Kawasaki disease: Clinical features and diagnosis

Official reprint from UpToDate® www.uptodate.com

©2022 UpToDate®

Kawasaki disease: Clinical features and diagnosis

Author: Robert Sundel, MD
Section Editors: Marisa Klein-Gitelman, MD, MPH, Sheldon L Kaplan, MD
Deputy Editor: Elizabeth TePas, MD, MS

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2022. | This topic last updated: Jun 29, 2020.

INTRODUCTION

Kawasaki disease (KD, previously called mucocutaneous lymph node syndrome) is one of the
most common vasculitides of childhood [1]. KD also occurs rarely in adults. It is typically a
self-limited condition, with fever and manifestations of acute inflammation lasting for an
average of 12 days without therapy [2]. However, complications such as coronary artery (CA)
aneurysms, depressed myocardial contractility and heart failure, myocardial infarction,
arrhythmias, and peripheral arterial occlusion may develop and lead to significant morbidity
and mortality. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and
evaluation".)

The clinical manifestations and diagnosis of KD are discussed in this topic review. The
epidemiology, etiology, treatment, and complications of KD, including cardiac sequelae, are
presented separately. Incomplete (atypical) KD and unique features in infants and adults are
also reviewed separately. (See "Kawasaki disease: Epidemiology and etiology" and "Kawasaki
disease: Initial treatment and prognosis" and "Cardiovascular sequelae of Kawasaki disease:
Clinical features and evaluation" and "Incomplete (atypical) Kawasaki disease" and "Kawasaki
disease: Complications".)

CLINICAL MANIFESTATIONS
- Page 1 of 20 -
Kawasaki disease: Clinical features and diagnosis

The clinical features of KD reflect widespread inflammation of primarily medium-sized

muscular arteries. Diagnosis is based upon evidence of systemic inflammation (eg, fever) in
association with signs of mucocutaneous inflammation. The characteristic bilateral
nonexudative conjunctivitis, erythema of the lips and oral mucosa, rash, extremity changes,
and cervical lymphadenopathy typically develop after a brief nonspecific prodrome of
respiratory or gastrointestinal symptoms [3-8] (see 'Other findings' below). These
characteristic clinical signs are the basis for the diagnostic criteria for KD (table 1) [9].

Variations in age have the greatest impact on a patient's likelihood of developing

mucocutaneous manifestations of KD. Oral mucous membrane findings are seen in
approximately 90 percent of cases of KD, polymorphous rash in 70 to 90 percent, extremity
changes in 50 to 85 percent, ocular changes in >75 percent, and cervical lymphadenopathy in
25 to 70 percent [7,10-12].

These findings are often not present at the same time, and there is no typical order of
appearance. As an example, some patients have only developed fever and cervical
lymphadenopathy by the time of admission (so-called KD with isolated cervical
lymphadenopathy, KDiL) [13]. In one case series, these patients tended to be older and to
have a more severe course, with increased risk of coronary artery (CA) disease and lack of
response to intravenous immune globulin (IVIG). Thus, repeated histories and physical
examinations are important both for making a timely diagnosis of KD in children who fail to
meet diagnostic criteria, as well as for appropriate consideration of alternative diagnoses.
(See 'Diagnosis' below.)

Fever — An elevated body temperature is the most consistent manifestation of KD. Fever is
minimally responsive to antipyretic agents, and it typically remains above 38.5ºC (101.3ºF)
during most of the illness. On the other hand, fever may be intermittent and may be missed
by parents who use tympanic, temporal, axillary, or similar temperature measurement
methods that are less reliable than oral or rectal methods. Thus, the diagnosis should be
considered in all children with prolonged, unexplained fever ≥5 days but should still be
considered in seemingly afebrile children who have other findings consistent with KD. (See
"Incomplete (atypical) Kawasaki disease".)

Conjunctivitis — Bilateral nonexudative conjunctivitis is present in more than 90 percent of

- Page 2 of 20 -
Kawasaki disease: Clinical features and diagnosis

patients. A predominantly bulbar injection typically begins within days of the onset of fever,
and the eyes often have a brilliant erythema, which characteristically spares the limbus
(picture 1). Children also are frequently photophobic. In addition, anterior uveitis may develop
in up to 70 percent of children with ocular findings [12,14]; therefore, slit-lamp examination
may be helpful in ambiguous cases. The presence of uveitis provides further evidence for the
diagnosis of KD since it is more commonly seen in KD than in other diseases with similar
presentations. (See "Uveitis: Etiology, clinical manifestations, and diagnosis".)

Mucositis — Mucositis often becomes evident as KD progresses. Cracked, red lips (picture 2)
and a "strawberry tongue" (picture 3) are characteristic. The latter is a result of sloughing of
filiform papillae and denuding of the inflamed glossal tissue. The bumps on the "strawberry"
are the remaining fungiform papillae. These manifestations of oral mucositis may occur
singly, in a very mild form, or not at all. Discrete oral lesions, such as vesicles or ulcers, and
tonsillar exudate are suggestive of a disease process other than KD [6].

Rash — The cutaneous manifestations of KD are polymorphous. The rash usually begins
during the first few days of illness, typically as perineal erythema and desquamation, followed
by macular, morbilliform, or targetoid skin lesions of the trunk and extremities. Vesicular or
bullous lesions generally are not observed, but KD may trigger a psoriasiform eruption in
children not previously recognized to have psoriasis [15-19]. Patients may also have redness
or crust formation at the site of Bacille Calmette-Guérin (BCG) inoculation. This finding is
more useful for increasing the level of suspicion for KD in countries where BCG vaccine is
routinely given. (See 'Diagnosis' below.)

Extremity changes — Changes of the extremities are generally the last manifestation to
appear. Children develop an indurated edema of the dorsum of their hands and feet
(picture 4) and a diffuse erythema of their palms and soles.

The convalescent phase of KD is often characterized by sheet-like desquamation that begins

in the periungual region of the hands and feet (picture 5) and by linear nail creases (Beau's
lines). The prevalence of periungual desquamation in patients with KD has been reported to
vary from 68 to 98 percent [20].

Lymphadenopathy — Cervical lymphadenopathy is the least consistent feature of KD, absent

- Page 3 of 20 -
Kawasaki disease: Clinical features and diagnosis

in as many as one-half to three-quarters of children with the disease, especially those under
one year of age [11]. When present, lymphadenopathy tends to primarily involve the anterior
cervical nodes overlying the sternocleidomastoid muscles [21]. Often, only a single, large
node is palpable, although ultrasound imaging of the neck typically reveals numerous
discrete nodes arranged like a bunch of grapes [22].

Diffuse lymphadenopathy or other signs of reticuloendothelial involvement (eg,

splenomegaly) should prompt a search for alternative diagnoses. (See 'Differential diagnosis'
below.)

Cardiovascular findings — Cardiovascular findings are not part of the diagnostic criteria of
KD, but they support the diagnosis since most conditions that mimic KD do not involve the
heart. Cardiac manifestations during the first week to 10 days of illness may include
tachycardia out of proportion to the degree of fever and gallop sounds [2]. These physical
exam findings are the result of lymphocytic myocarditis that is ubiquitous in children with KD.
In addition, heart sounds may be muffled due to a pericardial effusion, which is detected in
approximately 30 percent of children with KD. Such effusions are usually small; significant
fluid collections and tamponade are rare.

With improved echocardiographic techniques and better understanding of age and sex
norms for CA diameters, approximately 30 percent of patients with KD are found to have CA
dilatation at diagnosis [23,24]. Frank aneurysms are usually not seen until after day 10 of
illness. Severely ill patients, particularly young infants, may develop fusiform aneurysms of
other nonvisceral medium-sized arteries, most characteristically involving the brachial
arteries. These are easily palpable or visible in the axillae, although they may be mistaken for
enlarged lymph nodes. In addition, young infants may have cold, pale, or cyanotic digits of
the hands and feet due to reduced perfusion. Gangrene may, in rare cases, cause loss of
fingers or toes during this acute period. The cardiac complications associated with KD are
discussed in detail separately. (See "Kawasaki disease: Complications", section on 'Cardiac
complications' and "Cardiovascular sequelae of Kawasaki disease: Clinical features and
evaluation".)

Arthritis — Arthritis is not included in the diagnostic criteria but has been reported in 7.5 to
25 percent of patients with KD [25,26]. The prevalence of arthritis was 7.5 percent in a
- Page 4 of 20 -
Kawasaki disease: Clinical features and diagnosis

retrospective Canadian study of 414 consecutive patients diagnosed with KD [25]. The large
joints (ie, knee, ankle, and hip) were primarily involved. Oligoarticular involvement (arthritis of
four or fewer joints) occurred in 16 patients and polyarticular involvement (arthritis of five or
more joints) in 15 patients. With only very rare exceptions, the arthritis is self-limited and
nondeforming. Patients with arthritis were more likely to have increased levels of
inflammatory markers (C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]) and
neutrophils. Otherwise, there were no differences in clinical features, response to therapy, or
clinical outcomes between patients with or without arthritis.

Other findings — The following nonspecific symptoms commonly occur during the
prodrome of the illness, 7 to 10 days before the typical mucocutaneous features develop [2,5]:

● Diarrhea, vomiting, or abdominal pain – 61 percent

● Irritability – 50 percent (older children with KD more commonly present with lethargy
than irritability)
● Vomiting alone – 44 percent
● Cough or rhinorrhea – 35 percent
● Decreased oral intake – 37 percent
● Joint pain – 15 percent

Patients with gastrointestinal involvement often have pseudo-obstruction on radiologic

studies [27]. The presentation of gastrointestinal symptoms before typical KD features may
delay the diagnosis and lead to unnecessary invasive procedures including surgery.

Infants — Infants are at increased risk of CA aneurysms, possibly in part because of delay in
treatment due to their lack of complete diagnostic criteria [28-31]. In a retrospective
Taiwanese study of 120 patients with KD that included 20 infants ≤6 months of age, for
example, the infants were more likely to present with incomplete KD than patients older than
six months of age (35 versus 12 percent), have CA involvement (65 versus 19 percent), and
receive late immune globulin therapy [30]. Even in infants diagnosed and treated before the
10th day of illness, the incidence of CA abnormalities is significantly higher than it is in older
patients. In a retrospective study of 720 children with KD, 88 of whom were <6 months of age,
a larger proportion of infants <6 months old had a dilated or aneurysmal CA on the initial
echocardiogram compared with those ≥6 months old (43.4 versus 19.5 percent) [32]. Of
- Page 5 of 20 -
Kawasaki disease: Clinical features and diagnosis

infants <6 months old who had a normal echocardiogram at diagnosis, 18.6 percent
developed a dilated or aneurysmal CA on a subsequent echocardiogram within eight weeks of
diagnosis.

Adults — Approximately one-fourth of adult KD cases have occurred in patients with human
immunodeficiency virus (HIV) infection [33]. One review found that cervical lymphadenopathy,
hepatitis, and arthralgia were all more common in adults with KD than in children, and
meningitis, thrombocytosis, and CA aneurysms were less common [34]. A subsequent review
of 43 adult patients with KD in France, which excluded cases associated with HIV, found more
sobering outcomes [35]. The median time to diagnosis was 13 days, and morbidity was
correspondingly high: 26 percent of patients demonstrated CA vasculitis, 19 percent had CA
aneurysms, and 9 percent had a myocardial infarction. Patients diagnosed before day 10,
however, had outcomes similar to those seen in children. In a separate case report,
splenomegaly and elevated serum ferritin levels were reported in one adult patient, most
likely due to macrophage activation syndrome (MAS) complicating KD [36]. (See "Kawasaki
disease: Complications", section on 'Macrophage activation syndrome'.)

LABORATORY FINDINGS

No laboratory studies are included among the diagnostic criteria for typical KD. However,
certain findings may support the diagnosis of KD, particularly in incomplete cases [1] (see
'Diagnosis' below and "Incomplete (atypical) Kawasaki disease", section on 'Laboratory tests'):

● Systemic inflammation is characteristic of KD. Typical manifestations include elevation of

acute-phase reactants (eg, C-reactive protein [CRP] or erythrocyte sedimentation rate
[ESR]), thrombocytosis that generally develops after the seventh day of illness,
leukocytosis, and a left-shift (increased immature neutrophils) in the white blood cell
(WBC) count.

CRP elevations resolve well before ESR does. However, patients with more severe
disease can have persistently high levels of CRP for weeks. Treatment with intravenous
immune globulin (IVIG) usually raises the ESR, so this lab test should not be measured
after a child receives IVIG. On the other hand, control of inflammation by IVIG
- Page 6 of 20 -
Kawasaki disease: Clinical features and diagnosis

accelerates the decrease in CRP, making this a more useful marker of disease activity in
a treated child.

Ferritin is another acute-phase reactant that is elevated in inflammatory conditions such

as KD, usually less than five times the upper limit of normal. Much higher values,
typically >5000 ng/mL, are seen in macrophage activation syndrome (MAS). This serious
but rare complication of KD is associated with an increased resistance to IVIG treatment
and an increased risk of CA abnormalities. Elevations of that magnitude are essentially
diagnostic of MAS in the setting of KD. (See "Kawasaki disease: Complications", section
on 'Macrophage activation syndrome' and "Clinical features and diagnosis of
hemophagocytic lymphohistiocytosis", section on 'Rheumatologic disorders/MAS'.)

Lymphocyte numbers typically drop during the acute phase of KD, then rise dramatically
during convalescence. Early in the course of disease, a complete blood count with a
lymphocytic rather than neutrophilic preponderance is more suggestive of a viral illness.
(See 'Differential diagnosis' below.)

Platelet counts generally rise by the second week of illness and may reach
1,000,000/mm3 (reactive thrombocytosis) in the most severe cases. In some studies, the
degree of thrombocytosis correlates with the risk of coronary artery (CA) changes in KD.
On the other hand, rare children with KD develop thrombocytopenia due to a
consumptive coagulopathy. These patients are at significantly increased risk of
morbidity and mortality, particularly the development of CA abnormalities [37]. (See
"Kawasaki disease: Complications", section on 'Cardiac complications'.)

Thrombocytopenia, high triglycerides, low sodium, elevated liver function tests, and
monocytes/macrophages in cerebral spinal fluid (CSF) can all be signs of subclinical MAS
and may warrant further diagnostic testing. (See "Kawasaki disease: Complications",
section on 'Macrophage activation syndrome'.)

● Children with KD often present with a normocytic, normochromic anemia. Hemoglobin

concentrations more than two standard deviations below the mean for age are noted in
one-half of patients within the first two weeks of illness (table 2).

● Urinary microscopy commonly reveals WBCs [38]. Pyuria is usually of urethral origin and
- Page 7 of 20 -
Kawasaki disease: Clinical features and diagnosis

therefore may be missed on urinalyses obtained by bladder tap or catheterization [39].

The WBCs are not polymorphonuclear leukocytes and therefore are not detected by
dipstick tests for leukocyte esterase. Thus, children with suspected KD should have a
clean voided or bagged urine specimen collected for microscopic examination in order
to detect this characteristic feature.

● In one retrospective series of 259 patients, 45 percent had at least one abnormal liver
function test [40]. In a case-control series, approximately 30 percent of 280 patients with
KD had mild-to-moderate elevation of transaminases (eg, serum alanine
aminotransferase >50 units/L) [6]. The reason for this transaminitis is unclear. In
addition, a minority of children develop obstructive jaundice from hydrops of the
gallbladder.

● CSF may display a mononuclear pleocytosis without hypoglycorrhachia (decreased CSF

glucose) or elevation of CSF protein. In a retrospective review, 46 of 520 children with KD
underwent lumbar puncture [41]. In this subset of patients, 39 percent had elevated CSF
WBC counts. The median count was 22.5 cells/mm3 with 6 percent neutrophils and 92
percent mononuclear cells, although cell counts as high as 320/mm3 with up to 79
percent neutrophils were reported.

● Similarly, arthrocentesis of inflamed joints in KD typically demonstrates a pleocytosis,

with 125,000 to 300,000 WBCs/mm3, primarily neutrophils [42].

● Children with KD develop significant perturbations in serum lipid profiles, including

elevated triglycerides and low-density lipoproteins, and depressed high-density
lipoproteins [2,43-45], as is often observed in a variety of infectious and inflammatory
conditions. A return to normal generally occurs within weeks or months following IVIG
therapy, though abnormalities may persist for years in children who are not treated with
IVIG [44].

● Hyponatremia (serum sodium <135 mEq/L) may be seen and is associated with an
increased risk of CA aneurysms [46].

- Page 8 of 20 -
Kawasaki disease: Clinical features and diagnosis

DIAGNOSIS

Diagnosis of KD according to the criteria established by Tomisaku Kawasaki in 1967 [47]

requires the presence of fever lasting ≥5 days, combined with at least four of the five
following physical findings, without an alternative explanation (table 1) [1,2,48]:

● Bilateral bulbar conjunctival injection (picture 1)

● Oral mucous membrane changes, including injected or fissured lips (picture 2), injected
pharynx, or strawberry tongue (picture 3)

● Peripheral extremity changes, including erythema of palms or soles, edema of hands or

feet (acute phase) (picture 4), or periungual desquamation (convalescent phase)
(picture 5)

● Polymorphous rash

● Cervical lymphadenopathy (at least one lymph node >1.5 cm in diameter)

Approximately 40 percent of children with KD have a concurrent infection. Ascribing the fever
to such an infection or to KD requires clinical judgement.

Redness or crust formation at the site of Bacille Calmette-Guérin (BCG) inoculation is also
suggested as a useful sign in several diagnostic guidelines [2,9]. In one series of 15,524
patients with KD and a history of BCG vaccination, 50 percent had this finding compared with
none of the 53 children admitted with respiratory syncytial virus or rotavirus infection who
served as the control group [19].

Rash and conjunctival injection are seen with many illnesses, but other KD features, such as
red, cracked lips and redness and swelling of the hands and feet, are unusual in the illnesses
in the differential diagnosis and should increase the suspicion for KD. (See 'Differential
diagnosis' below.)

Typical versus incomplete KD — As with all clinical criteria, these are imperfect guidelines
with less than 100 percent sensitivity and specificity. In addition, Dr. Kawasaki published his

- Page 9 of 20 -
Kawasaki disease: Clinical features and diagnosis

guidelines before cardiac involvement was recognized in this disease, so they were never
intended to identify children at risk for developing coronary artery (CA) abnormalities. Thus, it
is not surprising that at least 10 percent of children who develop CA aneurysms never meet
criteria for KD [49]. Incomplete KD should be suspected in patients less than six months of
age with unexplained fever ≥7 days, even if they have no clinical findings of KD, and in
patients of any age with unexplained fever ≥5 days and only two or three clinical criteria. An
algorithmic approach can help identify such cases (algorithm 1) [2] and thereby significantly
decrease the number of children who develop CA abnormalities despite not meeting criteria
for the disease. (See "Incomplete (atypical) Kawasaki disease".)

Laboratory evaluation — As noted above, Dr. Kawasaki identified the first 50 cases of
"mucocutaneous lymph node syndrome" on the basis of clinical findings rather than
laboratory or imaging studies [47]. Thus, no laboratory values are included in the classical
diagnostic criteria, but they nonetheless may support a diagnosis of KD in ambiguous cases.
In fact, some laboratory tests are explicitly included in the algorithm for diagnosis of atypical
KD (algorithm 1) [2]. (See "Incomplete (atypical) Kawasaki disease", section on 'Laboratory
tests'.)

The following blood tests are typically obtained on children in whom a diagnosis of KD is
being considered:

● Complete blood counts with differential white blood cell (WBC) counts
● Liver function tests including aspartate transaminase (AST), alanine transaminase (ALT),
and albumin
● C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
● Urinalysis

Elevated WBC and platelet counts, transaminases, and acute-phase reactants, as well as
anemia and pyuria, are suggestive of KD.

In addition, when specific mimics of KD are strongly suspected, studies that are more specific
for these alternative diagnoses may help confirm the diagnosis. These can include rapid viral
testing (eg, adenovirus), serologic testing for leptospirosis and other bacterial infections, and
blood cultures. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated

- Page 10 of 20 -
Kawasaki disease: Clinical features and diagnosis

with an emerging syndrome (multisystem inflammatory syndrome in children [MIS-C]) of

persistent fever, systemic inflammation, and multiorgan failure children with some features
of KD [50]. Polymerase chain reaction (PCR) testing for SARS-CoV-2 should be performed in
children who present with features of MIS-C, particularly if there is evidence of coronavirus
disease 19 (COVID-19) exposure. (See "COVID-19: Multisystem inflammatory syndrome in
children (MIS-C) clinical features, evaluation, and diagnosis".)

Echocardiography — Echocardiography should be performed in all patients with KD as soon

as the diagnosis is suspected in order to establish a reference point for longitudinal follow-up
(algorithm 1) and treatment efficacy. In addition, initial CA diameter is a factor in identifying
patients at high risk of developing a coronary aneurysm and therefore warranting
augmentation of initial intravenous immune globulin (IVIG) therapy (see "Kawasaki disease:
Complications", section on 'Coronary artery abnormalities' and "Cardiovascular sequelae of
Kawasaki disease: Clinical features and evaluation", section on 'Risk factors'). Finally, CA
diameters are useful for identifying patients who should be treated with IVIG despite failing
to meet classical diagnostic criteria for KD. Echocardiographic evaluation for KD is discussed
in greater detail separately. (See "Cardiovascular sequelae of Kawasaki disease: Clinical
features and evaluation", section on 'Initial evaluation' and "Incomplete (atypical) Kawasaki
disease", section on 'Echocardiography'.)

DIFFERENTIAL DIAGNOSIS

KD is most commonly confused with infectious exanthems of childhood [2,51,52]. Early in the
course, KD is often mistaken for more routine childhood illnesses, such as viral
gastroenteritis, viral upper respiratory tract infection, or pneumonia, depending upon the
other presenting symptoms, such as vomiting or cough. Concurrent viral infections are
common, and, therefore, the presence of respiratory symptoms or positive respiratory viral
polymerase chain reaction (PCR) testing does not exclude the diagnosis of KD [53]. Meningitis
is sometimes suspected due to irritability.

Infectious diseases and other mimics of KD may have the following clinical features not
commonly found in KD [2]:

- Page 11 of 20 -
Kawasaki disease: Clinical features and diagnosis
● Exudative conjunctivitis (eg, adenovirus)
● Exudative pharyngitis (eg, streptococcal pharyngitis)
● Discrete intraoral lesions (eg, Koplik spots in measles)
● Bullous or vesicular rash (eg, Stevens-Johnson syndrome [SJS])
● Generalized lymphadenopathy (eg, Epstein-Barr virus [EBV] infection)

The presence of any of these findings and/or the absence of fever should suggest a diagnosis
other than KD. Of note, concurrent infections (both viral and bacterial) are common in
patients with KD, found in up to 33 percent of children in one study [54]. In this retrospective
analysis of 129 consecutive children seen with KD in Toronto, infection at the time of
diagnosis did not affect response to therapy or outcome. In any event, diagnosis of an
infectious condition does not preclude a concurrent diagnosis of KD.

The differential diagnosis of KD includes (table 3):

● Measles, echovirus, adenovirus [55], and EBV – These viral illnesses may share many of
the signs of mucocutaneous inflammation, but they typically have less evidence of
systemic inflammation and generally lack the extremity changes seen in KD. In addition,
EBV typically causes a polyclonal gammopathy while serum immunoglobulin G (IgG) in
KD is usually low or low normal [56]. (See "Measles: Clinical manifestations, diagnosis,
treatment, and prevention" and "Enterovirus and parechovirus infections: Clinical
features, laboratory diagnosis, treatment, and prevention" and "Pathogenesis,
epidemiology, and clinical manifestations of adenovirus infection" and "Clinical
manifestations and treatment of Epstein-Barr virus infection".)

● Toxin-mediated illnesses, especially group A streptococcal infections (eg, scarlet fever

and toxic shock syndrome) – These usually lack the ocular and articular involvement
typical of KD, though patients with staphylococcal toxic shock syndrome occasionally
have conjunctival erythema. Patients with toxic shock often have generalized edema.
The edema is rarely confined to the hands and feet, as it is in children with KD. Patients
with scarlet fever may have periungual desquamation. (See "Invasive group A
streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations,
and diagnosis" and "Staphylococcal toxic shock syndrome" and "Group A streptococcal
(Streptococcus pyogenes) bacteremia in children", section on 'Clinical manifestations'.)
- Page 12 of 20 -
Kawasaki disease: Clinical features and diagnosis
● Rocky Mountain spotted fever and leptospirosis – Headache and gastrointestinal
complaints typically are prominent features of these infections. (See "Clinical
manifestations and diagnosis of Rocky Mountain spotted fever" and "Leptospirosis:
Epidemiology, microbiology, clinical manifestations, and diagnosis".)

● Drug reactions such as SJS or serum sickness – These may mimic KD but with subtle
differences in the ocular and mucosal manifestations, such as keratitis in SJS rather than
uveitis in KD. Further, laboratory markers of inflammation are generally normal or only
mildly elevated. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis:
Pathogenesis, clinical manifestations, and diagnosis".)

● Systemic juvenile idiopathic arthritis (JIA) – Children with this condition generally lack the
conjunctival and oral findings of KD. Lymphadenopathy also is generalized, and it may
be accompanied by splenomegaly, unlike in KD. While systemic JIA is not generally
associated with cardiac involvement other than pericarditis, several case reports have
documented moderate coronary involvement (Z-score <3.0) in children with systemic JIA
[57]. (See "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis".)

Delayed diagnosis — Treatment with intravenous immune globulin (IVIG) within the first 10
days of illness reduces the prevalence of coronary artery (CA) aneurysms fivefold compared
with children not treated with IVIG [58,59]. Thus, it is desirable to diagnose KD as soon as
possible after the onset of symptoms in order to initiate treatment and reduce the risk of CA
lesions [60]. However, timely identification is challenging because the diagnosis is based upon
nonspecific clinical signs and there is no definitive diagnostic test. Thus, the clinicians in a
medical facility with the most experience taking care of patients with KD should be consulted
as early as possible in the course of the evaluation of suspected KD. These clinicians may
include pediatric rheumatologists, infectious disease specialists, cardiologists, and/or
hospitalists, depending upon the institution.

In a retrospective study of 562 patients diagnosed with KD at eight North American centers,
92 cases (16 percent) were diagnosed after the first 10 days of illness (ie, late diagnosis) [61].
Predictors of a delay in diagnosis of KD included age below six months, clinical presentation
of incomplete KD, greater distance from a tertiary center, and variability between clinical
centers. In contrast, socioeconomic status was not associated with a delay in diagnosis.
- Page 13 of 20 -
Kawasaki disease: Clinical features and diagnosis

These findings suggest that practice variation in confirming a diagnosis of KD may in part
contribute to a delayed diagnosis. The results of this study underscore the need for a high
index of suspicion of KD, especially in young infants and patients who present with
incomplete KD, in order to identify and treat patients in a timely manner. (See "Incomplete
(atypical) Kawasaki disease".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Kawasaki disease".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles on
a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Kawasaki disease (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Overview – Kawasaki disease (KD, also called mucocutaneous lymph node syndrome) is
one of the most common vasculitides of childhood. KD occurs only rarely in adults. It is
- Page 14 of 20 -
Kawasaki disease: Clinical features and diagnosis

typically a self-limited condition, with fever and manifestations of acute inflammation

lasting for an average of 12 days without therapy. (See 'Introduction' above.)

● Clinical manifestations – KD is characterized by systemic inflammation manifested by

fever and mucocutaneous involvement, including bilateral nonexudative conjunctivitis
(picture 1), erythema of the lips and oral mucosa (picture 2 and picture 3), polymorphous
rash, extremity changes (picture 4 and picture 5), and cervical lymphadenopathy
(table 1). These findings are often not present at the same time. Thus, repeated histories
and physical examinations are important in making a timely diagnosis of KD in children
with fever and signs of mucocutaneous inflammation. (See 'Clinical manifestations'
above.)

● Laboratory findings – No laboratory studies are included among the diagnostic criteria
for typical KD. However, the presence of compatible laboratory features strongly
supports the diagnosis. (See 'Laboratory findings' above and "Incomplete (atypical)
Kawasaki disease", section on 'Laboratory tests'.)

● Diagnosis – The diagnosis of KD according to classical criteria requires the presence of

fever ≥5 days, combined with at least four of the other five signs of mucocutaneous
inflammation, without any other explanation (table 1 and algorithm 1). A significant
proportion of children with KD have a concurrent infection; therefore, ascribing the fever
to such an infection or to KD requires clinical judgment. Additional clinical and
laboratory features are often used to guide diagnosis in children who have fewer than
five criteria for KD (incomplete KD). (See 'Diagnosis' above and "Incomplete (atypical)
Kawasaki disease".)

● Incomplete KD and delayed diagnosis in infants and adults – Infants and possibly
adults are more likely to present with incomplete KD. Infants are at greater risk for
cardiovascular sequelae, possibly due in part to a delay in diagnosis and intervention.
Thus, infants six months of age or younger with unexplained fever for at least seven
days should be evaluated for KD, even if they have no clinical findings of KD. Adults with
delayed diagnosis also have a higher rate of morbidity. (See 'Infants' above and 'Adults'
above.)

- Page 15 of 20 -
Kawasaki disease: Clinical features and diagnosis
● Differential diagnosis – KD is most commonly confused with infectious exanthems of
childhood. The presence of clinical features not commonly found in KD, including
exudative conjunctivitis, exudative pharyngitis, discrete intraoral lesions, bullous or
vesicular rash, splenomegaly, and/or generalized lymphadenopathy, suggest another
diagnosis (table 3). Nonetheless, KD is sufficiently pleomorphic that none of these
findings can definitively exclude the diagnosis. Children with KD can have concurrent
infections, particularly with viruses circulating in the community at the time of their
diagnosis. (See 'Differential diagnosis' above.)

REFERENCES

1. Burns JC, Glodé MP. Kawasaki syndrome. Lancet 2004; 364:533.

2. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term
Management of Kawasaki Disease: A Scientific Statement for Health Professionals From
the American Heart Association. Circulation 2017; 135:e927.
3. Morens DM, Anderson LJ, Hurwitz ES. National surveillance of Kawasaki disease.
Pediatrics 1980; 65:21.

4. Huang GY, Ma XJ, Huang M, et al. Epidemiologic pictures of Kawasaki disease in Shanghai
from 1998 through 2002. J Epidemiol 2006; 16:9.

5. Baker AL, Lu M, Minich LL, et al. Associated symptoms in the ten days before diagnosis of
Kawasaki disease. J Pediatr 2009; 154:592.

6. Burns JC, Mason WH, Glode MP, et al. Clinical and epidemiologic characteristics of
patients referred for evaluation of possible Kawasaki disease. United States Multicenter
Kawasaki Disease Study Group. J Pediatr 1991; 118:680.

7. Ozdemir H, Ciftçi E, Tapisiz A, et al. Clinical and epidemiological characteristics of children

with Kawasaki disease in Turkey. J Trop Pediatr 2010; 56:260.

8. Cai Z, Zuo R, Liu Y. Characteristics of Kawasaki disease in older children. Clin Pediatr
(Phila) 2011; 50:952.

9. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki

disease (the 5th revised edition). Pediatr Int 2005; 47:232.

10. Fukushige J, Takahashi N, Ueda Y, Ueda K. Incidence and clinical features of incomplete
- Page 16 of 20 -
Kawasaki disease: Clinical features and diagnosis

Kawasaki disease. Acta Paediatr 1994; 83:1057.

11. Sung RY, Ng YM, Choi KC, et al. Lack of association of cervical lymphadenopathy and
coronary artery complications in Kawasaki disease. Pediatr Infect Dis J 2006; 25:521.

12. Germain BF, Moroney JD, Guggino GS, et al. Anterior uveitis in Kawasaki disease. J Pediatr
1980; 97:780.

13. Nomura Y, Arata M, Koriyama C, et al. A severe form of Kawasaki disease presenting with
only fever and cervical lymphadenopathy at admission. J Pediatr 2010; 156:786.
14. Smith LB, Newburger JW, Burns JC. Kawasaki syndrome and the eye. Pediatr Infect Dis J
1989; 8:116.

15. Eberhard BA, Sundel RP, Newburger JW, et al. Psoriatic eruption in Kawasaki disease. J
Pediatr 2000; 137:578.

16. Kishimoto S, Muneuchi J, Takahashi Y, et al. Psoriasiform skin lesion and supprative
acrodermatitis associated with Kawasaki disease followed by the treatment with
infliximab: a case report. Acta Paediatr 2010; 99:1102.
17. Ergin S, Karaduman A, Demirkaya E, et al. Plaque psoriasis induced after Kawasaki
disease. Turk J Pediatr 2009; 51:375.

18. Liao YC, Lee JY. Psoriasis in a 3-month-old infant with Kawasaki disease. Dermatol Online J
2009; 15:10.

19. Uehara R, Igarashi H, Yashiro M, et al. Kawasaki disease patients with redness or crust
formation at the Bacille Calmette-Guérin inoculation site. Pediatr Infect Dis J 2010;
29:430.
20. Wang S, Best BM, Burns JC. Periungual desquamation in patients with Kawasaki disease.
Pediatr Infect Dis J 2009; 28:538.

21. April MM, Burns JC, Newburger JW, Healy GB. Kawasaki disease and cervical adenopathy.
Arch Otolaryngol Head Neck Surg 1989; 115:512.

22. Kanegaye JT, Van Cott E, Tremoulet AH, et al. Lymph-node-first presentation of Kawasaki
disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr
2013; 162:1259.
23. Dominguez SR, Anderson MS, El-Adawy M, Glodé MP. Preventing coronary artery

- Page 17 of 20 -
Kawasaki disease: Clinical features and diagnosis

abnormalities: a need for earlier diagnosis and treatment of Kawasaki disease. Pediatr
Infect Dis J 2012; 31:1217.

24. Printz BF, Sleeper LA, Newburger JW, et al. Noncoronary cardiac abnormalities are
associated with coronary artery dilation and with laboratory inflammatory markers in
acute Kawasaki disease. J Am Coll Cardiol 2011; 57:86.

25. Gong GW, McCrindle BW, Ching JC, Yeung RS. Arthritis presenting during the acute phase
of Kawasaki disease. J Pediatr 2006; 148:800.

26. Melish ME. Kawasaki syndrome: a 1986 perspective. Rheum Dis Clin North Am 1987; 13:7.

27. Colomba C, La Placa S, Saporito L, et al. Intestinal Involvement in Kawasaki Disease. J

Pediatr 2018; 202:186.

28. Yanagawa H, Tuohong Z, Oki I, et al. Effects of gamma-globulin on the cardiac sequelae
of Kawasaki disease. Pediatr Cardiol 1999; 20:248.

29. Burns JC, Capparelli EV, Brown JA, et al. Intravenous gamma-globulin treatment and
retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr
Infect Dis J 1998; 17:1144.

30. Chang FY, Hwang B, Chen SJ, et al. Characteristics of Kawasaki disease in infants younger
than six months of age. Pediatr Infect Dis J 2006; 25:241.

31. Yeom JS, Woo HO, Park JS, et al. Kawasaki disease in infants. Korean J Pediatr 2013;
56:377.

32. Salgado AP, Ashouri N, Berry EK, et al. High Risk of Coronary Artery Aneurysms in Infants
Younger than 6 Months of Age with Kawasaki Disease. J Pediatr 2017; 185:112.
33. Sève P, Lega JC. [Kawasaki disease in adult patients]. Rev Med Interne 2011; 32:17.

34. Wolff AE, Hansen KE, Zakowski L. Acute Kawasaki disease: not just for kids. J Gen Intern
Med 2007; 22:681.
35. Fraison JB, Sève P, Dauphin C, et al. Kawasaki disease in adults: Observations in France
and literature review. Autoimmun Rev 2016; 15:242.

36. Cunha BA, Pherez FM, Alexiadis V, et al. Adult Kawasaki's disease with myocarditis,
splenomegaly, and highly elevated serum ferritin levels. Heart Lung 2010; 39:164.

37. Nofech-Mozes Y, Garty BZ. Thrombocytopenia in Kawasaki disease: a risk factor for the
- Page 18 of 20 -
Kawasaki disease: Clinical features and diagnosis

development of coronary artery aneurysms. Pediatr Hematol Oncol 2003; 20:597.

38. Shike H, Kanegaye JT, Best BM, et al. Pyuria associated with acute Kawasaki disease and
fever from other causes. Pediatr Infect Dis J 2009; 28:440.

39. Watanabe T, Abe Y, Sato S, et al. Sterile pyuria in patients with Kawasaki disease
originates from both the urethra and the kidney. Pediatr Nephrol 2007; 22:987.

40. Eladawy M, Dominguez SR, Anderson MS, Glodé MP. Abnormal liver panel in acute
kawasaki disease. Pediatr Infect Dis J 2011; 30:141.
41. Dengler LD, Capparelli EV, Bastian JF, et al. Cerebrospinal fluid profile in patients with
acute Kawasaki disease. Pediatr Infect Dis J 1998; 17:478.

42. Hicks RV, Melish ME. Kawasaki syndrome. Pediatr Clin North Am 1986; 33:1151.
43. Salo E, Pesonen E, Viikari J. Serum cholesterol levels during and after Kawasaki disease. J
Pediatr 1991; 119:557.

44. Newburger JW, Burns JC, Beiser AS, Loscalzo J. Altered lipid profile after Kawasaki
syndrome. Circulation 1991; 84:625.

45. Cabana VG, Gidding SS, Getz GS, et al. Serum amyloid A and high density lipoprotein
participate in the acute phase response of Kawasaki disease. Pediatr Res 1997; 42:651.

46. Nakamura Y, Yashiro M, Uehara R, et al. Use of laboratory data to identify risk factors of
giant coronary aneurysms due to Kawasaki disease. Pediatr Int 2004; 46:33.

47. Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with
specific desquamation of the fingers and toes in children]. Arerugi 1967; 16:178.
48. Centers for Disease Control. Kawasaki disease — New York. MMWR Morb Mortal Wkly
Rep 1980; 29:61.

49. Sundel RP. Update on the treatment of Kawasaki disease in childhood. Curr Rheumatol
Rep 2002; 4:474.

50. Royal College of Paediatrics and Child Health (RCPCH). Guidance: Paediatric multisystem i
nflammatory syndrome temporally associated with COVID-19. https://www.rcpch.ac.uk/si
tes/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndro
me-20200501.pdf (Accessed on May 14, 2020).

51. Yanagihara R, Todd JK. Acute febrile mucocutaneous lymph node syndrome. Am J Dis
- Page 19 of 20 -
Kawasaki disease: Clinical features and diagnosis

Child 1980; 134:603.

52. Barron KS. Kawasaki disease in children. Curr Opin Rheumatol 1998; 10:29.

53. Turnier JL, Anderson MS, Heizer HR, et al. Concurrent Respiratory Viruses and Kawasaki
Disease. Pediatrics 2015; 136:e609.

54. Benseler SM, McCrindle BW, Silverman ED, et al. Infections and Kawasaki disease:
implications for coronary artery outcome. Pediatrics 2005; 116:e760.

55. Jaggi P, Kajon AE, Mejias A, et al. Human adenovirus infection in Kawasaki disease: a
confounding bystander? Clin Infect Dis 2013; 56:58.

56. Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma
globulin as compared with four infusions in the treatment of acute Kawasaki syndrome.
N Engl J Med 1991; 324:1633.

57. Binstadt BA, Levine JC, Nigrovic PA, et al. Coronary artery dilation among patients
presenting with systemic-onset juvenile idiopathic arthritis. Pediatrics 2005; 116:e89.

58. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gammaglobulin for

Kawasaki disease. Lancet 1984; 2:1055.

59. Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with
intravenous gamma globulin. N Engl J Med 1986; 315:341.
60. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term
management of Kawasaki disease: a statement for health professionals from the
Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on
Cardiovascular Disease in the Young, American Heart Association. Pediatrics 2004;
114:1708.

61. Minich LL, Sleeper LA, Atz AM, et al. Delayed diagnosis of Kawasaki disease: what are the
risk factors? Pediatrics 2007; 120:e1434.

Topic 6417 Version 35.0

© 2022 UpToDate, Inc. All rights reserved.

- Page 20 of 20 -