kawasaki

DOI: 10.1542/pir.29-9-308 2008;29;308-316 Pediatr. Rev.

Angela M. Fimbres and Stanford T. Shulman Kawasaki Disease

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Kawasaki DiseaseAngela M. Fimbres, MD,

MPH,* Stanford T.

Shulman, MD†

Author Disclosure

Drs Fimbres and

Shulman have

disclosed no financial

relationships relevant

to this article. This

commentary does not

contain a discussion

of an unapproved/

investigative use of a

commercial

product/device.

Objectives After completing this article, readers should be able to:

1. Describe the clinical and laboratory manifestations of Kawasaki disease (KD).2. Describe the features of atypical, or incomplete, KD.3. Discuss the value of high-dose aspirin and intravenous immune globulin (IVIG) in the

treatment of KD and possible therapies for IVIG-refractory KD.4. Identify the cardiac complications of KD and the importance of evaluation and

follow-up.5. Delineate the prognosis and management of KD.

IntroductionKawasaki disease (KD) is an acute, self-limited vasculitis of unknown cause that has astriking predilection for the coronary arteries of infants and young children. First describedin Japan in 1967 by Tomisaku Kawasaki, the disease now is known to occur in theAmericas, Europe, and Asia in children of all races. In retrospect, the entity known asinfantile polyarteritis nodosa likely is a part of the continuum of KD, and clinically mild KDprobably was confused with diseases such as measles or scarlet fever before the advent ofvaccines and antibiotics. In fact, old reports on infantile polyarteritis nodosa describepathologic findings that are identical to those of fatal KD.

EpidemiologyKD is markedly more prevalent in Japan and in children of Japanese ethnicity, having anannual incidence of 150 cases per 100,000 children younger than 5 years of age, about10 times the rate in the United States. In the United States, the incidence of KD has beenestimated recently by using hospital discharge data. An estimated 4,248 hospitalizationsassociated with KD occurred in the United States in the year 2000, with a median age of2 years. The incidence of KD was highest among Asians and Pacific Islanders and lowest inwhite children. Boys outnumbered girls by 3:2, and 76% of children were younger than age5 years. In-hospital mortality was 0.17%. Virtually all deaths in patients who have KD resultfrom cardiac sequelae. The peak mortality occurs 15 to 45 days after the onset of fever.However, sudden death from myocardial infarction (MI) may occur many years later inindividuals who developed coronary artery aneurysms and stenoses in childhood. Manycases of ischemic heart disease in young adults have been attributed to “missed” KD inchildhood.

Recurrence rates and the importance of genetic factors in KD are documented best inJapan, where the recurrence rate is approximately 3%. The proportion of cases that have apositive family history is approximately 1%. The risk of occurrence in twins is approximately13%. These data suggest that a genetic predisposition interacts with an environmentaletiologic agent to cause disease. The occasional occurrence of KD in children of parentswho had KD in childhood also supports the contribution of genetic factors. Reportedassociations of KD with respiratory illnesses and exposure to carpet-cleaning fluids havenot been confirmed.

*Fellow, Pediatric Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, Ill.†Professor of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Ill.

Article collagen vascular disorders

308 Pediatrics in Review Vol.29 No.9 September 2008. Provided by LSU School of Med-Shrevepo on July 5, 2010 http://pedsinreview.aappublications.orgDownloaded from


Causes and PathogenesisAlthough the cause of KD remains elusive, clinical andepidemiologic features strongly suggest an infectioussource. A self-limited, generally nonrecurring illness thatmanifests with fever fits well with an infectious cause ortrigger. Laboratory features also suggest an infectiousagent as the cause of the inflammation. However, despiteextensive efforts to identify an infectious agent in KDwith conventional bacterial and viral cultures and sero-logic methods, researchers have not yet been successfulin finding such an agent, although they are makingprogress. Recent investigations have discovered that theimmune response in KD is oligoclonal or antigen-driven(ie, similar to a response to a conventional antigen) ratherthan polyclonal, and immunoglobulin A (IgA) plasmacells play a central role. The prominence of IgA plasmacells in the respiratory tracts of patients who had fatalacute-stage KD, which is similar to findings in fatal viralrespiratory infections, suggests a respiratory pathogen.

KD is a generalized vasculitis affecting all blood ves-sels throughout the body, but preferentially involvingthe coronary arteries. The early stages in the develop-ment of vasculitis have been well studied in large muscu-lar arteries. An influx of neutrophils is found early afteronset, with a rapid transition to large mononuclear cellsin concert with lymphocytes and IgA plasma cells. Activeinflammation is replaced over several weeks to months byprogressive fibrosis, with scar formation.

DiagnosisClinical criteria have been established to assist physiciansin diagnosing KD because there is no definitive diagnos-tic test. The classic diagnosis of KD has been based on thepresence of five or more days of fever and four or more ofthe five principal clinical features (Table 1). Those fea-tures are 1) changes in the hands and feet (erythema,

edema, peeling), 2) polymorphous exanthema, 3) bilat-eral bulbar conjunctival injection without exudate,4) changes in the lips and oral cavity (erythema, straw-berry tongue), and 5) cervical lymphadenopathy. Ofcourse, exclusion of other diseases that have similar find-ings is necessary. Patients who have fever for 5 or moredays and only three principal features can be diagnosed ashaving classic KD when coronary artery disease is de-tected by two-dimensional echocardiography or coro-nary angiography. The fever typically is high-spiking andremittent. In the absence of therapy, fever persists for amean of 11 days. With appropriate therapy, fever usuallyresolves within 2 days.

Changes in the extremities include erythema of thepalms and soles or firm, sometimes painful induration ofthe hands and feet and later desquamation of the fingersand toes. The desquamation usually begins in the peri-ungual region within 2 to 3 weeks after the onset of feverand may extend to include the palms and soles. Inaddition, 1 to 2 months after the onset of fever, deeptransverse grooves across the nails, known as Beau lines,may appear.

An erythematous rash usually appears within 5 days ofthe onset of fever. The rash may have various forms, butmost common is a nonspecific diffuse rash consisting ofscattered macules and erythematous papules. Bullousand vesicular eruptions have not been described in KD; ifthey are present, the physician should consider otherdiagnoses. Occasionally seen in KD are urticarial exan-thems, a scarlatiniform rash, erythroderma, erythemamultiforme, or rarely, a fine micropustular eruption. Therash is accentuated in the perineal region, where earlydesquamation may begin.

Bilateral painless conjunctival injection usually beginsshortly after the onset of fever, typically involving thebulbar conjunctivae and usually not associated with anexudate or conjunctival edema. Changes of the lips andoral cavity are protean and include erythema, dryness,fissuring, peeling, cracking, and bleeding of the lips; a“strawberry tongue” that has erythema and prominentpapillae; and diffuse erythema of the oropharyngeal mu-cosa. Oral ulcers and pharyngeal exudate are not seen.

Cervical lymphadenopathy is the least common of theprincipal clinical features. It usually is unilateral, is con-fined to the anterior cervical triangle, and is defined as1.5 cm or more in diameter. The lymph nodes often arefirm and nontender and have no overlying erythema.

Multiple other clinical findings can be seen in patientswho have KD. Arthritis or arthralgia can occur in the firstweek and tends to involve multiple joints. Children whohave KD often are more irritable than are children who

Table 1. Diagnostic Criteria forKawasaki DiseaseFever for at least 5 days and four of the five following

criteria:

● Bilateral conjunctival injection● Changes of the mucous membranes of the upper

respiratory tract: injected pharynx; infected, fissuredlips; strawberry tongue

● Polymorphous rash● Changes of the extremities: peripheral edema,

peripheral erythema, periungual desquamation● Cervical adenopathy

collagen vascular disorders Kawasaki disease

Pediatrics in Review Vol.29 No.9 September 2008 309. Provided by LSU School of Med-Shrevepo on July 5, 2010 http://pedsinreview.aappublications.orgDownloaded from


have other febrile illnesses. Gastrointestinal complaints,including diarrhea, vomiting, and abdominal pain, occurin approximately one third of patients. Hepatomegalyand jaundice can develop, as can acute acalculous disten-tion of the gallbladder. In addition, up to 15% of affectedpatients have abnormal findings on chest radiography.

Laboratory EvaluationLeukocytosis is typical during the acute stage of theillness, with a predominance of immature and maturegranulocytes. About 50% of patients who have KD havewhite blood cell counts greater than 15.0�103/mcL(15.0�109/L). Anemia may develop, especially with aprolonged duration of active inflammation. Elevated val-ues for the acute-phase reactants, such as erythrocytesedimentation rate (ESR) and C-reactive protein (CRP),are nearly universal in KD. Both the ESR and CRPshould be measured, if possible, because of the potentialfor discordance of the values. For patients who alreadyhave been treated with intravenous immune globulin(IVIG), ESR is not useful as a marker of inflammationbecause an elevation can be the result of the IVIG therapy.

Thrombocytosis is a characteristic in the subacutestage of illness, with platelet counts ranging from500.0 to 1,000.0�103/mcL (500.0 to 1,000.0�109/L)or more. Thrombocytosis peaks in the third week andgradually returns to normal by 4 to 8 weeks after onset ofillness. Mild-to-moderate elevations in serum transami-nases occur in 40% or fewer of patients, and mild hyper-bilirubinemia is seen in approximately 10%. Hypoal-buminemia is common and is associated with moresevere and more prolonged acute disease. Urinalysisreveals mild-to-moderate sterile pyuria in about onethird of patients. If those who have KD undergo lumbarpuncture, approximately 50% have evidence of asepticmeningitis, with a predominance of mononuclear cells,as well as normal glucose and protein concentrations.

Laboratory tests can provide diagnostic support forpatients whose clinical presentations are suggestive butnot diagnostic of KD. A moderately-to-markedly ele-vated CRP (�30.0 mg/L [3.0 mg/dL]) or ESR(�40 mm/hr), for example, is nonspecific but nearlyuniversal in KD, while unlikely in viral infections. Pastexperience suggests that KD is unlikely if platelet countsand acute-phase reactant values are normal after theseventh day of fever.

Incomplete or Atypical KDSome patients do not fulfill the clinical criteria for KDand are diagnosed based on echocardiographic findingsof coronary artery abnormalities. Therefore, the conven-

tional diagnostic criteria should be viewed as guidelinesto prevent overdiagnosis, but strict adherence to thecriteria may result in failure to recognize incompleteforms of KD. Incomplete, or atypical, KD is more com-mon in young infants than in older children, makingaccurate diagnosis especially important because thesepatients are at higher risk for developing coronary abnor-malities. Echocardiography is useful in diagnosing KDamong patients who have only some of the classic fea-tures. Although aneurysms rarely form before day 10 ofillness, some evidence of arteritis can be present in theacute stage of KD before the formation of aneurysms.

Incomplete KD should be considered in all infantsand children who have unexplained fever for 5 or moredays associated with two or three of the principal clinicalfeatures of KD. In addition, supplemental laboratorycriteria, including albumin, hemoglobin, and transami-nase measurements as well as urinalysis, can be used tosupport the diagnosis. Because young infants maypresent with fever and little else, echocardiographyshould be considered in any infant younger than 6months who has fever lasting 7 days or more, laboratoryevidence of systemic inflammation, and no other expla-nation for the febrile illness. An algorithm for the evalu-ation of children suspected of having incomplete KD ispresented in the Figure.

Differential DiagnosisOther febrile illnesses of childhood can mimic KD (Table2). Measles, group A streptococcal or staphylococcalinfections, and drug hypersensitivity reactions are theillnesses that resemble KD most closely. In addition, thedifferential diagnosis includes Stevens-Johnson syn-drome, adenovirus infection, Rocky Mountain spottedfever, and Epstein-Barr virus infection. However, certainclinical features strongly suggest KD. Conjunctival injec-tion in KD primarily is bulbar and usually is not accom-panied by exudate. Lip redness and swelling can be severeenough to cause cracking and bleeding, and “strawberrytongue” is characteristic. Oral ulcers and exudative phar-yngitis are not features of the illness. Tense swelling ofthe hands and feet is distinctive and rarely seen in otherchildhood febrile illnesses. Perineal accentuation of therash is common in KD but not in other disorders. Vesi-cles, bullae, petechiae, and purpura are not seen. KDshould be considered in the differential diagnosis of everychild who has fever of at least several days’ duration, rash,and nonpurulent conjunctivitis, especially in childrenyounger than 1 year of age and in adolescents, in whomthe diagnosis frequently is missed and treatment delayed.




Cardiac ImagingCardiac imaging is critical in theevaluation of all patients who aresuspected of having KD, and echo-cardiography has been determinedto be the ideal imaging modalityfor cardiac assessment. Initial echo-cardiography should be performedas soon as the diagnosis is sus-pected, but treatment should notbe delayed by the timing ofthe study. Cardiac evaluation of pa-tients suspected of having KDshould focus on maximal efforts tosee all major coronary segments:the left main coronary artery(LMCA), left anterior descendingartery (LAD), left circumflex coro-nary artery (LCX), right coronaryartery (RCA), and the posterior de-scending coronary arteries. Themost common sites of coronary an-eurysms include the proximal LADand proximal RCA, followed by theLMCA, then LCX, and finally thedistal RCA and the junction be-tween the RCA and the posteriordescending coronary artery. In ad-dition, assessment of left ventricularfunction should be a part of theechocardiographic evaluation of allpatients in whom KD is suspectedbecause some degree of myocarditisis almost universal. Myocarditismay manifest as chest pain or tachy-cardia that can occur out of propor-tion to the degree of fever, valvulardysfunction, and electrocardio-graphic changes. The presence ofany pericardial effusion also shouldbe noted on echocardiography.

TreatmentThe current standard therapy forKD is a combination of aspirin andIVIG. In 1983, Japanese investiga-tors reported that children treatedwith IVIG had faster resolving feverand developed fewer coronary ar-tery abnormalities than did “his-toric” controls. A multicenter ran-

Figure. Evaluation of suspected incomplete Kawasaki disease (KD). 1) In the absence of a goldstandard for diagnosis, this algorithm cannot be evidence-based but rather represents the informedopinion of the Expert Committee. Consultation with an expert should be sought anytime assistanceis needed. 2) Infants 6 months old on day 7 of fever with no other explanation should undergolaboratory testing and, if evidence of systemic inflammation is found, echocardiography, even if theinfants have no clinical criteria. 3) Characteristics suggesting KD are listed in Table 1. Character-istics suggesting disease other than KD include exudative conjunctivitis, exudative pharyngitis,discrete intraoral lesions, bullous or vesicular rash, or generalized adenopathy. Consider alternativediagnoses (see Table 2). 4) Supplemental laboratory criteria include albumin value of 3.0 g/dL(30.0 g/L), anemia for age, elevation of alanine aminotransferase, platelet count of more than450.0�103/mcL (450.0�109/L) after 7 days, white blood cell count 15.0�103/mcL (15.0�109/L), and 10 white blood cells/high-power field in the urine. 5) Can treat before performingechocardiography (Echo). 6) Echocardiography is considered positive for purposes of this algorithmif any of three conditions are met: z score for left anterior descending or right coronary artery of2.5; coronary arteries meet Japanese Ministry of Health criteria for aneurysms; or three othersuggestive features exist, including perivascular brightness, lack of tapering, decreased leftventricular function, mitral regurgitation, pericardial effusion, or z scores in left anterior descendingor right coronary artery of 2 to 2.5. 7) If echocardiography is positive, children should be treatedwithin 10 days of fever onset and those beyond day 10 with clinical and laboratory signs(C-reactive protein, erythrocyte sedimentation rate) of ongoing inflammation. 8) Typical peelingbegins under nail bed of fingers and then toes. CRP�C-reactive protein, ESR�erythrocytesedimentation rate. Reprinted with permission from Newburger JW, Takahashi M, Gerber MA, et al.Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for healthprofessionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Councilon Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114:1708–1733.




domized trial in the United States showed that childrentreated with IVIG and high-dose aspirin had significantlyfaster resolution of fever and other inflammatory markersthan did children treated with high-dose aspirin aloneand confirmed that coronary artery abnormalities werereduced by about 85%. Subsequent studies have con-firmed that initial therapy with IVIG and high-doseaspirin should be the standard therapy for KD.

During the acute phase of illness, aspirin is adminis-tered at 80 to 100 mg/kg per day in four doses alongwith IVIG. High-dose aspirin and IVIG appear to havean additive anti-inflammatory effect. Most clinicians con-tinue high-dose aspirin until day 14 of illness if the childremains afebrile. When high-dose aspirin is discontinued,therapy is continued with low-dose aspirin at 3 to5 mg/kg per day until the patient shows no evidence ofcoronary changes by 6 to 8 weeks after the onset ofillness. This regimen applies to children who have nocoronary abnormalities on initial echocardiography.

For children who develop coronary abnormalities,aspirin may be continued indefinitely. Aspirin has anti-inflammatory properties at high doses and antiplateletactivity at low doses but alone does not appear to lowerthe frequency of the development of coronary abnormal-ities. Because Reye syndrome is a risk in children whotake salicylates while they are infected with varicella orinfluenza, parents should be instructed to contact theirchild’s physician immediately if the child develops symp-toms of or is exposed to influenza or varicella. Childrenon aspirin therapy should receive influenza immuniza-tions routinely.

The efficacy of IVIG in reducing the prevalence ofcoronary artery abnormalities in KD is well established,despite the mechanism of action being unknown. IVIGappears to have a generalized anti-inflammatory effect.

Patients who have KD should be treated with IVIG(2 g/kg in a single infusion) together with high-doseaspirin. Whenever possible, this therapy should be startedwithin the first 10 days of illness, with the first day of feverconsidered the first day of illness. IVIG also should beadministered to children presenting with KD after the10th day of illness if they have persistent fever with noother explanation or evidence of ongoing inflammationsuch as an elevated ESR or CRP, with or without coro-nary abnormalities. Measles and varicella immunizationsshould be deferred for 11 months after a child receivesIVIG. Even when treated appropriately within the first10 days of illness, approximately 5% of children who haveKD develop some coronary artery dilation, and 1% de-velop giant aneurysms, defined as a greater than 8 mminternal diameter.

Despite steroids being highly effective in treatingother forms of vasculitis, their use in KD has been lim-ited. Steroids were the initial therapy for KD before thediscovery of the efficacy of IVIG. Although early studiesmay have shown a detrimental effect of steroids, subse-quent studies have shown neither benefit nor ill effects.A recent investigation examined the effect on coronaryartery outcomes of pairing the initial dose of IVIG with adose of intravenous methylprednisolone. The results didnot support the addition of a single pulsed dose ofsteroids to conventional therapy because no significanteffect was seen on the development of coronary arteryabnormalities. However, there was a potential benefit inthe subset of patients who required retreatment withIVIG because of persistent or recurrent fever and, there-fore, were at greater risk for coronary abnormalities.More studies will need to be performed to delineate thiseffect further.

Approximately 10% of patients who have KD fail torespond to initial IVIG therapy. Failure to respond usu-ally is defined as persistent or recrudescent fever 36 hoursor more after completion of the initial IVIG infusion.Most experts recommend retreatment with IVIG at thesame dose. Treatment of patients who have true IVIG-refractory KD, defined as persistent fevers or elevatedinflammatory markers despite having received twocourses of IVIG, is controversial. There is no universallyaccepted “next step” in therapy. Some clinicians use athird dose of IVIG. Steroids also have been used to treatpatients whose disease is refractory to IVIG. Steroidshave been shown to reduce fever, but the steroid effecton coronary abnormalities remains uncertain. The ste-roid regimen used most commonly is intravenous pulsemethylprednisolone, 30 mg/kg for 2 to 3 hours, admin-istered once daily for 3 days.

Table 2. Differential Diagnosis ofKawasaki Disease● Viral infections (eg, measles, adenovirus, enterovirus,

Epstein-Barr virus)● Scarlet fever● Staphylococcal scalded skin syndrome● Toxic shock syndrome● Bacterial cervical lymphadenitis● Drug hypersensitivity● Stevens-Johnson syndrome● Juvenile idiopathic arthritis● Leptospirosis● Mercury hypersensitivity reaction (acrodynia)




A class of agents that may play a role in the treatmentof patients who have refractory KD is monoclonal anti-bodies to proinflammatory cytokines. A monoclonal an-tibody against tumor necrosis factor-alpha, infliximab, isbeing studied for treatment of children who fail to be-come afebrile after initial IVIG treatment. Although itseffectiveness in reducing the prevalence of coronary arteryaneurysms remains unproven, therapy with infliximab orother agents directed at tumor necrosis factor-alpha mightbe considered for patients who are refractory to IVIG.

Cytotoxic agents such as cyclophosphamide and meth-otrexate have been suggested as being useful for the treat-ment of refractory KD because they are used widely to treatother severe vasculitides. However, the risk of using cyto-toxic agents may exceed the benefits for most patients, andthey are not recommended routinely at this point. Becausecontrolled data are lacking, the roles for these adjunctivetherapies for IVIG-refractory patients remain uncertain.Ongoing research into various treatments is needed toguide clinicians in treating IVIG-refractory patients.

Long-term Follow-up and OutcomeThe following features of the natural history of KD havebeen established, based on large series of patients fromJapan and North America. Coronary artery aneurysmsoccur in 20% to 25% of untreated children. Other cardio-vascular complications include myocarditis, pericarditiswith effusion, and valvulitis, the latter occurring in about1% of patients, most commonly involving the mitralvalve. Resolution of aneurysms 1 to 2 years after diseaseonset has been observed in approximately 50% of vesselsthat have coronary aneurysms. The likelihood that ananeurysm will resolve is determined, in large part, by itsinitial size, with smaller aneurysms having a greater like-lihood of regression. Vessels in which resolution does notoccur are at risk for developing stenosis or occlusion bythrombus or myointimal proliferation. A coronary aneu-rysm can rupture within the first few months after KD,but this complication is exceedingly rare. The worstprognosis is noted in children who have giant aneurysms,where thrombosis is promoted by the sluggish and tur-bulent blood flow within the dilated vascular space andby the frequent occurrence of stenotic lesions at theproximal or distal end of the aneurysms.

MI caused by thrombotic occlusion of an abnormalcoronary artery is the principal cause of death from KD.The greatest risk of MI occurs in the first year afterdisease onset. The general belief is that if coronary aneu-rysms are not identified by complete and adequate echo-cardiography in the first 1 to 2 months after diagnosis, thedevelopment of new aneurysms is unlikely. Children who

have no known cardiac sequelae during the first month ofKD appear to return to their previous state of health with-out signs or symptoms of cardiac impairment. However,limited evidence suggests possible long-term endothelialdysfunction in children who have no obvious coronaryinvolvement, the significance of which is unknown.

Echocardiography should be performed at the time ofdiagnosis and subsequently usually at 2 and 6 weeks afterdisease onset. Children are stratified according to theirrelative risk of myocardial ischemia. Treatment can beindividualized according to risk level, as recommendedby the American Heart Association (Table 3). For chil-dren at higher risk, such as those who have persistentfever or coronary abnormalities, more frequent imagingmay be necessary to guide management. Patients whohave no coronary artery changes on echocardiography atany stage of the illness still should be counseled periodicallyabout cardiovascular risk factors (eg, hypertension, diet,exercise) because the future risk for ischemic heart disease inthis category of patients remains undetermined.

Patients who have small solitary aneurysms shouldtake long-term aspirin therapy until the aneurysms re-gress and be followed by a pediatric cardiologist or otherphysician experienced in the management of KD. Pa-tients who have giant aneurysms or multiple complexaneurysms should be considered candidates for long-term antiplatelet therapy and anticoagulation therapy.The choice of regimen depends on the degree of coro-nary enlargement. Regimens include combinations ofaspirin, clopidogrel, heparin, and warfarin. Treatmentwith aspirin usually is sufficient for aneurysms that have amaximum diameter of 5 mm, whereas patients who havegiant aneurysms generally are treated with a combinationof aspirin and warfarin, aiming for an International Nor-malized Ratio of 2.0 to 2.5. Such severely affected pa-tients should be followed by a cardiologist and haveechocardiography, electrocardiography, and stress testsperformed at regular intervals.

Other noninvasive tests may be used widely in thefuture to assess coronary stenoses, aneurysms, and occlu-sions. Multislice spiral computed tomography scan(MSCT) has been used successfully to “image” the distalsegments of coronary arteries in adolescents and youngadults to identify small areas of stenosis and aneurysm.Coronary magnetic resonance angiography (CMRA)also has been shown to define coronary artery aneurysmsaccurately as well as thickened vessel walls in free-breathing sedated children. In the future, MSCT andCMRA may be useful noninvasive alternatives for chil-dren who otherwise would need frequent catheteriza-tions as they grow older.




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Attempts at excising coronary artery aneurysms havebeen unsuccessful and have caused deaths. The primarysurgical management of KD is coronary artery bypassgrafts for obstructive lesions. Catheter interventions suchas balloon angioplasty, rotational ablation, and stentplacement have been performed in a relatively smallnumber of children who have KD. Catheter interventionfor patients who have KD should be considered whenischemic symptoms are present and in patients who have75% or more stenosis with or without ischemia in theLAD. Approximately 20 patients who have KD haveundergone cardiac transplantation for severe myocardialdysfunction, severe ventricular arrhythmias, and severecoronary arterial lesions. Cardiac transplantation shouldbe considered for individuals who have severe, irrevers-ible myocardial dysfunction and coronary lesions forwhich interventional catheterization procedures or cor-onary bypass are not feasible.

ConclusionAlthough great progress has been made in the treatmentof KD, much is left to learn about the cause of the illness.Until an etiologic agent is identified and a definitivediagnostic test devised, children who have KD still will bemisdiagnosed (under- and overdiagnosed), and somewho have KD will be untreated, suffering potentiallyserious morbidity or even mortality. Priorities for re-search are developing a diagnostic test, identifying ge-netic markers for susceptibility to KD, identifying prog-

nostic factors, developing improved therapies, anddiscovering the cause of KD. The ultimate goal of KDresearch is to prevent the grave cardiac consequences ofthe disease, and critical to this goal is elucidation of thecausative agent.

Suggested ReadingBurns JC, Glode MP. Kawasaki syndrome. Lancet. 2004;364:

533–544Danford D. Is there a role for corticosteroids in treatment of

Kawasaki disease? Commentary on article by Newburger,Sleeper, and McCrindle. AAP Grand Rounds. 2007;17(5):50

Freeman AF, Shulman ST. Refractory Kawasaki disease. PediatrInfect Dis J. 2004;23:463–464

Greil GF, Seeger A, Miller S, et al. Coronary magnetic resonanceangiography and vessel wall imaging in children with Kawasakidisease. Pediatr Radiol. 2007;37:666–673

Li SC. Is there a role for corticosteroids in treatment of Kawasakidisease? Commentary on article by Newburger, Sleeper, andMcCrindle. AAP Grand Rounds. 2007;17(5):50

Newburger JW, Fulton DR. Kawasaki disease. Curr Opin Pediatr.2004;16:508–514

Newburger JW, Sleeper LA, McCrindle BW, et al. Randomized trialof pulsed corticosteroid therapy for primary treatment of Ka-wasaki disease. N Engl J Med. 2007;356:663–675

Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treat-ment, and long-term management of Kawasaki disease: a state-ment for health professionals from the Committee on Rheu-matic Fever, Endocarditis, and Kawasaki Disease, Council onCardiovascular disease in the Young, American Heart Associa-tion. Pediatrics. 2004;14:1708–1733

PIR QuizQuiz also available online at www.pedsinreview.aappublications.org.

6. A 2-year-old child comes to the emergency department because of 6 days of fever (temperature to102.0°F [38.9°C]), “pinkeye,” red lips, and swollen hands and feet. His mother reports a rash today. Yoususpect Kawasaki disease but think the rash looks a bit atypical. Which of the following skin findings isthe most suggestive of a diagnosis other than Kawasaki disease?

A. Bullae on the hands and feet.B. Desquamation of the fingers and toes.C. Macules and papules over the trunk.D. Scarlatiniform rash over the back and chest.E. Urticaria over the back and chest.

7. Which of the following is the most typical physical examination finding in patients who have Kawasakidisease?

A. Aphthous oral ulcers.B. Diffuse lymphadenopathy.C. Exudative conjunctivitis.D. Periungual desquamation.E. Purulent tonsillar exudates.




8. You are seeing an 18-month-old boy who has had 8 days of a temperature to 101.5°F (38.6°C), diffusemaculopapular rash, and erythematous and cracked lips. His eyes, hands, and feet appear normal, and hehas no lymphadenopathy. You suspect incomplete Kawasaki disease and measure C-reactive protein anderythrocyte sedimentation rate, which are 50.0 mg/L (5.0 mg/dL) and 85 mm/hr, respectively. You orderechocardiography for the next day. The following laboratory finding that is most suggestive of the need totreat Kawasaki disease at this time is:

A. Elevated amylase concentration.B. Leukopenia.C. Metabolic acidosis.D. Polycythemia.E. Thrombocytosis.

9. A 3-year-old-girl who had typical features of Kawasaki disease was admitted to the hospital. Findings onechocardiography were normal. She was given 2 g/kg of intravenous immune globulin (IVIG) and 100 mg/kg of aspirin on admission. Two days after her treatment was initiated, she continues to have atemperature to 102.0°F (38.9°C) and her C-reactive protein concentration remains high, but her rash,conjunctivitis, and swollen hands and feet have improved. In addition to continuing high-dose aspirintherapy, which of the following is the best course of treatment at this time?

A. Administer a 30-mg/kg dose of methylprednisolone.B. Discharge from the hospital with cardiology follow-up.C. Initiate treatment with cyclophosphamide.D. Reconsider the diagnosis and obtain viral titers and blood cultures.E. Repeat the 2-g/kg dose of IVIG.

10. You are evaluating a 5-year-old boy who had typical Kawasaki disease 8 weeks ago. He received one doseof IVIG and high-dose aspirin for 2 weeks, followed by low-dose aspirin, which he still is taking. He isasymptomatic and doing very well on restricted activity. Initial echocardiography showed mild coronaryartery ectasia, but repeat imaging today shows completely normal findings. Of the following, the mostappropriate management for this patient at this time is to:

A. Add low-molecular-weight heparin, continue activity restriction, and repeat echocardiography in 2months.

B. Continue aspirin, continue activity restriction, and repeat echocardiography in 2 months.C. Discontinue aspirin, discontinue activity restriction, and initiate a cardiology follow-up in 3 years.D. Discontinue aspirin, continue activity restriction, and repeat echocardiography in 6 months.E. Discontinue aspirin, continue activity restriction, and initiate a cardiology follow-up in 1 year.




DOI: 10.1542/pir.29-9-308 2008;29;308-316 Pediatr. Rev.

Angela M. Fimbres and Stanford T. Shulman Kawasaki Disease

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