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Kawasaki disease is an acute vasculitis of childhood that predominantly affects the coronary arter-
ies. The etiology of Kawasaki disease remains unknown, although an infectious agent is strongly
suspected based on clinical and epidemiologic features. A genetic predisposition is also likely,
based on varying incidences among ethnic groups, with higher rates in Asians. Symptoms include
fever, conjunctival injection, erythema of the lips and oral mucosa, rash, and cervical lymphade-
nopathy. Some children with Kawasaki disease develop coronary artery aneurysms or ectasia,
ischemic heart disease, and sudden death. Kawasaki disease is the leading cause of acquired heart
disease among children in developed countries. This article provides a summary of the diagnos-
tic and treatment guidelines published by the American Heart Association. (Am Fam Physician
2006;74:1141-8, 1149-50. Copyright © 2006 American Academy of Family Physicians.)
K
awasaki disease was first described for at least five days and four or more of the
▲
Patient information:
A handout on Kawasaki in 1967 by Tomisaku Kawasaki five major clinical features (i.e., conjunctival
disease, written by the
authors of this article, is
and has replaced acute rheu- injection, cervical lymphadenopathy, oral
provided on page 1149. matic fever as the leading cause mucosal changes, polymorphous rash, and
of acquired heart disease among children in swelling or redness of the extremities), and
This article exem-
plifies the AAFP 2006 developed countries.1 The annual incidence exclusion of alternative diagnoses.3 Clinical
Annual Clinical Focus on of Kawasaki disease in children of Japanese features may not be present simultaneously,
caring for children and descent is about 150 per 100,000 children and taking a careful history is necessary in
adolescents.
younger than five years, and in the United children who lack a clear explanation for
States it affects approximately 10 to 15 per fever. If the typical clinical findings are pres-
100,000 children younger than five years.2 ent in a child with fever for less than five
Diagnosis relies on clinical criteria and sup- days, the diagnosis still can be made by expe-
porting ancillary studies. rienced physicians and treatment can be ini-
Recently, guidelines were published by the tiated.2 In addition, classic Kawasaki disease
American Heart Association (AHA) to aid in can be diagnosed with three clinical features
the diagnosis and management of Kawasaki if coronary artery abnormalities are observed
disease.2 Some children may present with on echocardiography.2 Because many of the
incomplete, or atypical, Kawasaki disease clinical features of Kawasaki disease may be
that displays some of the features of Kawa- present in other illnesses, exclusion of other
saki disease but does not meet the classic cri- illnesses in the differential diagnosis often is
teria. Diagnosis of Kawasaki disease in these necessary (Table 1).2
children often is difficult, and the incidence The fever of Kawasaki disease is usually
of coronary artery complications in patients higher than 102.2°F (39°C) and often above
with atypical disease is at least as high as in 104.0°F (40°C); if untreated, it lasts for an
those with classic Kawasaki disease. average of 11 days, although fever lasting
several weeks has been reported. Conjunc-
Diagnosis tival injection is typically bilateral and non-
classic (typical) clinical criteria purulent, and photophobia and eye pain are
There is no specific diagnostic assay for not often present. The injection is primarily
Kawasaki disease; therefore, diagnosis is of the bulbar conjunctiva with sparing of the
based on clinical criteria, which include fever limbus (the area immediately adjacent to the
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Kawasaki Disease
Evidence
Clinical recommendation rating References
CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; IVIG = intravenous immunoglobulin.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi-
dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information
about the SORT evidence rating system, see page 1079 or http://www.aafp.org/afpsort.xml.
cornea). Swelling or erythema of the hands usually does not occur until two to three
and feet is characterized by a sharp demar- weeks after onset of symptoms, when fever
cation at the ankles and wrists; the swelling typically has resolved. Oral mucosal changes
may be painful. Classic peeling of the fingers can manifest as red and cracked lips, straw-
and toes (starting in the periungual region) berry tongue, or diffuse erythema with no
focal lesions, ulcerations, or exudates.
Rash tends to appear within the first five
Table 1
days of illness and is truncal, often with
Differential Diagnosis
accentuation in the groin region (Figure 1).
of Kawasaki
Most commonly, the rash is erythematous
and maculopapular, although it may appear
urticarial, scarlatiniform, erythema multi-
forme-like, or as erythroderma. Bullous and
vesicular lesions are not present. Cervical
lymphadenopathy of at least 1.5 cm in diam-
The rightsholder did not eter is the least common clinical feature but
grant rights to reproduce may be the presenting and most prominent
this item in electronic sign (especially in older children), leading to
media. For the missing a misdiagnosis of bacterial lymphadenitis.4
item, see the original print There are other clinical features often shared
version of this publication. by children with Kawasaki disease that are
not incorporated into the diagnostic criteria
(Table 2).2
Laboratory and other ancillary studies,
although nonspecific, may support the diag-
nosis of Kawasaki disease (Table 3).2 With
more severe and prolonged illness, some
laboratory abnormalities (including anemia
and hypoalbuminemia) may become quite
1142 American Family Physician www.aafp.org/afp Volume 74, Number 7 ◆ October 1, 2006
Kawasaki Disease
Table 2
Clinical Features of Kawasaki Disease
Figure 1. Infant with Kawasaki disease with an Not Included in the Case Definition
erythematous, predominantly truncal rash.
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Kawasaki Disease
1144 American Family Physician www.aafp.org/afp Volume 74, Number 7 ◆ October 1, 2006
Kawasaki Disease
exists among medical centers concerning until six to eight weeks after disease onset if
when the aspirin dose should be reduced, there are no coronary artery abnormalities
either 48 to 72 hours after defervescence or indefinitely if abnormalities are present.
or 14 days after the onset of symptoms and In general, ibuprofen should be avoided
when the child has been afebrile for at least in children taking aspirin because it may
48 to 72 hours. Low-dose aspirin (3 to 5 mg antagonize the antiplatelet effect of aspirin.
per kg per day, given as a single dose) has an Reye’s syndrome is a risk for patients tak-
antiplatelet effect and should be continued ing high-dose aspirin during influenza or
Figure 2.
October 1, 2006 ◆ Volume 74, Number 7 www.aafp.org/afp American Family Physician 1145
Kawasaki Disease
varicella infection and is a possible but studies over a longer period may be indicated,
remote risk in patients receiving low-dose and consultation with a pediatric cardiologist
aspirin. Therefore, children on long-term is needed. The role of other cardiac imag-
aspirin therapy should receive annual influ- ing modalities, such as cardiac magnetic
enza vaccination. Also, parents should be resonance imaging and ultrafast computed
told to contact their physician if symptoms tomography, is currently under investigation.
of influenza or varicella arise, because alter- The acute management of patients with
native agents to aspirin may be considered. coronary artery abnormalities depends on
About 85 to 90 percent of patients respond the extent and severity of the lesion, and deci-
promptly to initial therapy of IVIG and high- sions usually are made in consultation with
dose aspirin; however, others have persistent a pediatric cardiologist. Although low-dose
or recurrent fever beyond 36 hours of therapy aspirin is adequate for patients with mild dis-
and require further treatment.12 In most ease (e.g., dilation; small, stable aneurysm),
centers, patients who fail to respond to the additional therapy such as antiplatelet agents
first dose of IVIG are given a second dose of and heparin may be required for patients with
2 g per kg. Steroids have been investigated more severe disease because of the increased
as an alternative to a second IVIG course, risk of thrombosis from the abnormal blood
but because their effects on coronary artery flow through coronary aneurysms.2
aneurysms are controversial, most experts Most patients with large or giant coronary
recommend withholding steroids unless fever artery aneurysms (i.e., internal diameter
persists after at least two courses of IVIG. greater than 8 mm) are maintained on aspi-
Other therapies, including pentoxifylline rin (or clopidogrel [Plavix]) and warfarin
(Trental), infliximab (Remicade; a monoclo- (Coumadin) to prevent thrombosis within
nal antibody against tumor necrosis factor the aneurysm and myocardial infarction.
a), plasma exchange, ulinastatin (a human No randomized controlled trials have been
trypsin inhibitor used in Japan; not available performed in children to determine the opti-
in the United States), abciximab (Reopro; mal prevention and treatment of coronary
a monoclonal platelet glycoprotein IIb/IIIa thrombosis, but a combination of therapies
receptor inhibitor), and cytotoxic agents such targeting different levels of the coagulation
as cyclophosphamide (Cytoxan), have been cascade is used most often. Abciximab has
used in small numbers of patients, but data are shown promise in restoring coronary artery
too limited for official recommendations.2 blood flow after acute thrombosis, but fur-
Serial echocardiography, performed at a ther study is needed.13
center experienced in examining the coro-
nary arteries of children, is indicated for Long-term Management
those with acute Kawasaki disease. The first Children who have Kawasaki disease with-
echocardiogram should be obtained when the out evidence of abnormalities on echocar-
diagnosis is suspected, but treatment should diography appear to return to their usual
not be delayed while waiting for the study to state of health without any cardiac sequelae;
be completed. Echocardiography provides a however, some follow-up studies have dem-
baseline for coronary artery dimensions and onstrated prolonged endothelial dysfunction
morphology and assesses cardiac function. and abnormal lipid profiles, even in chil-
For children with an uncomplicated course dren without demonstrable coronary abnor-
(e.g., fever resolves with initial therapy, no malities.14 Therefore, long-term surveillance
coronary artery abnormalities are present), studies are ongoing in this population.
echocardiography should be repeated at two About one half of the coronary artery
weeks and six to eight weeks after diagnosis.2 aneurysms associated with Kawasaki disease
Some centers also obtain a six- to 12-month resolve by echocardiography and angiog-
follow-up study. In children with a compli- raphy within one to two years, particularly
cated course (e.g., persistent fever, coronary those that are smaller and fusiform.15 Unfor-
or myocardial abnormalities), more frequent tunately, myointimal proliferation may lead
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Kawasaki Disease
October 1, 2006 ◆ Volume 74, Number 7 www.aafp.org/afp American Family Physician 1147
Kawasaki Disease
1148 American Family Physician www.aafp.org/afp Volume 74, Number 7 ◆ October 1, 2006