Kawasaki DiseaseKawasaki DiseaseMucocutaneous lymph nodeMucocutaneous lymph node syndromesyndrome

Ma LianMa Lian

IntroductionIntroduction Kawasaki disease Kawasaki disease

(KD) is a common (KD) is a common vasculitic disorder vasculitic disorder usually seen in usually seen in children below 5 children below 5 years of age years of age

The leading cause The leading cause of acquired heart of acquired heart disease in disease in childrenchildren

Kawaski T.Kawaski T. Acute febrile mucocutaneous syndrome Acute febrile mucocutaneous syndrome

withwith lymphoid involvement lymphoid involvement withwith specific specific desquamation of the fingers and toes in desquamation of the fingers and toes in children: clinical observations of 50 children: clinical observations of 50 cases.cases.

Jpn J Allergol.Jpn J Allergol.1967; 16 :178 –222 1967; 16 :178 –222

China kawasaki diseaseChina kawasaki disease

Epidemiologic study of admitted Epidemiologic study of admitted children with Kawasaki disease in children with Kawasaki disease in Beijing from 1995 to 1999 :The Beijing from 1995 to 1999 :The incidence of KD in Beijing is lower incidence of KD in Beijing is lower than that reported in Japan, similar to than that reported in Japan, similar to the incidence in the United States the incidence in the United States and higher than in those other and higher than in those other Western countries. Western countries.

Etiology Etiology No one knows what causes Kawasaki No one knows what causes Kawasaki

disease.disease. But it is thought to start from an But it is thought to start from an

infectioninfection or from exposure to some or from exposure to some toxintoxin. .

There is no firm evidence that the There is no firm evidence that the disease can spread from one person disease can spread from one person to another. to another.

Superantigen-producing bacteria. Superantigen-producing bacteria.

HistroyHistroy

Kawasaki disease has 3 stages, Kawasaki disease has 3 stages, as followsas follows

Acute stage (1-11 d)Acute stage (1-11 d) Subacute stage (11-30 d)Subacute stage (11-30 d) Convalescent/chronic phase Convalescent/chronic phase

((>>30 d)30 d)

Acute stage (1-11 d)Acute stage (1-11 d)1. High fever (temperature >39℃)1. High fever (temperature >39℃)2. Nonexudative bilateral conjunctivitis 2. Nonexudative bilateral conjunctivitis

(90%)(90%)3. Polymorphous erythematous rash 3. Polymorphous erythematous rash 4. Acral erythema and edema4. Acral erythema and edema that that

impede ambulationimpede ambulation5. Strawberry tongue and lip fissures5. Strawberry tongue and lip fissures6. Lymphadenopathy6. Lymphadenopathy (75%), generally a (75%), generally a

single, enlarged, nonsuppurative cervical single, enlarged, nonsuppurative cervical node measuring approximately node measuring approximately 1.5 cm1.5 cm

Acute stageAcute stage Nonexudative bilateral Nonexudative bilateral

conjunctivitis (90%)conjunctivitis (90%)

Acute stageAcute stage Polymorphous erythematous Polymorphous erythematous

rashrash

Acute stageAcute stage

Acral erythema and edemaAcral erythema and edema that that impede ambulationimpede ambulation

Acute stageAcute stage

Strawberry tongue and lip Strawberry tongue and lip fissuresfissures

Acute stageAcute stage LymphadenopathyLymphadenopathy (75%), (75%),

generally a single, enlarged, generally a single, enlarged, nonsuppurative cervical node nonsuppurative cervical node measuring approximately measuring approximately 1.5 cm1.5 cm

Acute stage (1-11 d)Acute stage (1-11 d)

7. Hepatic, renal, and gastrointestinal 7. Hepatic, renal, and gastrointestinal dysfunctiondysfunction

8. Myocarditis and pericarditis8. Myocarditis and pericarditis9. Irritability9. Irritability

10. Anterior uveitis (70%)10. Anterior uveitis (70%)

11. Perianal erythema (70%)11. Perianal erythema (70%)

IrritabilityIrritability

Subacute stageSubacute stage (11-30 d) (11-30 d)

Persistent irritability, anorexia, and Persistent irritability, anorexia, and conjunctival injectionconjunctival injection

Decreased temperatureDecreased temperature ThrombocytosisThrombocytosis Acral desquamationAcral desquamation Aneurysm formsAneurysm forms

Aneurysm formsAneurysm forms

Convalescent/chronic Convalescent/chronic phase (>30 d)phase (>30 d)

Expansion of aneurysmExpansion of aneurysm Possible MI Possible MI A tendency for smaller A tendency for smaller

aneurysms to resolve on their aneurysms to resolve on their own (60% of cases)own (60% of cases)

Diagnostic criteriaDiagnostic criteria

1.Fever(> 5 days) and refractory to 1.Fever(> 5 days) and refractory to appropriate antibiotic therapyappropriate antibiotic therapy

2.Polymorphous erythematous rash2.Polymorphous erythematous rash 3.Oropharyngeal changes, including 3.Oropharyngeal changes, including

diffuse hyperemia, strawberry diffuse hyperemia, strawberry tongue, and lip changes (eg, tongue, and lip changes (eg, swelling, fissuring, erythema, swelling, fissuring, erythema, bleeding)bleeding)

Diagnostic criteriaDiagnostic criteria

4.Peripheral extremity changes, 4.Peripheral extremity changes, including erythema, edema, including erythema, edema, induration, and desquamationinduration, and desquamation

5.Nonpurulent cervical 5.Nonpurulent cervical lymphadenopathylymphadenopathy

6.Nonexudative bilateral conjunctivitis6.Nonexudative bilateral conjunctivitis

Diagnostic criteriaDiagnostic criteria Patients with classic Patients with classic

Kawasaki disease must Kawasaki disease must have 5 of the former have 5 of the former symptoms, with fever an symptoms, with fever an absolute criterion.absolute criterion.

DifferentialsDifferentials Staphylococcal infection (such as Staphylococcal infection (such as

scalded skin syndrome, toxic shock scalded skin syndrome, toxic shock syndrome) syndrome)

Streptococcal infection (such as Streptococcal infection (such as scarlet fever, toxic shock-like scarlet fever, toxic shock-like syndrome). Throat carriage of group syndrome). Throat carriage of group A streptococcus does not exclude the A streptococcus does not exclude the possibility of Kawasaki disease possibility of Kawasaki disease

DifferentialsDifferentials Measles and other viral exanthemsMeasles and other viral exanthems Leptospirosis Leptospirosis Rickettsial disease Rickettsial disease Stevens-Johnson syndrome Stevens-Johnson syndrome Drug reaction Drug reaction Juvenile rheumatoid arthritis Juvenile rheumatoid arthritis

Lab StudiesLab Studies Mild-to-moderate normochromic Mild-to-moderate normochromic

anemia anemia moderate-to-high moderate-to-high WBCWBC count count ESR ESR ↑↑, C-reactive protein , C-reactive protein ↑↑, and , and

serum a-1-antitrypsin serum a-1-antitrypsin ↑↑.. Culture results are all negativeCulture results are all negative

Lab StudiesLab Studies ANA, RF,ASO normalANA, RF,ASO normal PlateletsPlatelets

• Thrombocytosis Thrombocytosis （（ 2-3w2-3w ））• associated with severe coronary associated with severe coronary

artery disease and MI.artery disease and MI. Liver enzymesLiver enzymes

• AST, ALTAST, ALT↑↑• bilirubin bilirubin ↑↑

Lab StudiesLab Studies Cardiac enzymes Cardiac enzymes ↑↑

（ （ CKCK ，， CK-MB, CK-MB, cardiac troponin, cardiac troponin, LDHLDH ））

RadiographyRadiography: rule out : rule out cardiomegaly or subclinical cardiomegaly or subclinical pneumonitis. pneumonitis.

Imaging StudiesImaging Studies EchocardiographyEchocardiography: rule out : rule out CAAs and CAAs and

myocarditis, valvulitis, or pericardial myocarditis, valvulitis, or pericardial effusion. effusion.

Diffuse dilatation of coronary lumina can Diffuse dilatation of coronary lumina can be observed in be observed in 50%50% of patients by the of patients by the 10th day of illness. 10th day of illness.

Echocardiography should be repeated in Echocardiography should be repeated in the second or third week of illness and 1 the second or third week of illness and 1 month after all other laboratory results month after all other laboratory results have normalized. have normalized.

Imaging StudiesImaging Studies UltrasonographyUltrasonography: :

• Gall bladder Gall bladder ultrasonographultrasonography y （（ liver or liver or gall bladder gall bladder dysfunction dysfunction ））

• scrotal scrotal ultrasound to ultrasound to evaluate for evaluate for epididymitis. epididymitis.

Imaging StudiesImaging Studies

MRAMRA: : •defines CAA defines CAA in patients in patients with with Kawasaki Kawasaki disease. disease.

•noninvasive.noninvasive.

Other TestsOther Tests ECGECG

• acute infarction.acute infarction.• Tachycardia,Tachycardia,• a prolonged PR interval, a prolonged PR interval, • ST-T wave changes, ST-T wave changes, • decreased voltage of R waves may decreased voltage of R waves may

indicate myocarditis. indicate myocarditis. • Q waves or ST-T wave changes may Q waves or ST-T wave changes may

indicate an MI.indicate an MI.

Medical CareMedical Care

The The main goalmain goal of treatment is to of treatment is to prevent coronary artery disease and prevent coronary artery disease and relieve symptoms.:relieve symptoms.:

Full doses of salicylates (aspirin);Full doses of salicylates (aspirin);

intravenous gammaglobulin are the intravenous gammaglobulin are the mainstays of treatment. mainstays of treatment.

Drug CategoryDrug Category IVIGIVIG (first line but not the sole therapy) (first line but not the sole therapy)

• Neutralizes circulating myelin antibodies Neutralizes circulating myelin antibodies through anti-idiotypic antibodies;through anti-idiotypic antibodies;

• down-regulates proinflammatory cytokines, down-regulates proinflammatory cytokines, • blocks Fc receptors on macrophagesblocks Fc receptors on macrophages• suppresses inducer T and B cells and suppresses inducer T and B cells and

augments suppressor T cells; augments suppressor T cells; • blocks complement cascade; blocks complement cascade; • promotes remyelinationpromotes remyelination

IVIGIVIG 400 400 mg/kg/d IV as a single mg/kg/d IV as a single

daily infusion for 4 d-5ddaily infusion for 4 d-5dAlternatively,;Alternatively,;

2 g/kg IV infused over 12 h 2 g/kg IV infused over 12 h once as single dose once as single dose

Drug CategoryDrug Category AspirinAspirin

• decrease inflammation,decrease inflammation,• inhibit platelet aggregationinhibit platelet aggregation• improve complications of venous improve complications of venous

stases and thrombosis. Irreversibly stases and thrombosis. Irreversibly inactivates cyclooxygenase, inactivates cyclooxygenase, ultimately preventing thromboxane ultimately preventing thromboxane A2 production in platelets. A2 production in platelets.

Drug CategoryDrug Category AspirinAspirin 80-100 80-100 mg/kg/d PO divided mg/kg/d PO divided

qid for 2 wk initially; then 5-10 mg/kg qid for 2 wk initially; then 5-10 mg/kg PO qd for 6-8 wk until sedimentation PO qd for 6-8 wk until sedimentation rate and platelet count are within the rate and platelet count are within the reference range, typically used for 6-reference range, typically used for 6-12 wk 12 wk

Drug CategoryDrug Category CorticosteroidCorticosteroid

•Not recommended to use only. Not recommended to use only. Prescript only when the Prescript only when the therapeutic effect of IVIG is not therapeutic effect of IVIG is not satisfied.satisfied.

•2mg/kg, 2—4 weeks2mg/kg, 2—4 weeks

ComplicationsComplications

CardiovascularCardiovascular• Significant heart failure or Significant heart failure or

myocardial dysfunction (unlikely to myocardial dysfunction (unlikely to occur once fever is resolved)occur once fever is resolved)

• Diffuse coronary artery ectasia and Diffuse coronary artery ectasia and aneurysm formation, giant aneurysm formation, giant aneurysm (internal luminal aneurysm (internal luminal diameter diameter >8 mm>8 mm))

• MIMI

ComplicationsComplications

CardiovascularCardiovascular• Myocarditis (common but rarely causes Myocarditis (common but rarely causes

CHF)CHF)• Valvulitis, usually mitral (only occurs in Valvulitis, usually mitral (only occurs in

1% of patients and rarely requires valve 1% of patients and rarely requires valve replacement)replacement)

• Pericarditis with small pericardial Pericarditis with small pericardial effusions (occurs in 25% of patients with effusions (occurs in 25% of patients with acute illness)acute illness)

• Systemic artery aneurysmsSystemic artery aneurysms• RuptureRupture of CAA with hemopericardium of CAA with hemopericardium

Other complicationsOther complications

Extreme irritabilityExtreme irritability, especially in , especially in younger infants younger infants

Aseptic meningitisAseptic meningitis ArthritisArthritis Mild hepatic dysfunctionMild hepatic dysfunction, rarely , rarely

jaundicejaundice 巨嗜细胞活化过度综合症：死亡原因之一巨嗜细胞活化过度综合症：死亡原因之一

Other complicationsOther complications

Gallbladder hydropsGallbladder hydrops (diagnosed by (diagnosed by means of ultrasonography but means of ultrasonography but usually resolves without surgical usually resolves without surgical intervention) intervention)

Diarrhea Diarrhea PneumonitisPneumonitis Otitis mediaOtitis media

Other complicationsOther complications Erythema and induration at the site Erythema and induration at the site

of BCG inoculation (reported in of BCG inoculation (reported in Japan) Japan)

Peripheral extremity gangrene Peripheral extremity gangrene (extremely rare) (extremely rare)

Bowel ischemia and necrosisBowel ischemia and necrosis

PrognosisPrognosis With prompt With prompt

treatment, the treatment, the prognosis is good. prognosis is good. The current The current mortality rate is mortality rate is 0.1-2%.0.1-2%.

2% to 4%% of treated 2% to 4%% of treated children still develop children still develop coronary artery disease coronary artery disease

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