar Conjunctival injection, which
typically begins within days of the onset
of fever, and leads to photophobia or discomfort
or pain to the eyes due to light exposure.
Then there’s polymorphous Rash that usually
begins during the first few days of illness
due to sensitivity to sunlight.
A stands for lymphadenopathy, which tends
to primarily involve the anterior cervical
nodes overlying the sternocleidomastoid muscles.
Next up, there are oral mucous membrane changes,
including injected or fissured lips, injected
pharynx, or Strawberry tongue.
And finally, there are peripheral extremity
changes, including erythema of palms or soles,
edema of Hands or feet, and periungual desquamation.
To make a diagnosis of Kawasaki, individuals
must meet at least four of these features.
Other common features include irritability,
rhinorrhea, cough, vomiting, diarrhea, abdominal
pain, and joint pain.
A severe complication of Kawasaki disease
is cardiovascular disease, which most commonly
presents as coronary artery aneurysms, and
can lead to arrhythmias, myocardial infarction,
and ultimately, heart failure.
Typically, an ECG and echocardiography are
done in individuals with Kawasaki to look
for cardiovascular involvement.
On rare occasion, if echocardiography isn’t
able to image the coronary arteries, computed
tomographic angiography or magnetic resonance
angiography can be used instead.
Individuals with coronary aneurysms have to
undergo stress testing to evaluate for myocardial
perfusion and inducible ischemia, which measures
the heart's ability to respond to increased
stress or demand in a controlled setting.
The stress is induced by exercise, which is
preferred, or with the medication dobutamine.
Some children are suspected of having Kawasaki
disease when they have an unexplained fever
for at least five days, even if they have
only two or three of the diagnostic criteria.
That’s because these children may have incomplete
or atypical Kawasaki disease.
This is also true of infants less than six
months of age with unexplained fever for at
least seven days, even without any of the
clinical findings of Kawasaki disease.
That’s important because infants are at
a greater risk for cardiovascular disease.
The criteria to diagnose incomplete Kawasaki
include an CRP above 3 milligrams per deciLiter
and ESR above 40 millimeters per hour, along
with three or more abnormal supplemental laboratory
findings, or abnormal echocardiography.
The supplementary blood tests include a white
blood cell count above 15,000 cells per microLiter,
platelet cell count above 450,000 cells per
microLiter, normocytic normochromic anemia
for age, an elevated serum alanine aminotransferase
above 50 units per Liter, or a serum albumin
level below 3 grams per deciLiter.
Another supplementary finding is a pyuria
- having than 10 white blood cells per high-power
field - on urine microscopy.
For management, individuals with Kawasaki
disease should get a single dose of IVIG - 2
grams per kilogram over 8 to 12 hours, administered
within the first 10 days of illness, before
aneurysms typically develop.
IVIG should be administered even beyond this
10-day window in individuals with evidence
of persistent vasculitis or systemic inflammation,
such as persistent fever and laboratory markers
like an elevated ESR and CRP.
In addition, individuals should get aspirin
during the acute phase of illness to prevent
blood clots from forming - giving a total
daily aspirin dose of 30 to 50 milligrams
per kilogram per day in four divided doses,
for a maximum dose of 4 grams per day.
Aspirin therapy is started at high doses while
the fever lasts, and then is continued 48
hours after the resolution of fever at a low
dose of 3 to 5 milligrams per kilogram per
day, until laboratory markers return to normal,
which usually takes about two months, unless
there’s coronary artery involvement, in
which case low dose aspirin therapy is continued.
Except for Kawasaki disease and a few other
indications, aspirin is otherwise normally
not recommended for children due to its association
with Reye syndrome, which is a rapidly progressive
encephalopathy.
Because children with Kawasaki disease will
be on aspirin for a long time, vaccination
against varicella and influenza is required,
because these infections are the ones that
are most likely to cause Reye syndrome.
Importantly, varicella vaccine should be postponed
until at least 11 months after the IVIG has
been given because it can interfere with vaccine
immunogenicity.
Now, if a child has a persistent fever even
24 hours after completion of initial therapy
or becomes afebrile and then develops a fever
without an alternative source within the two
week window after initial therapy - then that’s
considered refractory Kawasaki disease.
Refractory Kawasaki disease can put individuals
at higher risk for cardiovascular disease.
Risk factors for failing to respond to a single
dose of IVIG include male gender, age less
than 6 months, elevated CRP, and low sodium
or low platelet levels.
In refractory Kawasaki disease, the first
step is to give another dose of IVIG - 2 grams
per kilogram over 8 to 12 hours.
If that doesn’t work, and the fevers persist,
then glucocorticoids can be given.
Usually it’s pulsed-dose methylprednisolone,
giving 30 milligrams per kilogram per day,
given until there’s a full response, or
until three doses have been given.
Alternatively, you can give 15- to 30-day
course of twice or thrice daily oral prednisone,
for a total daily dose of 1 to 2 milligrams
per kilogram.
Since glucocorticoids can sometimes increase
the risk of coronary artery aneurysm, they’re
only given as an adjunct to initial treatment
in cases that are refractory to IVIG.
All right, as a quick recap, Kawasaki disease
causes a fever for at least five days.
In addition, as they can develop bilateral
bulbar Conjunctival injection; a polymorphous
Rash due to sensitivity to sunlight; cervical
lymphAdenopathy; oral mucous membrane changes,
including injected or fissured lips, injected
pharynx, or Strawberry tongue; and peripheral
extremity changes, including erythema of palms
or soles, edema of Hands or feet, and periungual
desquamation.
Diagnosis of Kawasaki is based on the presence
of at least four of those features.
A severe complication of Kawasaki disease
is cardiovascular disease, so all affected
individuals must get an ECG and echocardiography.
Children suspected of having Kawasaki disease
who do not fulfill diagnostic criteria may
be diagnosed with atypical or incomplete Kawasaki
if they present elevated ESR and CRP plus
three or more abnormal supplemental laboratory
findings, or abnormal echocardiography.
For treatment, individuals with Kawasaki disease
should get a single dose of IVIG - 2 grams
per kilogram over 8 to 12 hours, as well as
aspirin - giving a total daily aspirin dose
of 30 to 50 milligrams per kilogram per day
in four divided doses, for a maximum dose
of 4 grams per day, while the fever lasts.
Those with refractory Kawasaki may get a second
dose of IVIG.
If that doesn’t work, then glucocorticoids
can be given as an adjunct to initial treatment.
