KAWASAKI DISEASE

Dr. Sri Lilijanti Widjaja, Sp.A(K)

Department of Child Health

Medical School University of
Sebelas Maret
Surakarta
 INTRODUCTION

 Original case observed by dr. Kawasaki January

1961
4 y.o. boy, “diagnosis unknown”
 First Japanese report from dr. Kawasaki 1967
 50 children with acute febrile and exanthema
 Being diagnosed with Mucocutaneous Lymph Node
Syndrome
 First English language report from dr. Kawasaki
1974, simultaneously recognized in Hawaii
KAWASAKI DISEASE (KD)
 A self-limited vasculitis of unknown etiology
that predominantly affects children younger
than 5 years.

 Idiopathic multisystem disease characterized

by vasculitis of small & medium blood vessels,
including coronary arteries.
 EPIDEMIOLOGY

 In Japan, until 1999, there were >125.000 cases.

 In Indonesia (Jakarta), there were > 100 cases.

 Annual incidence

 Most happened in Japan-Korea

 50-100 cases/ 100.000 children under 5 years of age
 United States
 6-15 cases/ 100.000 children under 5 years of age
EPIDEMIOLOGY CONT...
 80% cases happened in children under 5 years of
age (50% at age of 1-2 years).
 Rarely happened in children under 3 months and over 8
years of age
 Males : females = 1.5-1.7 : 1
 Recurs in 3%
 Over-represented in Asian-Americans, African-
Americans next most prevalent
 More cases in winter and spring but occurs throughout
the year
ETIOLOGY
 Infectious agent most likely
 Age-restricted susceptible population
 Seasonal variation
 Well-defined epidemics
 Acute self-limited illness similar to known infections

 No causative agent identified

 Bacterial,retroviral, superantigenic bacterial toxin
 Immunologic response triggered by one of several
microbial agents
ETIOLOGY CONT...
 New Haven Coronavirus
 Identified a novel human coronavirus in respiratory
secretions from a 6-month-old with typical
Kawasaki Disease
 Subsequently isolated from 8/11 (72.7%) of
Kawasaki patients & 1/22 (4.5%) matched controls
(p = 0.0015)
 Suggests association between viral infection &
Kawasaki disease
 DIAGNOSTIC CRITERIA

 Age < 5 years old

 Fever for at least 5 days, no response to antipyretics
 At least 4 of the following 5 features:
1. Changes in the extremities
 Edema, erythema, desquamation
2. Polymorphous exanthem, usually truncal
3. Conjunctival injection
4. Erythema&/or fissuring of lips and oral cavity
5. Cervical lymphadenopathy
 Lymph nodes, by definition, must be > 1.5 cm in diameter
 Illness not explained by other known disease process
LABORATORY FINDINGS

EARLY LATE
 Leukocytosis  Thrombocytosis
 Left shift
 Elevated CRP
 Mild anemia
 Thrombocytopenia/
Thrombocytosis
 Elevated ESR
 Elevated CRP
 Hypoalbuminemia
 Elevated transaminases
 Sterile pyuria
 ATYPICAL OR INCOMPLETE
KAWASAKI DISEASE

 Present with < 4 of 5 diagnostic criteria

 Compatible laboratory findings

 Still develop coronary artery aneurysms

 No other explanation for the illness

 More common in children < 6 months of age

PHASES OF DISEASE

ACUTE SUBACUTE CONVALE

1-2 weeks 2-8 weeks SCENT
from onset from onset
Months to
years later
Febrile,
irritable, Desquamati
toxic on, may Symptoms
appearing have resolve &
persistent laboratory
arthritis or values
Oral arthralgias normalize
changes,
rash,
edema/ery Gradual
thema of improveme
feet nt even
without
treatment
Erythema and edema of hands and
feet (acute phase)
Edema of feet (acute phase)
Fingertip and toetip peeling (subacute phase)
Polymorphous
Non-vesicular rash
(99% of cases) -
usually
maculopapular
 In the first week:
Bilateral, painless bulbar
•Erythema - cracking of lips conjunctival injection
•A strawberry tongue and/or without exudate
•Diffuse injection of oral and
pharyngeal mucosae.
The lymphadenopathy occurs early
in the disease.
 OTHER MANIFESTATIONS OF
KAWASAKI DISEASE
 Respiratory
 Rhinorrhea, cough,
pulmonary infiltrate
 GI
 Diarrhea, vomiting,
abdominal pain, hydrops of
the gallbladder, jaundice
 Renal:
 RF, renal artery aneurysms
 Neurologic
 Irritability, aseptic
meningitis, facial palsy,
hearing loss
 Musculoskeletal
 Myositis, arthralgia,
arthritis
 Skin
 Transverse furrows of
fingernails (Beau’s lines)
during convalescence
 Others
 Peripheral gangrene,
orbital myositis, Avascular
necrosis of the femoral
head
 DIFFERENTIAL DIAGNOSIS
Infectious Immunological/Allergic Toxins

• Measles & Group A • JRA (systemic onset) • Mercury

beta-hemolytic strep • Atypical Acute Renal
• Bacterial: severe Failure (ARF)
staph infections • Hypersensitivity
w/toxin release reactions
• Viral: adenovirus, • Stevens-Johnson
enterovirus, EBV, syndrome
roseola
• Spirocheteal: Lyme
disease, Leptospirosis
• Parasitic:
Toxoplasmosis
• Rickettsial: Rocky
Mountain spotted
fever, Typhus
CARDIOVASCULAR MANIFESTATIONS OF
ACUTE KAWASAKI DISEASE
 EKG changes  Chest X-Ray
 Arrhythmias  Cardiomegaly

 Abnormal Q waves  Pulmonary edema

 Prolonged PR and/or
QT intervals
 Low voltage

 ST-T–wave changes.
 Suggestive of myocarditis (50%)  EMERGENCY
 Tachycardia, murmur, gallop rhythms

 Disproportionate to degree of fever & anemia

 Suggestive of pericarditis  EMERGENCY

 Present in 25% although symptoms are rare

 Distant heart tones, pericardial friction rub,

tamponade
 Can help diagnose “atypical” disease
ECHOCARDIOGRAPHIC FINDINGS

 Myocarditis with dysfunction

 Pericarditis with an effusion

 Valvar insufficiency

 Coronary arterial changes

 Themost common finding  mild coronary arterial

changes
CORONARY ARTERIAL CHANGES
 Untreated patients (15% - 25 % ) develop
coronary artery changes
 3-7% if treated in first 10 days of fever with

IVIG
 Most commonly proximal, can be distal
 Left main > LAD > Right
CORONARY ARTERIAL CONT...
 Vary in severity from echogenicity due to
thickening and edema or asymptomatic
coronary artery ectasia to giant
aneurysms
 May lead to myocardial infarction (MI),
sudden death, or ischemic heart disease
 CORONARY ANEURYSMS

Patients most likely to develop aneurysms

 Younger than 6 months, older than 8 years
 Males
 Fever persists for greater than 14 days
 Persistently elevated ESR
 Thrombocytosis
 Pts who manifest s/s of cardiac involvement
 CORONARY ANEURYSMS CONT...
 Classification based on:
SIZE
SHAPE AGE
(diameter)
• Small • Saccular • < 5 years old
• <5 mm • Fusiform • > 3 mm
• Medium • > 5 years old
• 5-8 mm • > 4 mm
• Giant
• > 8 mm
• Highest risk
for sequelae
CORONARY ANEURYSM HISTORY
 50 % regress to normal by echo, happened if:
 Smaller size
 Fusiform morphology
 Female gender
 Age less than 1 year

 25 % become smaller
 25 % do not regress
 7-20 % develop stenosis or myocardial infarction
attributed to their aneurysms
 Giant aneurysms (>8mm)  worst prognosis
CARDIOVASCULAR SEQUELAE
 0.3-2% mortality rate due to cardiac disease
 10% from early myocarditis
 Aneurysms may thrombose, cause MI/death
 Rarely, may rupture.
 MI is principal cause of death in KD
 32% mortality
 Most often in the first year

 Majority while at rest/sleeping

 About 1/3 asymptomatic

Acute Kawasaki Disease: Treatment
IVIG
 Beneficial effect 1st reported by Japanese
 Dose
 2g/kg as one-time dose
 Mechanism of action is unclear

 Efficacy unclear after day 10 of illness

 70-90% show symptom resolution within 2-3 days of

treatment
 IVIG plus aspirin vs. aspirin alone
 15-25% vs 3-5%
ASPIRIN: combined with IVIG

 High dose
 80-100 mg/kg/day (4 times a day)
 until 14 days after onset or 2-3 days after afebrile phase
 Decrease to low dose
 3-10 mg/kg/day (once a day)
 for 6-8 weeks or until platelet levels normalize
 Being stop if the result of echocardiography is normal
 Long term usage
 Beingsuggested for a patient with coronary aneurysm
 2-5 mg/kg
 Dueto potential risk of Reye syndrome instruct
parents about symptoms of influenza or varicella.
OTHER TREATMENTS

 For some patients with myocarditis

 Support with diuretics & inotropes
 Antibiotics while excluding bacterial
infection
 Conflicting data about steroids

 Reportsof higher incidence of aneurysms &

more ischemic heart disease in patients
w/aneurysms
PATIENT FOLLOW-UP CATEGORIES
Five categories based on coronary arteries
findings.
I. NO CORONARY CHANGES AT ANY STAGE
OF ILLNESS

 Pharmacologic Therapy
 None beyond 6-8 weeks
 Physical Activity
 No restrictions beyond 6-8 weeks
 Follow-up and diagnostic testing
 CV risk assessment, counseling @ 5 yr intervals
 Invasive testing
 None recommended
II. TRANSIENT CORONARY ARTERY ECTASIA,
RESOLVED WITHIN 6-8 WEEKS

 Pharmacologic Therapy
 None beyond 6-8 weeks
 Physical Activity
 No restrictions beyond 6-8 weeks
 Follow-up and diagnostic testing
 CV risk assessment, counseling @ 3-5 yr intervals
 Invasive testing
 None recommended
III. SINGLE SMALL OR MEDIUM SIZE
ANEURYSM
 Pharmacologic Therapy
 Low dose aspirin until regression documented
 Physical Activity
 None beyond 1st 6-8 weeks in patients <11 y.o.
 11-20 y.o.: Restrictions based on biennial stress
test/myocardial perfusion scan
 Contact/high-impact discouraged if taking anti-plt drugs

 Follow-up and diagnostic testing

 Annual exam, echo, EKG
 CV risk assessment, counseling

 Invasive testing
 Angiography if suggestion of ischemia
 IV. ANEURYSMS WITHOUT STENOSIS

 Pharmacologic Therapy
 Long term aspirin
 Long-term antiplatelet tx & warfarin or low molecular heparin (LMWH).
 Physical Activity
 Restrictions based on stress test/myocardial perfusion scan
 Contact/high-impact avoided due to risk of bleeding
 Follow-up and diagnostic testing
 Biannual exam, echo, EKG
 Annual stress test/myocardial perfusion scan
 Invasive testing
 Angiography @ 6-12 months, sooner/repeated if clinically indicated
 Elective repeat in certain circumstances
V. OBSTRUCTION
 Pharmacologic Therapy
 Long-term low-dose aspirin, ± warfarin or LMWH if giant aneurysm
persists
 Consider ß-blockade to reduce myocardial O2 consumption
 Physical Activity
 No contact or high impact sports
 Other activity guided by stress testing or perfusion scan
 Follow-up and diagnostic testing
 Biannual exam, echo and EKG
 Annual stress test/myocardial perfusion scan
 Invasive testing
 Angiography indicated to assess lesions and guide therapy. Repeat
angiography with change in symptoms.
THANK YOU