• In the absence of a specific diagnostic test or pathognomonic feature, clinical criteria have been established to assist physicians in diagnosing Kawasaki Disease
• Taking a careful history is necessary in children who lack a clear explanation for fever
• Clinical features may not be present simultaneously, watchful waiting is sometimes necessary before a diagnosis can be made
• Three clinical phases occur in the natural history of Kawasaki disease
  • Acute phase: 1st 2 weeks of illness; characterized by fever & other acute signs of illness
  • Subacute phase: 3rd & 4th week of illness; characterized by desquamation, thrombocytosis, development of coronary aneurysms & is associated w/ highest risk of sudden death in patients in whom aneurysms have developed
  • Convalescence phase: from 5th to 8th week since the onset of illness; all clinical signs of illness have disappeared & continues until erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP) returns to normal level

Incomplete Kawasaki Disease

• Patients w/ an inflammatory disorder who did not meet the clinical case definition but w/ persistent fever, at least 2 of the principal clinical features, & echocardiography revealing coronary artery abnormalities
• More common in young infants <1 year of age
• Accurate diagnosis & timely treatment is important due to substantial risk of developing coronary abnormalities
• Lab findings similar to those of classic cases
• These patients may also clinically display noncoronary cardiac lesions (eg pancarditis, conduction system abnormalities, subclinical ventricular dysfunction or subtle ventricular dilations) which are possibly independent of coronary artery abnormalities
• Atypical Kawasaki disease refers to patients who have a problem (ie renal impairment) that generally is not seen in patients w/ Kawasaki disease

• Approximately 10-20% of patients fail to respond to initial intravenous immunoglobulin (IVIG) treatment
  • Failure may be described as patients in whom inflammatory parameters do not subside & fever persists or recurs 24-48 hours after intravenous immunoglobulin (IVIG) infusion

• Several factors may predict patient’s unresponsiveness to intravenous immunoglobulin (IVIG):
  • Low levels of sodium & albumin
  • Low platelet count
  • Day of illness at initial treatment
  • Neutrophil leukocytosis
  • High C-reactive protein (CRP) level & transaminases
  • Patient’s age

• Patients who failed to respond to treatment have a higher risk of developing coronary artery abnormalities

• Even though nonspecific, can provide diagnostic support in patients w/ clinical features that are suggestive of Kawasaki disease
• Certain lab findings are characteristic of Kawasaki disease
• Complete blood count (CBC)
  • Neutrophil leukocytosis (predominance of immature & mature granulocytes)
  • Mild to moderate normochromic anemia [hemoglobin levels <2 standard deviation (SD) for age]
  • Platelet count rapidly increases w/in the next 2 weeks (ranges from 500,000 to >1 million/mm³)
    • A low platelet count at illness presentation is a risk factor for coronary aneurysm
    • Thrombocytopenia is seen rarely in the acute stage & may be a sign of disseminated intravascular coagulation

• Inflammatory markers
  • Elevated erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP), usually returns to normal by 6-10 weeks after the onset of illness
    • Erythrocyte sedimentation rate (ESR) often above 40 mm/hour; C-reactive protein (CRP) typically reaches levels of 3 mg/dL
    • C-reactive protein (CRP) is more accurate after intravenous immunoglobulin (IVIG) therapy since intravenous immunoglobulin (IVIG) elevates the erythrocyte sedimentation rate (ESR)
  • Elevated serum amyloid-A (SAA)

• Mild to moderate elevations of serum transaminase may occur in ≤40% of patients
• Mild hyperbilirubinemia in approximately 10%
  • Hypoalbuminemia is common & associated w/ more severe & prolonged acute disease

• Urinalysis: proteinuria, leukocytosis, Intermittent mild to moderate sterile pyuria
• Cerebrospinal fluid analysis
  • Approximately 50% demonstrate evidence of aseptic meningitis w/ predominance of mononuclear cells, as well as normal glucose & protein levels
• Synovial fluid analysis
  • Purulent fluid w/ white blood cell count of 125,000-300,000/mm³

• Plasma lipids are markedly altered; depressed plasma cholesterol, high density lipoprotein & apolipoprotein
• Cardiac enzymes
  • Serum cardiac troponin I - marker specific for myocardial damage reported in acute Kawasaki Disease

Electrocardiogram (ECG) at rest

• During acute phase, reveals findings suggestive of myocardial injury & abnormal repolarization: prolonged PR interval, deep Q waves, prolonged QT interval, low voltage, ST-T changes & arrhythmias

Holter Electrocardiogram (ECG)

• Patients w/ stenosis or giant aneurysm should undergo holter electrocardiogram (ECG) recording at least once to determine whether ischemic findings are present or development of high-risk arrhythmias is possible
• Used in patients complaining of frequent chest pain, chest discomfort &/or palpitations

• W/ the exception of echocardiography, imaging studies are not performed routinely in suspected Kawasaki disease patients
• Evaluation of cardiovascular sequelae requires serial cardiac ultrasound studies

Chest X-ray (X-ray)

• Abnormalities are observed in about 15% of patients
• Peribronchial cuffing or increased interstitial markings w/ occasional pulmonary nodules
• Abnormal or enlarged heart shadow in patients w/ poor cardiac function due to chronic myocardial infarction (MI) & in patients w/ volume overload caused by mitral or aortic insufficiency
• Presence of calcification of coronary aneurysm suggests the presence or progression of giant aneurysm or stenotic lesions

• For uncomplicated cases, should be performed at the time of diagnosis, at 2 weeks & at 6-8 weeks after the onset of illness
• More frequent echocardiographic evaluation is needed to guide management in children w/ higher risk
• Ideal imaging modality for cardiac assessment
  • Has a high sensitivity & specificity for the detection of abnormalities of the proximal left main coronary artery (LMCA) & right coronary artery (RCA)
  • Frequent sites of coronary aneurysms are the proximal left anterior descending coronary artery, proximal right coronary artery & left main coronary artery (LMCA)

• Can be used to evaluate coronary morphology over time to detect coronary dilatation specific to coronary artery lesions associated w/ Kawasaki disease
• Can also determine the presence/absence of thrombi w/in aneurysms
• Most useful method in evaluating cardiac function deterioration due to myocardial injury & the severity of valvular disease

Stress Echocardiography

• Indicated to assess the existence & functional consequences of coronary artery abnormalities in children w/ Kawasaki disease & coronary aneurysm
• Enables real time evaluation of left ventricular wall motion in patients during exercise (treadmill or ergometer) or w/ administration of Dobutamine or Dipyridamole

Other tests

• Doppler color echocardiography
• Magnetic resonance imaging (MRI) & magnetic resonance angiography (MRA)
• Dual-source computed tomography (DSCT)
• Coronary angiography
• Intravascular ultrasound
• Cardiac catheterization

• Coronary artery aneurysms or ectasia develop in approximately 15 to 25% of untreated children & may lead to myocardial infarction (MI), ischemic heart disease or sudden death
• Although damage of coronary vessels is the main complication of Kawasaki disease, systemic inflammation in other organs (eg myocardium, liver, lungs or kidneys) has been documented
• Leading cause of acquired heart disease in children <5 years of age living in developed countries