Kawasaki's Disease

1. Epidemiology: Incidence
   1. Japanese descent: 150 per 100,000 children <5 years
   2. Overall U.S.: 10-15 per 100,000 children <5 years
   3. Age of onset
      1. Most cases occur by age 5 years old (but can occur in older children)
      2. Peak age of onset: 1 to 2 years old
      3. Rare under 4 months of age
   4. Gender: Boys more often affected
   5. More common in winter and spring
2. Pathophysiology
   1. Idiopathic Vasculitis
   2. Postulated associations
      1. Retrovirus
      2. Rickettsia
3. Symptoms
   1. Fever for 5 days or more
   2. Irritability
4. Diagnosis: Requires fever and 4 other criteria
   1. Fever prolonged more than 5 days (100%)
      1. Fever >102.2 F (often >104 F) with abrupt onset
      2. Duration: Averages 11 days untreated
   2. Polymorphous skin eruption on trunk (80%)
      1. Starts within first five days with a 7 day duration
      2. Groin rash accentuated
      3. May appear morbiliform or Urticarial
      4. No bullae or vessicles
   3. Conjunctivitis (84%)
      1. Bilateral Conjunctival injection (bulbar)
      2. No Ciliary Flush (no limbus injection)
      3. No photophobia
      4. No Eye Pain
      5. Non-purulent
      6. May be associated with painless anterior Uveitis
   4. Acute Lymphadenopathy
      1. Typically a single, unilateral, minimally tender node >1.5 cm (73%)
      2. Cervical Lymphadenopathy is most common
   5. Changes in hands and feet
      1. Edema of hands and feet - may be painful (65%)
      2. Red palms and soles (69%)
         1. Sharp demarcation at ankles and wrists
      3. Desquamation of fingertips (80%)
         1. Late sign occurs at 1 to 2 weeks
         2. Starts at periungual area
   6. Mucus mebrane changes (92%)
      1. Dry, red, fissured, or vertically cracked lips
      2. Strawberry Tongue
      3. Diffuse reddening of the oropharynx
      4. No focal lesions, exudates, Vesicles or ulcers
5. Signs: Other Associated
   1. Urethritis with sterile pyuria (75%)
   2. Polyarthralgia
   3. Abdominal Pain and Diarrhea (25%)
   4. Aseptic Meningitis (25%)
   5. Cardiac Disease (20%)
      1. Pericardial Effusion
      2. Congestive Heart Failure
      3. Arrhythmias
   6. Obstructive Jaundice with acute gallbladder hydrops
6. Differential Diagnosis
   1. Juvenile Rheumatoid Arthritis
   2. Hypersensitivity Reaction
      1. Medication allergy
      2. Mercury Poisoning
      3. Serum Sickness
      4. Stevens-Johnson Syndrome
   3. Bacterial infection
      1. Leptospirosis
      2. Rocky Mountain Spotted Fever
      3. Scarlet Fever
      4. Staphylococcal scalded skin syndrome
      5. Toxic shock syndrome
   4. Viral infection
      1. Mononucleosis
      2. Measles
      3. Adenovirus
      4. Parvovirus B19
7. Labs
   1. Complete Blood Count with differential cell count
      1. Leukocytosis
      2. Thrombocytosis
   2. Erythrocyte Sedimentation Rate >40 mm/hr (may be >100)
   3. C-Reactive Protein (CRP) >3 mg/dl
      1. Preferred (unlike ESR, CRP is not altered with IVIG administration)
   4. Liver Function Tests
   5. Blood Culture
   6. Throat Culture
   7. Antistreptolysin-O Titer (ASO Titer)
   8. Urinalysis
      1. Sterile pyuria
   9. Consider Lumbar Puncture if Meningitis suspected
8. Diagnostics
   1. Electrocardiogram (EKG)
      1. May demonstrate strain pattern (ST and T Wave changes)
   2. Chest XRay
      1. Observe for cardiomegaly
9. Imaging: Echocardiogram Coronary Artery evaluation
   1. Initial Echocardiogram at presentation
   2. Follow-up Echocardiogram at 2 weeks and 6-8 weeks
   3. Indications for Echocardiogram at 6-12 months
      1. Abnormalities on prior Echocardiograms
      2. AHA guidelines currently recommend in all patients
      3. However no benefit if prior Echocardiograms normal
      4. Tuohy (2001) Am J Cardiol 88:328-30
   4. Findings
      1. Coronary Artery changes
         1. Acute: Tapering, perivascular brightness, ectasia
         2. Late: Coronary Artery aneurysm
      2. Other variable changes
         1. Decreased ventricular function
         2. Pericardial Effusion
10. Evaluation
    1. Diagnostic criteria met (five days of fever and 4 of the 5 other findings present)
       1. Treat as Kawasaki Disease
       2. May also treat at 4 days if criteria otherwise met
    2. Diagnostic criteria not met (five days of fever with only 2-3 other findings)
       1. CRP <3 mg/dl and ESR <40 mm/h
          1. Discharge home with follow-up
          2. Repeat labs and other testing if fever persists
       2. CRP >3 mg/dl or ESR >40 mm/h
          1. Obtain additional criteria (requires 3 or more)
             1. Serum Albumin <3 g/dl
             2. Anemia
             3. Serum ALT increased
             4. White Blood Cell count >12,000
             5. Platelet Count >450,000
             6. Sterile pyuria
          2. Three or more additional criteria present
             1. Treat as Kawasaki Disease
          3. Less than three additional criteria
             1. Obtain Echocardiogram
11. Management
    1. Admission
    2. Hydration
    3. Obtain Rheumatology and Cardiology consultation
    4. Observe for and treat Congestive Heart Failure
    5. Cardiac monitoring in all patients
    6. Start treatment as soon as possible
       1. Especially within 10 days of onset
    7. Aspirin
       1. Initial: 60-110 mg/kg/day divided every 6 hours
       2. Later: 5-10 mg/kg/day for 6-8 weeks
          1. Start after fever has resolved at least 2 days or
          2. 14 days passes since onset of illness
    8. Intravenous Gamma Globulin (IVIG)
       1. Dose: 2 mg/kg over 8-12 hours
       2. Must be given early in disease to be efficacious
       3. Risk of Hypotension and Seizures
    9. Other agents to consider
       1. Abciximab (Remicade)
12. Complications: General
    1. Late complications (>1-2 weeks)
       1. Coronary Artery aneurysm (see below)
    2. Early complications
       1. Myocarditis
       2. Pericarditis
       3. Valvular insufficiency
       4. Arrhythmia
13. Complications: Coronary Artery aneurysm
    1. Incidence
       1. Occurs in 20% of untreated Kawasaki's Disease
       2. Occurs in 2% of treated Kawasaki's Disease
    2. Mechanism: Coronary ArteryVasculitis
    3. Occurs 2-4 weeks after onset of illness
    4. Most aneurysms regress in 1-2 year
       1. Spontaneously resolve in 33-66% of cases
    5. Associated Risks
       1. Subsequent stenosis
       2. Thrombosis leading to Myocardial Infarction
       3. Sudden Death
    6. Risk Stratification
       1. Risk Level 1: Normal coronary arteries on imaging
          1. May stop Aspirin at 8 weeks following onset
          2. Life-long counseling on Cardiac Risk Factors
             1. Long-term endothelial dysfunction risk
       2. Risk Level 2: Transient coronary ectasia, dilation
          1. Same approach as Risk Level 1
       3. Risk Level 3: 3-6 mm coronary aneurysms (Z-Score 3-7)
          1. Aspirin for >8 weeks and until aneurysm regresses
          2. Stress Test every 2 years before sports if age >10
          3. Annual Echocardiogram and Electrocardiogram
       4. Risk Level 4: >6 mm coronary aneurysms or multiple
          1. Long-term Aspirin
          2. Warfarin for giant aneurysms
          3. Annual cardiac stress test
          4. Echocardiogram and Electrocardiogram every 6 months
          5. Cardiac angiogram 6-12 months after illness
          6. Avoid collision sports
       5. Risk Level 5: Obstructed Coronary Artery aneurysms
          1. Includes recommendations for risk level 4
          2. Beta Blocker
14. References
    1. Claudius in Majoewsky (2012) EM:Rap 12(11): 8-9
    2. Dummer (2004) Progress Pediatr Cardiol 19:129-35
    3. Freeman (2006) Am Fam Physician 74:1141-50
    4. Newburger (2004) Pediatrics 114:1708-33