Overview of Kawasaki Disease

1. Kawasaki Disease
Androu Waheeb
RCSI-Bahrain Medical Student
Acknowledgement:
Dr. Brian McCrindle at the Hospital for Sick
Children, Toronto

2. History
 Tomisaku Kawasaki, Red Cross Hospital,
Tokyo, Japan (Jan 1961)
 Alternative Names
 lymphnode syndrome
 Mucocutaneous lymph node syndrome
 Kawasaki syndrome
 Syndrome ?!

3. Definition
 Auto-immune mediated vasculitis
 Medium sized arteries
 Favours coronary arteries

4. Epidemiology
 85% younger than 5 years
 Uncommon in 1 year < age < 5 years
 Male:female ratio 1.6:1 2-5
 Increased prevalence in Asian decent
(10x)
 Japan highest (2006: 188.1/100k < 4 yo) 6
 Korea 2nd (2005: 104.6/100k < 5 yo)7
 Vs USA (2000:17.1/100k < 5 yo) 8

5. Epidemiology cont’d
 Average recurrence 3%
 Average sibling occurrence 1%
 Average mortality < 1%
 Racial Demographic
 Asian
and Pacific Island descent >
non-Hispanic African-American >
Hispanics >
Caucasian

6. Aetiology
 Unknown: infectious pattern
 Virus
 Bacterial(superantigenic toxin vs.
conventional antigen)
 Genetics
 Auto-immune

7. 6 cardinal symptoms/signs
1. Fever
• ≥ 5 days
• ≥ 40oC
• self-remitting
• onset
1. Non-purulent bilateral conjunctivitis
• Onset after fever

8. 6 cardinal symptoms/signs cont’d
3. Oromucosal changes
• Lips
 Red
 Cracked
 Bleeding
 Swollen
• Strawberry tongue
3. Erythematous rash
• Truncal peripheral extremities

9. 6 cardinal symptoms/signs cont’d
5. Changes in extremities
• Erythema of hands and feet
 a/w pain
 a/w brawny oedema dorsum of hand
• Desquamation of fingers and toes

10. 6 cardinal symptoms/signs cont’d
6. Cervical lymphadenopathy
• Least common
• ≥ 1 lymph node, ≥ 1.5 cm in diameter
• Unilateral
• Anterior cervical triangle

11. Diagnostics
 No specific diagnosis or test
 Use clinical presentation
 Not always simultaneous

12. Diagnostic Criteria
 Japanese MOH
 Complete KD
Fever + 5/6 cardinal symptoms
 Incomplete KD
Fever + 4/6 cardinal symptoms
+ evidence of coronary artery abnormality
 Echo:
≥ 3mm ≤ 5 yo; ≥ 4mm ≥ 5 yo
 Internal diameter >1.5 x from adjacent segment
More common in younger children

13. Cardiac Findings
 Prominent in the acute phase
 leading cause of long-term morbidity and
mortality.
 Involvement of
1. Pericardium
2. Myocardium
3. Endocardium
4. Valves
5. Coronary arteries

14. Cardiac Findings cont’d
 Cardiac auscultation
 hyperdynamic precordium
 Tachycardia
 a gallop rhythm
 innocent flow murmur
 Anemia
 Fever
 depressed myocardial contractility (myocarditis)
 significant MR  pansystolic regurgitation
murmur
 low cardiac output syndrome or shock (poor
myocardial function)

15. Non-Cardiac Findings
 increased irritability vs. other febrile
diseases
 Arthritis or arthralgia (first week)
 multiplejoints
 favours knees and ankles.
 Gastrointestinal complaints (33%)
 Diarrhoea
 Vomiting
 abdominal pain, occur in approximately

16. Non-Cardiac Findings cont’d
 Hepatic enlargement + jaundice
 Acute acalculous gallbladder distension
 first
two weeks
 Cause hydrops
 identified by abdominal ultrasound

17. Non-Cardiac Findings cont’d
 siteof previous BCG erythema +
induration
 Common
 Younger than 1 year
 perianal erythematous desquamation

18. Characteristic Lab Findings
 acute stage (4-6w)
 Leukocytosis
 predominance of immature and mature granulocytes
 Upregulated apoptosisDepleted peripheral lymphocytes.
 Anemia
 RBC indices,
 particularly with a prolonged duration of active inflammation.
 Elevated Acute Phase Reactants
 ESR
 CRP
 Platelet count rapidly increases week 2-3, (can be >
1,000,000/mm3)
 ANA and RF -ve

19. Lab Findings cont’d
 serum transaminases moderately elevated
 Hypoalbuminemia
 a/w with increased severity + duration
 Intermittent sterile pyuria
 (Urinalysis not suprapubic)urethritis
 CSF pleocytosis
 mononuclear cells predominance
 normal glucose and protein
 Inflammatory synovial fluid
 Decreased plasma cholesterol, HDL,
apolipoprotein A-I

20. Treatment
 Conventional=IVIG + Aspirin
 IVIG
 Reduces the prevalence of coronary artery
abnormalities
 MOA unknown (neutralization of antigen or immune
inhibition?)
 2g/kg infusion 10-12 h
 Higher dose
 Less infusions
 Best within 7 days (earlier better)
 Live vaccines 11 mo reduced immunogenicity

21. Treatment cont’d
 Aspirin
 Anti-platelet
and anti-inflammatory; no reduction of
CAA incidence
 80-100 mg/kg/d/4 doses
 3-5 mg/kg/d afebrile 72 hours + ≥ day 14 of illness.
 D/C no CAA 6 week follow-up
 Reye syndrome a/w varicella and influenza vaccine
 Steroids
 Controversial
 Combined (30mg/kg steroids + conventional)
 No significant

22. Treatment failure
 Retreatment IVIG 2g/kg
 Methylprednisolone IV pulse 30mg/kg 2-3
h od 1-3 d
 Infliximab (monoclonal anti-TNF-a
antibody)

23. Treatment Failure cont’d
 Ulinastatin
 Plasmapheresis
 Cytotoxic agents
 Cyclophosphamide
 Cyclosporin A
 MTX: dihydrofolate reductase inhibitor
(anti-inflammatory)
 10mg/BSA, once weekly
 MOA unclear

24. Management
 Serialstress test
 Follow up 4-6 w, 6m, 1 y
 Echo
 20% AneurysmstenosisMI
 Percutaneous Transluminal Angioplasty
 Rotational atherectomy
 Stent
 Bypass graft
 transplant

25. Complications
 Cardiac
 Coronary artery dilations and aneurysms (5%)
 Thrombosis
 Myointimal proliferation  stenosis (20%)myocardial ischemia
 1% giant aneurysms
 Aspirin, clopidogrel, ticlopidine
 LMW Heparin, Warfarin, anti platelet receptor monoclonal
antibodies
 Pericarditis + effusion
 Myocarditis
 Valvulitis (1%. Mitral Valve)

26. Coronary Aneurysms
 Smaller with time
 Risk factors
 Male
8 year < Age < 1 year
 Fever non-responsive to IVIG
 Decreased
 Hb
 Serum[albumin]
 Increased
 WBC
 Band
 CRP

27. Morbidity & Mortality
 Thrombosis principal cause
 MI highest rate 1 year after onset
 LMCA
 RCA + LAD
 Nocardiac sequelae within 1st mo  full
recovery + asymptomatic

28. Take Home Message
 Auto-immune mediated vasculitis
(mucuopurulent lymphadenopathy)
 6 Cardinal Symptoms, don’t have to occur
in totality (Japanese Diagnostic Criteria)
 Etiology unknown: behaves as infectious
and genetic
 Devastating cardiac complications
 MI, anurysms, vasculitis
 Treatment: IVIG + Aspirin + Complications

29. References
1. Kim, D. S. (2006). "Kawasaki Disease." Yonsei Medical Journal 47(6): 759-772.
2. Li, X.-h., X.-j. Li, et al. (2008). "Epidemiological Survey of Kawasaki Disease in Sichuan Province
of China." Journal of tropical pediatrics 54(2): 133-136.
3. Huang, W.-C., L.-M. Huang, et al. (2009). "Epidemiologic Features of Kawasaki Disease in
Taiwan, 2003-2006." Pediatrics 123(3): e401-405.
4. Chang, R.-K. R. (2002). "Epidemiologic characteristics of children hospitalized for Kawasaki
disease in California." Pediatric Infectious Disease Journal 21(12): 1150-1155.
5. Morens, D. M., L. J. Anderson, et al. (1980). "National Surveillance of Kawasaki Disease."
Pediatrics 65(1): 21-25.
6. Yosikazu Nakamura, M. Y., Ritei Uehara, Izumi Oki, Makoto Watanabe, and Hiroshi Yanagawa
(2008). "Epidemiologic Features of Kawasaki Disease in Japan: Results from the Nationwide
Survey in 2005-2006." J Epidemiol 18(4): 167-172.
7. Park, Y., J. Han, et al. (2007). "Kawasaki Disease in Korea, 2003-2005." Pediatric Infectious
Disease Journal 26(9): 821-823.
8. Robert C. Holman, A. T. C., Ermias D. Belay, Claudia A. Steiner and Lawrence B. (2003).
"Kawasaki Syndrome Hospitalizations in the United States, 1997 and 2000." Pediatrics 112(3):
495-501.