Childrens Hospital Los Angeles: Multidisciplinary Action Plan
KAWASAKI SYNDROME
Qualifying Criteria: See below
Exclusion Criteria: Shock, congestive heart failure, purpura, peripheral
extremity ischemia, myocardial infarction
Estimated Length of Stay: 2 days
CHLA Resources: Wilbert Mason, M.D., MPH (209-2005) – Infectious
Diseases
Masato Takahashi, M.D. (209-1690) - Cardiology
Kawasaki syndrome (KS) is an acute febrile exanthematous illness of infants and children, which is self limited in course but is associated with important cardiac sequellae
1- 2(Level II). The etiology of the illness is not known but pathologically it appears to be a vasculitis affecting medium to large arteries in the systemic circulation. The arteritis results in coronary artery aneurysms in 20% of children who do not receive treatment in a timely manner. Of greatest significance is that KS is THE MOST COMMON CAUSE OF ACQUIRED HEART DISEASE IN CHILDREN in the United States1-2 (Level II).The diagnosis of KS is established by the fulfillment of the following diagnostic criteria: (% of patients with findings)
2.1. Fever for 5 days or mores. (>95%)
2. Bilateral conjuctival injection. (>90%)
3. Changes of the lips and oral cavity: redness and cracking of the lips,
diffuse erythema of the buccal mucosa. Strawberry tongue. (>90%)
4. Polymorphous exanthem (>90%)
5. Changes of the peripheral extremities: exanthem of the palms and soles,
swelling of the dorsum of thehands and feet; later (2
Fever and at least 4 of the 5 principal findings should be present to establish the diagnosis of KS. Diseases of known etiology with similar finding should be excluded. (See Differential Diagnosis). In the presence of >4 of the supporting symptoms, treatment may be initiated when the patient has had fewer than 5 days of fever.
Atypical KS: Some patients with KS present with fever and fewer than 4 of the other findings
3. This occurs especially in infants <12 months of age and may involve as few as only 1 or 2 of the mucocutaneous findings. It is important to recognize these children because THEY HAVE AN ESPECIALLY HIGH RATE OF CORONARY ARTERY ANEURYSMS. Atypical KS should be suspected in infants and children with prolonged fever, irritability, and incomplete presentations, in whom no other cause for the illness can be found. Consultation with one of the resource physicians should be sought3 (Level III).DIFFERENTIAL DIAGNOSIS
Other illnesses which should be excluded by history, physical examination, or when indicated, testing include the following: Group A
â-hemolytic streptococcal (GAS) infections, (scarlet fever), staphylococcal toxic shock syndrome, measles, Epstein Barr virus infections, JRA, adenovirus infections, and drug reactions (including Stevens-Johnson syndrome) 1-2 (Level III).EVALUATION
Evaluation of a typical KS patient should include the following:
CBC with differential
Sedimentation rate and CRP
Liver panel (AST, ALT, alkaline phosphatase, total bilirubin, albumin) (40% of children with KS have elevated ALT or AST
Two-dimensional echocardiogram
(Assessment of heart for pericardial effusion, LV
dilatation/dysfunction, mitral regurgitation, as well as coronary
artery changes.)
Other tests occasionally necessary include the following:
ASO titer, and/or throat culture for GAS
EBV panel, measles IgG and IgM, respiratory virus panel (to exclude
adenovirus)
Lumbar puncture (if meningitis is suspected clinically)
MANAGEMENT
Therapy is directed at controlling the vasculitis and preventing arterial thrombosis.
Patients receive:
Aspirin 80-100 mg/kg/day divided doses Q 6 hours until afebrile for 48 hours; then they receive 3-5 mg/kg/day as a single dose. Low dose aspirin may be started when fever has completely resolved. Occasionally 1 – 2 days of high dose aspirin may be needed following discharge because of continued irritability or pain.
Intravenous gamma globulin 2gm/kg over 10-12 hours. 85 – 90 % of KS patients respond to this therapy; 10 –15% may require additional treatment with IVGG because of persistent fever or other symptoms5 (Level III). Consultation with a Physician Resource should be sought in these cases.
RETREATMENT PROTOCOL5-6 (Level II)
If the patient remains febrile (> 38.3° C) 48 hours following completion of IVGG or has recurrent fever following at least 24 hours of no fever (>38.3° C) after the initial dose of IVGG, then consider the following:
1. Continue high dose aspirin
2. Administer a second dose of 2 gm/kg of IVGG
If fevers persist or recur following a second dose of IVGG then, consider the following:
1. Continue high dose aspirin
2. Administer methyl prednisolone 30mg/kg IV and observe for response6 (Level III).
DISCHARGE CRITERIA AND INSTRUCTIONS
Discharge criteria are as follows:
Afebrile > 12 – 24 hours following IVGG therapy
Resolving mucocutaneous findings
Decreasing irritability
Adequate oral intake and urinary output
Absence of cardiac dysfunction (normal pulse rate, blood pressure, and
perfusion)
Normal coronary arteries or minor abnormalities that do not require
anticoagulation.
Parents will be provided the Parent Information Sheet and Home Discharge
Instruction Sheet. PARENTS MUST BE TOLD THAT IF FEVER OR MUCOCUTANEOUS CHANGES RECUR, THEY MUST CALL DR. MASON OR DR. TAKAHASHI, OR PHYSICIAN ON CALL FOR INFECTIOUS DISEASE OR CARDIOLOGY, FOR INSTRUCTIONS. THERE SHOULD BE NO MISUNDERSTANDING ABOUT ASPIRIN DOSES AND THE TIMING OF TRANSITION FROM HIGH DOSE TO LOW DOSE.
Parents must be instructed on the complication of aspirin therapy: abdominal pain, vomiting, melena, tinnitus, hematochezia, and encephalopathy. STOP ASA AND REPORT TO PMD OR DR. MASON, DR. TAKAHASHI, OR PHYSICIAN ON CALL IF ABOVE SIGNS OR SYMPTOMS OCCUR.
Follow-up appointment in Kawasaki clinic (Wednesday morning in Heart Center, Ext. 2461) should be provided for 1-2 weeks after discharge. If the patient is < 3 years old, parents will be instructed to withhold breakfast on the morning of the appointment in case sedation is necessary to perform the echocardiogram (See Appendix A).
OUTCOME
IF IVGG therapy is instituted within 10 days of onset of fever, the rate of coronary artery abnormalities is reduced from 20% to about 3% and the risk of formation of giant coronary artery aneurysm greatly reduced (Level I). The goal is to diagnose patients as early as possible to prevent coronary artery complications. Patients should still be treated with IVGG and ASA if they are still febrile and sick even if they present after 10 days and/or they have aneurysms. Treatment may limit the damage.
Monitored outcomes:
1. Start IVGG within 4 hours of diagnosis of KS
2. Follow-up appointment arranged before discharge
3. Afebrile at time of discharge
Levels of Evidence
The referenced studies in this MAP are notated with regard to the strength of evidence available according to the following hierarchy:
Levels of Evidence
I. Well conducted randomized placebo-controlled trials: strong
evidence.
II. Well designed controlled studies without randomization including cohort and
case control studies: fair evidence.
III. Expert opinion, case studies, and before and after studies: poor evidence.